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Minds Handbook for Clinical Practice Guideline Development 2014

Editorial Supervisors: Tsuguya Fukui, Naohito Yamaguchi Editors: Toshio Morizane, Masahiro Yoshida, Noriko Kojimahara

VERSION 1.0

February 1, 2015

Minds Guideline Center Japan Council for Quality Health Care

This document is translated from “Minds 診療ガイドライン作成の手引 2014” (Japanese) issued by IGAKU-SHOIN Ltd. with

permission.

Minds H

andbook for Clinical P

ractice Guideline D

evelopment 2014



VERSION 1.0

February 1, 2015



permission.

天地センター 1



VERSION 1.0

February 1, 2015



permission.

天地センター 1

Minds Handbook for Clinical Practice Guideline Development 2014 Publication:　 February 1, 2015. Version 1.0 Editorial Supervisors:

Tsuguya Fukui, Naohito Yamaguchi Editors: Toshio Morizane, Masahiro Yoshida, Noriko Kojimahara Publisher: Minds Guideline Center, Japan Council for Quality

Health Care

Reproduction of this work (copying, scanning, digitizing, etc.) without permission is prohibited with limited exceptions permitted under the Copyright Act, such as “reproduction for private use.”

Recommended citation form Minds Guideline Center, Japan Council for Quality Health Care (2014). Minds Handbook for Clinical Practice Guideline Development 2014.

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Minds Handbook for Clinical Practice Guideline Development 2014 Publication:　 February 1, 2015. Version 1.0 Editorial Supervisors:

Tsuguya Fukui, Naohito Yamaguchi Editors: Toshio Morizane, Masahiro Yoshida, Noriko Kojimahara Publisher: Minds Guideline Center, Japan Council for Quality

Health Care

Reproduction of this work (copying, scanning, digitizing, etc.) without permission is prohibited with limited exceptions permitted under the Copyright Act, such as “reproduction for private use.”

Recommended citation form Minds Guideline Center, Japan Council for Quality Health Care (2014). Minds Handbook for Clinical Practice Guideline Development 2014.

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Editorial Supervisors Tsuguya Fukui

Chairman, Guideline Evaluation and Approval Committee, Minds Guideline Center, Japan Council for Quality Health Care Chairman of the Board of Trustees, St. Luke’s International University President, St. Luke’s International Hospital

Naohito Yamaguchi

Director, Minds Guideline Center, Executive Board Member, Japan Council for Quality Health Care Professor, Department of Public Health, School of Medicine, Tokyo Women’s Medical University

Editors Toshio Morizane

Chairman, EBM and Guideline Development Support Committee, Minds Guideline Center, Senior Visiting Researcher, Japan Council for Quality Health Care Part-time Lecturer, Department of Internal Medicine, School of Medicine, Keio University Visiting Professor, Faculty of Medicine, Toho University Part-time Physician, Center for Digestive and Liver Diseases, Ofuna Chuo Hospital

Masahiro Yoshida

General Manager, Department of EBM and Guidelines, Minds Guideline Center, Japan Council for Quality Health Care Professor, Clinical Research Centers for Medicine, International University of Health and Welfare Director, Department of Hemodialysis and Surgery, Chemotherapy Research Institute, KAKEN Hospital

Noriko Kojimahara

Member, EBM and Guideline Development Support Committee, Minds Guideline Center, Visiting Researcher, Japan Council for Quality Health Care Associate Professor, Department of Public Health, School of Medicine, Tokyo Women’s Medical University

Grateful acknowledgment is made to the individuals who contributed to the production of this handbook.

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Editorial Supervisors Tsuguya Fukui

Chairman, Guideline Evaluation and Approval Committee, Minds Guideline Center, Japan Council for Quality Health Care Chairman of the Board of Trustees, St. Luke’s International University President, St. Luke’s International Hospital

Naohito Yamaguchi


Editors Toshio Morizane


Masahiro Yoshida


Noriko Kojimahara


Grateful acknowledgment is made to the individuals who contributed to the production of this handbook.

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Authors (in the order of the Japanese hiragana) Akiko Okumura

Leader, Department of EBM and Guidelines, Minds Guideline Center, Japan Council for Quality Health Care

Fujimi Kawai

Member, EBM and Guideline Development Support Committee, Minds Guideline Center, Japan Council for Quality Health Care Manager, St. Luke’s International University Library

Kosuke Kiyohara

Visiting Researcher, Japan Council for Quality Health Care Assistant Professor, Department of Public Health, School of Medicine, Tokyo Women’s Medical University

Noriko Kojimahara


Yasuto Sato

Member, EBM and Guideline Development Support Committee, Minds Guideline Center, Visiting Researcher, Japan Council for Quality Health Care Lecturer, Department of Public Health, School of Medicine, Tokyo Women’s Medical University

Yosuke Hatakeyama

Department of EBM and Guidelines, Minds Guideline Center, Japan Council for Quality Health Care

Toshio Morizane


Naohito Yamaguchi


Masahiro Yoshida


External Review Committee Members (in the order of the Japanese alphabet) Takahiro Okamoto

Professor, Department of Endocrine Surgery, Tokyo Women’s Medical University

Hiromichi Kuwabara

Director, Jinho Law Office Visiting Professor, Faculty of Medicine, Toho University

Kiichiro Tsutani

Project Professor, Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, University of Tokyo

Takeo Nakayama

Professor, Department of Health Informatics, School of Public Health, Graduate School of Medicine, Kyoto University

Toshio Fukuoka

Chief Director, Department of General Medicine, Ohara Memorial Healthcare Foundation Kurashiki Central Hospital

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Authors (in the order of the Japanese hiragana) Akiko Okumura

Leader, Department of EBM and Guidelines, Minds Guideline Center, Japan Council for Quality Health Care

Fujimi Kawai

Member, EBM and Guideline Development Support Committee, Minds Guideline Center, Japan Council for Quality Health Care Manager, St. Luke’s International University Library

Kosuke Kiyohara

Visiting Researcher, Japan Council for Quality Health Care Assistant Professor, Department of Public Health, School of Medicine, Tokyo Women’s Medical University

Noriko Kojimahara


Yasuto Sato

Member, EBM and Guideline Development Support Committee, Minds Guideline Center, Visiting Researcher, Japan Council for Quality Health Care Lecturer, Department of Public Health, School of Medicine, Tokyo Women’s Medical University

Yosuke Hatakeyama

Department of EBM and Guidelines, Minds Guideline Center, Japan Council for Quality Health Care

Toshio Morizane


Naohito Yamaguchi


Masahiro Yoshida


External Review Committee Members (in the order of the Japanese alphabet) Takahiro Okamoto

Professor, Department of Endocrine Surgery, Tokyo Women’s Medical University

Hiromichi Kuwabara

Director, Jinho Law Office Visiting Professor, Faculty of Medicine, Toho University

Kiichiro Tsutani

Project Professor, Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, University of Tokyo

Takeo Nakayama

Professor, Department of Health Informatics, School of Public Health, Graduate School of Medicine, Kyoto University

Toshio Fukuoka

Chief Director, Department of General Medicine, Ohara Memorial Healthcare Foundation Kurashiki Central Hospital

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Editorial Management Kyoko Tamura, Madoka Utagawa Minds Guideline Center, Japan Council for Quality Health Care For general comments or inquiries about the contents Minds Guideline Center, Japan Council for Quality Health Care [email protected] Toyo Bldg. 1-4-17 Misaki-cho, Chiyoda-ku, Tokyo 101-0061 TEL: 03─5217─2325/FAX: 03─5217─2330

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Editorial Management Kyoko Tamura, Madoka Utagawa Minds Guideline Center, Japan Council for Quality Health Care For general comments or inquiries about the contents Minds Guideline Center, Japan Council for Quality Health Care [email protected] Toyo Bldg. 1-4-17 Misaki-cho, Chiyoda-ku, Tokyo 101-0061 TEL: 03─5217─2325/FAX: 03─5217─2330

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2014 Edition Preface

Approximately seven years have passed since the publication of the “Minds Handbook for Clinical Practice Guideline Development 2007.” In the meantime, Japan followed the United States and several advanced nations in Europe and saw a large number of high-quality “clinical practice guidelines (CPGs) founded on the principle of evidence-based medicine (EBM)” developed by specialized medical societies and such. Many of these CPGs can be viewed on the Minds website and a growing number of them are becoming available in both Japanese and English. As one of the advocates who have long urged the development of “evidence-based CPGs” as the most effective method to disseminate EBM since the time when no such guidelines existed in Japan, I now reflect with amazement on how much progress has been made over these years. At the same time, I would like to pay my respects to many individuals who have dedicated their efforts to the development of CPGs.

Structurally, there is a limit to how many CPGs Minds can publish in a certain period of time. Therefore, a process is required for selecting the ones to be published from the numerous CPGs that have been developed. For this purpose, the Guideline Evaluation and Approval Committee was established within Minds and I have been taking part in its bimonthly selection process with the secretariat staff and other committee members. In the selection process, we refer to the Appraisal of Guidelines for Research and Evaluation II (AGREE II), which is the 2009 revised edition of AGREE, a global evaluation instrument released in 2003, and place particular emphasis on the points relating to the stringency of the development process. Although there has been an increase in the number of “evidence-based CPGs” that are close to ideal, we have also been able to identify the areas for improvement shared by the majority of CPGs. For example, many of them fail to provide sufficient descriptions about intentions or views of the groups targeted by the CPGs (patients, the public, etc.), as well as about the criteria for monitoring or supervising the degree of conformity with the CPGs at clinical sites. Particularly with regard to the latter, such criteria can help promote the use of CPGs in clinical settings, and are essential in the measurement of Quality Indicators, which are becoming increasingly prevalent in Japan, and in the adoption of the Plan–Do–Check–Act (PDCA) cycle.

Since the time when “evidence-based CPGs” first became a topic of discussion in the medical community of our nation, one issue that had worried many was the legal aspect of CPGs. Analysis of the data on recent medical lawsuits revealed that CPGs may constitute at least a part of the medical standards but are not considered normative, as clinicians had originally feared. Nevertheless, if the treatment actually provided was found inconsistent with CPGs, the doctor might not be questioned for the violation of “duty of care,” but would still be held responsible for an infringement of the duty to explain. Therefore, it is necessary for doctors to stay abreast of the latest CPGs and be ready to provide adequate explanations for patients whenever needed. In addition, when providing treatment not in line with the recommendations in CPGs, it is strongly suggested that the doctor state the reason in the patient’s medical record.

This book (Handbook 2014) describes the procedure of developing CPGs in great detail and provides many templates that can be used in the process. Compared to the previous edition (Handbook 2007), the

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2014 Edition Preface

Approximately seven years have passed since the publication of the “Minds Handbook for Clinical Practice Guideline Development 2007.” In the meantime, Japan followed the United States and several advanced nations in Europe and saw a large number of high-quality “clinical practice guidelines (CPGs) founded on the principle of evidence-based medicine (EBM)” developed by specialized medical societies and such. Many of these CPGs can be viewed on the Minds website and a growing number of them are becoming available in both Japanese and English. As one of the advocates who have long urged the development of “evidence-based CPGs” as the most effective method to disseminate EBM since the time when no such guidelines existed in Japan, I now reflect with amazement on how much progress has been made over these years. At the same time, I would like to pay my respects to many individuals who have dedicated their efforts to the development of CPGs.

Structurally, there is a limit to how many CPGs Minds can publish in a certain period of time. Therefore, a process is required for selecting the ones to be published from the numerous CPGs that have been developed. For this purpose, the Guideline Evaluation and Approval Committee was established within Minds and I have been taking part in its bimonthly selection process with the secretariat staff and other committee members. In the selection process, we refer to the Appraisal of Guidelines for Research and Evaluation II (AGREE II), which is the 2009 revised edition of AGREE, a global evaluation instrument released in 2003, and place particular emphasis on the points relating to the stringency of the development process. Although there has been an increase in the number of “evidence-based CPGs” that are close to ideal, we have also been able to identify the areas for improvement shared by the majority of CPGs. For example, many of them fail to provide sufficient descriptions about intentions or views of the groups targeted by the CPGs (patients, the public, etc.), as well as about the criteria for monitoring or supervising the degree of conformity with the CPGs at clinical sites. Particularly with regard to the latter, such criteria can help promote the use of CPGs in clinical settings, and are essential in the measurement of Quality Indicators, which are becoming increasingly prevalent in Japan, and in the adoption of the Plan–Do–Check–Act (PDCA) cycle.

Since the time when “evidence-based CPGs” first became a topic of discussion in the medical community of our nation, one issue that had worried many was the legal aspect of CPGs. Analysis of the data on recent medical lawsuits revealed that CPGs may constitute at least a part of the medical standards but are not considered normative, as clinicians had originally feared. Nevertheless, if the treatment actually provided was found inconsistent with CPGs, the doctor might not be questioned for the violation of “duty of care,” but would still be held responsible for an infringement of the duty to explain. Therefore, it is necessary for doctors to stay abreast of the latest CPGs and be ready to provide adequate explanations for patients whenever needed. In addition, when providing treatment not in line with the recommendations in CPGs, it is strongly suggested that the doctor state the reason in the patient’s medical record.

This book (Handbook 2014) describes the procedure of developing CPGs in great detail and provides many templates that can be used in the process. Compared to the previous edition (Handbook 2007), the

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contents are far more advanced, but there is no change to the basic concept of EBM. To improve the validity on both scientific and ethical grounds, the methods of developing “evidence-based CPGs” themselves are evolving worldwide. At the initiative of the editors, Dr. Toshio Morizane, Dr. Masahiro Yoshida, and Dr. Noriko Kojimahara, doctors who are well versed in the latest information on the methods of developing CPGs had made substantial changes to the previous edition within the range considered feasible in Japan. The book was then subjected to external reviews by experts in the field before being completed.

We hope that this book will be widely used to further enhance the quality of “evidence-based CPGs,” which serve as an essential tool in improving the quality of the medical care of our nation.

March 2014 On behalf of the editorial supervisors

Tsuguya Fukui

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contents are far more advanced, but there is no change to the basic concept of EBM. To improve the validity on both scientific and ethical grounds, the methods of developing “evidence-based CPGs” themselves are evolving worldwide. At the initiative of the editors, Dr. Toshio Morizane, Dr. Masahiro Yoshida, and Dr. Noriko Kojimahara, doctors who are well versed in the latest information on the methods of developing CPGs had made substantial changes to the previous edition within the range considered feasible in Japan. The book was then subjected to external reviews by experts in the field before being completed.

We hope that this book will be widely used to further enhance the quality of “evidence-based CPGs,” which serve as an essential tool in improving the quality of the medical care of our nation.

March 2014 On behalf of the editorial supervisors

Tsuguya Fukui

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Preface to the First Edition

A broad range of medical knowledge and understanding of each patient’s individuality play an essential role in treating diseases and resolving problems in medical care. However, with medical knowledge alone, there is a diverse range of fields to cover and scientific information and techniques in each field continue to expand and advance. It is virtually impossible for a single medical practitioner to adequately resolve all diseases and problems. By preparing guidelines that describe the clinical practice actually performed by the most skilled experts in each field, many other medical practitioners can refer to the guidelines in their practice, which should allow more patients to receive high-quality medical care equivalent to expert levels. Such ideas must have emerged when it first became the norm for medical care to be provided by specialists. In fact, since the time of Hippocrates in ancient Greece, a myriad of “clinical practice guidelines” have been created.

These guidelines were conventionally developed at individual levels using various methods. However, around 1990, when efficacy, safety, and economic efficiency became important in medical care, attempts were initiated to develop “clinical practice guidelines” through reasonable (scientific) methods among Western nations, which were eventually developed into national projects to promote the dissemination of such guidelines, while objectively evaluating their clinical efficacy.

The Institute of Medicine, a subsidiary organization of the U.S. National Academy of Sciences, defined clinical practice guidelines (CPGs) in its 1990 report as “systematically developed statements to assist practitioners and patients make decisions about appropriate health care for specific clinical circumstances.”1) It said that the greatest characteristic of CPGs is that they are developed through a procedure founded on the principle of evidence-based medicine (EBM). In the United States, due to the widespread use of CPGs developed by an external Federal agency known as the Agency for Health Care Policy and Research (AHCPR), currently the Agency for Healthcare Research and Quality (AHRQ), as well as those developed through allocated research grants, it seems impossible to talk about the nation’s medical care without referring to “evidence-based CPGs.”

On the other hand, Japan’s Ministry of Health, Labour and Welfare has also played a significant role in the

dissemination of “evidence-based CPGs” in our nation. In the Study Group on Health Technology Assessment (HTA) for 1996–97, the status of the overseas dissemination of the concept of EBM and EBM-based procedure was shared for the first time, and the subsequently established Study Group on the Promotion of HTA (1998–99) decided on implementing educational workshops and research promotion for CPG developers as measures to disseminate EBM in Japan. At the same time, the group collected expert opinions from the aspects of morbidity rates and individual/social burdens and set the priority order for diseases and conditions to develop CPGs for. After 1990, specialized medical societies and research groups approved for research grants were required to attend a briefing session on the EBM-based procedure before

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Preface to the First Edition

A broad range of medical knowledge and understanding of each patient’s individuality play an essential role in treating diseases and resolving problems in medical care. However, with medical knowledge alone, there is a diverse range of fields to cover and scientific information and techniques in each field continue to expand and advance. It is virtually impossible for a single medical practitioner to adequately resolve all diseases and problems. By preparing guidelines that describe the clinical practice actually performed by the most skilled experts in each field, many other medical practitioners can refer to the guidelines in their practice, which should allow more patients to receive high-quality medical care equivalent to expert levels. Such ideas must have emerged when it first became the norm for medical care to be provided by specialists. In fact, since the time of Hippocrates in ancient Greece, a myriad of “clinical practice guidelines” have been created.

These guidelines were conventionally developed at individual levels using various methods. However, around 1990, when efficacy, safety, and economic efficiency became important in medical care, attempts were initiated to develop “clinical practice guidelines” through reasonable (scientific) methods among Western nations, which were eventually developed into national projects to promote the dissemination of such guidelines, while objectively evaluating their clinical efficacy.

The Institute of Medicine, a subsidiary organization of the U.S. National Academy of Sciences, defined clinical practice guidelines (CPGs) in its 1990 report as “systematically developed statements to assist practitioners and patients make decisions about appropriate health care for specific clinical circumstances.”1) It said that the greatest characteristic of CPGs is that they are developed through a procedure founded on the principle of evidence-based medicine (EBM). In the United States, due to the widespread use of CPGs developed by an external Federal agency known as the Agency for Health Care Policy and Research (AHCPR), currently the Agency for Healthcare Research and Quality (AHRQ), as well as those developed through allocated research grants, it seems impossible to talk about the nation’s medical care without referring to “evidence-based CPGs.”

On the other hand, Japan’s Ministry of Health, Labour and Welfare has also played a significant role in the

dissemination of “evidence-based CPGs” in our nation. In the Study Group on Health Technology Assessment (HTA) for 1996–97, the status of the overseas dissemination of the concept of EBM and EBM-based procedure was shared for the first time, and the subsequently established Study Group on the Promotion of HTA (1998–99) decided on implementing educational workshops and research promotion for CPG developers as measures to disseminate EBM in Japan. At the same time, the group collected expert opinions from the aspects of morbidity rates and individual/social burdens and set the priority order for diseases and conditions to develop CPGs for. After 1990, specialized medical societies and research groups approved for research grants were required to attend a briefing session on the EBM-based procedure before

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developing CPGs. Finally, the 2001 Study Group on the Dissemination of Health Technology Information decided that completed CPGs were to be disseminated via the Internet and other media by the Japan Council for Quality Health Care. As of August 2007, a total of 38 CPGs are being published on the Minds website by the Medical Information Network Distribution Service within the Japan Council for Quality Health Care, which are accessible to not just doctors but the general public as well.

As a member, I participate in all of the three study groups relating to EBM and CPGs mentioned above,

and since 1999, have explained the concept of EBM and the procedure to develop CPGs to specialized medical societies and research groups in briefing sessions before they undertake CPG development. In November 2001, “the Procedure to Develop Clinical Practice Guidelines, ver. 4.3”2) was published in print and on the Internet, which has served as a reference guide for the development of many CPGs. Now, we once again worked out the procedure to develop CPGs that is considered the most valid at this time based on our accumulated experience of developing CPGs and evaluating the quality of CPGs to select the ones to be published on the Minds website.

It is our sincere hope that this handbook will be widely used for the development of CPGs of higher

quality to help improve patient outcomes, which is its ultimate objective. August 2007

On behalf of the editors Tsuguya Fukui

[Literature] 1) Field MJ, Lohr KN, (eds.). Clinical Practice Guidelines: Directions for a new program. Washington, DC,

National Academy Press, 1990. 2) Fukui T, Tango T. Shinryo Gaidorain no Sakusei no Tejun (The Procedure to Develop Clinical Practice

Guidelines) ver. 4.3, 7 Nov 2001.

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developing CPGs. Finally, the 2001 Study Group on the Dissemination of Health Technology Information decided that completed CPGs were to be disseminated via the Internet and other media by the Japan Council for Quality Health Care. As of August 2007, a total of 38 CPGs are being published on the Minds website by the Medical Information Network Distribution Service within the Japan Council for Quality Health Care, which are accessible to not just doctors but the general public as well.

As a member, I participate in all of the three study groups relating to EBM and CPGs mentioned above,

and since 1999, have explained the concept of EBM and the procedure to develop CPGs to specialized medical societies and research groups in briefing sessions before they undertake CPG development. In November 2001, “the Procedure to Develop Clinical Practice Guidelines, ver. 4.3”2) was published in print and on the Internet, which has served as a reference guide for the development of many CPGs. Now, we once again worked out the procedure to develop CPGs that is considered the most valid at this time based on our accumulated experience of developing CPGs and evaluating the quality of CPGs to select the ones to be published on the Minds website.

It is our sincere hope that this handbook will be widely used for the development of CPGs of higher

quality to help improve patient outcomes, which is its ultimate objective. August 2007

On behalf of the editors Tsuguya Fukui

[Literature] 1) Field MJ, Lohr KN, (eds.). Clinical Practice Guidelines: Directions for a new program. Washington, DC,

National Academy Press, 1990. 2) Fukui T, Tango T. Shinryo Gaidorain no Sakusei no Tejun (The Procedure to Develop Clinical Practice

Guidelines) ver. 4.3, 7 Nov 2001.

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Introduction

The Japan Council for Quality Health Care launched the Medical Information Network Distribution Service (Minds) in 2002 under the Project for EBM Guideline Promotion. Clinical practice guidelines (CPGs), which were selected as highly credible from the viewpoint of development method, are shared online on the Minds website (http://Minds.jcqhc.or.jp/n/). Furthermore, Minds assigns the highest priority to proposing the method of developing CPGs based on the principle of EBM to relevant medical societies and research groups – the primary developers of CPGs – and providing support for their guideline development. In 2007, Minds published the “Minds Handbook for Clinical Practice Guideline Development 2007” (Handbook 2007) to propose the procedure to develop CPGs that was considered appropriate at that time. Now, as seven years have passed, the method has evolved substantially across the world, and newly improved methods are being established. Accordingly, Minds decided to compile a revised edition of the Handbook 2007 and publish the “Minds Handbook for Clinical Practice Guideline Development 2014” (Handbook 2014) to introduce the newly established methods. The Handbook 2014 covers much of the same contents as the Handbook 2007, but provides better descriptions of certain contents that were not sufficiently described in the Handbook 2007.

The Handbook 2014 emphasizes the importance of the idea of “body of evidence.” To develop a CPG, the established method called systematic review should be adopted, in which the evidence is searched for systematically in published research articles or other sources and is evaluated and integrated as the body of evidence. The Handbook 2014 also emphasizes the importance of the idea of “balance between benefit and harm.” When a CPG proposes a recommendation of an intervention method that can be considered the most appropriate among alternative intervention options in certain clinical circumstances of diagnosis, treatment, prevention, or nursing care, the harm of interventions should be given as high an emphasis as the benefit in comparing alternative intervention methods.

Potential users of this handbook are all of those involved in the development of CPGs; those such as directors of medical societies or research groups who make decisions about which guidelines should be developed; those who determine the scope of a CPG and formulate the recommendations of CPGs; and those who conduct the systematic reviews of evidence. This handbook proceeds in the same order as the process of CPG development, and therefore, the entire picture of the development process can be grasped by reading from beginning to end. We also ensured that the contents can easily be understood without having special knowledge about medicine, epidemiology, or biology.

The evidence on which a CPG is based is universal, but a CPG itself can vary from country to country, because different countries adopt different healthcare policies and systems. Thus, we take account of circumstances specific to Japan, when we propose our method. We explored the CPG development method that is considered appropriate for our healthcare system, while studying various CPG development methods developed overseas. To develop this handbook, a series of finalization process was adopted: the authors first drafted the preliminary version; the preliminary version was reviewed and modified by a series of editorial

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Introduction

The Japan Council for Quality Health Care launched the Medical Information Network Distribution Service (Minds) in 2002 under the Project for EBM Guideline Promotion. Clinical practice guidelines (CPGs), which were selected as highly credible from the viewpoint of development method, are shared online on the Minds website (http://Minds.jcqhc.or.jp/n/). Furthermore, Minds assigns the highest priority to proposing the method of developing CPGs based on the principle of EBM to relevant medical societies and research groups – the primary developers of CPGs – and providing support for their guideline development. In 2007, Minds published the “Minds Handbook for Clinical Practice Guideline Development 2007” (Handbook 2007) to propose the procedure to develop CPGs that was considered appropriate at that time. Now, as seven years have passed, the method has evolved substantially across the world, and newly improved methods are being established. Accordingly, Minds decided to compile a revised edition of the Handbook 2007 and publish the “Minds Handbook for Clinical Practice Guideline Development 2014” (Handbook 2014) to introduce the newly established methods. The Handbook 2014 covers much of the same contents as the Handbook 2007, but provides better descriptions of certain contents that were not sufficiently described in the Handbook 2007.

The Handbook 2014 emphasizes the importance of the idea of “body of evidence.” To develop a CPG, the established method called systematic review should be adopted, in which the evidence is searched for systematically in published research articles or other sources and is evaluated and integrated as the body of evidence. The Handbook 2014 also emphasizes the importance of the idea of “balance between benefit and harm.” When a CPG proposes a recommendation of an intervention method that can be considered the most appropriate among alternative intervention options in certain clinical circumstances of diagnosis, treatment, prevention, or nursing care, the harm of interventions should be given as high an emphasis as the benefit in comparing alternative intervention methods.

Potential users of this handbook are all of those involved in the development of CPGs; those such as directors of medical societies or research groups who make decisions about which guidelines should be developed; those who determine the scope of a CPG and formulate the recommendations of CPGs; and those who conduct the systematic reviews of evidence. This handbook proceeds in the same order as the process of CPG development, and therefore, the entire picture of the development process can be grasped by reading from beginning to end. We also ensured that the contents can easily be understood without having special knowledge about medicine, epidemiology, or biology.

The evidence on which a CPG is based is universal, but a CPG itself can vary from country to country, because different countries adopt different healthcare policies and systems. Thus, we take account of circumstances specific to Japan, when we propose our method. We explored the CPG development method that is considered appropriate for our healthcare system, while studying various CPG development methods developed overseas. To develop this handbook, a series of finalization process was adopted: the authors first drafted the preliminary version; the preliminary version was reviewed and modified by a series of editorial

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meetings; and then the final version was edited by reflecting comments in external evaluations by external panel members and public comments. Finally, I would like to comment on how the method we propose here should be situated among different methods proposed elsewhere; our method is one of various methods recognized as appropriate worldwide and it is not our intention to insist that our method should be adopted for all CPGs in Japan.

We hope that this handbook can help further improve the quality of CPGs, and thereby can contribute to improving the quality of healthcare in Japan.

March 2014

Naohito Yamaguchi Director, Minds Guideline Center,

Executive Board Member, Japan Council for Quality Health Care

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meetings; and then the final version was edited by reflecting comments in external evaluations by external panel members and public comments. Finally, I would like to comment on how the method we propose here should be situated among different methods proposed elsewhere; our method is one of various methods recognized as appropriate worldwide and it is not our intention to insist that our method should be adopted for all CPGs in Japan.

We hope that this handbook can help further improve the quality of CPGs, and thereby can contribute to improving the quality of healthcare in Japan.

March 2014

Naohito Yamaguchi Director, Minds Guideline Center,

Executive Board Member, Japan Council for Quality Health Care

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Contents 2014 Edition Preface ......................................................................................................... vii

Preface to the First Edition ................................................................................................. ix

Introduction ........................................................................................................................ xi

About This Handbook .................................................................................................................. 2

About the Method Proposed in This Handbook ........................................................................... 2

About Clinical Practice Guidelines ............................................................................................... 3

The overall picture of the CPG development process ................................................................. 3

Procedures for Developing Clinical Practice Guidelines and Schedule ....................................... 8

Determination of Development Body of Clinical Practice Guidelines ........................................... 8

Establishment of Task Forces to Develop Clinical Practice Guidelines ........................................ 9

Funds to Develop Clinical Practice Guidelines .......................................................................... 10

Conflict of Interest (COI) ............................................................................................................ 11

Participation of Patients and Citizens in Developing Clinical Practice Guidelines ..................... 12

What is Scope? ......................................................................................................................... 20

Structure of Scope ..................................................................................................................... 20

Process of Scope Development ................................................................................................ 21

Formulation of Clinical Question ................................................................................................ 22

Specification of Systematic Review ........................................................................................... 25

Procedures from Formulating Recommendations to Finalization and Publication of the CPG .. 25

Overview of Systematic Review ................................................................................................ 30

Identifying the Evidence ............................................................................................................. 32

Evaluation of the Body of Evidence ........................................................................................... 34

Integration of the Body of Evidence ........................................................................................... 37

Determination of the Strength of Evidence of the Body of Evidence ......................................... 39

Preparation of Systematic Review Report ................................................................................. 39

Chapter 1 Overview 1

1

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3

4

Chapter 2 Preparation 7

1

2

3

4

5

6

Chapter 3 Scope 19

1

2

3

4

5

6

Chapter 4 Systematic Review 29

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2

3

4

5

6

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Contents 2014 Edition Preface ......................................................................................................... vii

Preface to the First Edition ................................................................................................. ix

Introduction ........................................................................................................................ xi

About This Handbook .................................................................................................................. 2

About the Method Proposed in This Handbook ........................................................................... 2

About Clinical Practice Guidelines ............................................................................................... 3

The overall picture of the CPG development process ................................................................. 3

Procedures for Developing Clinical Practice Guidelines and Schedule ....................................... 8

Determination of Development Body of Clinical Practice Guidelines ........................................... 8

Establishment of Task Forces to Develop Clinical Practice Guidelines ........................................ 9

Funds to Develop Clinical Practice Guidelines .......................................................................... 10

Conflict of Interest (COI) ............................................................................................................ 11

Participation of Patients and Citizens in Developing Clinical Practice Guidelines ..................... 12

What is Scope? ......................................................................................................................... 20

Structure of Scope ..................................................................................................................... 20

Process of Scope Development ................................................................................................ 21

Formulation of Clinical Question ................................................................................................ 22

Specification of Systematic Review ........................................................................................... 25

Procedures from Formulating Recommendations to Finalization and Publication of the CPG .. 25

Overview of Systematic Review ................................................................................................ 30

Identifying the Evidence ............................................................................................................. 32

Evaluation of the Body of Evidence ........................................................................................... 34

Integration of the Body of Evidence ........................................................................................... 37

Determination of the Strength of Evidence of the Body of Evidence ......................................... 39

Preparation of Systematic Review Report ................................................................................. 39

Chapter 1 Overview 1

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Chapter 2 Preparation 7

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Chapter 3 Scope 19

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Chapter 4 Systematic Review 29

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Outline of the Recommendation Development Process – Method for Unbiased Determination ... 52

A Draft of Recommendation and the Strength of Recommendation .......................................... 52

Consensus Methods.................................................................................................................. 55

Comment Writing ....................................................................................................................... 56

Summary for the Public ............................................................................................................. 56

Additional Documents to Be Created for Finalization .................................................................. 62

Drafting Clinical Practice Guidelines ......................................................................................... 63

External Review ........................................................................................................................ 66

AGREE II (The Appraisal of Guidelines for Research & Evaluation II) ...................................... 67

Publication ................................................................................................................................. 68

Outline ....................................................................................................................................... 74

Organizational issues after publication ...................................................................................... 74

Implementation .......................................................................................................................... 75

Effectiveness assessment ......................................................................................................... 78

Revision .................................................................................................................................... 79

A collection of templates ................................................................................................... 81

Literature ......................................................................................................................... 107

References ...................................................................................................................... 111

INDEX ............................................................................................................................. 117

Chapter 5 Recommendations 51

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Chapter 6 Finalization 61

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Chapter 7 Dissemination, Implementation, and Assessment of Clinical Practice Guidelines 73

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Outline of the Recommendation Development Process – Method for Unbiased Determination ... 52

A Draft of Recommendation and the Strength of Recommendation .......................................... 52

Consensus Methods.................................................................................................................. 55

Comment Writing ....................................................................................................................... 56

Summary for the Public ............................................................................................................. 56

Additional Documents to Be Created for Finalization .................................................................. 62

Drafting Clinical Practice Guidelines ......................................................................................... 63

External Review ........................................................................................................................ 66

AGREE II (The Appraisal of Guidelines for Research & Evaluation II) ...................................... 67

Publication ................................................................................................................................. 68

Outline ....................................................................................................................................... 74

Organizational issues after publication ...................................................................................... 74

Implementation .......................................................................................................................... 75

Effectiveness assessment ......................................................................................................... 78

Revision .................................................................................................................................... 79

A collection of templates ................................................................................................... 81

Literature ......................................................................................................................... 107

References ...................................................................................................................... 111

INDEX ............................................................................................................................. 117

Chapter 5 Recommendations 51

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Chapter 6 Finalization 61

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Chapter 7 Dissemination, Implementation, and Assessment of Clinical Practice Guidelines 73

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Chapter 1

Overview

About this handbook ........................................................ 2

About the method proposed in this handbook ............... 2

About clinical practice guidelines .................................... 3

The overall picture of the CPG development process ... 3

1 2

3

4

15

Chapter 1

Overview

About this handbook ........................................................ 2

About the method proposed in this handbook ............... 2

About clinical practice guidelines .................................... 3

The overall picture of the CPG development process ... 3

1 2

3

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15

2

Chapter 1 Overview

Seven years have passed since the publication of the “Minds Handbook for Clinical Practice Guideline Development 2007.” Meanwhile, the method of developing clinical practice guidelines (CPGs) made substantial progress on a global scale. Accordingly, we decided to create the “Minds Manual for Clinical Practice Guideline Development” (Manual). The Manual is available on the Minds website, but for the convenience of users, we decided to publish the summarized version of the Manual as a book titled the “Minds Handbook for Clinical Practice Guideline Development 2014” (Handbook 2014). Those who wish to know the details of CPG development method should refer to the Manual, because some explanations were omitted due to space limitations. The Handbook 2014 focuses on the method of conducting de novo systematic reviews for evaluation of the body of evidence; the methods of applying existing systematic review articles and adaptation of existing CPGs are beyond the scope of this handbook. The Handbook 2014 also focuses on the formulation of recommendations regarding treatment interventions; formulation of recommendations on other interventions such as diagnosis will be covered by the Manual. The method of incorporating health economics analysis into CPG development will also be covered by the Manual in the future.

This handbook provides step-by-step explanations according to the process of developing CPGs we propose, and a series of templates are provided so that, by filling relevant information and documents into the templates, the draft of CPG can easily be compiled. The Handbook 2014 follows the steps of CPG development so that it can guide the members of the guideline development group. This handbook is also hopefully useful for CPG users to understand the key points of using CPGs.

The CPG development method we propose in this handbook was adopted as an appropriate one for CPG development in Japan, after an extensive review of existing methods proposed by world recognized organizations, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, the Cochrane Collaboration, the Agency for Healthcare Research and Quality (AHRQ), and the Oxford EBM Centre. Those who wish to use any of the original methods proposed by these organizations should refer to their original literature. (See the bibliography at the end of the book [p.107].)

The method we propose in this handbook is not the only one of choice. The method can be modified in accordance with the actual situation that the guideline development group faces.

1 About this handbook

2 About the method proposed in this handbook

16

2

Chapter 1 Overview

Seven years have passed since the publication of the “Minds Handbook for Clinical Practice Guideline Development 2007.” Meanwhile, the method of developing clinical practice guidelines (CPGs) made substantial progress on a global scale. Accordingly, we decided to create the “Minds Manual for Clinical Practice Guideline Development” (Manual). The Manual is available on the Minds website, but for the convenience of users, we decided to publish the summarized version of the Manual as a book titled the “Minds Handbook for Clinical Practice Guideline Development 2014” (Handbook 2014). Those who wish to know the details of CPG development method should refer to the Manual, because some explanations were omitted due to space limitations. The Handbook 2014 focuses on the method of conducting de novo systematic reviews for evaluation of the body of evidence; the methods of applying existing systematic review articles and adaptation of existing CPGs are beyond the scope of this handbook. The Handbook 2014 also focuses on the formulation of recommendations regarding treatment interventions; formulation of recommendations on other interventions such as diagnosis will be covered by the Manual. The method of incorporating health economics analysis into CPG development will also be covered by the Manual in the future.

This handbook provides step-by-step explanations according to the process of developing CPGs we propose, and a series of templates are provided so that, by filling relevant information and documents into the templates, the draft of CPG can easily be compiled. The Handbook 2014 follows the steps of CPG development so that it can guide the members of the guideline development group. This handbook is also hopefully useful for CPG users to understand the key points of using CPGs.

The CPG development method we propose in this handbook was adopted as an appropriate one for CPG development in Japan, after an extensive review of existing methods proposed by world recognized organizations, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, the Cochrane Collaboration, the Agency for Healthcare Research and Quality (AHRQ), and the Oxford EBM Centre. Those who wish to use any of the original methods proposed by these organizations should refer to their original literature. (See the bibliography at the end of the book [p.107].)

The method we propose in this handbook is not the only one of choice. The method can be modified in accordance with the actual situation that the guideline development group faces.

1 About this handbook

2 About the method proposed in this handbook

16

3

Chapter

1 O

verview

In this handbook, a CPG is defined as follows:

Minds Definition of Clinical Practice Guidelines A clinical practice guideline is a document that presents appropriate recommendations to assist patients and practitioners in making decisions regarding clinical practice of high importance, based on the body of evidence evaluated and integrated by systematic reviews and the balance between benefits and harms.

As proposed in the “Minds Handbook for Clinical Practice Guideline Development

2007” (Handbook 2007), a CPG is developed according to the principle of evidence-based medicine (EBM), which is considered a global standard. The Handbook 2014 proposes a process involving three separate task forces to ensure unbiased development procedures, and emphasizes the importance of evaluating the body of evidence that takes into consideration the balance between benefits and harms.

1) The structure of the three task forces

The Guideline Executive Committee is assumed to make decisions on what CPGs should be developed, to arrange budgetary issues, and to organize the Guideline Development Group. The Guideline Executive Committee is often organized in the governing board of medical society or research group or as a standing committee within the governing board. The Guideline Development Group confirms the scope by deciding on topics and clinical questions (CQ*1) to be covered in the CPG. The Systematic Review Team (SR Team) conducts systematic reviews for CQs defined by the Guideline Development Group according to the method described in the scope. The Guideline Development Group formulates recommendations, based on the systematic review report compiled by the SR Team, and finalizes the CPG.

Members of the Guideline Executive Committee, the Guideline Development Group, and the SR Team may undertake more than one task or may discuss with other groups, but, as a general rule, these three groups function independently to ensure transparency

*1: Other than the term “clinical questions,” expressions such as “health questions,” “healthcare questions,”

or “review questions” are used.

3 About clinical practice guidelines

4 The overall picture of the CPG development process

17

3

Chapter

1 O

verview

In this handbook, a CPG is defined as follows:

Minds Definition of Clinical Practice Guidelines A clinical practice guideline is a document that presents appropriate recommendations to assist patients and practitioners in making decisions regarding clinical practice of high importance, based on the body of evidence evaluated and integrated by systematic reviews and the balance between benefits and harms.

As proposed in the “Minds Handbook for Clinical Practice Guideline Development

2007” (Handbook 2007), a CPG is developed according to the principle of evidence-based medicine (EBM), which is considered a global standard. The Handbook 2014 proposes a process involving three separate task forces to ensure unbiased development procedures, and emphasizes the importance of evaluating the body of evidence that takes into consideration the balance between benefits and harms.

1) The structure of the three task forces

The Guideline Executive Committee is assumed to make decisions on what CPGs should be developed, to arrange budgetary issues, and to organize the Guideline Development Group. The Guideline Executive Committee is often organized in the governing board of medical society or research group or as a standing committee within the governing board. The Guideline Development Group confirms the scope by deciding on topics and clinical questions (CQ*1) to be covered in the CPG. The Systematic Review Team (SR Team) conducts systematic reviews for CQs defined by the Guideline Development Group according to the method described in the scope. The Guideline Development Group formulates recommendations, based on the systematic review report compiled by the SR Team, and finalizes the CPG.

Members of the Guideline Executive Committee, the Guideline Development Group, and the SR Team may undertake more than one task or may discuss with other groups, but, as a general rule, these three groups function independently to ensure transparency

*1: Other than the term “clinical questions,” expressions such as “health questions,” “healthcare questions,”

or “review questions” are used.

3 About clinical practice guidelines

4 The overall picture of the CPG development process

17

4

Chapter 1 Overview

throughout the development process. The completed CPG is approved by the Guideline Executive Committee, before being published.

While the Guideline Executive Committee is the group representing the primary development body, such as a medical society, the Guideline Development Group should be made up of not just members of the medical society but also of individuals representing patients, citizens, and other stakeholders with various backgrounds, and thus is assumed to have different constituents from the Guideline Executive Committee. Since the SR Team is required to have expertise to conduct systematic reviews, it is likely to be a separate task force.

Fig. 1-1 Process of Developing CPGs by the Three Task Forces

2) Unbiasedness of Development Process In the process of CPG development, developers are frequently required to make

important decisions, in situations, for example, when evaluating the body of evidence, and when formulating recommendations. Those involved in the development process take every precaution not to let prejudice cloud their judgment, but there is a limit to how careful one can be and it is not easy to avoid making a biased judgment. Therefore,

Guideline Executive Committee

Guideline Development Group

Systematic Review Team (SR Team)

Clarification of the development purpose and determination of the

framework

Understanding of the current situation of the theme targeted

by the scope

<Scope>

Defining CQs based on key clinical issues

Identifying the evidence

Evaluation/integration of evidence

Formulation of recommendations

<SR report>

Revision

Dissemination/ Implementation/Assessment

Publication

Development of a draft of the CPG

External evaluation

Finalization of the CPG

18

4

Chapter 1 Overview

throughout the development process. The completed CPG is approved by the Guideline Executive Committee, before being published.

While the Guideline Executive Committee is the group representing the primary development body, such as a medical society, the Guideline Development Group should be made up of not just members of the medical society but also of individuals representing patients, citizens, and other stakeholders with various backgrounds, and thus is assumed to have different constituents from the Guideline Executive Committee. Since the SR Team is required to have expertise to conduct systematic reviews, it is likely to be a separate task force.

Fig. 1-1 Process of Developing CPGs by the Three Task Forces

2) Unbiasedness of Development Process In the process of CPG development, developers are frequently required to make

important decisions, in situations, for example, when evaluating the body of evidence, and when formulating recommendations. Those involved in the development process take every precaution not to let prejudice cloud their judgment, but there is a limit to how careful one can be and it is not easy to avoid making a biased judgment. Therefore,



Systematic Review Team (SR Team)

Clarification of the development purpose and determination of the

framework

Understanding of the current situation of the theme targeted

by the scope

<Scope>

Defining CQs based on key clinical issues

Identifying the evidence

Evaluation/integration of evidence


<SR report>

Revision

Dissemination/ Implementation/Assessment

Publication

Development of a draft of the CPG

External evaluation

Finalization of the CPG

18

5

Chapter

1 O

verview

it is necessary to adopt a framework to avoid biases in judgment throughout the development process.

One factor that can cause biased decisions is a conflict of interest (COI). In addition to such problems as shareholdings of companies related to drugs or medical equipment mentioned in the CPG, or monetary contributions from these companies, research grants can also lead to financial COI. One may have more positive opinions about treatment methods that he/she specializes in, and if recommendations by the CPG can affect one’s professional position, it is possible for the person to make a biased judgment due to academic COI. Besides personal COI, it is also necessary to consider organizational COI, which affects the organizations involved in CPG development, as a whole.

A biased judgment can occur at an unconscious level and there is a limit to one’s desire to remain unbiased. One effective measure against academic COI is to include those with various intellectual interests as members of the Guideline Development Group, thus making it possible to balance intellectual interests through discussion among such members. As a measure against financial COI, rules should be set in advance to restrict the appointment of concerned individuals to the Guideline Development Group, or restrict participation in certain decision-making processes. Furthermore, in all phases of the development process, grounds or reasons for judgments and decisions are required to be disclosed in writing.

3) Evaluation of body of evidence

All selected research reports with the same study design are evaluated for each outcome of CQ, and the set of summaries of evidence arranged by outcome and study design is called the body of evidence. Clinical studies, even when they are conducted on the same theme, do not necessarily produce the same results, due to differences in the study design, study population, intervention method, method of measuring patient outcomes, or statistical uncertainty. A systematic review, consisting of searching relevant clinical studies and evaluating and integrating the identified findings into the body of evidence, is considered to be the best method to avoid biases.

4) Balance between benefits and harms

Patient outcomes resulting from interventions include not only expected effects (benefits) but also adverse events (harms) as well. All critical and important patient outcomes of benefits and harms should be listed when formulating a CQ; the body of evidence should be evaluated by systematic review of all listed critical and important outcomes; and thus the balance of benefits and harms should be taken into account in formulating recommendations for the CQ. In addition to harmful outcomes, increased expenses and physical or psychological burdens should also be considered as a disadvantage for patients.

19

5

Chapter

1 O

verview

it is necessary to adopt a framework to avoid biases in judgment throughout the development process.

One factor that can cause biased decisions is a conflict of interest (COI). In addition to such problems as shareholdings of companies related to drugs or medical equipment mentioned in the CPG, or monetary contributions from these companies, research grants can also lead to financial COI. One may have more positive opinions about treatment methods that he/she specializes in, and if recommendations by the CPG can affect one’s professional position, it is possible for the person to make a biased judgment due to academic COI. Besides personal COI, it is also necessary to consider organizational COI, which affects the organizations involved in CPG development, as a whole.

A biased judgment can occur at an unconscious level and there is a limit to one’s desire to remain unbiased. One effective measure against academic COI is to include those with various intellectual interests as members of the Guideline Development Group, thus making it possible to balance intellectual interests through discussion among such members. As a measure against financial COI, rules should be set in advance to restrict the appointment of concerned individuals to the Guideline Development Group, or restrict participation in certain decision-making processes. Furthermore, in all phases of the development process, grounds or reasons for judgments and decisions are required to be disclosed in writing.

3) Evaluation of body of evidence

All selected research reports with the same study design are evaluated for each outcome of CQ, and the set of summaries of evidence arranged by outcome and study design is called the body of evidence. Clinical studies, even when they are conducted on the same theme, do not necessarily produce the same results, due to differences in the study design, study population, intervention method, method of measuring patient outcomes, or statistical uncertainty. A systematic review, consisting of searching relevant clinical studies and evaluating and integrating the identified findings into the body of evidence, is considered to be the best method to avoid biases.

4) Balance between benefits and harms

Patient outcomes resulting from interventions include not only expected effects (benefits) but also adverse events (harms) as well. All critical and important patient outcomes of benefits and harms should be listed when formulating a CQ; the body of evidence should be evaluated by systematic review of all listed critical and important outcomes; and thus the balance of benefits and harms should be taken into account in formulating recommendations for the CQ. In addition to harmful outcomes, increased expenses and physical or psychological burdens should also be considered as a disadvantage for patients.

19

Chapter 2

Preparation

Procedures for Developing Clinical Practice Guidelines and Schedule ...................................................................... 8

Determination of Development Body of Clinical Practice Guidelines ............................................................ 8

Establishment of Task Forces to Develop Clinical Practice Guidelines ............................................................ 9

Funds to Develop Clinical Practice Guidelines ............. 10

Conflict of Interest (COI) ................................................... 11

Participation of Patients and Citizens in Developing Clinical Practice Guidelines ............................................ 12

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Chapter 2

Preparation

Procedures for Developing Clinical Practice Guidelines and Schedule ...................................................................... 8

Determination of Development Body of Clinical Practice Guidelines ............................................................ 8

Establishment of Task Forces to Develop Clinical Practice Guidelines ............................................................ 9

Funds to Develop Clinical Practice Guidelines ............. 10

Conflict of Interest (COI) ................................................... 11

Participation of Patients and Citizens in Developing Clinical Practice Guidelines ............................................ 12

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Chapter 2 Preparation

A clinical practice guideline (CPG) shall be developed in accordance with the following procedures. It is necessary to make definite plans in consideration of the time needed to develop the CPG as a whole, and the time and money needed for each procedure. (1) Clarification of development objectives (2) Determination of development body (3) Establishment of secretariat and task forces (4) Scope development (5) Systematic review (6) Formulation of recommendations (7) Development of CPG draft (8) External review and invitation of public comments (9) Publication (10) Dissemination/Implementation/Assessment (11) Revision [Template ID: 2-1 Procedures and Schedule for Guideline Development O*1]

The development body is the organization, such as a medical society or research group, responsible for CPG development. The development body may consist of a single medical society or research group, or may consist of multiple related medical societies or research groups to jointly take the responsibility to develop a CPG from the preparatory stage, depending on selected themes and topics. For example, with various views of experts from societies of internists and surgeons, societies of physicians and dentists, societies of physicians and nurses, and so forth, it will be possible to develop less biased CPGs through the entire CPG development process.

[Template ID: 2-2 Preparation for CPG Development_(1)G*2]

*1: Templates shall be given the following symbols at the end of their names in response to relevant

documents. G: Clinical Practice Guideline, O: For operation

*2: Numbers shown in parentheses, such as (1) and (2), indicate the fields in Template 2-2.

1 Procedures for Developing Clinical Practice Guidelines and Schedule

2 Determination of Development Body of Clinical Practice Guideline

22

8


A clinical practice guideline (CPG) shall be developed in accordance with the following procedures. It is necessary to make definite plans in consideration of the time needed to develop the CPG as a whole, and the time and money needed for each procedure. (1) Clarification of development objectives (2) Determination of development body (3) Establishment of secretariat and task forces (4) Scope development (5) Systematic review (6) Formulation of recommendations (7) Development of CPG draft (8) External review and invitation of public comments (9) Publication (10) Dissemination/Implementation/Assessment (11) Revision [Template ID: 2-1 Procedures and Schedule for Guideline Development O*1]

The development body is the organization, such as a medical society or research group, responsible for CPG development. The development body may consist of a single medical society or research group, or may consist of multiple related medical societies or research groups to jointly take the responsibility to develop a CPG from the preparatory stage, depending on selected themes and topics. For example, with various views of experts from societies of internists and surgeons, societies of physicians and dentists, societies of physicians and nurses, and so forth, it will be possible to develop less biased CPGs through the entire CPG development process.

[Template ID: 2-2 Preparation for CPG Development_(1)G*2]



*2: Numbers shown in parentheses, such as (1) and (2), indicate the fields in Template 2-2.

1 Procedures for Developing Clinical Practice Guidelines and Schedule

2 Determination of Development Body of Clinical Practice Guideline

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9

Chapter

2 P

reparation

One of the most important points in developing CPGs is to establish task forces with unbiased member structure. In particular, representatives of task forces, including the chairperson of the Guideline Executive Committee, should be carefully selected in consideration of financial and academic conflict of interests (COI). [For further information, see Chapter 2 Conflict of Interest (COI), p. 11].

1) Guideline Executive Committee The Guideline Executive Committee established under the development body is the

committee responsible for making decisions on which health topic is covered by the CPG, budgets for CPG development, and appointing members of other task forces. In the case of a single medical society or research group, its board meeting or standing committee often takes a role as the Guideline Executive Committee. In cases where multiple medical societies and research groups work together to develop CPGs, a “council”-like organization may be the Guideline Executive Committee consisting of persons representing societies and research groups. As for roles of the Guideline Executive Committee, see Fig. 1-1 (p. 4). [Template ID: 2-2 Preparation for CPG Development_(2)G]

2) Secretariat of Guideline Development The Secretariat should be established to manage the progress of CPG development,

communications between members of the Guideline Development Group, adjustment of schedule for development meetings, reservation of conference room, clerical work such as literature collection, management of funds, and so forth. [Template ID: 2-2 Preparation for CPG Development_(3)G]

3) Guideline Development Group The Guideline Development Group is responsible for establishing the scope, which is a

written planning document for CPG development, determining clinical questions (CQs), formulating recommendations in response to systematic review reports, and developing a draft CPG (Fig. 1-1). The Guideline Executive Committee appoints the members of the Guideline Development Group. The Guideline Development Group will consist of approximately a dozen members, depending on the characteristics of the health topic and the type of the CPG. It should include experts from various fields related to contents of the CPG. It is desirable that the members include experts who are selected from medical societies related to the topics covered by the CPG, in a balanced manner, with careful consideration of interests. The members should also include diverse members in consideration of sex and economic and academic interests: practitioners, such as primary care physicians, nurses, and pharmacists, experts specialized in CPG development (experts on medical literature search, such as librarians, epidemiologists, and statisticians), healthcare economists, lawyers, patients, the public, and policymakers. Also, it is necessary to consider COI to be mentioned in Chapter 2 . [Template ID: 2-2 Preparation for CPG Development_(4)G]

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3 Establishment of Task Forces to Develop Clinical Practice Guidelines

23

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Chapter

2 P

reparation

One of the most important points in developing CPGs is to establish task forces with unbiased member structure. In particular, representatives of task forces, including the chairperson of the Guideline Executive Committee, should be carefully selected in consideration of financial and academic conflict of interests (COI). [For further information, see Chapter 2 Conflict of Interest (COI), p. 11].

1) Guideline Executive Committee The Guideline Executive Committee established under the development body is the

committee responsible for making decisions on which health topic is covered by the CPG, budgets for CPG development, and appointing members of other task forces. In the case of a single medical society or research group, its board meeting or standing committee often takes a role as the Guideline Executive Committee. In cases where multiple medical societies and research groups work together to develop CPGs, a “council”-like organization may be the Guideline Executive Committee consisting of persons representing societies and research groups. As for roles of the Guideline Executive Committee, see Fig. 1-1 (p. 4). [Template ID: 2-2 Preparation for CPG Development_(2)G]

2) Secretariat of Guideline Development The Secretariat should be established to manage the progress of CPG development,

communications between members of the Guideline Development Group, adjustment of schedule for development meetings, reservation of conference room, clerical work such as literature collection, management of funds, and so forth. [Template ID: 2-2 Preparation for CPG Development_(3)G]

3) Guideline Development Group The Guideline Development Group is responsible for establishing the scope, which is a

written planning document for CPG development, determining clinical questions (CQs), formulating recommendations in response to systematic review reports, and developing a draft CPG (Fig. 1-1). The Guideline Executive Committee appoints the members of the Guideline Development Group. The Guideline Development Group will consist of approximately a dozen members, depending on the characteristics of the health topic and the type of the CPG. It should include experts from various fields related to contents of the CPG. It is desirable that the members include experts who are selected from medical societies related to the topics covered by the CPG, in a balanced manner, with careful consideration of interests. The members should also include diverse members in consideration of sex and economic and academic interests: practitioners, such as primary care physicians, nurses, and pharmacists, experts specialized in CPG development (experts on medical literature search, such as librarians, epidemiologists, and statisticians), healthcare economists, lawyers, patients, the public, and policymakers. Also, it is necessary to consider COI to be mentioned in Chapter 2 . [Template ID: 2-2 Preparation for CPG Development_(4)G]

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3 Establishment of Task Forces to Develop Clinical Practice Guidelines

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4) Systematic Review Team (SR Team) The Systematic Review Team (SR Team) is a group responsible for conducting

systematic reviews, and the Team should be independent from the Guideline Development Group and members should be appointed by the Guideline Executive Committee. It is desirable that the SR Team members have training and experience in conducting systematic reviews. For each CQ, the SR Team should judge the possibility of adopting existing systematic review articles or of adapting the systematic reviews in overseas CPGs, and should conduct a de novo systematic review if no existing systematic review is found. In Japan, healthcare practitioners, such as physicians, often perform systematic reviews, but it is desirable that experts on medical literature search, such as librarians, epidemiologists, and statisticians, who are familiar with systematic review methodology, are invited to the Team in order to gain the technical support necessary for systematic review. Also, it is necessary to consider COI to be mentioned in Chapter 2 . [Template ID: 2-2 Preparation for CPG Development_(5)G]

5) External Review Committee The External Review Committee evaluates the draft CPG from a neutral standpoint, and it

advises on the improvement of a CPG draft. The members of the External Review Committee are appointed by the Guideline Executive Committee. It is necessary to consider COI to be mentioned in Chapter 2 . It is necessary to consider the method of receiving review results from disease specialists and primary care physicians of multiple interested medical societies, other healthcare practitioners, epidemiologists, economists, legal experts, patients, and the public. It might be necessary, depending on the topics, to broadly seek public comments by disclosing the CPG draft on websites of medical societies for a certain period. [Template ID: 2-2 Preparation for CPG Development_(6)G]

The Guideline Executive Committee estimates the budget necessary for CPG

development, and records the source of funds. Major costs necessary for CPG development include cost of transportation fares, cost of conference venues, cost of literature search and collection, and cost of publishing. Not only public funds and company funds but also funds from medical societies should be recorded.

[Template ID: 2-3 Funds for Guideline Development O]

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4 Funds to Develop Clinical Practice Guidelines

24

10


4) Systematic Review Team (SR Team) The Systematic Review Team (SR Team) is a group responsible for conducting

systematic reviews, and the Team should be independent from the Guideline Development Group and members should be appointed by the Guideline Executive Committee. It is desirable that the SR Team members have training and experience in conducting systematic reviews. For each CQ, the SR Team should judge the possibility of adopting existing systematic review articles or of adapting the systematic reviews in overseas CPGs, and should conduct a de novo systematic review if no existing systematic review is found. In Japan, healthcare practitioners, such as physicians, often perform systematic reviews, but it is desirable that experts on medical literature search, such as librarians, epidemiologists, and statisticians, who are familiar with systematic review methodology, are invited to the Team in order to gain the technical support necessary for systematic review. Also, it is necessary to consider COI to be mentioned in Chapter 2 . [Template ID: 2-2 Preparation for CPG Development_(5)G]

5) External Review Committee The External Review Committee evaluates the draft CPG from a neutral standpoint, and it

advises on the improvement of a CPG draft. The members of the External Review Committee are appointed by the Guideline Executive Committee. It is necessary to consider COI to be mentioned in Chapter 2 . It is necessary to consider the method of receiving review results from disease specialists and primary care physicians of multiple interested medical societies, other healthcare practitioners, epidemiologists, economists, legal experts, patients, and the public. It might be necessary, depending on the topics, to broadly seek public comments by disclosing the CPG draft on websites of medical societies for a certain period. [Template ID: 2-2 Preparation for CPG Development_(6)G]

The Guideline Executive Committee estimates the budget necessary for CPG

development, and records the source of funds. Major costs necessary for CPG development include cost of transportation fares, cost of conference venues, cost of literature search and collection, and cost of publishing. Not only public funds and company funds but also funds from medical societies should be recorded.

[Template ID: 2-3 Funds for Guideline Development O]

5

5

4 Funds to Develop Clinical Practice Guidelines

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1) COI in Development of Clinical Practice Guidelines

It is essential to manage and disclose in advance the COI of all candidates potentially engaged in CPG development in order to ensure rigor and transparency in the process of CPG development. COI is classified broadly into academic COI and financial COI: Academic COI is related to intellectual interests, such as specialties and personal preferences, and professional interests, such as promotion and career formation, whereas Financial COI is related to economic relations with specific companies or groups and acquisition of research funds (Table 2-1). In addition to personal COI, organizational COI, both academic and economic, may influence the CPG development. Organizational COI is related to organizations, such as the medical society to which members of the Guideline Development Group belong. Especially pertaining to academic COI, specialties of members of Guideline Development Group may influence important processes of CPG development, such as CQ selection and formulation of recommendations.

Table 2-1 Types of COI Academic COI Financial COI

Personal COI

Specialties and preferences Promotion Career formation

Provision of economic benefits from specific companies/organizations to the member or his/her family

Benefits from acquisition of research fund

Provision of equipment, human resources, and research environment

Organizational COI

Specialties promoted by scientific/medical societies and research groups

Academic advancement of scientific/medical societies and research groups

Competition with other interested organizations

Academic support from specific companies/organizations to scientific /medical societies and research groups

Economic advancement of scientific/medical societies and research groups

2) Management of and Response to COI

Personal COI

• Judgment about the appropriateness of participation in task forces Prior to establishing task forces mentioned in Chapter 2 , financial COI should be

self-reported by candidates to the Guideline Executive Committee, and the Committee shall discuss the appropriateness of participation in task forces. Candidates receiving funds from companies or organizations related to the content of CPG might have limited roles in CPG development. It is necessary to give careful consideration especially to the

3

5 Conflict of Interest (COI)

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1) COI in Development of Clinical Practice Guidelines

It is essential to manage and disclose in advance the COI of all candidates potentially engaged in CPG development in order to ensure rigor and transparency in the process of CPG development. COI is classified broadly into academic COI and financial COI: Academic COI is related to intellectual interests, such as specialties and personal preferences, and professional interests, such as promotion and career formation, whereas Financial COI is related to economic relations with specific companies or groups and acquisition of research funds (Table 2-1). In addition to personal COI, organizational COI, both academic and economic, may influence the CPG development. Organizational COI is related to organizations, such as the medical society to which members of the Guideline Development Group belong. Especially pertaining to academic COI, specialties of members of Guideline Development Group may influence important processes of CPG development, such as CQ selection and formulation of recommendations.

Table 2-1 Types of COI Academic COI Financial COI

Personal COI

Specialties and preferences Promotion Career formation

Provision of economic benefits from specific companies/organizations to the member or his/her family

Benefits from acquisition of research fund

Provision of equipment, human resources, and research environment

Organizational COI

Specialties promoted by scientific/medical societies and research groups

Academic advancement of scientific/medical societies and research groups

Competition with other interested organizations

Academic support from specific companies/organizations to scientific /medical societies and research groups

Economic advancement of scientific/medical societies and research groups

2) Management of and Response to COI

Personal COI

• Judgment about the appropriateness of participation in task forces Prior to establishing task forces mentioned in Chapter 2 , financial COI should be

self-reported by candidates to the Guideline Executive Committee, and the Committee shall discuss the appropriateness of participation in task forces. Candidates receiving funds from companies or organizations related to the content of CPG might have limited roles in CPG development. It is necessary to give careful consideration especially to the

3

5 Conflict of Interest (COI)

25

12


Chairpersons of the Guideline Executive Committee and the Guideline Development Group. The executive board of medical societies or research groups should select an appropriate person after fully discussing whether he/she would be subject to suspicion from outside.

Concerning the management of academic COI, it is necessary to ensure that the Guideline Development Group is not biased toward specific specialties. (Chapter 2 3) Guideline Development Group, p. 9.).

[Template ID: 2-4 COI Report (1)–Declaration Form of Financial COI O]

• Management of COI in the process of CPG development All members should be requested to self-report to the Chairperson of the Guideline

Development Group if any change occurs in financial COI in the process of CPG development.

Management of financial COI in the process of CPG development should be decided through discussion in the Guideline Development Group. Specifically, restriction of participation, such as (1) withdrawal from the Guideline Development Group or SR Team, and (2) restriction of voting right for each specific role, can be considered.

Organizational COI Funds to develop CPGs are especially important in organizational COI. The Guideline

Executive Committee should fully discuss whether donations from specific organizations might influence the CPG development.

As a response to academic organizational COI, it is very important that medical societies and research groups that may be involved in the content of CPGs widely and jointly participate in the CPG development [Chapter 2 1)].

Management and Disclosure of Information Concerning COI Measures taken for management of COI should be described in CPGs. However, since

individually collected COI declarations may contain confidential personal information, the Guideline Executive Committee should strictly manage them, and store them for a certain period until the time of next revision.

[Template ID: 2-5 COI Report (2)–Summary of Financial COI Declaration and Response Policy O]

A CPG is intended to support decision making by patients and practitioners in clinical practice, and it is extremely important to reflect values of patients and citizens in CPG development. If CPGs are developed only by healthcare practitioners, the values, preferences, and needs of the target population may be overlooked or misunderstood even if careful consideration is apparently given. It is essential to have patients and citizens participate in the CPG development in order to evaluate appropriately the patient outcomes, based on the actual situation of the target population.

3

3

6 Participation of Patients and Citizens in Developing Clinical Practice Guidelines

26

12


Chairpersons of the Guideline Executive Committee and the Guideline Development Group. The executive board of medical societies or research groups should select an appropriate person after fully discussing whether he/she would be subject to suspicion from outside.

Concerning the management of academic COI, it is necessary to ensure that the Guideline Development Group is not biased toward specific specialties. (Chapter 2 3) Guideline Development Group, p. 9.).

[Template ID: 2-4 COI Report (1)–Declaration Form of Financial COI O]

• Management of COI in the process of CPG development All members should be requested to self-report to the Chairperson of the Guideline

Development Group if any change occurs in financial COI in the process of CPG development.

Management of financial COI in the process of CPG development should be decided through discussion in the Guideline Development Group. Specifically, restriction of participation, such as (1) withdrawal from the Guideline Development Group or SR Team, and (2) restriction of voting right for each specific role, can be considered.

Organizational COI Funds to develop CPGs are especially important in organizational COI. The Guideline

Executive Committee should fully discuss whether donations from specific organizations might influence the CPG development.

As a response to academic organizational COI, it is very important that medical societies and research groups that may be involved in the content of CPGs widely and jointly participate in the CPG development [Chapter 2 1)].

Management and Disclosure of Information Concerning COI Measures taken for management of COI should be described in CPGs. However, since

individually collected COI declarations may contain confidential personal information, the Guideline Executive Committee should strictly manage them, and store them for a certain period until the time of next revision.

[Template ID: 2-5 COI Report (2)–Summary of Financial COI Declaration and Response Policy O]

A CPG is intended to support decision making by patients and practitioners in clinical practice, and it is extremely important to reflect values of patients and citizens in CPG development. If CPGs are developed only by healthcare practitioners, the values, preferences, and needs of the target population may be overlooked or misunderstood even if careful consideration is apparently given. It is essential to have patients and citizens participate in the CPG development in order to evaluate appropriately the patient outcomes, based on the actual situation of the target population.

3

3

6 Participation of Patients and Citizens in Developing Clinical Practice Guidelines

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The ways to have patients and citizens participate in CPG development include making decisions on topics through discussion with target population in the early stage of scope development, having patient representatives participate as members of the Guideline Development Group in formulating recommendations, and receiving feedback from the target population about the CPG draft prior to publication. The opinions of the target population on the value and preferences can be obtained by literature review, interview survey, or questionnaire survey.

27

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The ways to have patients and citizens participate in CPG development include making decisions on topics through discussion with target population in the early stage of scope development, having patient representatives participate as members of the Guideline Development Group in formulating recommendations, and receiving feedback from the target population about the CPG draft prior to publication. The opinions of the target population on the value and preferences can be obtained by literature review, interview survey, or questionnaire survey.

27

14


2-1 Procedures and Schedule for Guideline Development O: Entry Method

Time Schedule

Clarification of development objectives

Determination of development body

Establishment of Secretariat and task forces

Scope development

Systematic review


Development of draft CPG

External Review and collection of public comments

Publication

Dissemination, implementation, and assessment

Revision

Enter date of target completion of each process and review as needed.

Date:

Date:

Date:

To seek public comments broadly, disclose draft clinical practice guidelines and seek opinions.

Date:

Date:

Date:

28

14


2-1 Procedures and Schedule for Guideline Development O: Entry Method

Time Schedule

Clarification of development objectives



Scope development

Systematic review




Publication


Revision

Enter date of target completion of each process and review as needed.

Date:

Date:

Date:

To seek public comments broadly, disclose draft clinical practice guidelines and seek opinions.

Date:

Date:

Date:

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2-2 Preparation for CPG Development G: Entry Guide Organization for Developing Clinical Practice Guidelines (CPG)

(1) Development Body

Principal medical society /research group

Collaborative medical society /research group



(2) Guideline Executive

Committee

Chairperson (indicate by ✓) Name Affiliated organization/specialty Affiliated medical society Role in CPG

development

(3) Secretariat

Representative (indicate by ✓) Name Affiliated organization/specialty Affiliated medical society Role in CPG

development

(4) Guideline Development Group


development

(5) Systematic Review Team

Name Affiliated organization/specialty Affiliated scientific/medical society

(6) External Review Committee


Clearly enter the specialized field.

Enter the role and responsibility in CPG development.

Place a check mark ✓ on chairperson.

A CPG is often developed by collaboration of two or more medical societies or research groups related to the theme and topic.

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15

Chapter

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2-2 Preparation for CPG Development G: Entry Guide Organization for Developing Clinical Practice Guidelines (CPG)






(2) Guideline Executive

Committee


development

(3) Secretariat

Representative (indicate by ✓) Name Affiliated organization/specialty Affiliated medical society Role in CPG

development



development





Clearly enter the specialized field.

Enter the role and responsibility in CPG development.

Place a check mark ✓ on chairperson.

A CPG is often developed by collaboration of two or more medical societies or research groups related to the theme and topic.

29

16


2-3 Funds for Guideline Development O: Entry Guide

Cost items Budget Funder Remarks

List the cost items necessary for CPG development, and enter the budget and funders for each cost item.

30

16


2-3 Funds for Guideline Development O: Entry Guide

Cost items Budget Funder Remarks

List the cost items necessary for CPG development, and enter the budget and funders for each cost item.

30

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2-4 COI Report (1) - Declaration Form of Financial COI O: Entry Guide

Clinical Practice Guideline

Name

Affiliation

I hereby declare the economic relationship with the companies, organizations, or parties during the period between (date: / / ) and (date: / / ) to the above clinical practice guidelines as follows.

Related items Declaration criteria*

Presence of COI Declarer/family Period

Name of the company,

organization, or party

Remarks

Board member, Consultant

More than ●● million-yen

/year

Present/ Absent Declarer/family

Stocks More than ●● million-yen

/year


Patent royalty More than ●● million-yen

/year


Lecture fee More than ●● million-yen

/year


Manuscript fee More than ●● million-yen

/year


Research fee (contract or joint research fee)


/year

Present/ Absent The said person

Scholarship (incentive) donation


/year

Present/ Absent Declarer

Endowed chair More than ●● million-yen

/year


Others ( )


/year


Date of declaration :

Signature :

This form is compiled according to “The Guideline for Management of Conflict of Interest in Medical Research (February 2011)” issued by the Conflict of Interest Committee, Section of Clinical Medicine, the Japanese Association of Medical Sciences. *) Declaration criteria shall be determined by the Guideline Executive Committee.

For the first declaration, enter data of the latest 3 years.

If there is any COI, enter the timing when the relationship started.

• Describe who is actually related, the declarer himself or his family member.

• Criteria are usually set as to who should be included in family members, such as within the second degree of relationship.

Specify the declaration criteria for each related item, such as more than ●● million yen annually.

If the sign is an autograph, stamp can be omitted.

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17

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2-4 COI Report (1) - Declaration Form of Financial COI O: Entry Guide


Name

Affiliation

I hereby declare the economic relationship with the companies, organizations, or parties during the period between (date: / / ) and (date: / / ) to the above clinical practice guidelines as follows.





Remarks

Board member, Consultant


/year


Stocks More than ●● million-yen

/year


Patent royalty More than ●● million-yen

/year


Lecture fee More than ●● million-yen

/year


Manuscript fee More than ●● million-yen

/year




/year

Present/ Absent The said person



/year


Endowed chair More than ●● million-yen

/year


Others ( )


/year


Date of declaration :

Signature :

This form is compiled according to “The Guideline for Management of Conflict of Interest in Medical Research (February 2011)” issued by the Conflict of Interest Committee, Section of Clinical Medicine, the Japanese Association of Medical Sciences. *) Declaration criteria shall be determined by the Guideline Executive Committee.

For the first declaration, enter data of the latest 3 years.

If there is any COI, enter the timing when the relationship started.

• Describe who is actually related, the declarer himself or his family member.

• Criteria are usually set as to who should be included in family members, such as within the second degree of relationship.

Specify the declaration criteria for each related item, such as more than ●● million yen annually.

If the sign is an autograph, stamp can be omitted.

31

18


2-5 COI Report (2) - Summary of Financial COI Declaration and Response Policy O: Entry Guide

COI report

Summary of financial COI declaration

Policy for response to the above

It is acceptable to disclose several COIs related to the subject topics at a time. Disclosure standards shall be specified, but how to disclose shall be decided by organizations developing the guidelines.

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18


2-5 COI Report (2) - Summary of Financial COI Declaration and Response Policy O: Entry Guide

COI report



It is acceptable to disclose several COIs related to the subject topics at a time. Disclosure standards shall be specified, but how to disclose shall be decided by organizations developing the guidelines.

32

Chapter 3

Scope

What is Scope? ................................................................. 20

Structure of Scope ........................................................... 20

Process of Scope Development ..................................... 21

Formulation of Clinical Question .................................... 22

Specification of Systematic Review ............................... 25

Procedures from Formulating Recommendations to Finalization and Publication of the CPG ........................ 25

1

2

3

4

5

6

33

Chapter 3

Scope

What is Scope? ................................................................. 20

Structure of Scope ........................................................... 20

Process of Scope Development ..................................... 21

Formulation of Clinical Question .................................... 22

Specification of Systematic Review ............................... 25

Procedures from Formulating Recommendations to Finalization and Publication of the CPG ........................ 25

1

2

3

4

5

6

33

20

Chapter 3 Scope

The scope is defined as a document to be prepared at the beginning of CPG development, to clarify the basic characteristics of the health topic and contents to be covered in the CPG, and to specify the methods of systematic review, formulation of recommendations, finalization, and publishing of the CPG. Thus, the scope can be considered as a planning document of CPG development.

A CPG is developed by the Guideline Development Group and the Systematic Review Team (SR Team), and the scope is prepared through discussions by the members of the Guideline Development Group at the beginning of CPG development. Public comments for the drafted scope may be sought to hear the opinions of all stakeholders, including healthcare professionals and patients who may use the CPG, and governments and groups that may be influenced by the CPG, before finalizing the scope.

The scope should be prepared at the beginning of the CPG development process, but it can be revised, if necessary, during the course of CPG development. In this case, the reason and approval process of revision should be described clearly in the scope with the date and version of the revised edition.

The items to be described in the standard scope are those included in the following

template [Template ID: 3-3 Scope S], but in this handbook, we recommend using the structure in the following box, in which “Basic characteristics of the health topic” are included.

Basic characteristics of the health topic Clinical characteristics of the health topic Epidemiological characteristics of the health topic Overall flow of clinical practice of the health topic

(The above shall be summarized in the following templates) [Template ID: 3-1 Basic Characteristics of Health Topic S*1] [Template ID: 3-2 Clinical Practice Flowchart (Fig.) S]

Scope [Template ID: 3-3 Scope S]


documents. S: Template included in scope, O: For operation

1 What is Scope?

2 Structure of Scope

34

20

Chapter 3 Scope

The scope is defined as a document to be prepared at the beginning of CPG development, to clarify the basic characteristics of the health topic and contents to be covered in the CPG, and to specify the methods of systematic review, formulation of recommendations, finalization, and publishing of the CPG. Thus, the scope can be considered as a planning document of CPG development.

A CPG is developed by the Guideline Development Group and the Systematic Review Team (SR Team), and the scope is prepared through discussions by the members of the Guideline Development Group at the beginning of CPG development. Public comments for the drafted scope may be sought to hear the opinions of all stakeholders, including healthcare professionals and patients who may use the CPG, and governments and groups that may be influenced by the CPG, before finalizing the scope.

The scope should be prepared at the beginning of the CPG development process, but it can be revised, if necessary, during the course of CPG development. In this case, the reason and approval process of revision should be described clearly in the scope with the date and version of the revised edition.

The items to be described in the standard scope are those included in the following

template [Template ID: 3-3 Scope S], but in this handbook, we recommend using the structure in the following box, in which “Basic characteristics of the health topic” are included.

Basic characteristics of the health topic Clinical characteristics of the health topic Epidemiological characteristics of the health topic Overall flow of clinical practice of the health topic

(The above shall be summarized in the following templates) [Template ID: 3-1 Basic Characteristics of Health Topic S*1] [Template ID: 3-2 Clinical Practice Flowchart (Fig.) S]

Scope [Template ID: 3-3 Scope S]


documents. S: Template included in scope, O: For operation

1 What is Scope?

2 Structure of Scope

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21

Chapter

3 S

cope

The process to formulate clinical questions (CQs), which is the most important part

of scope development, is explained below.

1) Overall flow of clinical practice of the health topic The overall flow of clinical practice should be summarized as the basic characteristics

of the health topic to be covered in the CPG. It is advisable to display graphically the overall flow of clinical practice in the form of a clinical practice flowchart.

An example of simple clinical practice flowchart is shown in Fig. 3-1. Target disease X can be classified into Stage 1 and Stage 2, and while surgery has been established as the standard therapy for Stage 1, surgery alone as well as the combination therapy of surgery and radiation are considered to be alternative care options for Stage 2 patients. In the CPG, recommendations should be made for CQs with multiple care options as for Stage 2, based on the evaluation of the body of evidence. In cases where therapeutic methods are already established as Stage 1, it is enough to describe briefly the established therapeutic methods, and not necessary to pick up this topic as a key clinical issue and CQ.

Fig. 3-1 Example of a clinical practice flowchart

3 Process of Scope Development

Disease X

Stage 1 Stage 2

Clinical Question: Which is the more appropriate therapeutic method for Stage 2: surgery alone or combination therapy of surgery and radiation?

Surgery Surgery Surgery + Radiation therapy

35

21

Chapter

3 S

cope

The process to formulate clinical questions (CQs), which is the most important part

of scope development, is explained below.

1) Overall flow of clinical practice of the health topic The overall flow of clinical practice should be summarized as the basic characteristics

of the health topic to be covered in the CPG. It is advisable to display graphically the overall flow of clinical practice in the form of a clinical practice flowchart.

An example of simple clinical practice flowchart is shown in Fig. 3-1. Target disease X can be classified into Stage 1 and Stage 2, and while surgery has been established as the standard therapy for Stage 1, surgery alone as well as the combination therapy of surgery and radiation are considered to be alternative care options for Stage 2 patients. In the CPG, recommendations should be made for CQs with multiple care options as for Stage 2, based on the evaluation of the body of evidence. In cases where therapeutic methods are already established as Stage 1, it is enough to describe briefly the established therapeutic methods, and not necessary to pick up this topic as a key clinical issue and CQ.

Fig. 3-1 Example of a clinical practice flowchart

3 Process of Scope Development

Disease X

Stage 1 Stage 2

Clinical Question: Which is the more appropriate therapeutic method for Stage 2: surgery alone or combination therapy of surgery and radiation?

Surgery Surgery Surgery + Radiation therapy

35

22

Chapter 3 Scope

2) Key clinical issues The clinical issues to be covered in the CPG should be clearly determined as “key

clinical issues.” It is necessary to focus on key clinical issues, in which improvement of patient outcomes is highly expected, among important points of decision making by patients and practitioners; such key clinical issues include whether a highly invasive test should be conducted for diagnostic procedure, or what should be selected as an appropriate therapeutic method. Important candidates are issues where significant improvement in patient outcomes is expected because a new therapeutic method emerged, or issues where a non-negligible diversity exists in patient outcomes because different therapeutic methods prevail in parallel due to longstanding tradition.

As shown on page 32 in Chapter 4, domestic as well as foreign CPGs and key literature are sometimes referred to by conducting a scoping search to understand the current situation.

1) What is a Clinical Question? After key clinical issues are determined in the scope, CQs should be formulated based

on them. A CQ is defined in this handbook as “an interrogative sentence that is formulated based on components of key clinical issues covered in the scope.” The number of CQs to be formulated from one key clinical issue may be single or multiple. Since disease specialists usually develop CPGs in Japan, they have enough knowledge about where the CQ is situated in the process of clinical practice. On the other hand, the formulations of CQs by disease specialists tend to depend on their expert perspectives; it is necessary, therefore, to make efforts to actively pick up outcomes important for patients.

The components of CQ are important for exhaustive retrieval of evidence, which is performed for systematic review (Chapter 4 , p. 32). Clear formulation of components of CQ is useful to evaluate the indirectness of evidence (Chapter 4 , p. 37). The outcomes concerning benefits and harms should be set and their importance for patients should be scored at the time of CQ formulation. This information is necessary to formulate recommendations later. (Chapter 5 , p. 52). [Template ID: 3-4 Formulation of Clinical Question O]

2

3

2

4 Formulation of Clinical Question

36

22

Chapter 3 Scope

2) Key clinical issues The clinical issues to be covered in the CPG should be clearly determined as “key

clinical issues.” It is necessary to focus on key clinical issues, in which improvement of patient outcomes is highly expected, among important points of decision making by patients and practitioners; such key clinical issues include whether a highly invasive test should be conducted for diagnostic procedure, or what should be selected as an appropriate therapeutic method. Important candidates are issues where significant improvement in patient outcomes is expected because a new therapeutic method emerged, or issues where a non-negligible diversity exists in patient outcomes because different therapeutic methods prevail in parallel due to longstanding tradition.

As shown on page 32 in Chapter 4, domestic as well as foreign CPGs and key literature are sometimes referred to by conducting a scoping search to understand the current situation.

1) What is a Clinical Question? After key clinical issues are determined in the scope, CQs should be formulated based

on them. A CQ is defined in this handbook as “an interrogative sentence that is formulated based on components of key clinical issues covered in the scope.” The number of CQs to be formulated from one key clinical issue may be single or multiple. Since disease specialists usually develop CPGs in Japan, they have enough knowledge about where the CQ is situated in the process of clinical practice. On the other hand, the formulations of CQs by disease specialists tend to depend on their expert perspectives; it is necessary, therefore, to make efforts to actively pick up outcomes important for patients.

The components of CQ are important for exhaustive retrieval of evidence, which is performed for systematic review (Chapter 4 , p. 32). Clear formulation of components of CQ is useful to evaluate the indirectness of evidence (Chapter 4 , p. 37). The outcomes concerning benefits and harms should be set and their importance for patients should be scored at the time of CQ formulation. This information is necessary to formulate recommendations later. (Chapter 5 , p. 52). [Template ID: 3-4 Formulation of Clinical Question O]

2

3

2

4 Formulation of Clinical Question

36

23

Chapter

3 S

cope

2) Extraction of components of clinical question The PICO format (P standing for patients, problem, population, I for interventions, C

for comparison, controls, comparator, and O for outcomes) is usually used to formulate the components of CQs.

• P (patients, problem, population) The characteristics (sex, age, etc.) of the patient subject to intervention should be

clarified. The disease, condition, or symptom to be targeted should be clarified in detail. Specific constraints, such as geographical constraint, if any, should be added. • I/C (intervention/comparison, controls, comparator) The interventions to be evaluated for recommendations for P should be listed. I and

C may be determined specifically, but it might sometimes be impossible to decide on which alternative options should be I or C. In other cases, three or more alternative options might be evaluated simultaneously. Taking these situations into account, this handbook adopts a method where I and C are not separately defined, but alternative options of interventions are to be listed interchangeably as I/C.

Characteristics of interventions, such as duration, dosage, or dosing methods, should also be considered.

Alternative options should be specified in all cases. (e.g., a target intervention is compared with standard treatment or no treatment.)

• O (outcomes) All the outcomes to be evaluated to determine the recommendation should be listed

exhaustively. Both desired outcomes and undesired outcomes for patients should be selected;

desired outcomes are “benefits,” such as decrease in mortality rate, improvement in quality of life (QOL), or decrease in hospitalization, while undesirable outcomes are “harms,” such as occurrence of adverse reactions and adverse events.

“Patient-important outcomes” should be selected, not just “surrogate outcomes.” Surrogate outcomes include substitute, alternative, physiological outcomes, such as changes in laboratory values that may be emphasized by practitioners. Patient-important outcomes include direct outcomes that patients would take as important, such as death versus survival, symptoms, and change in QOL.

3) Evaluation of relative importance of extracted outcomes Each outcome should be evaluated regarding “how important it is for patients

receiving the interventions.” This handbook explains a method to score outcomes by 1 to 9 points, where a higher score indicates that the outcome is more important for patients. Scoring is conducted subjectively and relatively by the Guideline Development Group, based on experience and preliminary knowledge regarding existing research results. It is desirable to incorporate patient views into evaluation. The method often used to evaluate outcomes according to the points is as follows: points from 1 to 3 are regarded as “not

37

23

Chapter

3 S

cope

2) Extraction of components of clinical question The PICO format (P standing for patients, problem, population, I for interventions, C

for comparison, controls, comparator, and O for outcomes) is usually used to formulate the components of CQs.

• P (patients, problem, population) The characteristics (sex, age, etc.) of the patient subject to intervention should be

clarified. The disease, condition, or symptom to be targeted should be clarified in detail. Specific constraints, such as geographical constraint, if any, should be added. • I/C (intervention/comparison, controls, comparator) The interventions to be evaluated for recommendations for P should be listed. I and

C may be determined specifically, but it might sometimes be impossible to decide on which alternative options should be I or C. In other cases, three or more alternative options might be evaluated simultaneously. Taking these situations into account, this handbook adopts a method where I and C are not separately defined, but alternative options of interventions are to be listed interchangeably as I/C.

Characteristics of interventions, such as duration, dosage, or dosing methods, should also be considered.

Alternative options should be specified in all cases. (e.g., a target intervention is compared with standard treatment or no treatment.)

• O (outcomes) All the outcomes to be evaluated to determine the recommendation should be listed

exhaustively. Both desired outcomes and undesired outcomes for patients should be selected;

desired outcomes are “benefits,” such as decrease in mortality rate, improvement in quality of life (QOL), or decrease in hospitalization, while undesirable outcomes are “harms,” such as occurrence of adverse reactions and adverse events.

“Patient-important outcomes” should be selected, not just “surrogate outcomes.” Surrogate outcomes include substitute, alternative, physiological outcomes, such as changes in laboratory values that may be emphasized by practitioners. Patient-important outcomes include direct outcomes that patients would take as important, such as death versus survival, symptoms, and change in QOL.

3) Evaluation of relative importance of extracted outcomes Each outcome should be evaluated regarding “how important it is for patients

receiving the interventions.” This handbook explains a method to score outcomes by 1 to 9 points, where a higher score indicates that the outcome is more important for patients. Scoring is conducted subjectively and relatively by the Guideline Development Group, based on experience and preliminary knowledge regarding existing research results. It is desirable to incorporate patient views into evaluation. The method often used to evaluate outcomes according to the points is as follows: points from 1 to 3 are regarded as “not

37

24

Chapter 3 Scope

important,” 4 to 6 as “important,” and 7 to 9 as “critical” (Fig. 3-2). “Important” and “critical” outcomes are selected for actual systematic review. A consensus formation method, such as the Delphi method, is used to determine the points for each outcome by the Guideline Development Group consisting of diverse members, such as disease experts and patient representatives. If there are too many outcomes classified into “critical” or “important,” outcomes shall be further selected if necessary. The number of outcomes to be evaluated shall be decided considering experience and skill of members who conduct systematic review and time to be spent for developing the CPG. As a guide, a maximum of about seven outcomes with higher points of importance classified into “critical” or “important” are often adopted.

Fig. 3-2 Scoring of Outcome Importance

4) Expression of Clinical Question Using Extracted Components A CQ shall be expressed in an interrogative sentence using components (P, I, C, O)

extracted in the above process. As an example of expressing a CQ where two interventions are to be compared, a

sentence “For P, which is recommended, I or C (or I1 or I2)?” can be considered. In addition to the expression “which is recommended,” the expression “which is useful” is sometimes used.

5) Selection of Clinical Question In usual clinical practice, there are a number of situations where a decision is made on

which intervention is to be adopted. It is sometimes impossible, however, to cover all of them in a CPG. Systematic review is always laborious. It is advisable, therefore, to carefully select CQs for systematic reviews, considering whether they are important enough for patients and practitioners to make a decision at an important point that influences the patient outcomes; such situations include a decision on whether invasive diagnostic intervention should be applied or not, or a decision on which alternative intervention options should be selected for treatment.

Outcome importance

Not important Important Critical

38

24

Chapter 3 Scope

important,” 4 to 6 as “important,” and 7 to 9 as “critical” (Fig. 3-2). “Important” and “critical” outcomes are selected for actual systematic review. A consensus formation method, such as the Delphi method, is used to determine the points for each outcome by the Guideline Development Group consisting of diverse members, such as disease experts and patient representatives. If there are too many outcomes classified into “critical” or “important,” outcomes shall be further selected if necessary. The number of outcomes to be evaluated shall be decided considering experience and skill of members who conduct systematic review and time to be spent for developing the CPG. As a guide, a maximum of about seven outcomes with higher points of importance classified into “critical” or “important” are often adopted.

Fig. 3-2 Scoring of Outcome Importance

4) Expression of Clinical Question Using Extracted Components A CQ shall be expressed in an interrogative sentence using components (P, I, C, O)

extracted in the above process. As an example of expressing a CQ where two interventions are to be compared, a

sentence “For P, which is recommended, I or C (or I1 or I2)?” can be considered. In addition to the expression “which is recommended,” the expression “which is useful” is sometimes used.

5) Selection of Clinical Question In usual clinical practice, there are a number of situations where a decision is made on

which intervention is to be adopted. It is sometimes impossible, however, to cover all of them in a CPG. Systematic review is always laborious. It is advisable, therefore, to carefully select CQs for systematic reviews, considering whether they are important enough for patients and practitioners to make a decision at an important point that influences the patient outcomes; such situations include a decision on whether invasive diagnostic intervention should be applied or not, or a decision on which alternative intervention options should be selected for treatment.

Outcome importance

Not important Important Critical

38

25

Chapter

3 S

cope

1) Strategy of search for evidence and selection criteria The search strategy is specified regarding the evidence type to be searched: (1)

individual study articles of randomized controlled trial (RCT), non-randomized controlled trial (non-RCT), and observational study, (2) systematic review, and (3) existing CPGs.

2) Method of evidence evaluation and integration The method of evaluating the body of evidence, the method of expressing the strength

of the body of evidence, and method of integrating the evidence should be determined.

Procedure from formulating recommendations to finalization, external review, and publication of the CPG shall be decided.

5 Specification of Systematic Review

6 Procedures from Formulating Recommendations to Finalization and Publication of the CPG

39

25

Chapter

3 S

cope

1) Strategy of search for evidence and selection criteria The search strategy is specified regarding the evidence type to be searched: (1)

individual study articles of randomized controlled trial (RCT), non-randomized controlled trial (non-RCT), and observational study, (2) systematic review, and (3) existing CPGs.

2) Method of evidence evaluation and integration The method of evaluating the body of evidence, the method of expressing the strength

of the body of evidence, and method of integrating the evidence should be determined.

Procedure from formulating recommendations to finalization, external review, and publication of the CPG shall be decided.

5 Specification of Systematic Review

6 Procedures from Formulating Recommendations to Finalization and Publication of the CPG

39

26

Chapter 3 Scope

3-1 Basic Characteristics of Health Topic, S: Entry Guide

Clinical characteristics

Describe clinical items necessary to understand and utilize the recommendations of the CPG in clinical practice. Pathophysiology, clinical classification, historical items, etc.

Epidemiological characteristics

Describe epidemiological items necessary to understand and utilize the recommendations of the CPG in clinical practice. Current status such as morbidity rate, mortality rate, survival rate, etc., time-course change, regional characteristics, etc.

Overall flow of clinical practice

Explain overall flow of actual clinical practice. For example, the patient is clinically classified into Stage 1 or Stage 2. Stage 1: Surgical therapy has been established as a standard therapy. Stage 2: Both surgical therapy and surgery + radiation therapy have been used, and it is necessary to evaluate as clinical questions. (Prepare recommendations in the guidelines.)

3-2 Clinical Practice Flowchart (Fig.) S: Entry Guide

Clinical practice flowchart

It is advisable to add a clinical practice flowchart to help in understanding the explanation. As shown in Stage 2 in the above example, in cases where an issue is subject to preparation of recommendations as a clinical question at the stage of scope preparation, enter “Prepare recommendations as clinical question (CQ No.)” at the stage of scope, and complete clinical practice flowchart after completion of preparation of recommendations by adding the content of recommendations (Chapter 6).

40

26

Chapter 3 Scope

3-1 Basic Characteristics of Health Topic, S: Entry Guide


Describe clinical items necessary to understand and utilize the recommendations of the CPG in clinical practice. Pathophysiology, clinical classification, historical items, etc.


Describe epidemiological items necessary to understand and utilize the recommendations of the CPG in clinical practice. Current status such as morbidity rate, mortality rate, survival rate, etc., time-course change, regional characteristics, etc.


Explain overall flow of actual clinical practice. For example, the patient is clinically classified into Stage 1 or Stage 2. Stage 1: Surgical therapy has been established as a standard therapy. Stage 2: Both surgical therapy and surgery + radiation therapy have been used, and it is necessary to evaluate as clinical questions. (Prepare recommendations in the guidelines.)

3-2 Clinical Practice Flowchart (Fig.) S: Entry Guide


It is advisable to add a clinical practice flowchart to help in understanding the explanation. As shown in Stage 2 in the above example, in cases where an issue is subject to preparation of recommendations as a clinical question at the stage of scope preparation, enter “Prepare recommendations as clinical question (CQ No.)” at the stage of scope, and complete clinical practice flowchart after completion of preparation of recommendations by adding the content of recommendations (Chapter 6).

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Chapter

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cope

3-3 Scope S: Entry Guide

1. Items concerning the contents to be covered by CPG

(1) Title Enter the title of CPGs. For the revised version, it is advisable to enter the title indicating the revised version.

(2) Objective Enter the aim of improving patient outcomes that the CPG seeks as a whole.

(3) Topic Enter the theme covered by the CPG. If the whole of a disease is covered, describe “name of disease,” and if only treatment is covered, describe the topic to be covered by combining words, such as “treatment of pediatric acute otitis media.”

(4) Expected users and institutions

Describe institutions and healthcare professionals expected to use the CPGs.

(5) Relationship with existing CPGs

For the revised version, clearly specify which CPG has been revised. In cases where it is not a revised version, but there are related CPGs, clarify the relationship.

(6) Key clinical issues

Enter issues to be covered in the CPG as key clinical issues. Perform preliminary literature retrieval and understand the overview of issues prior to entering key clinical issues. Key clinical issue 1: Key clinical issue 2: Key clinical issue 3: ⋮ ⋮

(7) Range to be covered by CPG

Define in detail topics to be covered in the CPG. Describe separately the range to be covered and not to be covered by the CPG.

(8) Clinical Question (CQ) List

Based on issues covered as “key clinical issues,” establish CQs as issues necessary for improving important outcomes for patients. In scope, list the table of established CQs. CQ1: CQ2: CQ3: ⋮ ⋮

2. Items concerning Systematic Review (1) Schedule Describe implementation schedule for systematic review.

(2) Search of Evidence

Select a search target as evidence type from individual study paper (randomized controlled trial [RCT], non-randomized controlled trial [non-RCT], observational study, etc.), systematic review (SR) paper, and existing CPG and describe the priority order of search. For individual research paper, select and describe research types to be included in retrieval subject among research types, such as RCT, non-RCT, observational study, etc. Describe the standard policy for deciding search strategy. Describe database selection by evidence type. Describe the date-range for each database in a year-month-day format.

(3) Inclusion and exclusion criteria for research reports

In case there are numerous papers, describe the basic policy of priority order and adoption conditions on how to select from the existing CPGs, SR papers, RCT, non-RCT, and observational study.

(4) Method of evidence evaluation and integration

Describe how to evaluate evidence consisting of selected literature. Describe how to express the strength of the body of evidence. Describe the basic concept of qualitative and quantitative integration of the body of evidence.

3. Items from Formulation of Recommendations to Finalization and Publication of CPG (1) Basic policy for

formulating recommendations

Decide in advance a concrete method of consensus building, factors to be considered for preparing recommendations, rules to be complied with when expressing recommendations in writing, and standard for expressing the strength of recommendations.

(2) Finalization of the CPG Describe procedures for finalizing the completed draft of the CPG.

(3) Method of external review

Describe how to conduct external review. For example, evaluation by external review committee members, implementation of public comments, trial at medical institutions, etc.

(4) Publication of the CPG Describe the scheduled date for disclosure, how to disclose, etc.

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27

Chapter

3 S

cope

3-3 Scope S: Entry Guide

1. Items concerning the contents to be covered by CPG

(1) Title Enter the title of CPGs. For the revised version, it is advisable to enter the title indicating the revised version.

(2) Objective Enter the aim of improving patient outcomes that the CPG seeks as a whole.

(3) Topic Enter the theme covered by the CPG. If the whole of a disease is covered, describe “name of disease,” and if only treatment is covered, describe the topic to be covered by combining words, such as “treatment of pediatric acute otitis media.”


Describe institutions and healthcare professionals expected to use the CPGs.


For the revised version, clearly specify which CPG has been revised. In cases where it is not a revised version, but there are related CPGs, clarify the relationship.


Enter issues to be covered in the CPG as key clinical issues. Perform preliminary literature retrieval and understand the overview of issues prior to entering key clinical issues. Key clinical issue 1: Key clinical issue 2: Key clinical issue 3: ⋮ ⋮


Define in detail topics to be covered in the CPG. Describe separately the range to be covered and not to be covered by the CPG.


Based on issues covered as “key clinical issues,” establish CQs as issues necessary for improving important outcomes for patients. In scope, list the table of established CQs. CQ1: CQ2: CQ3: ⋮ ⋮

2. Items concerning Systematic Review (1) Schedule Describe implementation schedule for systematic review.


Select a search target as evidence type from individual study paper (randomized controlled trial [RCT], non-randomized controlled trial [non-RCT], observational study, etc.), systematic review (SR) paper, and existing CPG and describe the priority order of search. For individual research paper, select and describe research types to be included in retrieval subject among research types, such as RCT, non-RCT, observational study, etc. Describe the standard policy for deciding search strategy. Describe database selection by evidence type. Describe the date-range for each database in a year-month-day format.


In case there are numerous papers, describe the basic policy of priority order and adoption conditions on how to select from the existing CPGs, SR papers, RCT, non-RCT, and observational study.


Describe how to evaluate evidence consisting of selected literature. Describe how to express the strength of the body of evidence. Describe the basic concept of qualitative and quantitative integration of the body of evidence.

3. Items from Formulation of Recommendations to Finalization and Publication of CPG (1) Basic policy for

formulating recommendations

Decide in advance a concrete method of consensus building, factors to be considered for preparing recommendations, rules to be complied with when expressing recommendations in writing, and standard for expressing the strength of recommendations.

(2) Finalization of the CPG Describe procedures for finalizing the completed draft of the CPG.


Describe how to conduct external review. For example, evaluation by external review committee members, implementation of public comments, trial at medical institutions, etc.

(4) Publication of the CPG Describe the scheduled date for disclosure, how to disclose, etc.

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Chapter 3 Scope

3-4 Formulation of Clinical Question (CQ) O: Entry Guide

Key clinical issues covered by the scope Describe one of the key clinical issues to be covered by the scope.

Components of CQ P (patients, problem, population)

Sex (Not specified/man/woman) Age (Not specified/ _____________)

Disease/ clinical condition

Geographical constraints

Others List of I (interventions)/C (comparisons, controls, comparators)

List of O (outcomes) Outcomes Benefit or harm Importance Adopt or not

O1 (Benefit/harm) ___ point(s) O2 (Benefit/harm) ___ point(s) O3 (Benefit/harm) ___ point(s) O4 (Benefit/harm) ___ point(s) O5 O6 O7 O8 (Benefit / harm) ___ point(s) O9 (Benefit/harm) ___ point(s) O10 (Benefit/harm) ___ point(s) O11 (Benefit/harm) ___ point(s) O12 (Benefit/harm) ___ point(s) O13 (Benefit/harm) ___ point(s) O14 (Benefit/harm) ___ point(s) O15 (Benefit/harm) ___ point(s)

Formulated CQ Express and describe CQ in one sentence using PICO extracted in the above.

Extract component of CQ (P, I/C) from key clinical issues covered, and describe it.

Establish O (outcomes) concerning benefit and harm, and evaluate the importance for patients. By consensual decision making, enter or × for whether to adopt or not adopt each outcome.

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Chapter 3 Scope

3-4 Formulation of Clinical Question (CQ) O: Entry Guide

Key clinical issues covered by the scope Describe one of the key clinical issues to be covered by the scope.


Sex (Not specified/man/woman) Age (Not specified/ _____________)


Geographical constraints


List of O (outcomes) Outcomes Benefit or harm Importance Adopt or not

O1 (Benefit/harm) ___ point(s) O2 (Benefit/harm) ___ point(s) O3 (Benefit/harm) ___ point(s) O4 (Benefit/harm) ___ point(s) O5 O6 O7 O8 (Benefit / harm) ___ point(s) O9 (Benefit/harm) ___ point(s) O10 (Benefit/harm) ___ point(s) O11 (Benefit/harm) ___ point(s) O12 (Benefit/harm) ___ point(s) O13 (Benefit/harm) ___ point(s) O14 (Benefit/harm) ___ point(s) O15 (Benefit/harm) ___ point(s)

Formulated CQ Express and describe CQ in one sentence using PICO extracted in the above.

Extract component of CQ (P, I/C) from key clinical issues covered, and describe it.

Establish O (outcomes) concerning benefit and harm, and evaluate the importance for patients. By consensual decision making, enter or × for whether to adopt or not adopt each outcome.

42

Chapter 4

Systematic Review

Overview of Systematic Review ..................................... 30

Identifying the Evidence .................................................. 32

Evaluation of the Body of Evidence ............................... 34

Integration of the Body of Evidence ............................... 37

Determination of the Strength of Evidence of the Body of Evidence ....................................................... 38

Preparation of Systematic Review Report ..................... 39

1

2

3

4

5

6

43

Chapter 4

Systematic Review

Overview of Systematic Review ..................................... 30

Identifying the Evidence .................................................. 32

Evaluation of the Body of Evidence ............................... 34

Integration of the Body of Evidence ............................... 37

Determination of the Strength of Evidence of the Body of Evidence ....................................................... 38

Preparation of Systematic Review Report ..................... 39

1

2

3

4

5

6

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30

Chapter 4 Systematic Review

1) What is systematic review? Systematic review consists of systematic search of studies relevant to clinical

questions (CQs) to be answered in the clinical practice guideline (CPG); compilation of studies with similar study designs; and evaluation and integration of evidence expressed by study results, while evaluating biases potentially distorting the study results. A number of systematic reviews and meta-analyses, including Cochrane reviews, have been published. A website is now operated to register systematic reviews at the time when the protocol is completed. An individual systematic review for a CQ of CPG should be registered in the International Prospective Register of Systematic Reviews (PROSPERO), if the systematic review is planned to be published as an independent article.

Qualitative systematic review

Qualitative systematic review is defined as qualitative synthesis of studies to give deep understanding of study results, by recording the numbers of included and excluded studies, clinical profiles, and the number of subjects; describing the methods of interventions and comparators; and evaluating the risk of bias. Results of qualitative systematic reviews shall be reflected to the grading of strength of evidence.

Quantitative systematic review (meta-analysis)

Even for quantitative systematic review, it is necessary to evaluate qualitatively the biases potentially distorting study results and to evaluate the heterogeneity of study results to decide on the possibility of integrating the results quantitatively by meta-analysis. Meta-analysis is a statistical and quantitative integration of values of effect measures by calculating integrated values and confidence intervals.

2) Utilization of existing systematic reviews The systematic review for a CPG aims at evaluating the strength of the body of

evidence and providing a summary of the body of evidence to help formulate the recommendations. Thus, the systematic review for a CPG is different from the usual stand-alone systematic review. What should be noted in particular is that comprehensive literature search and firm criteria for adopting literature are required for each of the CQs; both benefit and harm outcomes are emphasized; and comprehensive literature data management is needed, because one study could often be a source of systematic reviews for different outcomes.

In cases where a systematic review for a CQ has already been published, it may be possible to use it, instead of performing a de novo systematic review. When existing systematic reviews of independent articles or published CPGs are considered to be adapted for CPG development, tools such as AGREE II (Appraisal of Guidelines for Research & Evaluation II) and AMSTAR (Assessment of Multiple Systematic Reviews)

1 Overview of Systematic Review

44

30


1) What is systematic review? Systematic review consists of systematic search of studies relevant to clinical

questions (CQs) to be answered in the clinical practice guideline (CPG); compilation of studies with similar study designs; and evaluation and integration of evidence expressed by study results, while evaluating biases potentially distorting the study results. A number of systematic reviews and meta-analyses, including Cochrane reviews, have been published. A website is now operated to register systematic reviews at the time when the protocol is completed. An individual systematic review for a CQ of CPG should be registered in the International Prospective Register of Systematic Reviews (PROSPERO), if the systematic review is planned to be published as an independent article.

Qualitative systematic review

Qualitative systematic review is defined as qualitative synthesis of studies to give deep understanding of study results, by recording the numbers of included and excluded studies, clinical profiles, and the number of subjects; describing the methods of interventions and comparators; and evaluating the risk of bias. Results of qualitative systematic reviews shall be reflected to the grading of strength of evidence.

Quantitative systematic review (meta-analysis)

Even for quantitative systematic review, it is necessary to evaluate qualitatively the biases potentially distorting study results and to evaluate the heterogeneity of study results to decide on the possibility of integrating the results quantitatively by meta-analysis. Meta-analysis is a statistical and quantitative integration of values of effect measures by calculating integrated values and confidence intervals.

2) Utilization of existing systematic reviews The systematic review for a CPG aims at evaluating the strength of the body of

evidence and providing a summary of the body of evidence to help formulate the recommendations. Thus, the systematic review for a CPG is different from the usual stand-alone systematic review. What should be noted in particular is that comprehensive literature search and firm criteria for adopting literature are required for each of the CQs; both benefit and harm outcomes are emphasized; and comprehensive literature data management is needed, because one study could often be a source of systematic reviews for different outcomes.

In cases where a systematic review for a CQ has already been published, it may be possible to use it, instead of performing a de novo systematic review. When existing systematic reviews of independent articles or published CPGs are considered to be adapted for CPG development, tools such as AGREE II (Appraisal of Guidelines for Research & Evaluation II) and AMSTAR (Assessment of Multiple Systematic Reviews)

1 Overview of Systematic Review

44

31

Chapter

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ystematic R

eview

should be used to evaluate the quality of systematic reviews and to select the most appropriate one. The policy options to be considered for such a case are shown in Fig. 4-1. A policy option should be selected by evaluating how many new studies were published after the CPG or systematic review article had been published and whether the result of systematic review could have changed if newly emerged studies were included.

The following number corresponds to the number in the figure:

(1) Use the results of existing SR. (2) Perform a new SR of studies that are selected from studies adopted in the existing

SR as suitable for the CQ of interest. (3) Perform a new SR based on studies obtained using the same literature search

strategy as the existing SR. (4) Perform a meta-analysis or qualitative SR by adding latest studies not included in

the existing SR. (5) Perform a new SR based on the part of literature search strategy identified in the

existing SR.

*: Systematic reviews (SRs) included in existing CPGs shall be covered.

**: Add in the evaluation sheet of the body of evidence (Step 2).

Fig. 4-1 Flowchart of Policy Selection for Utilizing Existing Systematic Reviews

3) Overview of systematic review procedures

The scope received from the Guideline Development Group can be considered as the written instructions on systematic review procedures to the SR Team. An independent SR Team should confirm the systematic review methods stated in the scope, and perform systematic reviews from a neutral standpoint, according to the procedures below, following the method described in the scope. It is desired to prepare a systematic review protocol compatible with PROSPERO (Reference 1).

Reference 1 Systematic Review Protocol (p. 112)

SR* exists? No

No “Yes” for all items of AMSTAR? Perform de novo SR

Yes No No

PICO of CQ matches? Literature search strategy is

appropriate? No

No

Yes

Yes No

Yes

No Yes

Yes Yes

The latest studies are cited?

The latest studies are known?

Parts of studies correspond to CQ?

Part of literature search strategy corresponds to

CQ?

(1) Use as it is ** (2) Perform sensitivity

analysis (4) Perform

meta-analysis or qualitative SR by adding

latest studies

(3) Perform new SR based on literature search strategy of

existing SR

(5) Perform new SR based on the part of literature

search strategy identified in existing SR

Yes

45

31

Chapter

4 S

ystematic R

eview

should be used to evaluate the quality of systematic reviews and to select the most appropriate one. The policy options to be considered for such a case are shown in Fig. 4-1. A policy option should be selected by evaluating how many new studies were published after the CPG or systematic review article had been published and whether the result of systematic review could have changed if newly emerged studies were included.

The following number corresponds to the number in the figure:

(1) Use the results of existing SR. (2) Perform a new SR of studies that are selected from studies adopted in the existing

SR as suitable for the CQ of interest. (3) Perform a new SR based on studies obtained using the same literature search

strategy as the existing SR. (4) Perform a meta-analysis or qualitative SR by adding latest studies not included in

the existing SR. (5) Perform a new SR based on the part of literature search strategy identified in the

existing SR.

*: Systematic reviews (SRs) included in existing CPGs shall be covered.

**: Add in the evaluation sheet of the body of evidence (Step 2).

Fig. 4-1 Flowchart of Policy Selection for Utilizing Existing Systematic Reviews

3) Overview of systematic review procedures

The scope received from the Guideline Development Group can be considered as the written instructions on systematic review procedures to the SR Team. An independent SR Team should confirm the systematic review methods stated in the scope, and perform systematic reviews from a neutral standpoint, according to the procedures below, following the method described in the scope. It is desired to prepare a systematic review protocol compatible with PROSPERO (Reference 1).

Reference 1 Systematic Review Protocol (p. 112)

SR* exists? No

No “Yes” for all items of AMSTAR? Perform de novo SR

Yes No No

PICO of CQ matches? Literature search strategy is

appropriate? No

No

Yes

Yes No

Yes

No Yes

Yes Yes

The latest studies are cited?

The latest studies are known?

Parts of studies correspond to CQ?

Part of literature search strategy corresponds to

CQ?

(1) Use as it is ** (2) Perform sensitivity

analysis (4) Perform

meta-analysis or qualitative SR by adding

latest studies

(3) Perform new SR based on literature search strategy of

existing SR

(5) Perform new SR based on the part of literature

search strategy identified in existing SR

Yes

45

32


(1) Conduct a systematic literature search based on PICO (2) Compile a collection of studies by primary screening (selection according to titles

and abstracts) and by secondary screening (selection according to evaluation of full text), based on explicit criteria for each combination of interventions/exposure and outcomes. Make a list of studies excluded by secondary screening, with reasons for exclusion.

(3) Perform qualitative evaluation of individual studies for each outcome and compile the results of evaluation by the combination of intervention/exposure, outcome, and study design. At this time, the indirectness of PICO should be evaluated, and comments should be recorded. (Qualitative systematic review)

(4) Perform quantitative systematic review by selecting studies that are based on similar PICO and give data of effect measures for meta-analysis.

(5) Evaluate the body of evidence, and determine the strength of evidence. (6) Compile the results of systematic reviews in the systematic review report, and

submit the report to the Guideline Development Group.

1) Search of preceding guidelines The search of preceding CPGs in Japan and overseas had better be conducted as a part

of a scoping search to know the current situation. As shown in Reference 2, world recognized guideline databases such as the National Guideline Clearinghouse (NGC) and the National Institute for Health and Care Excellence (NICE) should be included in a scoping search. The search of Minds is desirable, since high-quality CPGs developed in Japan are listed in the Minds database. In cases where there are preceding CPGs published by other organizations in Japan, they should be carefully examined with regard to the appropriateness of developing a new CPG.

Reference 2 Main database for guidelines search (p. 113)

2) Database for literature search Three databases, PubMed/MEDLINE, the Cochrane Library, and the Ichushi-Web,

should be included for search. In addition, EMBASE and JMEDPlus in the medical field, PsycINFO® in the social and psychological fields, and CINAHL® in the field of nursing research should be included. If necessary, other databases, such as PROSPERO, clinical trial registration, conference abstracts, and adverse drug reaction information, should also be included for search. In particular, in cases where a large-scale unpublished randomized controlled trial (RCT) registered in advance is already known, information of the Grey Literature Report (New York Academy of Sciences) should actively be checked.

Reference 3 Bibliographic database (p. 113)

Identifying the Evidence 2

46

32


(1) Conduct a systematic literature search based on PICO (2) Compile a collection of studies by primary screening (selection according to titles

and abstracts) and by secondary screening (selection according to evaluation of full text), based on explicit criteria for each combination of interventions/exposure and outcomes. Make a list of studies excluded by secondary screening, with reasons for exclusion.

(3) Perform qualitative evaluation of individual studies for each outcome and compile the results of evaluation by the combination of intervention/exposure, outcome, and study design. At this time, the indirectness of PICO should be evaluated, and comments should be recorded. (Qualitative systematic review)

(4) Perform quantitative systematic review by selecting studies that are based on similar PICO and give data of effect measures for meta-analysis.

(5) Evaluate the body of evidence, and determine the strength of evidence. (6) Compile the results of systematic reviews in the systematic review report, and

submit the report to the Guideline Development Group.

1) Search of preceding guidelines The search of preceding CPGs in Japan and overseas had better be conducted as a part

of a scoping search to know the current situation. As shown in Reference 2, world recognized guideline databases such as the National Guideline Clearinghouse (NGC) and the National Institute for Health and Care Excellence (NICE) should be included in a scoping search. The search of Minds is desirable, since high-quality CPGs developed in Japan are listed in the Minds database. In cases where there are preceding CPGs published by other organizations in Japan, they should be carefully examined with regard to the appropriateness of developing a new CPG.

Reference 2 Main database for guidelines search (p. 113)

2) Database for literature search Three databases, PubMed/MEDLINE, the Cochrane Library, and the Ichushi-Web,

should be included for search. In addition, EMBASE and JMEDPlus in the medical field, PsycINFO® in the social and psychological fields, and CINAHL® in the field of nursing research should be included. If necessary, other databases, such as PROSPERO, clinical trial registration, conference abstracts, and adverse drug reaction information, should also be included for search. In particular, in cases where a large-scale unpublished randomized controlled trial (RCT) registered in advance is already known, information of the Grey Literature Report (New York Academy of Sciences) should actively be checked.

Reference 3 Bibliographic database (p. 113)

Identifying the Evidence 2

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3) Designing search strategies Two members of the SR team are to be engaged in establishing the best search

strategy for each CQ, combining keywords and a thesaurus such as MeSH. One of them is desirably an expert of medical literature search, such as a librarian. Search strategy, including the search formula and date-range, and the date of search should be recorded for each database. If any studies on the citation list of identified articles and textbooks are included for search, the information should also be recorded. [Template ID: 4-1 Results of Database Search R*1]

As shown in [Template ID: 4-2 Flowchart of Literature Search R], the progress of literature selection should be described for each CQ in the flowchart with a revised flow diagram of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. [Template ID: 4-2 Flowchart of Literature Search R]

Reference 4 Plan of benefit search (p. 114).

4) Screening Screening should be performed based on inclusion and exclusion criteria in the scope.

Primary screening

In principle, two members of the SR Team should independently perform the primary screening. In primary screening, articles not compatible with the CQ of interest are excluded based on titles and abstracts. Articles that cannot be judged in primary screening are retained for secondary screening. After the results of the two members are crosschecked, a dataset for secondary screening is prepared, and full-text articles are collected.

Secondary screening

In principle, two members of the SR Team independently read full-text articles, and perform the secondary screening. Articles that meet the inclusion criteria are selected independently, and the results of the two members are crosschecked. Where two members have different opinions that cannot be resolved by discussion, a third person’s opinion is invited to make a final decision. A list of articles after the secondary screening is summarized in [Template ID: 4-3 List after the Secondary Screening R].

5) Literature management Careful attention should be paid to copyright violation when electronic databases are

shared on the Web cloud or when hard copies are distributed to SR team members. It is advisable to manage the literature database using literature codes in an integrated fashion.


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3) Designing search strategies Two members of the SR team are to be engaged in establishing the best search

strategy for each CQ, combining keywords and a thesaurus such as MeSH. One of them is desirably an expert of medical literature search, such as a librarian. Search strategy, including the search formula and date-range, and the date of search should be recorded for each database. If any studies on the citation list of identified articles and textbooks are included for search, the information should also be recorded. [Template ID: 4-1 Results of Database Search R*1]

As shown in [Template ID: 4-2 Flowchart of Literature Search R], the progress of literature selection should be described for each CQ in the flowchart with a revised flow diagram of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. [Template ID: 4-2 Flowchart of Literature Search R]

Reference 4 Plan of benefit search (p. 114).

4) Screening Screening should be performed based on inclusion and exclusion criteria in the scope.

Primary screening

In principle, two members of the SR Team should independently perform the primary screening. In primary screening, articles not compatible with the CQ of interest are excluded based on titles and abstracts. Articles that cannot be judged in primary screening are retained for secondary screening. After the results of the two members are crosschecked, a dataset for secondary screening is prepared, and full-text articles are collected.

Secondary screening

In principle, two members of the SR Team independently read full-text articles, and perform the secondary screening. Articles that meet the inclusion criteria are selected independently, and the results of the two members are crosschecked. Where two members have different opinions that cannot be resolved by discussion, a third person’s opinion is invited to make a final decision. A list of articles after the secondary screening is summarized in [Template ID: 4-3 List after the Secondary Screening R].

5) Literature management Careful attention should be paid to copyright violation when electronic databases are

shared on the Web cloud or when hard copies are distributed to SR team members. It is advisable to manage the literature database using literature codes in an integrated fashion.


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Although there are several methods of literature management, it is recommended to use the Harvard referencing style (e.g., Smith 2013) in which the author name and publication year are inserted into the text. Cited articles should be summarized for each CQ, since the same article may be cited repeatedly for different CQs. Cited articles should be listed in the alphabetical order of first authors for each CQ, categorizing by included, excluded, and other articles. It is important to record the reasons for exclusion. [Template ID: 4-4 List of Cited Literature R]

Evidence shall be integrated for each outcome of CQ, summarized for each

combination of study design and intervention/exposure, and the evidence summarized for each outcome shall be integrated to form the body of evidence. Collection of studies summarized in [Template ID: 4-3 List after the Secondary Screening R] shall be classified by outcome and study design to prepare the evaluation of the body of evidence.

1) Body of evidence and overall body of evidence Body of evidence

The body of evidence is a summary of results of all research reports evaluated for a certain CQ arranged by the combination of intervention/exposure, outcome, and study design. The strength of evidence is graded for each body of evidence (Table 4-1, p. 39). Overall body of evidence

The whole of bodies of evidence integrated across outcomes is called “overall body of evidence.” In the process of CPG development, a unique strength is determined for the overall body of evidence when a recommendation of clinical practice is presented for a CQ (Table 5-1, p. 53).

2) Overview of evaluation of the body of evidence. For each individual study included for evaluation of any outcomes, the risk of bias

and indirectness is evaluated taking into account the study design, such as RCT and observational study, and the number of subjects is extracted. Next, studies are grouped by study design and outcome, and the indirectness, inconsistency, imprecision, and publication bias shall be evaluated. We propose a 2-stage evaluation method with Step 1 and Step 2 specifically.

In Step 1, individual studies are evaluated using the evaluation sheet. The risk of bias, indirectness, the number of subjects at risk, effect measures, and confidence intervals, shall be recorded for each study.

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Although there are several methods of literature management, it is recommended to use the Harvard referencing style (e.g., Smith 2013) in which the author name and publication year are inserted into the text. Cited articles should be summarized for each CQ, since the same article may be cited repeatedly for different CQs. Cited articles should be listed in the alphabetical order of first authors for each CQ, categorizing by included, excluded, and other articles. It is important to record the reasons for exclusion. [Template ID: 4-4 List of Cited Literature R]

Evidence shall be integrated for each outcome of CQ, summarized for each

combination of study design and intervention/exposure, and the evidence summarized for each outcome shall be integrated to form the body of evidence. Collection of studies summarized in [Template ID: 4-3 List after the Secondary Screening R] shall be classified by outcome and study design to prepare the evaluation of the body of evidence.

1) Body of evidence and overall body of evidence Body of evidence

The body of evidence is a summary of results of all research reports evaluated for a certain CQ arranged by the combination of intervention/exposure, outcome, and study design. The strength of evidence is graded for each body of evidence (Table 4-1, p. 39). Overall body of evidence

The whole of bodies of evidence integrated across outcomes is called “overall body of evidence.” In the process of CPG development, a unique strength is determined for the overall body of evidence when a recommendation of clinical practice is presented for a CQ (Table 5-1, p. 53).

2) Overview of evaluation of the body of evidence. For each individual study included for evaluation of any outcomes, the risk of bias

and indirectness is evaluated taking into account the study design, such as RCT and observational study, and the number of subjects is extracted. Next, studies are grouped by study design and outcome, and the indirectness, inconsistency, imprecision, and publication bias shall be evaluated. We propose a 2-stage evaluation method with Step 1 and Step 2 specifically.

In Step 1, individual studies are evaluated using the evaluation sheet. The risk of bias, indirectness, the number of subjects at risk, effect measures, and confidence intervals, shall be recorded for each study.

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In Step 2, the strength of evidence is determined using the evaluation sheet of the body of evidence. The following items are evaluated for each study design; the risk of bias (as the summary of Step 1 evaluation results of risk of bias of individual studies), indirectness (as the summary of Step 1 results of indirectness of individual studies in addition to the result of overall evaluation of indirectness as a group of studies), inconsistency, imprecision, publication bias, and three items that grade up the strength of evidence in case of observational studies. If possible, the total number of subjects at risk, the number of subjects with outcome, effect measure, and confidence intervals are calculated and entered into the evaluation sheet. Based on these results, the strength of evidence of the body of evidence shall be determined, and the importance of outcomes shall be reevaluated. Template to be used in Step 1

• For RCTs: [Template ID: 4-5 Evaluation Sheet for Interventional Study R]

• For observational studies: [Template ID: 4-6 Evaluation Sheet for Observational Study R]

Template to be used in Step 2 • For evaluation of the body of evidence

[Template ID: 4-7 Evaluation Sheet for the Body of Evidence R]

3) Evaluation of risk of bias and indirectness for an individual study and extraction of data related to effect measures

The risk of bias is evaluated for individual studies, using [Template ID: 4-5 Evaluation Sheet for Interventional Study R] and [Template ID: 4-6 Evaluation Sheet for Observational Study R]. The homogeneity of PICO components is evaluated as the summary of critical appraisal of PICO of individual studies, data relevant to effect measures are extracted, and if the method of presenting effect measures is different across studies, the risk ratio or risk difference may be used as common measures. It is convenient to calculate the common effect measures when doing a meta-analysis with RevMan (Review Manager) or other software for meta-analysis. [See Chapter 4 2), p.38]. Risk of bias

The risk of bias is evaluated as the quality of individual studies. The concept of each domain is intended for RCTs, but it also applies to observational studies.

(1) Selection bias: Random allocation; concealment of allocation

It refers to a bias due to imbalance in allocation of study subjects. Especially, it refers to the bias due to difference between groups in certain factors affecting the outcomes, other than intervention/exposure to be compared.

(2) Performance bias: Blinding of study participants and personnel administering interventions

It refers to a bias due to a systematic difference between groups in implementation of intervention/care.

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In Step 2, the strength of evidence is determined using the evaluation sheet of the body of evidence. The following items are evaluated for each study design; the risk of bias (as the summary of Step 1 evaluation results of risk of bias of individual studies), indirectness (as the summary of Step 1 results of indirectness of individual studies in addition to the result of overall evaluation of indirectness as a group of studies), inconsistency, imprecision, publication bias, and three items that grade up the strength of evidence in case of observational studies. If possible, the total number of subjects at risk, the number of subjects with outcome, effect measure, and confidence intervals are calculated and entered into the evaluation sheet. Based on these results, the strength of evidence of the body of evidence shall be determined, and the importance of outcomes shall be reevaluated. Template to be used in Step 1

• For RCTs: [Template ID: 4-5 Evaluation Sheet for Interventional Study R]

• For observational studies: [Template ID: 4-6 Evaluation Sheet for Observational Study R]

Template to be used in Step 2 • For evaluation of the body of evidence


3) Evaluation of risk of bias and indirectness for an individual study and extraction of data related to effect measures

The risk of bias is evaluated for individual studies, using [Template ID: 4-5 Evaluation Sheet for Interventional Study R] and [Template ID: 4-6 Evaluation Sheet for Observational Study R]. The homogeneity of PICO components is evaluated as the summary of critical appraisal of PICO of individual studies, data relevant to effect measures are extracted, and if the method of presenting effect measures is different across studies, the risk ratio or risk difference may be used as common measures. It is convenient to calculate the common effect measures when doing a meta-analysis with RevMan (Review Manager) or other software for meta-analysis. [See Chapter 4 2), p.38]. Risk of bias

The risk of bias is evaluated as the quality of individual studies. The concept of each domain is intended for RCTs, but it also applies to observational studies.

(1) Selection bias: Random allocation; concealment of allocation

It refers to a bias due to imbalance in allocation of study subjects. Especially, it refers to the bias due to difference between groups in certain factors affecting the outcomes, other than intervention/exposure to be compared.

(2) Performance bias: Blinding of study participants and personnel administering interventions

It refers to a bias due to a systematic difference between groups in implementation of intervention/care.

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(3) Detection bias: Blinding of personnel measuring outcomes It refers to the bias due to a systematic difference between groups in outcome measurement.

(4) Attrition bias: Intention to treat (ITT) analysis; incomplete outcome data It refers to the bias due to a systematic difference between groups in censored subjects supposed to be included in the analysis of outcomes. Since the outcomes of censored subjects are unknown, they can be regarded as incomplete outcome data. The ITT analysis is a method to reduce the effect of attrition bias by analyzing the outcomes between groups as allocated, including censored and protocol ineligible subjects as non-responsive.

(5) Other risks of bias Bias of selective outcome report

In cases where only a part of outcomes measured are reported, only preferable results showing a large effect may be reported, leading to a bias of selective outcome report.

Bias of trial stopping In cases where a clinical trial is discontinued prior to meeting the sample size initially planned because effects are statistically proven, a bias leading to overestimation of effects may be produced. This happens when the interim analysis is not planned at all or when it is planned but not appropriately in the study design.

Indirectness In general, the term indirectness is used synonymously with external validity,

generalizability, and applicability. It is a difference in clinical context, population, and conditions between the CQ of the CPG and the clinical studies forming the body of evidence. In the Handbook 2014, a method is adopted in which the indirectness of individual studies is evaluated in Step 1, and again the following items are evaluated as overall evaluation in Step 2: (1) Difference in study target population (2) Difference in interventions (3) Difference in comparison (4) Difference in outcome measurement Inconsistency

Inconsistency means a large difference in estimates of therapeutic effects across studies extracted to evaluate a certain outcome (that is, the results have heterogeneity, which is possibly caused by sampling errors and/or biases). Inconsistency might also mean there is a true difference in fundamental therapeutic effect. Imprecision

This refers to undesirably broad confidence intervals of estimates of effect measures in studies forming the body of evidence. It is caused by inadequate sample size or number of events in individual studies. The target number of subjects stated in the protocol should be achieved. Publication bias

Publication bias means under- or overestimation of true effects, both benefits and harms, due to selective publication of studies. It may be evaluated using funnel plots.

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(3) Detection bias: Blinding of personnel measuring outcomes It refers to the bias due to a systematic difference between groups in outcome measurement.

(4) Attrition bias: Intention to treat (ITT) analysis; incomplete outcome data It refers to the bias due to a systematic difference between groups in censored subjects supposed to be included in the analysis of outcomes. Since the outcomes of censored subjects are unknown, they can be regarded as incomplete outcome data. The ITT analysis is a method to reduce the effect of attrition bias by analyzing the outcomes between groups as allocated, including censored and protocol ineligible subjects as non-responsive.

(5) Other risks of bias Bias of selective outcome report

In cases where only a part of outcomes measured are reported, only preferable results showing a large effect may be reported, leading to a bias of selective outcome report.

Bias of trial stopping In cases where a clinical trial is discontinued prior to meeting the sample size initially planned because effects are statistically proven, a bias leading to overestimation of effects may be produced. This happens when the interim analysis is not planned at all or when it is planned but not appropriately in the study design.

Indirectness In general, the term indirectness is used synonymously with external validity,

generalizability, and applicability. It is a difference in clinical context, population, and conditions between the CQ of the CPG and the clinical studies forming the body of evidence. In the Handbook 2014, a method is adopted in which the indirectness of individual studies is evaluated in Step 1, and again the following items are evaluated as overall evaluation in Step 2: (1) Difference in study target population (2) Difference in interventions (3) Difference in comparison (4) Difference in outcome measurement Inconsistency

Inconsistency means a large difference in estimates of therapeutic effects across studies extracted to evaluate a certain outcome (that is, the results have heterogeneity, which is possibly caused by sampling errors and/or biases). Inconsistency might also mean there is a true difference in fundamental therapeutic effect. Imprecision

This refers to undesirably broad confidence intervals of estimates of effect measures in studies forming the body of evidence. It is caused by inadequate sample size or number of events in individual studies. The target number of subjects stated in the protocol should be achieved. Publication bias

Publication bias means under- or overestimation of true effects, both benefits and harms, due to selective publication of studies. It may be evaluated using funnel plots.

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4) Evaluation of risk of bias, indirectness, inconsistency, imprecision, and publication bias of the body of evidence

Five items that decrease the strength of evidence The above five items on the study limitation: risk of bias, indirectness,

inconsistency, imprecision, publication bias, shall be evaluated based on the following 3-point scale.

No problem at all 0 Slight problem 0 Enter comments. Serious problem -1 Enter comments. Significant problem -2 Enter comments.

Note: Scales 0 to 2 indicate the seriousness of each item, and they are not to be added.

Three items that increase the strength of evidence

For an observational study, the following three items shall be evaluated: (1) Large effect of intervention (2) Dose-response gradient (3) Confounding factors potentially bias the effect estimate

1) Qualitative systematic review

Qualitative synthesis of evidence is called qualitative systematic review. Qualitative systematic reviews include the evaluation of risk of bias and indirectness of individual studies, evaluation of risk of bias and indirectness of the body of evidence reflecting the evaluation of individual studies, evaluation of inconsistency, imprecision, and publication bias of studies forming the body of evidence, and evaluation of clinical context.

Even if a quantitative systematic review is performed, the strength of evidence should not be determined based solely on the integrated value of effect measure and its confidence interval. The results of qualitative systematic review should be reflected to the strength of evidence.

In cases where there is only one study or where the heterogeneity across studies is large, quantitative synthesis cannot be performed, and the strength of evidence should be determined based on a qualitative systematic review to decide on recommendations. [Template ID: 4-8 Qualitative Systematic Review R]

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4) Evaluation of risk of bias, indirectness, inconsistency, imprecision, and publication bias of the body of evidence

Five items that decrease the strength of evidence The above five items on the study limitation: risk of bias, indirectness,

inconsistency, imprecision, publication bias, shall be evaluated based on the following 3-point scale.

No problem at all 0 Slight problem 0 Enter comments. Serious problem -1 Enter comments. Significant problem -2 Enter comments.

Note: Scales 0 to 2 indicate the seriousness of each item, and they are not to be added.

Three items that increase the strength of evidence

For an observational study, the following three items shall be evaluated: (1) Large effect of intervention (2) Dose-response gradient (3) Confounding factors potentially bias the effect estimate

1) Qualitative systematic review

Qualitative synthesis of evidence is called qualitative systematic review. Qualitative systematic reviews include the evaluation of risk of bias and indirectness of individual studies, evaluation of risk of bias and indirectness of the body of evidence reflecting the evaluation of individual studies, evaluation of inconsistency, imprecision, and publication bias of studies forming the body of evidence, and evaluation of clinical context.

Even if a quantitative systematic review is performed, the strength of evidence should not be determined based solely on the integrated value of effect measure and its confidence interval. The results of qualitative systematic review should be reflected to the strength of evidence.

In cases where there is only one study or where the heterogeneity across studies is large, quantitative synthesis cannot be performed, and the strength of evidence should be determined based on a qualitative systematic review to decide on recommendations. [Template ID: 4-8 Qualitative Systematic Review R]

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2) Quantitative systematic review (meta-analysis)

In cases where the study design is the same, and the component of PICO shows high similarity between studies, it is possible to perform a meta-analysis for quantitative synthesis of effect measure. The result of meta-analysis gives us an integrated value of effect measure and its confidence interval as well as the forest plot. The forest plot is useful to judge the inconsistency and imprecision. Either of two models, fixed effects model or random effects model, is used. In cases where only the mean value of effect measure and its confidence interval of multiple studies are considered, the former shall be used, whereas in cases where the variability between studies is considered, the latter shall be used. Usually, it is recommended to use the latter.

[Template ID: 4-9 Meta-analysis R]

Software for meta-analysis

Since a number of software products exist for meta-analysis, you may choose one you think the most useful according to the functions you need. Free software products that are openly available are listed below.

• Review Manager (RevMan) (the latest version, 5.2.9)

http://tech.cochrane.org/revman/download • metafor (using R as a platform)

http://www.rproject.org/

The strength of evidence in CPG indicates the adequacy of support that the estimate of

effect, such as therapeutic effect, provides for recommendation. A set of scores to be used to evaluate the strength of evidence is shown as an example in Table 4-1. The Guideline Development Group should decide in advance, at the stage of scope development, which scoring system is to be used to evaluate the strength of evidence. The strength of evidence should not be scored based solely on the study design, as was often given to an individual study as the evidence level previously.

The following description is an example of the procedure to determine the strength of evidence of the body of evidence in the systematic review for CPG development.

In the case of RCTs, the score “A (strong)” is given at the start of evaluation, and the final score might be downgraded to B, C, or D, according to the results of evaluation of five items as described in this chapter. In the case of observational studies, the score “C (weak)” is given at the start of evaluation, and five items lowering the strength are evaluated similarly as for RCTs. In addition, three items increasing the strength are evaluated as well, as described in this chapter.

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2) Quantitative systematic review (meta-analysis)

In cases where the study design is the same, and the component of PICO shows high similarity between studies, it is possible to perform a meta-analysis for quantitative synthesis of effect measure. The result of meta-analysis gives us an integrated value of effect measure and its confidence interval as well as the forest plot. The forest plot is useful to judge the inconsistency and imprecision. Either of two models, fixed effects model or random effects model, is used. In cases where only the mean value of effect measure and its confidence interval of multiple studies are considered, the former shall be used, whereas in cases where the variability between studies is considered, the latter shall be used. Usually, it is recommended to use the latter.

[Template ID: 4-9 Meta-analysis R]

Software for meta-analysis

Since a number of software products exist for meta-analysis, you may choose one you think the most useful according to the functions you need. Free software products that are openly available are listed below.

• Review Manager (RevMan) (the latest version, 5.2.9)

http://tech.cochrane.org/revman/download • metafor (using R as a platform)

http://www.rproject.org/

The strength of evidence in CPG indicates the adequacy of support that the estimate of

effect, such as therapeutic effect, provides for recommendation. A set of scores to be used to evaluate the strength of evidence is shown as an example in Table 4-1. The Guideline Development Group should decide in advance, at the stage of scope development, which scoring system is to be used to evaluate the strength of evidence. The strength of evidence should not be scored based solely on the study design, as was often given to an individual study as the evidence level previously.

The following description is an example of the procedure to determine the strength of evidence of the body of evidence in the systematic review for CPG development.

In the case of RCTs, the score “A (strong)” is given at the start of evaluation, and the final score might be downgraded to B, C, or D, according to the results of evaluation of five items as described in this chapter. In the case of observational studies, the score “C (weak)” is given at the start of evaluation, and five items lowering the strength are evaluated similarly as for RCTs. In addition, three items increasing the strength are evaluated as well, as described in this chapter.

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Table 4-1 Definition of the Strength of Body of Evidence in Evaluation of Systematic Review

A (strong) : Strongly confident in the effect of estimate. B (moderate) : Moderately confident in the effect of estimate. C (weak) : Confidence in the effect of estimate is limited. D (very weak) : Almost no confidence in the effect of estimate.

For details of evaluation of the strength of evidence, the following may be helpful. • GRADE

http://www.gradeworkinggroup.org/ • The Cochrane Handbook for Systematic Reviews of Interventions

http://handbook.cochrane.org/

The SR Team submits a systematic review report to the Guideline Development Group, which is responsible for formulating recommendations. The systematic review report consists of the results of qualitative and quantitative systematic reviews, with the strength of evidence of the body of evidence. [Template ID: 4-10 Summary of Systematic Review Report R]

If appropriate studies are not found for the CQ or all studies identified by search are of poor quality, the CQ withdrawal shall be proposed to the Guideline Development Group. If the SR Team judges that future research is necessary, it should be recorded as a future research question.

[Template ID: 4-11 Future Research Question R]

The Guideline Development Group shall move forward to the step of formulating recommendations, based on the SR report submitted.

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Table 4-1 Definition of the Strength of Body of Evidence in Evaluation of Systematic Review

A (strong) : Strongly confident in the effect of estimate. B (moderate) : Moderately confident in the effect of estimate. C (weak) : Confidence in the effect of estimate is limited. D (very weak) : Almost no confidence in the effect of estimate.

For details of evaluation of the strength of evidence, the following may be helpful. • GRADE

http://www.gradeworkinggroup.org/ • The Cochrane Handbook for Systematic Reviews of Interventions

http://handbook.cochrane.org/

The SR Team submits a systematic review report to the Guideline Development Group, which is responsible for formulating recommendations. The systematic review report consists of the results of qualitative and quantitative systematic reviews, with the strength of evidence of the body of evidence. [Template ID: 4-10 Summary of Systematic Review Report R]

If appropriate studies are not found for the CQ or all studies identified by search are of poor quality, the CQ withdrawal shall be proposed to the Guideline Development Group. If the SR Team judges that future research is necessary, it should be recorded as a future research question.

[Template ID: 4-11 Future Research Question R]

The Guideline Development Group shall move forward to the step of formulating recommendations, based on the SR report submitted.

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4-1 Results of Database Search R: Entry Guide

Title: Each template should include a title to avoid confusion. CQ: Each template should include CQ number and CQ sentence to avoid confusion. Database: Enter the name of database and date-range. Date: Enter the date of search. Searcher: Enter two searchers. When disclosing, the data shall be deleted or changed to initials.

# Search formula Hits Enter the search strategy including AND/OR,

ti/ab/kw, etc. Enter the number of hits.

It is acceptable to enter the final search results in either the top paragraph or the last paragraph, but the description should be unified as a whole.

These shall be prepared according to the number of databases searched, but it is acceptable to only enter representative data in clinical practice guidelines.

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4-1 Results of Database Search R: Entry Guide

Title: Each template should include a title to avoid confusion. CQ: Each template should include CQ number and CQ sentence to avoid confusion. Database: Enter the name of database and date-range. Date: Enter the date of search. Searcher: Enter two searchers. When disclosing, the data shall be deleted or changed to initials.

# Search formula Hits Enter the search strategy including AND/OR,

ti/ab/kw, etc. Enter the number of hits.

It is acceptable to enter the final search results in either the top paragraph or the last paragraph, but the description should be unified as a whole.

These shall be prepared according to the number of databases searched, but it is acceptable to only enter representative data in clinical practice guidelines.

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4-2 Flowchart of Literature Search R: Entry Guide

NGC NICE PubMed Cochrane Ichushi-Web EMBASE WHO PsycINFO® CINAHL Others ( ) Enter the number of literatures obtained from the literature DB used for each CQ. Enter NA for literatures not used. It is possible to enter these for each CQ, but it is also acceptable to list representative literatures as materials at the end of the document.

It is possible to add useful literature if any even if they are not found in search.

Delete duplicates, since the same paper is often found in multiple DB.

Corresponds to the number of rejected papers in Template 4-4.

Corresponds to the number of adopted papers in Template 4-4.

If meta-analysis is not performed, enter 0.

[PRISMA announcement is revised.]

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4-2 Flowchart of Literature Search R: Entry Guide

NGC NICE PubMed Cochrane Ichushi-Web EMBASE WHO PsycINFO® CINAHL Others ( ) Enter the number of literatures obtained from the literature DB used for each CQ. Enter NA for literatures not used. It is possible to enter these for each CQ, but it is also acceptable to list representative literatures as materials at the end of the document.

It is possible to add useful literature if any even if they are not found in search.

Delete duplicates, since the same paper is often found in multiple DB.

Corresponds to the number of rejected papers in Template 4-4.

Corresponds to the number of adopted papers in Template 4-4.

If meta-analysis is not performed, enter 0.

[PRISMA announcement is revised.]

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4-3 List after the Secondary Screening R: Entry Guide

Citation Study design P I C O Exclusion Comments

Manage using the name of author and publisher in an integrated fashion.

Describe the number of samples, setting, and characteristics of P.

I listed and its format

C listed and its format

O listed and its format

P: Patients, Population, I: Interventions, C: Controls, Comparisons, Comparators, O: Outcomes.

4-4 List of Cited Literature R: Entry Guide

Adopted reports

Literature sorting ID using Harvard referencing (in response to the text)

Bibliographic information of papers remaining in [4.3 List after the Secondary Screening R] and used for systematic reviews

Excluded reports

Literature sorting ID using Harvard referencing style (in response to the text)

Bibliographic information of papers deleted from [4.3 List after the Secondary Screening R] after the following step

Other cited reports


Bibliographic information of papers cited in chapters such as Review, Epidemiology, etc. in which no systematic review is performed

If there is any paper retained after the secondary screening, but excluded in the evaluation of bias risks, enter in this column and the reason(s) in the column of Comments.

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4-3 List after the Secondary Screening R: Entry Guide

Citation Study design P I C O Exclusion Comments

Manage using the name of author and publisher in an integrated fashion.

Describe the number of samples, setting, and characteristics of P.

I listed and its format

C listed and its format

O listed and its format

P: Patients, Population, I: Interventions, C: Controls, Comparisons, Comparators, O: Outcomes.

4-4 List of Cited Literature R: Entry Guide

Adopted reports


Bibliographic information of papers remaining in [4.3 List after the Secondary Screening R] and used for systematic reviews

Excluded reports

Literature sorting ID using Harvard referencing style (in response to the text)

Bibliographic information of papers deleted from [4.3 List after the Secondary Screening R] after the following step

Other cited reports


Bibliographic information of papers cited in chapters such as Review, Epidemiology, etc. in which no systematic review is performed

If there is any paper retained after the secondary screening, but excluded in the evaluation of bias risks, enter in this column and the reason(s) in the column of Comments.

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4-5 Evaluation Sheet for Interventional Study R: Example

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4-5 Evaluation Sheet for Interventional Study R: Example

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4-6 Evaluation Sheet for Observational Study R: Example

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4-6 Evaluation Sheet for Observational Study R: Example

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4-7-(1) Evaluation Sheet for the Body of Evidence R: Example

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4-8 Qualitative Systematic Review R: Entry Guide

CQ Identifier ( )

Enter the CQ.

P

Detailed description sufficient to supplement the CQ. Describe timing and setting as needed.

I

Detail of interventions

C

It is advisable to compare at the ratio of 1 to 1, but perform multiple comparisons as needed.

Clinical context

Describe where it is placed in the process of clinical practice, and whether it is classified into diagnosis, treatment, prevention, prognosis estimation, or others.

O1

Although it may not be shown in the CQ as harm, clearly describe the subject of the body of evidence.

Summary of indirectness

Describe the gap between CQ obtained and the body of evidence. Be sure to describe if comparison of intervention is indirect or there is any problem in applying to Japanese patients.

Summary of risk of bias

Describe specifically problematic risk of bias, and risk of bias that influences the decision of recommendations.

Summary of inconsistency and others

Summarize the size of difference between multiple researches, uncertainty judged from confidence interval and risk of bias, and effect size, etc. If different research designs are summarized, enter the summary.

Comments

Enter special considerations for evaluation of the body of evidence concerning this outcome if any.

O2

O3

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47

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4 S

ystematic R

eview

4-8 Qualitative Systematic Review R: Entry Guide

CQ Identifier ( )

Enter the CQ.

P

Detailed description sufficient to supplement the CQ. Describe timing and setting as needed.

I

Detail of interventions

C

It is advisable to compare at the ratio of 1 to 1, but perform multiple comparisons as needed.

Clinical context

Describe where it is placed in the process of clinical practice, and whether it is classified into diagnosis, treatment, prevention, prognosis estimation, or others.

O1

Although it may not be shown in the CQ as harm, clearly describe the subject of the body of evidence.


Describe the gap between CQ obtained and the body of evidence. Be sure to describe if comparison of intervention is indirect or there is any problem in applying to Japanese patients.


Describe specifically problematic risk of bias, and risk of bias that influences the decision of recommendations.


Summarize the size of difference between multiple researches, uncertainty judged from confidence interval and risk of bias, and effect size, etc. If different research designs are summarized, enter the summary.

Comments

Enter special considerations for evaluation of the body of evidence concerning this outcome if any.

O2

O3

61

48


4-9 Meta-analysis R: Entry Guide

CQ Enter the CQ in a similar way to [4-8 Qualitative Systematic Review]

P I

C O

Research design

Search number

Code

Model Randomization effect

Method Inverse-variance method (RevMan5.2)

Effect indicators Risk ratio Integrated value

0.93 (0.84−1.03) p = 0.17

Forest plot

Example

Comments: Although results show that the effect around NNT = 1/(1 – 0.93) = 14.3 is expected, significant level has not been achieved.

Funnel plot

Example

Comments: There is no distribution suggesting bias of report.

Other analyses □ Meta-regression □ Sensitivity

analysis

Not conducted. Comments: Significant level has not been achieved.

Example for entry is shown as follows.

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48


4-9 Meta-analysis R: Entry Guide

CQ Enter the CQ in a similar way to [4-8 Qualitative Systematic Review]

P I

C O

Research design

Search number

Code

Model Randomization effect

Method Inverse-variance method (RevMan5.2)

Effect indicators Risk ratio Integrated value

0.93 (0.84−1.03) p = 0.17

Forest plot

Example

Comments: Although results show that the effect around NNT = 1/(1 – 0.93) = 14.3 is expected, significant level has not been achieved.

Funnel plot

Example

Comments: There is no distribution suggesting bias of report.


analysis

Not conducted. Comments: Significant level has not been achieved.

Example for entry is shown as follows.

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4 S

ystematic R

eview

4-10 Summary of Systematic Review Report R: Entry Guide

Summarize the results of [4-8 Qualitative Systematic Review R] and [4-9 Meta-analysis R]. Clearly describe contents decided in the scope that need to be revised.

4-11 Future Research Question R: Entry Guide

Prepare CQ whose answer will be obtained by future research based on issues that have not been clarified in researches so far. Describe the following items. Research question Background Overview of possible research project

63

49

Chapter

4 S

ystematic R

eview

4-10 Summary of Systematic Review Report R: Entry Guide

Summarize the results of [4-8 Qualitative Systematic Review R] and [4-9 Meta-analysis R]. Clearly describe contents decided in the scope that need to be revised.

4-11 Future Research Question R: Entry Guide

Prepare CQ whose answer will be obtained by future research based on issues that have not been clarified in researches so far. Describe the following items. Research question Background Overview of possible research project

63

Chapter 5

Recommendations

Outline of the recommendations development process – Method for unbiased determination ............. 52

A draft of recommendation and the strength of recommendation .............................................................. 52

Consensus methods ........................................................ 55

Comment writing .............................................................. 56

Summary for the public ................................................... 56

1

2

3

4

5

65

Chapter 5

Recommendations

Outline of the recommendations development process – Method for unbiased determination ............. 52

A draft of recommendation and the strength of recommendation .............................................................. 52

Consensus methods ........................................................ 55

Comment writing .............................................................. 56

Summary for the public ................................................... 56

1

2

3

4

5

65

52

Chapter 5 Recommendations

The Guideline Development Group formulates the recommendation for each CQ, determining its direction and strength, based on the systematic review report, also taking account of the benefit and harm balance, patients’ value and preferences, and resource use. The Guideline Development Group records the method to formulate recommendations, the method for reaching the final decision (such as the Delphi method), and the process and result of voting, if conducted, during consensus formation.

A draft of recommendation will be formulated in the form of a reply to the CQ.

The recommendation could be in favor of one intervention or the other, but it should be kept in mind that possibly neither of alternative interventions could be recommended or both interventions could be recommended as well.

[Template ID: 5-1 A Draft of A Recommendation O *1]

The strength of recommendation will be determined with special reference to the balance between benefits and harms, as well as the strength of evidence on serious outcomes, based on the results of systematic reviews provided as systematic review reports by the SR Team. In addition, it is desirable to take full account of the diversity of the value and preference of patients, and the performance of recommended intervention in response to the cost and resource use should also be considered. An anonymous vote by all members of the Guideline Development Group may be conducted.

[Template ID: 5-2 Ballot for Determination of Strength of Recommendation O]

1) Factors to be assessed to determine the strength of recommendations

Summary of the body of evidence (the overall strength of evidence for all outcomes) (See Chapter 4 , p. 34)

The body of evidence is a summary of results of all research reports evaluated for a certain CQ arranged by the combination of intervention/exposure, outcome, and study design.


documents. O: For operation, G: Clinical Practice Guideline

3

1 Outline of the recommendations development process ─ Method for unbiased determination

2 A draft of recommendation and the strength of recommendation

66

52


The Guideline Development Group formulates the recommendation for each CQ, determining its direction and strength, based on the systematic review report, also taking account of the benefit and harm balance, patients’ value and preferences, and resource use. The Guideline Development Group records the method to formulate recommendations, the method for reaching the final decision (such as the Delphi method), and the process and result of voting, if conducted, during consensus formation.

A draft of recommendation will be formulated in the form of a reply to the CQ.

The recommendation could be in favor of one intervention or the other, but it should be kept in mind that possibly neither of alternative interventions could be recommended or both interventions could be recommended as well.

[Template ID: 5-1 A Draft of A Recommendation O *1]

The strength of recommendation will be determined with special reference to the balance between benefits and harms, as well as the strength of evidence on serious outcomes, based on the results of systematic reviews provided as systematic review reports by the SR Team. In addition, it is desirable to take full account of the diversity of the value and preference of patients, and the performance of recommended intervention in response to the cost and resource use should also be considered. An anonymous vote by all members of the Guideline Development Group may be conducted.

[Template ID: 5-2 Ballot for Determination of Strength of Recommendation O]

1) Factors to be assessed to determine the strength of recommendations

Summary of the body of evidence (the overall strength of evidence for all outcomes) (See Chapter 4 , p. 34)

The body of evidence is a summary of results of all research reports evaluated for a certain CQ arranged by the combination of intervention/exposure, outcome, and study design.


documents. O: For operation, G: Clinical Practice Guideline

3

1 Outline of the recommendations development process ─ Method for unbiased determination

2 A draft of recommendation and the strength of recommendation

66

53

Chapter

5 R

ecomm

endations

The summary of the body of evidence refers to the integration of the body of evidence for each outcome into the summary for all outcomes. The summary of the body of evidence gives unique strength of recommendation for a CQ in CPG development.

The recommendation would be more likely to be labeled as “strong,” as the overall strength of evidence across outcomes increases. In contrast, the recommendation would be more likely to be labeled as “weak,” as the overall strength of evidence decreases. The basic principle of determining the strength of evidence is the degree of confidence to which the estimates of effects of intervention to be recommended are supporting the recommendation.

Table 5-1 Summary of the body of evidence for formulating recommendations (the overall strength of evidence across outcomes)

A (strong) : strongly confident of the estimate of effect B (moderate) : moderately confident of the estimate of effect C (weak) : limited confidence of the estimate of effect D (very weak) : very little confident of the estimate of effect

Balance between benefits and harms After evaluating if the net benefit outweighs the net harm in the balance between

benefits and harms, the balance between benefits and disadvantages (harm, burden, and cost) will be assessed by adding the burden and the cost. The harm, such as an adverse reaction or adverse event, is negative events that occur unintentionally. Meanwhile, the burden is an intended negative event, including the burden of attending a hospital or hospitalization, surgical operation and accompanying pain, operative scar, and loss of function. Regarding the cost, not only the financial burden associated with treatment but also the cost for follow-up management should be considered, and if cost-effectiveness studies were performed, they should be referred to.

The greater the difference between the desirable outcome (benefit) and the undesirable outcome (disadvantage except the cost) is, the more likely the recommendation for the intervention would become stronger. On the other hand, the smaller the net benefit is and the larger the magnitude of disadvantage is as compared to benefits, the lower the certainty of benefit becomes and the more likely the recommendation against the intervention would become strong.

67

53

Chapter

5 R

ecomm

endations

The summary of the body of evidence refers to the integration of the body of evidence for each outcome into the summary for all outcomes. The summary of the body of evidence gives unique strength of recommendation for a CQ in CPG development.

The recommendation would be more likely to be labeled as “strong,” as the overall strength of evidence across outcomes increases. In contrast, the recommendation would be more likely to be labeled as “weak,” as the overall strength of evidence decreases. The basic principle of determining the strength of evidence is the degree of confidence to which the estimates of effects of intervention to be recommended are supporting the recommendation.

Table 5-1 Summary of the body of evidence for formulating recommendations (the overall strength of evidence across outcomes)

A (strong) : strongly confident of the estimate of effect B (moderate) : moderately confident of the estimate of effect C (weak) : limited confidence of the estimate of effect D (very weak) : very little confident of the estimate of effect

Balance between benefits and harms After evaluating if the net benefit outweighs the net harm in the balance between

benefits and harms, the balance between benefits and disadvantages (harm, burden, and cost) will be assessed by adding the burden and the cost. The harm, such as an adverse reaction or adverse event, is negative events that occur unintentionally. Meanwhile, the burden is an intended negative event, including the burden of attending a hospital or hospitalization, surgical operation and accompanying pain, operative scar, and loss of function. Regarding the cost, not only the financial burden associated with treatment but also the cost for follow-up management should be considered, and if cost-effectiveness studies were performed, they should be referred to.

The greater the difference between the desirable outcome (benefit) and the undesirable outcome (disadvantage except the cost) is, the more likely the recommendation for the intervention would become stronger. On the other hand, the smaller the net benefit is and the larger the magnitude of disadvantage is as compared to benefits, the lower the certainty of benefit becomes and the more likely the recommendation against the intervention would become strong.

67

54


“What is obtained as an individual and as a society,

and the compensation therefor”

Fig. 5-1 Balance between benefit and harm

Factors to be considered for the strength of recommendations (1) Values, preferences, and burden of patients

The method to reflect the value and preference of patients and caregivers on recommendations is still at the stage of trial and error. If possible, it is desirable that the representatives of patients and citizens participate in the process of formulation and determination of recommendations, or their feedback had better be obtained on the draft. Even when health professionals make estimation, it is more likely that recommendations become stronger, when the values, preferences, and burden of patients are more certain. (2) Cost and resource use

It should be assessed whether the net benefit is sufficiently balanced with the cost and resource use. If there are articles on cost-effectiveness analyses, they should be referred to. If possible, listing of the National Health Insurance (NHI) points would also be useful. If not covered by insurance, it should be mentioned accordingly.

It is expected that scientific methods by which the values and preferences of patients and the cost analyses can be reflected in CPGs would be examined and established.

2) Presentation of the strength of recommendations The presentation of the strength of recommendations will be determined and

described in the scope in advance by the Guideline Development Group. The strength of recommendations is usually presented in two ways: “1”: strongly recommended, and “2”: weakly recommended (suggested). If the strength of recommendations cannot be determined by any means, it is occasionally presented as “no definite recommendation can be made.” In such a case, enter the process and the contents of discussion in the comment. Recommendations will be entered as follows by putting down the strength of evidence (A, B, C, D) with the strength of recommendations “1”: strong or “2”: weak.

Desirable outcome Undesirable outcome

Study Study Study ......

A body of evidence • Effect size • Certainty



Cost

Burden

Harm

Benefit Disadvantage Interventional

Comprehensively judged, while considering the importance of each outcome, the effect size, and certainty

Recommendations

68

54


“What is obtained as an individual and as a society,

and the compensation therefor”

Fig. 5-1 Balance between benefit and harm

Factors to be considered for the strength of recommendations (1) Values, preferences, and burden of patients

The method to reflect the value and preference of patients and caregivers on recommendations is still at the stage of trial and error. If possible, it is desirable that the representatives of patients and citizens participate in the process of formulation and determination of recommendations, or their feedback had better be obtained on the draft. Even when health professionals make estimation, it is more likely that recommendations become stronger, when the values, preferences, and burden of patients are more certain. (2) Cost and resource use

It should be assessed whether the net benefit is sufficiently balanced with the cost and resource use. If there are articles on cost-effectiveness analyses, they should be referred to. If possible, listing of the National Health Insurance (NHI) points would also be useful. If not covered by insurance, it should be mentioned accordingly.

It is expected that scientific methods by which the values and preferences of patients and the cost analyses can be reflected in CPGs would be examined and established.

2) Presentation of the strength of recommendations The presentation of the strength of recommendations will be determined and

described in the scope in advance by the Guideline Development Group. The strength of recommendations is usually presented in two ways: “1”: strongly recommended, and “2”: weakly recommended (suggested). If the strength of recommendations cannot be determined by any means, it is occasionally presented as “no definite recommendation can be made.” In such a case, enter the process and the contents of discussion in the comment. Recommendations will be entered as follows by putting down the strength of evidence (A, B, C, D) with the strength of recommendations “1”: strong or “2”: weak.

Desirable outcome Undesirable outcome





Cost

Burden

Harm

Benefit Disadvantage Interventional

Comprehensively judged, while considering the importance of each outcome, the effect size, and certainty

Recommendations

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endations

e.g., 1) It is recommended to give treatment I to patient P (1A) = (strong recommendation, based on strong evidence)

2) It is proposed to give treatment I rather than treatment C to patient P (2C) = (weak recommendation, based on weak evidence)

3) It is proposed not to give treatment C nor treatment I to patient P (2D) = (weak recommendation, based on very weak evidence)

4) It is strongly recommended not to give treatment I to patient P (1B) = (strong recommendation, based on moderate evidence)

It may be difficult to present a recommendation in this formulation, depending on the contents of recommendations. In such cases, the formulation should be used according to the context.

[Template ID: 5-3 Presentation of A Recommendation G]

1) Formal consensus method Delphi method

In this method, several recommendations are prepared for a CQ, panelists vote independently, and a summary of the voting results is disclosed. This procedure is repeated several times. If an agreement cannot be reached, a revote will be conducted based on the previous results. This will be repeated until a consensus of opinion is reached. Basically, the above procedure is performed by mail, and the panelists have no opportunity to discuss with each other directly. ➡ Power games can be avoided, fair consideration can be given, and cost can be saved

(creative ideas may not be generated compared with face-to-face meetings). Nominal group technique (NGT) method or expert panel

(1) Each member records his/her idea individually for a CQ. Next, each member presents his/her idea in turn until all ideas are presented.

(2) All ideas are discussed in turn. Then, each member independently rates each idea individually, or ranks all ideas. After many discussions, the ratings or rankings are totaled again, and the idea as a group or the ranking as a group is determined. ➡ It is possible to completely distinguish between creation of ideas and discussion, to

control the session so that all members may express opinions, and to discuss fairly (creative ideas may not be generated).

NIH consensus development conferences The NIH consensus development conferences have been held for more than 20 years,

and the conference is held to scientifically assess the medical technology at that time and reach a consensus. The panel consists of disinterested specialists and the conferences are held in public.

3 Consensus methods

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Chapter

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ecomm

endations

e.g., 1) It is recommended to give treatment I to patient P (1A) = (strong recommendation, based on strong evidence)

2) It is proposed to give treatment I rather than treatment C to patient P (2C) = (weak recommendation, based on weak evidence)

3) It is proposed not to give treatment C nor treatment I to patient P (2D) = (weak recommendation, based on very weak evidence)

4) It is strongly recommended not to give treatment I to patient P (1B) = (strong recommendation, based on moderate evidence)

It may be difficult to present a recommendation in this formulation, depending on the contents of recommendations. In such cases, the formulation should be used according to the context.

[Template ID: 5-3 Presentation of A Recommendation G]

1) Formal consensus method Delphi method

In this method, several recommendations are prepared for a CQ, panelists vote independently, and a summary of the voting results is disclosed. This procedure is repeated several times. If an agreement cannot be reached, a revote will be conducted based on the previous results. This will be repeated until a consensus of opinion is reached. Basically, the above procedure is performed by mail, and the panelists have no opportunity to discuss with each other directly. ➡ Power games can be avoided, fair consideration can be given, and cost can be saved

(creative ideas may not be generated compared with face-to-face meetings). Nominal group technique (NGT) method or expert panel

(1) Each member records his/her idea individually for a CQ. Next, each member presents his/her idea in turn until all ideas are presented.

(2) All ideas are discussed in turn. Then, each member independently rates each idea individually, or ranks all ideas. After many discussions, the ratings or rankings are totaled again, and the idea as a group or the ranking as a group is determined. ➡ It is possible to completely distinguish between creation of ideas and discussion, to

control the session so that all members may express opinions, and to discuss fairly (creative ideas may not be generated).

NIH consensus development conferences The NIH consensus development conferences have been held for more than 20 years,

and the conference is held to scientifically assess the medical technology at that time and reach a consensus. The panel consists of disinterested specialists and the conferences are held in public.

3 Consensus methods

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56


The summary of the conference, the NIH consensus statement, is prepared based on: (1) The research presentation by the researchers related to the consensus for 2 days, (2) Open discussion with the participants in the conference, and (3) The results of deliberations on the 2nd day and on the morning of the 3rd day.

2) Informal consensus method Several panelists express their opinions, discuss fully, and formulate a

recommendation together. ➡ By sharing the problems with all members, a solution that could not have been

thought of at the beginning may be found (a chairperson who can summarize arguments and pull them together plays an important role).

After the CQs and corresponding recommendations with the strength of

recommendations are determined, the comments will be written. The Guideline Development Group will describe the process to finally determine the recommendations. Based on the qualitative systematic reviews and the results of meta-analyses (when performed) in the systematic review report prepared by the SR Team, the process of the determination of recommendations will be described in detail.

If there are descriptions of decreasing the strength of evidence of RCTs or of increasing the strength of evidence of observational studies in the systematic review report, the reasons will be described in the comments.

In addition, the references used in systematic reviews will be presented at the end of chapter for each CQ and recommendation or at the end of the CPG, so that the correspondence relationship between recommendations and supporting evidence can be clearly shown.

Presentation and wording used should be as clear and unambiguous as possible. When several interventions are compared, ranking all interventions might not be insisted upon in some instances; they might be expressed flexibly so that they might be useful in clinical practice as well. [Template ID-5-4: Development Process of A Recommendation G]

The Guideline Development Group will briefly comment on the CQs and

recommendations in plain words so that patients and citizens are able to understand them as well. The possibility to prepare a popular edition of CPG could be discussed, in which summary descriptions arranged by CQs are presented for the public. [Template ID: 5-5 Summary for the Public G]

4 Comment writing

5 Summary for the public

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56


The summary of the conference, the NIH consensus statement, is prepared based on: (1) The research presentation by the researchers related to the consensus for 2 days, (2) Open discussion with the participants in the conference, and (3) The results of deliberations on the 2nd day and on the morning of the 3rd day.

2) Informal consensus method Several panelists express their opinions, discuss fully, and formulate a

recommendation together. ➡ By sharing the problems with all members, a solution that could not have been

thought of at the beginning may be found (a chairperson who can summarize arguments and pull them together plays an important role).

After the CQs and corresponding recommendations with the strength of

recommendations are determined, the comments will be written. The Guideline Development Group will describe the process to finally determine the recommendations. Based on the qualitative systematic reviews and the results of meta-analyses (when performed) in the systematic review report prepared by the SR Team, the process of the determination of recommendations will be described in detail.

If there are descriptions of decreasing the strength of evidence of RCTs or of increasing the strength of evidence of observational studies in the systematic review report, the reasons will be described in the comments.

In addition, the references used in systematic reviews will be presented at the end of chapter for each CQ and recommendation or at the end of the CPG, so that the correspondence relationship between recommendations and supporting evidence can be clearly shown.

Presentation and wording used should be as clear and unambiguous as possible. When several interventions are compared, ranking all interventions might not be insisted upon in some instances; they might be expressed flexibly so that they might be useful in clinical practice as well. [Template ID-5-4: Development Process of A Recommendation G]

The Guideline Development Group will briefly comment on the CQs and

recommendations in plain words so that patients and citizens are able to understand them as well. The possibility to prepare a popular edition of CPG could be discussed, in which summary descriptions arranged by CQs are presented for the public. [Template ID: 5-5 Summary for the Public G]

4 Comment writing

5 Summary for the public

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Chapter

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endations

5-1 A Draft of A Recommendation O: Entry Guide

1. CQ

(A person in charge will prepare a plan for 1 to 4 below, and the Guideline Development Group will make the draft)

2. Draft of a recommendation

3. Values and preferences of members of Guideline Development Group related to the recommendation Enter the outcomes with a value considered to be most important or significant by the Guideline Development Group in making a draft of recommendations among all outcomes presented for the CQs or a general summary of all outcomes.

4. Summary of the body of evidence for the CQ (the overall strength of evidence across outcomes)

A (strong) B (moderate) C (weak) D (very weak)

5. Items to be assessed to determine the strength of recommendations

1) Factors affecting the determination of the strength of recommendation Determination Explanation

(a) Overall evidence across outcomes is strong The stronger the overall evidence across outcomes is,

the more likely recommendations will be considered to be “strong.”

In contrast, the weaker the overall evidence is, the more likely recommendations will be considered to be “weak.”

□ Yes □ No Except definite “Yes,” the determination will be “No” including “uncertain”

(b) Certainty of the balance between benefit and harm As the difference between the desirable effect and the

undesirable effect becomes larger, the recommendation is more likely to be labeled as strong.

As the net benefit becomes smaller and the adverse events become greater, the certainty of benefit becomes lower and the recommendation is more likely to be labeled as weak.

□ Yes □ No

2) Other factors to be considered to determine the strength of recommendations

(a) Is there consistency and certainty (or diversity) in the values, preferences, and burden of patients? (b) Is the net benefit sufficiently balanced with the cost and resource use?

Collect as much information on the values and hope of patients, the assessment of the burden, or the cost and resource use as possible, and list them in this section.

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57

Chapter

5 R

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endations

5-1 A Draft of A Recommendation O: Entry Guide

1. CQ

(A person in charge will prepare a plan for 1 to 4 below, and the Guideline Development Group will make the draft)

2. Draft of a recommendation

3. Values and preferences of members of Guideline Development Group related to the recommendation Enter the outcomes with a value considered to be most important or significant by the Guideline Development Group in making a draft of recommendations among all outcomes presented for the CQs or a general summary of all outcomes.



5. Items to be assessed to determine the strength of recommendations

1) Factors affecting the determination of the strength of recommendation Determination Explanation

(a) Overall evidence across outcomes is strong The stronger the overall evidence across outcomes is,


In contrast, the weaker the overall evidence is, the more likely recommendations will be considered to be “weak.”

□ Yes □ No Except definite “Yes,” the determination will be “No” including “uncertain”

(b) Certainty of the balance between benefit and harm As the difference between the desirable effect and the


As the net benefit becomes smaller and the adverse events become greater, the certainty of benefit becomes lower and the recommendation is more likely to be labeled as weak.

□ Yes □ No

2) Other factors to be considered to determine the strength of recommendations


Collect as much information on the values and hope of patients, the assessment of the burden, or the cost and resource use as possible, and list them in this section.

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58


5-2 Ballot for Determination of Strength of Recommendation O: Entry Guide

CQ: The person in charge of the Secretariat will enter the CQ discussed so far and distribute them to the committee members.

Recommendation: The person in charge of the Secretariat will scrutinize the text that has been examined as the draft of recommendations, present them as “recommendation text,” and distribute them to the committee members.

Strength of recommendation (Circle any one)

Strongly recommend to perform Weakly recommend (suggest) to perform Weakly recommend (suggest) not to perform Strongly recommend not to perform

5-3 Presentation of A Recommendation G: Entry Guide

CQ: Recommendation: Strength of recommendation (Circle either one)

1 (Strong): Recommend to “perform” or “not to perform” 2 (Weak): Propose to “perform” or “not to perform”

5-4 Development Process of A Recommendation G: Entry Guide

Describe the advantage and limit of each study adopted for the determination of a recommendation and the results of qualitative systematic reviews. When meta-analyses are performed, enter the results of qualitative systematic reviews as well, and explain the process of reaching the recommendation. If the recommendation cannot be determined by any means, it is rarely stated as “no definite recommendation can be made.” In such a case, enter the process and the contents of the discussions in this comment box. If an external review on the recommendation has been obtained, enter the external review and the results of discussion in the Guideline Development Group in the chapter where the recommendation is to be entered.

The committee members will select and submit any one

Select either one, which will be the final determination

Enter the summary of a body of evidence

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5-2 Ballot for Determination of Strength of Recommendation O: Entry Guide

CQ: The person in charge of the Secretariat will enter the CQ discussed so far and distribute them to the committee members.

Recommendation: The person in charge of the Secretariat will scrutinize the text that has been examined as the draft of recommendations, present them as “recommendation text,” and distribute them to the committee members.


Strongly recommend to perform Weakly recommend (suggest) to perform Weakly recommend (suggest) not to perform Strongly recommend not to perform

5-3 Presentation of A Recommendation G: Entry Guide

CQ: Recommendation: Strength of recommendation (Circle either one)

1 (Strong): Recommend to “perform” or “not to perform” 2 (Weak): Propose to “perform” or “not to perform”

5-4 Development Process of A Recommendation G: Entry Guide

Describe the advantage and limit of each study adopted for the determination of a recommendation and the results of qualitative systematic reviews. When meta-analyses are performed, enter the results of qualitative systematic reviews as well, and explain the process of reaching the recommendation. If the recommendation cannot be determined by any means, it is rarely stated as “no definite recommendation can be made.” In such a case, enter the process and the contents of the discussions in this comment box. If an external review on the recommendation has been obtained, enter the external review and the results of discussion in the Guideline Development Group in the chapter where the recommendation is to be entered.

The committee members will select and submit any one

Select either one, which will be the final determination

Enter the summary of a body of evidence

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endations

5-5 Summary for the Public G: Entry Guide

Comment on the results of systematic reviews and recommendations by CQ in plain words easy to understand from the patients’ and citizens’ perspectives. It is desirable to figure out the expressions of Q & A, etc. by assuming that they will be used for decision-making in real clinical situations.

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Chapter

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endations

5-5 Summary for the Public G: Entry Guide

Comment on the results of systematic reviews and recommendations by CQ in plain words easy to understand from the patients’ and citizens’ perspectives. It is desirable to figure out the expressions of Q & A, etc. by assuming that they will be used for decision-making in real clinical situations.

73

Chapter 6

Finalization

Additional documents to be created for finalization .... 62

Drafting clinical practice guidelines ............................... 63

External review ................................................................. 66

AGREE II (The Appraisal of Guidelines for Research&Evaluation II) .................................................. 67

Publication ........................................................................ 68

1

2

3

4

5

75

Chapter 6

Finalization

Additional documents to be created for finalization .... 62

Drafting clinical practice guidelines ............................... 63

External review ................................................................. 66

AGREE II (The Appraisal of Guidelines for Research&Evaluation II) .................................................. 67

Publication ........................................................................ 68

1

2

3

4

5

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62

Chapter 6 Finalization

Most of the CPG draft can be provided by the templates explained in previous

chapters. The items to be added to finalize the draft will be explained below.

1) Guideline summary As a document to summarize the contents of the CPG, a list of CQs and

recommendations had better be included as the guideline summary of the CPG. [Template ID: 6-1 Guidelines Summary G*1]

2) Completion of clinical practice flowchart The clinical practice flowchart provided in the scope will be completed by reflecting

the recommendations. [Template ID: 3-2 Clinical practice flowchart (Fig.) S]

3) Terms The definition of important terms used in the CPG will be listed. Then, it should be

confirmed that the important terms are appropriately unified in the draft. The abbreviations used in the CPG will also be explained collectively.

[Template ID: 6-2 Definition of Important Terms G]

[Template ID: 6-3 List of Abbreviations G]

4) Development process

The following items determined mainly by the Guideline Executive Committee will be described. If there are other items to be described, they will be added. • Development policy • Precautions for use • Conflict of interest (COI) • Development funds • Organizational formation • Development process

[Template ID: 6-4 Development Process G]



1 Additional documents to be created for finalization

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62


Most of the CPG draft can be provided by the templates explained in previous

chapters. The items to be added to finalize the draft will be explained below.

1) Guideline summary As a document to summarize the contents of the CPG, a list of CQs and

recommendations had better be included as the guideline summary of the CPG. [Template ID: 6-1 Guidelines Summary G*1]

2) Completion of clinical practice flowchart The clinical practice flowchart provided in the scope will be completed by reflecting

the recommendations. [Template ID: 3-2 Clinical practice flowchart (Fig.) S]

3) Terms The definition of important terms used in the CPG will be listed. Then, it should be

confirmed that the important terms are appropriately unified in the draft. The abbreviations used in the CPG will also be explained collectively.

[Template ID: 6-2 Definition of Important Terms G]

[Template ID: 6-3 List of Abbreviations G]

4) Development process

The following items determined mainly by the Guideline Executive Committee will be described. If there are other items to be described, they will be added. • Development policy • Precautions for use • Conflict of interest (COI) • Development funds • Organizational formation • Development process

[Template ID: 6-4 Development Process G]



1 Additional documents to be created for finalization

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Chapter

6 Finalization

The organization of a CPG is shown below, regarding the arrangements of templates

in CPGs (detailed version):

Title page Title Development body (the names of medical societies, etc.) Version Date of publication

Preliminaries Guideline summary

[Template ID: 6-1 Guidelines Summary G]


[Template ID: 3-3 Clinical practice flowchart (Fig.) S]

A list of terms/abbreviations

[Template ID: 6-2 Definition of Important Terms G] [Template ID: 6-3 List of Abbreviations G]

(I) Development organization/development policy 1. Development organization 1.1 Development body 1.2 Guidelines Executive Committee 1.3 Secretariat of Guideline Development 1.4 Guideline Development Group 1.5 Systematic Review Team (SR Team) 1,6 External Review Committee

(By putting the above together) [Template ID: 2-2 Preparation for CPG Development_(6)G]

2. Development process 2.1 Development policy 2.2 Precautions for use 2.3 Conflict of interest 2.4 Development funds 2.5 Organizational formation 2.6 Development process

(By putting the above together) [Template ID: 6-4 Development Process G]

(To be continued)

2 Drafting clinical practice guidelines

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63

Chapter

6 Finalization

The organization of a CPG is shown below, regarding the arrangements of templates

in CPGs (detailed version):

Title page Title Development body (the names of medical societies, etc.) Version Date of publication

Preliminaries Guideline summary

[Template ID: 6-1 Guidelines Summary G]


[Template ID: 3-3 Clinical practice flowchart (Fig.) S]

A list of terms/abbreviations

[Template ID: 6-2 Definition of Important Terms G] [Template ID: 6-3 List of Abbreviations G]

(I) Development organization/development policy 1. Development organization 1.1 Development body 1.2 Guidelines Executive Committee 1.3 Secretariat of Guideline Development 1.4 Guideline Development Group 1.5 Systematic Review Team (SR Team) 1,6 External Review Committee

(By putting the above together) [Template ID: 2-2 Preparation for CPG Development_(6)G]

2. Development process 2.1 Development policy 2.2 Precautions for use 2.3 Conflict of interest 2.4 Development funds 2.5 Organizational formation 2.6 Development process

(By putting the above together) [Template ID: 6-4 Development Process G]

(To be continued)

2 Drafting clinical practice guidelines

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64


(Continued)

(II) Scope 1. Basic features of health topics 1.1 Clinical features 1.2 Epidemiological features 1.3 Overall flow of clinical practice

(By putting the above together) [Template ID: 3-1 Basic Characteristics of Health Topic S]

2. Contents covered by CPG 3. Issues on systematic reviews 4. Issues on determination of recommendations to finalize and publish

(By putting 2, 3, and 4 together) [Template ID: 3-3 Scope S]

(III) Recommendations 1. CQ1 (The following items will be entered for each CQ) 1.1 Summary 1.1.1. CQ text 1.1.2. Recommendations with strength of recommendations

(By putting 1.1.1 and 1.1.2 together) [Template ID: 5-3 Presentation of A Recommendation G]

1.1.3. Comments

[Template ID: 5-4 Development Process of A Recommendation G]

1.1.4. Summary for the public

[Template ID: 5.5 Summary for the Public G]

1.2 Results of systematic reviews 1.2.1. Collection and selection of evidence

1.2.2. Evaluation and integration of evidence

[Template ID: 4-8 Qualitative Systematic Review R] [Template ID: 4-9 Meta-analysis R]

1.2.3. Systematic review summary

[Template ID: 4-10 Summary of Systematic Review Report R]

1.2.4. References

[Template ID: 4-4 List of Cited Literature R] (To be continued)

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64


(Continued)

(II) Scope 1. Basic features of health topics 1.1 Clinical features 1.2 Epidemiological features 1.3 Overall flow of clinical practice

(By putting the above together) [Template ID: 3-1 Basic Characteristics of Health Topic S]

2. Contents covered by CPG 3. Issues on systematic reviews 4. Issues on determination of recommendations to finalize and publish

(By putting 2, 3, and 4 together) [Template ID: 3-3 Scope S]

(III) Recommendations 1. CQ1 (The following items will be entered for each CQ) 1.1 Summary 1.1.1. CQ text 1.1.2. Recommendations with strength of recommendations

(By putting 1.1.1 and 1.1.2 together) [Template ID: 5-3 Presentation of A Recommendation G]

1.1.3. Comments

[Template ID: 5-4 Development Process of A Recommendation G]

1.1.4. Summary for the public

[Template ID: 5.5 Summary for the Public G]

1.2 Results of systematic reviews 1.2.1. Collection and selection of evidence

1.2.2. Evaluation and integration of evidence

[Template ID: 4-8 Qualitative Systematic Review R] [Template ID: 4-9 Meta-analysis R]

1.2.3. Systematic review summary

[Template ID: 4-10 Summary of Systematic Review Report R]

1.2.4. References

[Template ID: 4-4 List of Cited Literature R] (To be continued)

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65

Chapter

6 Finalization

(Continued) 2. CQ2

: :

(IV) Activities after publication The activities to be performed for the implementation of the CPG in daily clinical practice

and for promoting the utilization will be described. Revision schedules are specified.

1. The system after publication

[Template ID: 7-1 Organizational Issues after Publication G] 2. Implementation

[Template ID: 7-2 Implementation G]

3. Effectiveness assessment

[Template ID: 7-3 Effectiveness Assessment G]

4. Revision

[Template ID: 7-4 Revision G]

(V) Appendices 1. Reference data

2. Operation data Table for setting of the clinical questions

[Template ID: 3-4 Formulation of Clinical Question O]

Search formula and flowchart by each literature search database

[Template ID: 4-1 Results of Database Search R] [Template ID: 4-2 Flow Chart of Literature Search R]

Assessment sheet of evidence STEP 1 sheet by outcome

[Template ID: 4-5 Evaluation Sheet for Interventional Study R] [Template ID: 4-6 Evaluation Sheet for Observational Study R]

Integration sheet of evidence STEP 2 sheet by CQ


Summary of the external review

[Template ID: 6-6 Summary of External Review G]

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65

Chapter

6 Finalization

(Continued) 2. CQ2

: :

(IV) Activities after publication The activities to be performed for the implementation of the CPG in daily clinical practice

and for promoting the utilization will be described. Revision schedules are specified.

1. The system after publication

[Template ID: 7-1 Organizational Issues after Publication G] 2. Implementation

[Template ID: 7-2 Implementation G]

3. Effectiveness assessment

[Template ID: 7-3 Effectiveness Assessment G]

4. Revision

[Template ID: 7-4 Revision G]

(V) Appendices 1. Reference data

2. Operation data Table for setting of the clinical questions

[Template ID: 3-4 Formulation of Clinical Question O]

Search formula and flowchart by each literature search database

[Template ID: 4-1 Results of Database Search R] [Template ID: 4-2 Flow Chart of Literature Search R]

Assessment sheet of evidence STEP 1 sheet by outcome

[Template ID: 4-5 Evaluation Sheet for Interventional Study R] [Template ID: 4-6 Evaluation Sheet for Observational Study R]

Integration sheet of evidence STEP 2 sheet by CQ


Summary of the external review

[Template ID: 6-6 Summary of External Review G]

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66


1) What is external review? External review is a review of the draft of scope, CQs, systematic reviews, evidence

evaluation, recommendations, and the whole CPG by groups other than the group that developed the CPG.

2) Purpose, reviewers, and method of the external review Since the role of reviewers differs according to the purpose of external review, the

purpose of external review should be set and a wide variety of reviewers who match the purpose, for example, stakeholders including disease specialists, primary care physicians, epidemiology specialists, and patients and citizens will be requested to review. In addition, it is even better to receive public comments by posting on the websites of patient groups or related medical societies. Examples of external review by purpose are shown below:

(1) Review on the scientific appropriateness of CPG The scientific appropriateness of the evidence on which recommendations are

based, the method to evaluate the evidence, and the degree of sufficiency to which the evidence was evaluated will be assessed.

Reviewers: Disease specialists, specialists on systematic reviews statistics, such as statisticians and epidemiologists.

Method: By using a method such as the systematic review criteria of the Institute of Medicine of the United States.

(2) Review on the applicability and feasibility of recommendations

The applicability and feasibility of recommendations in CPGs will be assessed from the perspectives of users and social contexts.

Reviewers: Disease specialists, general practitioners, representatives of patients and citizens, administrative agencies, etc.

Method: In a free form and descriptively

(3) Review on the appropriateness of formulation of recommendations and/or CPG

The process of formulating recommendations and/or CPG will be reviewed with reference to methodological appropriateness using an assessment tool of CPGs, such as AGREE II.

Reviewers: Specialists in CPGs, disease specialists, statisticians, etc. Method: Utilization of AGREE II

External review 3

80

66


1) What is external review? External review is a review of the draft of scope, CQs, systematic reviews, evidence

evaluation, recommendations, and the whole CPG by groups other than the group that developed the CPG.

2) Purpose, reviewers, and method of the external review Since the role of reviewers differs according to the purpose of external review, the

purpose of external review should be set and a wide variety of reviewers who match the purpose, for example, stakeholders including disease specialists, primary care physicians, epidemiology specialists, and patients and citizens will be requested to review. In addition, it is even better to receive public comments by posting on the websites of patient groups or related medical societies. Examples of external review by purpose are shown below:

(1) Review on the scientific appropriateness of CPG The scientific appropriateness of the evidence on which recommendations are

based, the method to evaluate the evidence, and the degree of sufficiency to which the evidence was evaluated will be assessed.

Reviewers: Disease specialists, specialists on systematic reviews statistics, such as statisticians and epidemiologists.

Method: By using a method such as the systematic review criteria of the Institute of Medicine of the United States.

(2) Review on the applicability and feasibility of recommendations

The applicability and feasibility of recommendations in CPGs will be assessed from the perspectives of users and social contexts.

Reviewers: Disease specialists, general practitioners, representatives of patients and citizens, administrative agencies, etc.

Method: In a free form and descriptively

(3) Review on the appropriateness of formulation of recommendations and/or CPG

The process of formulating recommendations and/or CPG will be reviewed with reference to methodological appropriateness using an assessment tool of CPGs, such as AGREE II.

Reviewers: Specialists in CPGs, disease specialists, statisticians, etc. Method: Utilization of AGREE II

External review 3

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Chapter

6 Finalization

3) Procedure for the external review The Guideline Development Group should request the reviewers for an external

review by clearly specifying the purpose of review. When reviewed, the Guideline Development Group will examine the review results and reply if necessary. The series of works in response to the review results will be summarized using a table, such as [Template ID: 6-5 Response to External review O]. After that, the results of external review will be summarized as in [Template ID: 6-6 Summary of External Review G] and published. When summarizing the results in 6-6, the results can be presented using a simplified version of 6-5.

When requesting the assessment of the development method of the CPG, the check sheet of AGREE II can be attached.

The review results will be summarized in a standard format, and the text of CPGs will be modified or revised as needed. A summary of the external review will be published, together with the response.

After the publication of the CPG, a permanent mechanism to receive feedback from the users should be set, for example, on the websites of medical societies, as well. The review obtained here will be summarized and utilized as the information in considering revisions.

1) What is AGREE II? It is an assessment tool of CPGs developed by the AGREE Next Steps Consortium. It

was published in 2009 (the first version in 2003) on the AGREE Research Trust website (http://www.agreetrust.org/). AGREE II assesses the quality of the guidelines based on their description focusing on the development method/process of guidelines.

2) Overall Structure of AGREE II AGREE II consists of a 7-grade assessment of six domains and an overall assessment.

Domain 1. Scope and Purpose (items 1–3) Domain 2. Stakeholder Involvement (items 4–6) Domain 3. Rigour of Development (items 7–14) Domain 4. Clarity of Presentation (items 15–17) Domain 5. Applicability (items 18–21) Domain 6. Editorial Independence (items 22–23) Overall Guideline Assessment (items 24–25)

4 AGREE II (The Appraisal of Guidelines for Research & Evaluation II)

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Chapter

6 Finalization

3) Procedure for the external review The Guideline Development Group should request the reviewers for an external

review by clearly specifying the purpose of review. When reviewed, the Guideline Development Group will examine the review results and reply if necessary. The series of works in response to the review results will be summarized using a table, such as [Template ID: 6-5 Response to External review O]. After that, the results of external review will be summarized as in [Template ID: 6-6 Summary of External Review G] and published. When summarizing the results in 6-6, the results can be presented using a simplified version of 6-5.

When requesting the assessment of the development method of the CPG, the check sheet of AGREE II can be attached.

The review results will be summarized in a standard format, and the text of CPGs will be modified or revised as needed. A summary of the external review will be published, together with the response.

After the publication of the CPG, a permanent mechanism to receive feedback from the users should be set, for example, on the websites of medical societies, as well. The review obtained here will be summarized and utilized as the information in considering revisions.

1) What is AGREE II? It is an assessment tool of CPGs developed by the AGREE Next Steps Consortium. It

was published in 2009 (the first version in 2003) on the AGREE Research Trust website (http://www.agreetrust.org/). AGREE II assesses the quality of the guidelines based on their description focusing on the development method/process of guidelines.

2) Overall Structure of AGREE II AGREE II consists of a 7-grade assessment of six domains and an overall assessment.

Domain 1. Scope and Purpose (items 1–3) Domain 2. Stakeholder Involvement (items 4–6) Domain 3. Rigour of Development (items 7–14) Domain 4. Clarity of Presentation (items 15–17) Domain 5. Applicability (items 18–21) Domain 6. Editorial Independence (items 22–23) Overall Guideline Assessment (items 24–25)

4 AGREE II (The Appraisal of Guidelines for Research & Evaluation II)

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Since the evaluation and integration process of the body of evidence by systematic

reviews is recorded and the process of formulating recommendations is also described in the detailed version of the CPG, it could often become voluminous, with a few hundred pages. Therefore, it is more realistic to publish the detailed full version of the CPG electronically on the website than to publish it as a book.

The documents created for implementation and promotion of utilization of the CPG based on the detailed version, including a practical version and a brief version, will be explained in Chapter 7 (p.73).

5 Publication

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68


Since the evaluation and integration process of the body of evidence by systematic

reviews is recorded and the process of formulating recommendations is also described in the detailed version of the CPG, it could often become voluminous, with a few hundred pages. Therefore, it is more realistic to publish the detailed full version of the CPG electronically on the website than to publish it as a book.

The documents created for implementation and promotion of utilization of the CPG based on the detailed version, including a practical version and a brief version, will be explained in Chapter 7 (p.73).

5 Publication

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69

Chapter

6 Finalization

6-1 Guidelines Summary G: Entry Guide

Guidelines summary

Present a list of CQs and recommendations covered by CPGs.

6-2 Definition of Important Terms G: Entry Guide

Term Explanation

6-3 List of Abbreviations G: Entry Guide

Abbreviation Formal name

Present the explanation of the important terms used in CPGs. It is desirable to consider that people other than specialists must be able to understand the CPGs.

Present official names of the abbreviations frequently used in CPGs collectively.

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6 Finalization

6-1 Guidelines Summary G: Entry Guide

Guidelines summary

Present a list of CQs and recommendations covered by CPGs.

6-2 Definition of Important Terms G: Entry Guide

Term Explanation

6-3 List of Abbreviations G: Entry Guide

Abbreviation Formal name

Present the explanation of the important terms used in CPGs. It is desirable to consider that people other than specialists must be able to understand the CPGs.

Present official names of the abbreviations frequently used in CPGs collectively.

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70


6-4 Development Process G: Entry Guide

Item Text

Development policy Enter the overall policy emphasized in the development of CPGs.

Precautions for use Enter the precautions the users should take in using CPGs.

Development funds Enter the resources of the development funds.

Conflict of interest (From p.63)

Organizational formation

Guideline Executive Committee Enter the policy, process, and results of the formation.

Guideline Development Group Enter the policy, process, and results of the formation.

Systematic Review Team Enter the policy, process, and results of the formation.

(Add if other committees are organized) Enter the policy, process, and results of the formation.

Development process Preparation Enter the process, results, and problems, etc.

Scope Enter the process, results, and problems, etc.

Systematic reviews Enter the process, results, and problems, etc.

Formulation of Recommendations Enter the process, results, and problems, etc.

Finalization Enter the process, results, and problems, etc.

Publication Enter the process, results, and problems, etc.

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6-4 Development Process G: Entry Guide

Item Text

Development policy Enter the overall policy emphasized in the development of CPGs.

Precautions for use Enter the precautions the users should take in using CPGs.

Development funds Enter the resources of the development funds.

Conflict of interest (From p.63)


Guideline Executive Committee Enter the policy, process, and results of the formation.

Guideline Development Group Enter the policy, process, and results of the formation.

Systematic Review Team Enter the policy, process, and results of the formation.

(Add if other committees are organized) Enter the policy, process, and results of the formation.

Development process Preparation Enter the process, results, and problems, etc.

Scope Enter the process, results, and problems, etc.

Systematic reviews Enter the process, results, and problems, etc.

Formulation of Recommendations Enter the process, results, and problems, etc.

Finalization Enter the process, results, and problems, etc.

Publication Enter the process, results, and problems, etc.

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Chapter

6 Finalization

6-5 Response to External Review O: Entry Guide

No. Review date Version Reviewer

(affiliation/post) organization

Review comments

Response comments

Response date

Enter the date when the review was accepted.

Enter the version in which the review was accepted.

Enter the name, affiliation, and post of the reviewer based on the permission of the reviewer.

Enter the review contents. * Summarize only important cases.

Enter the response contents.

Enter the response date.

e.g., “Scope” “Draft”

* If the reviewer is an organization, enter the name of the organization.

6-6 Summary of External Review G: Entry Guide

Purpose

Method

Version

Period

Reviewers

Tool

Others

Process

Results

Enter the purpose of the external review.

Enter the method of the external review. Enter scope, draft, or others in “Version.”

Enter the process of the external review. Summarize what was conducted by date.

Enter the contents of the external review and the response to the review collectively. It is acceptable to enter by extracting from the summary table. When assessed using a standard tool, enter in the standard method to express the results.

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Chapter

6 Finalization

6-5 Response to External Review O: Entry Guide

No. Review date Version Reviewer

(affiliation/post) organization

Review comments

Response comments

Response date

Enter the date when the review was accepted.

Enter the version in which the review was accepted.

Enter the name, affiliation, and post of the reviewer based on the permission of the reviewer.

Enter the review contents. * Summarize only important cases.

Enter the response contents.

Enter the response date.

e.g., “Scope” “Draft”

* If the reviewer is an organization, enter the name of the organization.

6-6 Summary of External Review G: Entry Guide

Purpose

Method

Version

Period

Reviewers

Tool

Others

Process

Results

Enter the purpose of the external review.

Enter the method of the external review. Enter scope, draft, or others in “Version.”

Enter the process of the external review. Summarize what was conducted by date.

Enter the contents of the external review and the response to the review collectively. It is acceptable to enter by extracting from the summary table. When assessed using a standard tool, enter in the standard method to express the results.

85

Chapter 7

Dissemination, Implementation, and Assessment

of Clinical Practice Guidelines

Outline ............................................................................... 74

Organizational issues after publication ......................... 74

Implementation ................................................................. 75

Effectiveness assessment .............................................. 78

Revision ............................................................................. 79

1

2

3

4

5

4

87

Chapter 7

Dissemination, Implementation, and Assessment

of Clinical Practice Guidelines

Outline ............................................................................... 74

Organizational issues after publication ......................... 74

Implementation ................................................................. 75

Effectiveness assessment .............................................. 78

Revision ............................................................................. 79

1

2

3

4

5

4

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74

Chapter 7 Dissemination, Implementation, and Assessment of Clinical Practice Guidelines

The method of CPG development is explained in this handbook, but it is desirable to

include in the CPG the process of dissemination, implementation, and assessment of the completed CPG (Fig. 7-1) as well.

Fig. 7-1 Four steps of development, dissemination, implementation, and

assessment of clinical practice guidelines It is desirable to include in the CPG the activities to be performed continuously on the

items - below:

Even after the CPG is published, there are many operations required of the Guideline

Executive Committee and the Guideline Development Group, such as promoting CPG implementation, assessing the effectiveness of the CPG, and checking the emergence of new studies that may affect recommendations in the CPG. Therefore, it is desirable for the Guideline Executive Committee and the Guideline Development Group to continue their activities even after the publication of the CPG until the next Guideline Executive Committee and the Guideline Development Group are newly organized.

The follow-up structure after the publication of the CPG should be described in the CPG. [Template ID: 7-1 Organizational Issues after Publication G*1]

*1: Templates shall be given the following symbol at the end of their names in response to relevant

documents. G: Clinical Practice Guideline

2 5

1 Outline

2 Organizational issues after publication

Development Dissemination Implementation Assessment

88

74


The method of CPG development is explained in this handbook, but it is desirable to

include in the CPG the process of dissemination, implementation, and assessment of the completed CPG (Fig. 7-1) as well.

Fig. 7-1 Four steps of development, dissemination, implementation, and

assessment of clinical practice guidelines It is desirable to include in the CPG the activities to be performed continuously on the

items - below:

Even after the CPG is published, there are many operations required of the Guideline

Executive Committee and the Guideline Development Group, such as promoting CPG implementation, assessing the effectiveness of the CPG, and checking the emergence of new studies that may affect recommendations in the CPG. Therefore, it is desirable for the Guideline Executive Committee and the Guideline Development Group to continue their activities even after the publication of the CPG until the next Guideline Executive Committee and the Guideline Development Group are newly organized.

The follow-up structure after the publication of the CPG should be described in the CPG. [Template ID: 7-1 Organizational Issues after Publication G*1]

*1: Templates shall be given the following symbol at the end of their names in response to relevant

documents. G: Clinical Practice Guideline

2 5

1 Outline

2 Organizational issues after publication

Development Dissemination Implementation Assessment

88

75

Chapter

7 D

issemination , Im

plementation, and A

ssessment of C

linical Practice Guidelines

Implementation is to increase the applicability of the CPG by various efforts in order

for the CPG to be appropriately utilized in the places where the utilization is expected.

1) Development of summary version CPG utilization will be promoted by developing a “practical version” as well as a

“brief version,” based on the detailed version of the CPG. The practical version can be referred to in daily clinical practice, while brief version can be used promptly in daily clinical practice as a quick reference. When the practical version and brief version are developed, the detailed version can be viewed as a reference to be checked when needed. It is also strongly desired that a plain explanation of the CPG for the public be developed for patients and their families. The description plan of the detailed version, practical version, brief version, and plain explanation for the public is shown in Table 7-1.

3 Implementation

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75

Chapter

7 D

issemination , Im

plementation, and A

ssessment of C


Implementation is to increase the applicability of the CPG by various efforts in order

for the CPG to be appropriately utilized in the places where the utilization is expected.

1) Development of summary version CPG utilization will be promoted by developing a “practical version” as well as a

“brief version,” based on the detailed version of the CPG. The practical version can be referred to in daily clinical practice, while brief version can be used promptly in daily clinical practice as a quick reference. When the practical version and brief version are developed, the detailed version can be viewed as a reference to be checked when needed. It is also strongly desired that a plain explanation of the CPG for the public be developed for patients and their families. The description plan of the detailed version, practical version, brief version, and plain explanation for the public is shown in Table 7-1.

3 Implementation

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76


Table 7-1 The description plan of the practical version and brief version of CPGs and the plain explanation of the guidelines for the public

Title page Detailed version

Practical version

Brief version

For the public

Title Development body (the name of academic societies, etc.) Version Date of publication

Preliminaries Guidelines summary Clinical practice flowchart A list of terms/abbreviations

(I) Development organization/development policy 1 Development organization 1.1 Development body 1.2 Guideline Executive Committee 1.3 Guideline Development Group 1.4 Systematic Review Team 1.5 External review Committee 1.6 Secretariat of Guideline Development 2 Development process 2.1 Development policy 2.2 Precautions for use 2.3 Conflict of interest 2.4 Development funds 2.5 Organizational formation 2.6 Development process (II) Scope 1 Basic features of health topics 1.1 Clinical features 1.2 Epidemiological features 1.3 Overall flow of clinical practice of health topics 2 Items on the contents covered by clinical practice guideline

(Table)

3 Items on systematic reviews (Table) 4 From the determination of recommendations to the

finalization and the implementation policy (Table)

(III) Recommendations 1 CQ1 1.1 Summary 1.1.1. CQ text 1.1.2. The text of recommendations/strength of evidence/strength

of recommendations

1.1.3. Comments 1.1.4. Summary for the public 1.2 Results of systematic reviews 1.2.1. Collection and selection of evidence 1.2.2. Assessment and integration of evidence 1.2.3. Systematic review summary 1.2.4 References 2 CQ2 (developed for the number of the CQs) : (IV) Approach after publication 1 The system after publication 2 Implementation 3 Efficacy assessment 4 Revision (V) Appendices

1. Reference data 2. Operation data

• Template for setting the CQs • Search formula and flowchart by each literature search database • Assessment sheet of evidence Step 1 sheet by outcome • Integration sheet of evidence Step 2 sheet by CQ • Summary of the external review

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76


Table 7-1 The description plan of the practical version and brief version of CPGs and the plain explanation of the guidelines for the public

Title page Detailed version

Practical version

Brief version

For the public

Title Development body (the name of academic societies, etc.) Version Date of publication

Preliminaries Guidelines summary Clinical practice flowchart A list of terms/abbreviations

(I) Development organization/development policy 1 Development organization 1.1 Development body 1.2 Guideline Executive Committee 1.3 Guideline Development Group 1.4 Systematic Review Team 1.5 External review Committee 1.6 Secretariat of Guideline Development 2 Development process 2.1 Development policy 2.2 Precautions for use 2.3 Conflict of interest 2.4 Development funds 2.5 Organizational formation 2.6 Development process (II) Scope 1 Basic features of health topics 1.1 Clinical features 1.2 Epidemiological features 1.3 Overall flow of clinical practice of health topics 2 Items on the contents covered by clinical practice guideline

(Table)

3 Items on systematic reviews (Table) 4 From the determination of recommendations to the

finalization and the implementation policy (Table)

(III) Recommendations 1 CQ1 1.1 Summary 1.1.1. CQ text 1.1.2. The text of recommendations/strength of evidence/strength

of recommendations

1.1.3. Comments 1.1.4. Summary for the public 1.2 Results of systematic reviews 1.2.1. Collection and selection of evidence 1.2.2. Assessment and integration of evidence 1.2.3. Systematic review summary 1.2.4 References 2 CQ2 (developed for the number of the CQs) : (IV) Approach after publication 1 The system after publication 2 Implementation 3 Efficacy assessment 4 Revision (V) Appendices

1. Reference data 2. Operation data

• Template for setting the CQs • Search formula and flowchart by each literature search database • Assessment sheet of evidence Step 1 sheet by outcome • Integration sheet of evidence Step 2 sheet by CQ • Summary of the external review

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2) Utilization of various information media It is important to make effective use of various media for promoting the applicability

of CPG by implementation. The comparison between printed hard copy and electronic service is shown in Table 7-2.

Table 7-2 Comparison of the publication methods of CPGs

Printed hard copy Electronic service

Limitation to a large volume

Academic journal: up to about 10 pages Book: up to about 300 pages Booklet: up to about 100 pages

No limitation

Portability in the site of practice

Academic journal, book: Can be read in the library, medical office, and outpatient department Booklet: Can be carried to the bedside

Fixed terminal: Can be set in the library and medical office. Not appropriate for carrying to the bedside. Laptop terminal: Can be moved to some extent in the site of practice. Portable terminal: Can be carried everywhere in the site of practice

Information search Search by table of contents and index

Various search functions are available

Access by a wide range of users

Academic journal: May be restricted to the members of medical societies Book: Must be bought Booklet: By distribution

Online information service: Online connection is required Offline application: Online connection is not required at the time of reference

Cost required for publication

Academic journal: Can be obtained at a low price Book: The cost can be procured by selling for value Booklet: The development body bears the cost if it is provided for free

Minds site: Free Minds offline application: Under planning Websites of medical societies: The cost of page creation is borne by the development body

3) Promoters and barriers of the CPG utilization In implementing a CPG, promoters and barriers should be considered in relation to the

CPG itself, CPG dissemination methods, and factors on the user side. Factors related to CPG

One of the most important factors that promote CPG utilization in daily clinical practice is the user’s perception on the trustworthiness of the CPG. The CPG development methods proposed in this handbook, including the method to formulate recommendations taking into consideration the body of evidence evaluated and integrated with systematic reviews, the diversity of patients’ value and preference, and economic perspectives, are expected to improve the perception on the trustworthiness of the CPG. These methods were not included in the Handbook 2007.

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Chapter

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issemination , Im

plementation, and A

ssessment of C


2) Utilization of various information media It is important to make effective use of various media for promoting the applicability

of CPG by implementation. The comparison between printed hard copy and electronic service is shown in Table 7-2.

Table 7-2 Comparison of the publication methods of CPGs

Printed hard copy Electronic service

Limitation to a large volume

Academic journal: up to about 10 pages Book: up to about 300 pages Booklet: up to about 100 pages

No limitation

Portability in the site of practice

Academic journal, book: Can be read in the library, medical office, and outpatient department Booklet: Can be carried to the bedside

Fixed terminal: Can be set in the library and medical office. Not appropriate for carrying to the bedside. Laptop terminal: Can be moved to some extent in the site of practice. Portable terminal: Can be carried everywhere in the site of practice

Information search Search by table of contents and index

Various search functions are available

Access by a wide range of users

Academic journal: May be restricted to the members of medical societies Book: Must be bought Booklet: By distribution

Online information service: Online connection is required Offline application: Online connection is not required at the time of reference

Cost required for publication

Academic journal: Can be obtained at a low price Book: The cost can be procured by selling for value Booklet: The development body bears the cost if it is provided for free

Minds site: Free Minds offline application: Under planning Websites of medical societies: The cost of page creation is borne by the development body

3) Promoters and barriers of the CPG utilization In implementing a CPG, promoters and barriers should be considered in relation to the

CPG itself, CPG dissemination methods, and factors on the user side. Factors related to CPG

One of the most important factors that promote CPG utilization in daily clinical practice is the user’s perception on the trustworthiness of the CPG. The CPG development methods proposed in this handbook, including the method to formulate recommendations taking into consideration the body of evidence evaluated and integrated with systematic reviews, the diversity of patients’ value and preference, and economic perspectives, are expected to improve the perception on the trustworthiness of the CPG. These methods were not included in the Handbook 2007.

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Many early CPGs adopted the textbook-style description of recommendations structured by chapters and sections. Gradually CPGs structured by clinical questions (CQ) and their recommendation increased in number, partly because this CQ–recommendation structure was proposed in the Handbook 2007. This CQ–recommendation structure is preferred to textbook-style description, because it can be more directly related to the issues on which patients and practitioners try to make decisions together. Further improvement is expected regarding how CQs should be formulated, however; a CQ such as “what are the epidemiologic features of …?,” is still found in some CPGs, which is not directly related to the decision making by patients and practitioners.

Factors related to CPG dissemination It is of fundamental importance to disseminate CPGs to users, so that users can always

refer to what they need at the site of use. This handbook proposes three different versions of CPG: detailed version, practical version, and brief version, to be provided for different purposes and different information needs. Furthermore, it is important to select an appropriate medium, printed hard copy or electronic service, considering in which situations the CPG, detailed version, practical version, and brief version, is referred to.

Factors on the user side Since the purpose of CPGs is to support the decision-making by patients and

practitioners, patients and practitioners are the main users of CPGs. Since compliance with CPGs is not mandatory in Japan, however, patients and practitioners are supposed to examine by themselves the applicability of recommendations presented in CPGs. Therefore, the perception and attitude toward CPGs of users, patients and practitioners, are the most important factors affecting their utilization. It is required for CPG developers to make efforts to advise both patients and practitioners on preferable ways and cautions to be exercised when utilizing CPGs. [Template ID: 7-2 Implementation G]

The improvement in patient outcomes by the implementation of CPGs should be assessed for the effectiveness of CPGs, and assessment by quality indicators (QIs) can be considered. The QI is a quantitative measurement of quality of care, such as the proportion in total number of practice of the practice recommended in CPGs and the improvement in surrogates. In addition, the assessment of satisfaction of patients and practitioners for CPGs is also important.

If the effectiveness assessment is planned at the time of publishing CPG, the method and specific policies should be described in the CPG. [Template ID: 7-3 Effectiveness Assessment G]

4 Effectiveness assessment

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Many early CPGs adopted the textbook-style description of recommendations structured by chapters and sections. Gradually CPGs structured by clinical questions (CQ) and their recommendation increased in number, partly because this CQ–recommendation structure was proposed in the Handbook 2007. This CQ–recommendation structure is preferred to textbook-style description, because it can be more directly related to the issues on which patients and practitioners try to make decisions together. Further improvement is expected regarding how CQs should be formulated, however; a CQ such as “what are the epidemiologic features of …?,” is still found in some CPGs, which is not directly related to the decision making by patients and practitioners.

Factors related to CPG dissemination It is of fundamental importance to disseminate CPGs to users, so that users can always

refer to what they need at the site of use. This handbook proposes three different versions of CPG: detailed version, practical version, and brief version, to be provided for different purposes and different information needs. Furthermore, it is important to select an appropriate medium, printed hard copy or electronic service, considering in which situations the CPG, detailed version, practical version, and brief version, is referred to.

Factors on the user side Since the purpose of CPGs is to support the decision-making by patients and

practitioners, patients and practitioners are the main users of CPGs. Since compliance with CPGs is not mandatory in Japan, however, patients and practitioners are supposed to examine by themselves the applicability of recommendations presented in CPGs. Therefore, the perception and attitude toward CPGs of users, patients and practitioners, are the most important factors affecting their utilization. It is required for CPG developers to make efforts to advise both patients and practitioners on preferable ways and cautions to be exercised when utilizing CPGs. [Template ID: 7-2 Implementation G]

The improvement in patient outcomes by the implementation of CPGs should be assessed for the effectiveness of CPGs, and assessment by quality indicators (QIs) can be considered. The QI is a quantitative measurement of quality of care, such as the proportion in total number of practice of the practice recommended in CPGs and the improvement in surrogates. In addition, the assessment of satisfaction of patients and practitioners for CPGs is also important.

If the effectiveness assessment is planned at the time of publishing CPG, the method and specific policies should be described in the CPG. [Template ID: 7-3 Effectiveness Assessment G]

4 Effectiveness assessment

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Generally, since the life expectancy of CPGs and systematic reviews is considered to be 5 years or so, it is desirable to revise a CPG within 5 years. Actually, an appropriate time interval for revision varies from 2 to 5 years, according to the theme and area of health topic. Therefore, the group that developed the CPG should consider revising it when any event that may affect the recommendations happens, such as the publication of the results of a large-scale study or official approval of new therapies. The policy for future revisions should be included in the CPG.

As the type of revisions of CPGs, a complete revision, a partial revision, an addition, and a withdrawal can be considered. In any case, this should be widely announced without delay on the websites of the relevant medical societies in order to avoid confusion among users. [Template ID: 7-4 Revision G]

"A revision review sheet" useful in considering a revision is provided in Reference 5. Reference 5 Revision review sheet (p.115)

5 Revision

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Generally, since the life expectancy of CPGs and systematic reviews is considered to be 5 years or so, it is desirable to revise a CPG within 5 years. Actually, an appropriate time interval for revision varies from 2 to 5 years, according to the theme and area of health topic. Therefore, the group that developed the CPG should consider revising it when any event that may affect the recommendations happens, such as the publication of the results of a large-scale study or official approval of new therapies. The policy for future revisions should be included in the CPG.

As the type of revisions of CPGs, a complete revision, a partial revision, an addition, and a withdrawal can be considered. In any case, this should be widely announced without delay on the websites of the relevant medical societies in order to avoid confusion among users. [Template ID: 7-4 Revision G]

"A revision review sheet" useful in considering a revision is provided in Reference 5. Reference 5 Revision review sheet (p.115)

5 Revision

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7-1 Organizational Issues after Publication G: Entry Guide

Name of the system Plan after publication Guideline Executive Committee Guideline Development Group

Enter the response, such as continuation, reorganization, and dissolution.

Systematic Review Team

7-2 Implementation G: Entry Guide

Development of the summary version

Enter the plan when the practical version, the brief version, or the explanation for the public is developed based on the detailed version.

Utilization of various information media

Enter the plan for the method of information provision, such as an academic journal, a book, or a booklet as the print version, and the information provision by the Internet or that for portable terminal as the electronic version.

Promoters and barriers for the utilization of CPG

Enter the results of the analyses of promotional and obstructive factors for the utilization of CPGs on the guidelines themselves, response to the users, and the providing method.

7-3 Effectiveness Assessment G: Entry Guide

Assessment method Specific policy Enter the name

of the method.

Enter the outline of the method and the implementation period, etc. specifically.

7-4 Revision G: Entry Guide

Item Policy

Timing of revision Enter the plan, such as to start the revision work in certain years after publication or to revise according to the change in the trend of the medical care.

Method of revision Enter the method, such as a complete revision and a partial revision, as a method of revision.

Organization of revision Enter whether a Guideline Development Group, etc. will be newly organized or the same organization will respond continuously.

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7-1 Organizational Issues after Publication G: Entry Guide

Name of the system Plan after publication Guideline Executive Committee Guideline Development Group

Enter the response, such as continuation, reorganization, and dissolution.


7-2 Implementation G: Entry Guide

Development of the summary version

Enter the plan when the practical version, the brief version, or the explanation for the public is developed based on the detailed version.


Enter the plan for the method of information provision, such as an academic journal, a book, or a booklet as the print version, and the information provision by the Internet or that for portable terminal as the electronic version.

Promoters and barriers for the utilization of CPG

Enter the results of the analyses of promotional and obstructive factors for the utilization of CPGs on the guidelines themselves, response to the users, and the providing method.

7-3 Effectiveness Assessment G: Entry Guide

Assessment method Specific policy Enter the name

of the method.

Enter the outline of the method and the implementation period, etc. specifically.

7-4 Revision G: Entry Guide

Item Policy

Timing of revision Enter the plan, such as to start the revision work in certain years after publication or to revise according to the change in the trend of the medical care.

Method of revision Enter the method, such as a complete revision and a partial revision, as a method of revision.

Organization of revision Enter whether a Guideline Development Group, etc. will be newly organized or the same organization will respond continuously.

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A collection of templates

S: Templates included in the scope R: Templates included in the systematic review report (SR report) G: Templates for clinical practice guidelines* O: Templates for operation

*: Clinical practice guidelines will be published by combining the scope and the SR report together.

• The Excel or Word versions of the blank templates included in this collection of templates will also be published in GUIDE (http://Minds.jcqhc.or.jp/guide/pages/GuideTopHome.aspx).

• The size of each template can be changed as needed.

95


S: Templates included in the scope R: Templates included in the systematic review report (SR report) G: Templates for clinical practice guidelines* O: Templates for operation

*: Clinical practice guidelines will be published by combining the scope and the SR report together.

• The Excel or Word versions of the blank templates included in this collection of templates will also be published in GUIDE (http://Minds.jcqhc.or.jp/guide/pages/GuideTopHome.aspx).

• The size of each template can be changed as needed.

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2-1 Procedures and Schedule for Guideline Development O

Time schedule

Clarification of development purpose



Scope development

Systematic review




Publication


Revision

Date:

Date:

Date:

Date:

Date:

Date:

Date:

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2-1 Procedures and Schedule for Guideline Development O

Time schedule

Clarification of development purpose



Scope development

Systematic review




Publication


Revision

Date:

Date:

Date:

Date:

Date:

Date:

Date:

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2-2 Preparation for CPG Development G Organization for Developing Clinical Practice Guideline (CPG)






(2) Guideline Executive Committee

Chairperson (indicate by X) Name Affiliated

organization/specialty Affiliated medical

society Role in CPG development

(3) Secretariat









Name Affiliated organization/specialty

Affiliated scientific/medical

society




society

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2-2 Preparation for CPG Development G Organization for Developing Clinical Practice Guideline (CPG)






(2) Guideline Executive Committee




(3) Secretariat











society




society

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2-3 Funds for Guideline Development O

Cost item Budget Funder Remarks

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2-3 Funds for Guideline Development O

Cost item Budget Funder Remarks

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2-4 COI report (1) – Declaration Form of Financial COI O


Name

Affiliation

I hereby declare the economic relationship with companies, organizations, or parties during the period between (date: / / ) and (date: / / ) in relation to the above clinical practice guideline as follows:





Remarks

Board member, Consultant Present/Absent Declarer/family

Stocks Present/Absent Declarer/family

Patent royalty Present/Absent Declarer/family

Lecture fee Present/Absent Declarer/family

Manuscript fee Present/Absent Declarer/family


Present/Absent Declarer



Endowed chair Present/Absent Declarer

Others ( )

Present/Absent Declarer/family

Date of declaration

:

Signature :

This form was compiled according to “The Guideline for Management of Conflict of Interest in Medical Research (February 2011)” issued by the Conflict of Interest Committee, Section of Clinical Medicine, the Japanese Association of Medical Sciences. *) Declaration criteria will be determined by the Guideline Executive Committee.

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2-4 COI report (1) – Declaration Form of Financial COI O


Name

Affiliation

I hereby declare the economic relationship with companies, organizations, or parties during the period between (date: / / ) and (date: / / ) in relation to the above clinical practice guideline as follows:





Remarks

Board member, Consultant Present/Absent Declarer/family

Stocks Present/Absent Declarer/family

Patent royalty Present/Absent Declarer/family

Lecture fee Present/Absent Declarer/family

Manuscript fee Present/Absent Declarer/family





Endowed chair Present/Absent Declarer

Others ( )

Present/Absent Declarer/family

Date of declaration

:

Signature :

This form was compiled according to “The Guideline for Management of Conflict of Interest in Medical Research (February 2011)” issued by the Conflict of Interest Committee, Section of Clinical Medicine, the Japanese Association of Medical Sciences. *) Declaration criteria will be determined by the Guideline Executive Committee.

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2-5 COI Report (2) – Summary of Financial COI Declaration and Response Policy O

COI report



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2-5 COI Report (2) – Summary of Financial COI Declaration and Response Policy O

COI report



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3-1 Basic Characteristics of Health Topic S




3-2 Clinical Practice Flowchart (Fig.) S

Clinical practice flowchart (Fig.)

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3-1 Basic Characteristics of Health Topic S




3-2 Clinical Practice Flowchart (Fig.) S

Clinical practice flowchart (Fig.)

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3-3 Scope S

1. Items regarding the contents to be covered by CPG

(1) Title

(2) Objective

(3) Topic




Key clinical issue 1: Key clinical issue 2: Key clinical issue 3: ⋮ ⋮



CQ1: CQ2: CQ3: ⋮ ⋮

2. Items Regarding Systematic Review

(1) Schedule




3. Items from Formulation of Recommendations to Finalization and Publication of CPG

(1) Basic policy for formulating recommendations

(2) Finalization of CPG


(4) Publication of CPG

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3-3 Scope S

1. Items regarding the contents to be covered by CPG

(1) Title

(2) Objective

(3) Topic




Key clinical issue 1: Key clinical issue 2: Key clinical issue 3: ⋮ ⋮



CQ1: CQ2: CQ3: ⋮ ⋮

2. Items Regarding Systematic Review

(1) Schedule




3. Items from Formulation of Recommendations to Finalization and Publication of CPG

(1) Basic policy for formulating recommendations

(2) Finalization of CPG


(4) Publication of CPG

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3-4 Formulation of Clinical Question (CQ) O

Key clinical issues covered by scope


Sex (Not specified/male/female) Age (Not specified/___ __)


Geographical constraint


List of O (outcomes) Outcome Benefit or harm Score of

Importance Adopt or

not O1 (Benefit/harm) ___ point(s) O2 (Benefit/harm) ___ point(s) O3 (Benefit/harm) ___ point(s) O4 (Benefit/harm) ___ point(s) O5 (Benefit/harm) ___ point(s) O6 (Benefit/harm) ___ point(s) O7 (Benefit/harm) ___ point(s) O8 (Benefit/harm) ___ point(s) O9 (Benefit/harm) ___ point(s) O10 (Benefit/harm) ___ point(s) O11 (Benefit/harm) ___ point(s) O12 (Benefit/harm) ___ point(s) O13 (Benefit/harm) ___ point(s) O14 (Benefit/harm) ___ point(s) O15 (Benefit/harm) ___ point(s)

Formulated CQ

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3-4 Formulation of Clinical Question (CQ) O

Key clinical issues covered by scope


Sex (Not specified/male/female) Age (Not specified/___ __)


Geographical constraint


List of O (outcomes) Outcome Benefit or harm Score of

Importance Adopt or

not O1 (Benefit/harm) ___ point(s) O2 (Benefit/harm) ___ point(s) O3 (Benefit/harm) ___ point(s) O4 (Benefit/harm) ___ point(s) O5 (Benefit/harm) ___ point(s) O6 (Benefit/harm) ___ point(s) O7 (Benefit/harm) ___ point(s) O8 (Benefit/harm) ___ point(s) O9 (Benefit/harm) ___ point(s) O10 (Benefit/harm) ___ point(s) O11 (Benefit/harm) ___ point(s) O12 (Benefit/harm) ___ point(s) O13 (Benefit/harm) ___ point(s) O14 (Benefit/harm) ___ point(s) O15 (Benefit/harm) ___ point(s)

Formulated CQ

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4-1 Results of Database Search R

Title:

CQ:

Database:

Date:

Searcher:

# Search Formula Hits

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4-1 Results of Database Search R

Title:

CQ:

Database:

Date:

Searcher:

# Search Formula Hits

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4-2 Flowchart of Literature Search R

NGC NICE PubMed Cochrane Ichushi-Web EMBASE WHO PsycINFO® CINAHL Others ( )

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4-2 Flowchart of Literature Search R

NGC NICE PubMed Cochrane Ichushi-Web EMBASE WHO PsycINFO® CINAHL Others ( )

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4-3 List after the Secondary Screening R

Citation Study design P I C O

Exclusion

Comments

4-4 List of Cited Literature R

Adopted reports

Excluded reports

Other cited reports

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4-3 List after the Secondary Screening R

Citation Study design P I C O

Exclusion

Comments

4-4 List of Cited Literature R

Adopted reports

Excluded reports

Other cited reports

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4-5 Evaluation Sheet for Interventional Study R

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4-5 Evaluation Sheet for Interventional Study R

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4-6 Evaluation Sheet for Observational Study R

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4-6 Evaluation Sheet for Observational Study R

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4-7 Evaluation Sheet for the Body of Evidence R

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4-7 Evaluation Sheet for the Body of Evidence R

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4-8 Qualitative Systematic Review R

CQ Identifier ( )

P

I

C

Clinical context

O1




Comments

O2

O3

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CQ Identifier ( )

P

I

C

Clinical context

O1




Comments

O2

O3

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4-9 Meta-analysis R

CQ

P I

C O

Study design

Number of studies

Code

Model Method

Effect measures

Integrated value

( - ) p =

Forest plot

Comments:

Funnel plot

Comments:


analyses

Comments:

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4-9 Meta-analysis R

CQ

P I

C O

Study design

Number of studies

Code

Model Method

Effect measures

Integrated value

( - ) p =

Forest plot

Comments:

Funnel plot

Comments:


analyses

Comments:

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4-10 Summary of Systematic Review Report R

4-11 Future Research Question R

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4-10 Summary of Systematic Review Report R

4-11 Future Research Question R

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5-1 A Draft of A Recommendation O

1. CQ

2. Draft of recommendation

3. Values and preferences of members of Guideline Development Group related to the recommendation



5. Items to be assessed to determine the strength of recommendation

1) Factors affecting the determination of strength of recommendation Assessment Explanation

(a) Overall evidence across outcomes is strong • The stronger the overall evidence across outcomes is,


• In contrast, the weaker the overall evidence is, the more likely recommendations will be considered to be “weak.”

□ Yes □ No

(b) Certainty of the balance between benefit and harm • As the difference between the desirable effect and the


• As the net benefit becomes smaller and the adverse events become greater, the certainty of benefit becomes lower and the recommendation is more likely to be labeled as weak.

□ Yes □ No

2) Other factors to be considered to determine the strength of recommendation


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5-1 A Draft of A Recommendation O

1. CQ

2. Draft of recommendation

3. Values and preferences of members of Guideline Development Group related to the recommendation



5. Items to be assessed to determine the strength of recommendation

1) Factors affecting the determination of strength of recommendation Assessment Explanation

(a) Overall evidence across outcomes is strong • The stronger the overall evidence across outcomes is,


• In contrast, the weaker the overall evidence is, the more likely recommendations will be considered to be “weak.”

□ Yes □ No

(b) Certainty of the balance between benefit and harm • As the difference between the desirable effect and the


• As the net benefit becomes smaller and the adverse events become greater, the certainty of benefit becomes lower and the recommendation is more likely to be labeled as weak.

□ Yes □ No

2) Other factors to be considered to determine the strength of recommendation


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5-2 Ballot for Determination of Strength of Recommendation O

CQ:

Recommendation:


• Strongly recommend to perform • Weakly recommend (propose) to perform • Weakly recommend (propose) not to perform • Strongly recommend not to perform

5-3 Presentation of A Recommendation G

CQ:

Recommendation:

Strength of recommendation (Circle either one)

1 (Strong): recommend to “perform” or “not to perform” 2 (Weak): propose to “perform” or “not to perform”

5-4 Development Process of A Recommendation G

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CQ:

Recommendation:


• Strongly recommend to perform • Weakly recommend (propose) to perform • Weakly recommend (propose) not to perform • Strongly recommend not to perform

5-3 Presentation of A Recommendation G

CQ:

Recommendation:

Strength of recommendation (Circle either one)

1 (Strong): recommend to “perform” or “not to perform” 2 (Weak): propose to “perform” or “not to perform”

5-4 Development Process of A Recommendation G

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5-5 Summary for the Public G

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5-5 Summary for the Public G

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6-1 Guidelines Summary G

Guidelines summary

6-2 Definition of Important Terms G

Term Explanation

6-3 List of Abbreviations G

Abbreviation Formal Name

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6-1 Guidelines Summary G

Guidelines summary

6-2 Definition of Important Terms G

Term Explanation

6-3 List of Abbreviations G

Abbreviation Formal Name

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6-4 Development Process G

Item Text

Development policy

Precautions for use

Development funds

Conflict of interest





(Add if other committees are organized)

Development process

Preparation

Scope

Systematic reviews

Formulation of Recommendations

Finalization

Publication

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6-4 Development Process G

Item Text

Development policy

Precautions for use

Development funds

Conflict of interest





(Add if other committees are organized)

Development process

Preparation

Scope

Systematic reviews

Formulation of Recommendations

Finalization

Publication

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6-5 Response to External Review O

No. Review date Version

Reviewer (affiliation/post) Organization

Review comments

Response comments

Response date

6-6 Summary of External Review G

Purpose

Method

Version Period Reviewers Tool Others

Process

Results

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6-5 Response to External Review O

No. Review date Version

Reviewer (affiliation/post) Organization

Review comments

Response comments

Response date

6-6 Summary of External Review G

Purpose

Method

Version Period Reviewers Tool Others

Process

Results

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7-1 Organizational Issues after Publication G

Name of the system Plan after publication




7-2 Implementation G

Development of summary version


Promoters and barriers for the utilization of clinical practice guideline

7-3 Effectiveness Assessment G

Assessment method Specific policy

7-4 Revision G

Item Policy

Timing of revision

Method of revision

Organization of revision

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Name of the system Plan after publication




7-2 Implementation G

Development of summary version


Promoters and barriers for the utilization of clinical practice guideline

7-3 Effectiveness Assessment G

Assessment method Specific policy

7-4 Revision G

Item Policy

Timing of revision

Method of revision

Organization of revision

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Literature

AGREE Next Steps Consortium. The AGREE II Instrument [Electronic version]. 2009. Retrieved February 28, 2013, from http://www.agreetrust.org.

Aihara M, et al. GRADE System for Clinical Practice Guidelines. Therapeutic Intervention. Toppan Media, Hirosaki, 2010.

AMSTAR (Assessment of Multiple Systematic Reviews). Available from http://www.nccmt.ca/ registry/view/eng/97.html ()

Bernard L, Marilyn JF (eds.). Conflict of Interest in Medical Research, Education, and Practice. National Academies Press, Washington, DC, 2009.

Clancy CM, Slutsky J, Chang S, (eds.). Methods Guide for Effectiveness and Comparative Effectiveness Reviews. AHRQ Publication No. 10 (12)-EHC063-EF. Rockville, MD, April 2012. Available from http://www.effectivehealthcare. ahrq.gov ()

The COI committee, Clinical Division, Japanese Association of Medical Sciences. Guidelines on the Management of Conflict of Interest (COI) in Medical Research. 2011. Available from http://jams.med.or.jp/guideline/index.html ()

Eden J, Levit L, Berg A, et al. (eds.). Finding What Works in Health Care: Standards for Systematic Reviews. National Academies Press, Washington, DC, 2011.

Field, MJ, Lohr, KN (eds.). Clinical Practice Guidelines: Directions for a New Program. National Academies Press, Washington, DC, 1990.

Fink A, Kosecoff J, Chassin M, et al. Consensus Methods: Characteristics and Guidelines for Use. Am J Public Health 74:979–983, 1984.

G-I-N PUBLIC. G-I-N PUBLIC Toolkit: Patient and Public Involvement in Guidelines, 2012. Available from http://www.g-i-n. net/activities/ginpublic/toolkit ()

The Grading of Recommendations Assessment, Development and Evaluation (GRADE). Available from http://www.gradeworkinggroup.org/ ()

Graham R, Mancher M, Wolman DM, et al. (eds.). Clinical Practice Guidelines We Can Trust. National Academies Press, Washington, DC, 2011.

Higgins JPT, Green S (eds.). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. Available from http://handbook.cochrane. org/ ()

ICMJE (International Committee of Medical Journal Editors). Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication. Available from http://www.icmje.org/ ()

Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA Statement for Reporting Systematic Reviews and Meta-analyses of Studies that Evaluate Health Care Interventions: Explanation and Elaboration. PLoS Med 6:e1000100, 2009.

Lo B, Field MJ (eds.). Conflict of Interest in Medical Research, Education, and Practice. National Academies Press, Washington, DC, 2009.

The Ministry of Health, Labour and Welfare. Guidelines on the Management of Conflict of Interest (COI) in Health and Labour Science Research. 2008. Available from http://www.mhlw.go.jp/stf/seisakunitsuite/bunya/hokabunya/kenkyujigyou/i-kenkyu/index.html/ ()

NICE (National Institute for Health and Care Excellence). Factsheet 2: How Organisations Representing Patients and Carers Can Get Involved. In: Factsheets for Patients and Carers: Contributing to a NICE Clinical Guideline. NICE, London, 2013.

NICE (National Institute for Health and Care Excellence). The Guidelines Manual: Process and Methods Guide. NICE, London, 2012.

Oxford Center for Evidence Based Medicine. OCEBM Levels of Evidence System, 2011. Available from http://www.cebm.net/?o=5653 ()

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Available from http://www.prismastatement.org/statement.htm ()

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AGREE Next Steps Consortium. The AGREE II Instrument [Electronic version]. 2009. Retrieved February 28, 2013, from http://www.agreetrust.org.

Aihara M, et al. GRADE System for Clinical Practice Guidelines. Therapeutic Intervention. Toppan Media, Hirosaki, 2010.

AMSTAR (Assessment of Multiple Systematic Reviews). Available from http://www.nccmt.ca/ registry/view/eng/97.html ()

Bernard L, Marilyn JF (eds.). Conflict of Interest in Medical Research, Education, and Practice. National Academies Press, Washington, DC, 2009.

Clancy CM, Slutsky J, Chang S, (eds.). Methods Guide for Effectiveness and Comparative Effectiveness Reviews. AHRQ Publication No. 10 (12)-EHC063-EF. Rockville, MD, April 2012. Available from http://www.effectivehealthcare. ahrq.gov ()

The COI committee, Clinical Division, Japanese Association of Medical Sciences. Guidelines on the Management of Conflict of Interest (COI) in Medical Research. 2011. Available from http://jams.med.or.jp/guideline/index.html ()

Eden J, Levit L, Berg A, et al. (eds.). Finding What Works in Health Care: Standards for Systematic Reviews. National Academies Press, Washington, DC, 2011.

Field, MJ, Lohr, KN (eds.). Clinical Practice Guidelines: Directions for a New Program. National Academies Press, Washington, DC, 1990.

Fink A, Kosecoff J, Chassin M, et al. Consensus Methods: Characteristics and Guidelines for Use. Am J Public Health 74:979–983, 1984.

G-I-N PUBLIC. G-I-N PUBLIC Toolkit: Patient and Public Involvement in Guidelines, 2012. Available from http://www.g-i-n. net/activities/ginpublic/toolkit ()

The Grading of Recommendations Assessment, Development and Evaluation (GRADE). Available from http://www.gradeworkinggroup.org/ ()

Graham R, Mancher M, Wolman DM, et al. (eds.). Clinical Practice Guidelines We Can Trust. National Academies Press, Washington, DC, 2011.

Higgins JPT, Green S (eds.). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. The Cochrane Collaboration, 2011. Available from http://handbook.cochrane. org/ ()

ICMJE (International Committee of Medical Journal Editors). Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication. Available from http://www.icmje.org/ ()

Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA Statement for Reporting Systematic Reviews and Meta-analyses of Studies that Evaluate Health Care Interventions: Explanation and Elaboration. PLoS Med 6:e1000100, 2009.

Lo B, Field MJ (eds.). Conflict of Interest in Medical Research, Education, and Practice. National Academies Press, Washington, DC, 2009.

The Ministry of Health, Labour and Welfare. Guidelines on the Management of Conflict of Interest (COI) in Health and Labour Science Research. 2008. Available from http://www.mhlw.go.jp/stf/seisakunitsuite/bunya/hokabunya/kenkyujigyou/i-kenkyu/index.html/ ()

NICE (National Institute for Health and Care Excellence). Factsheet 2: How Organisations Representing Patients and Carers Can Get Involved. In: Factsheets for Patients and Carers: Contributing to a NICE Clinical Guideline. NICE, London, 2013.

NICE (National Institute for Health and Care Excellence). The Guidelines Manual: Process and Methods Guide. NICE, London, 2012.

Oxford Center for Evidence Based Medicine. OCEBM Levels of Evidence System, 2011. Available from http://www.cebm.net/?o=5653 ()

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Available from http://www.prismastatement.org/statement.htm ()

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PROSPERO (International Prospective Register of Systematic Reviews). Available from http://www.crd.york.ac.uk/PROSPERO/ ()

Shea BJ, Grimshaw JM, Wells GA, et al. Development of AMSTAR: A Measurement Tool to Assess the Methodological Quality of Systematic Reviews. BMC Med Res Methodol 7:10, 2007.

Shekelle PG, Ortiz E, Rhodes S, et al. Validity of the Agency for Healthcare Research and Quality Clinical Practice Guidelines: How Quickly Do Guidelines Become Outdated? JAMA 286:1461–1467, 2001.

Shiffman RN, Dixon J, Brandt C, et al. The GuideLine Implementability Appraisal (GLIA): Development of an Instrument to Identify Obstacles to Guideline Implementation. BMC Med Inform Decis Mak 5:23, 2005.

Shiffman RN, Shekelle P, Overhage JM, et al. Standardized Reporting of Clinical Practice Guidelines: A Proposal from the Conference on Guideline Standardization. Ann Intern Med 139:493–498, 2003.

Shojania KG, Sampson M, Ansari MT, et al. How Quickly Do Systematic Reviews Go Out of Date? A Survival Analysis. Ann Intern Med 147:224–233, 2007.

SIGN (Scottish Intercollegiate Guidelines Network). SIGN 50: A Guideline Developer’s Handbook, Revised Edition. Scottish Intercollegiate Guidelines Network, Edinburgh, 2011.

WHO (World Health Organization). WHO Handbook for Guideline Development. WHO Press, Geneva, 2012.

Woolf SH. Practice Guidelines, A New Reality in Medicine. II. Methods of Developing Guidelines. Arch Intern Med 152:946–952, 1992.

mark: URL was confirmed on February 25, 2014

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109

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PROSPERO (International Prospective Register of Systematic Reviews). Available from http://www.crd.york.ac.uk/PROSPERO/ ()

Shea BJ, Grimshaw JM, Wells GA, et al. Development of AMSTAR: A Measurement Tool to Assess the Methodological Quality of Systematic Reviews. BMC Med Res Methodol 7:10, 2007.

Shekelle PG, Ortiz E, Rhodes S, et al. Validity of the Agency for Healthcare Research and Quality Clinical Practice Guidelines: How Quickly Do Guidelines Become Outdated? JAMA 286:1461–1467, 2001.

Shiffman RN, Dixon J, Brandt C, et al. The GuideLine Implementability Appraisal (GLIA): Development of an Instrument to Identify Obstacles to Guideline Implementation. BMC Med Inform Decis Mak 5:23, 2005.

Shiffman RN, Shekelle P, Overhage JM, et al. Standardized Reporting of Clinical Practice Guidelines: A Proposal from the Conference on Guideline Standardization. Ann Intern Med 139:493–498, 2003.

Shojania KG, Sampson M, Ansari MT, et al. How Quickly Do Systematic Reviews Go Out of Date? A Survival Analysis. Ann Intern Med 147:224–233, 2007.

SIGN (Scottish Intercollegiate Guidelines Network). SIGN 50: A Guideline Developer’s Handbook, Revised Edition. Scottish Intercollegiate Guidelines Network, Edinburgh, 2011.

WHO (World Health Organization). WHO Handbook for Guideline Development. WHO Press, Geneva, 2012.

Woolf SH. Practice Guidelines, A New Reality in Medicine. II. Methods of Developing Guidelines. Arch Intern Med 152:946–952, 1992.

mark: URL was confirmed on February 25, 2014

123

124 124

References

125

References

125

112

References

Reference 1 Systematic Review protocol

Item Entries Note Target Literature Database

PubMed/MEDLINE Ichushi-Web The Cochrane Library Others ( )

Hand Search Not performed Performed Target medical journals: Method:

Grey Literature

Not adopted Adopted Target studies: Abstracts Proceedings Team meeting materials in the MHLW Administrative materials Others ( )

Selection Method Primary screening: Secondary screening: Coping with inconsistency:

Data Extraction Method

Classification of Study Design

RCT, non-randomized controlled trial (non-RCT), cohort study, case-control study, cross-sectional study, case series, case report, others ( )

Risk of Bias Assessed by

Individual Studies and Other

Assessment Items

Selection bias (randomization, concealment) Implementation bias (blinding) Detection bias (blinding) Attrition bias (incomplete outcome reports) Others (selective outcome reports) Indirectness (PICO)

Assessment Method of Each Item and Classification of

Results

For each domain: 3 steps of high, medium/suspected, and low For summary: 3 steps of high, medium, and low

Assessment Items of Body of Evidence

Risk of bias, inconsistency, imprecision, publication bias

Meta-Analysis Method

Randomized effects model, fixed effects model, others (specific names)

Effect Indicators Used

Risk ratio, odds ratio, risk difference (rate difference), NNT, rate, sensitivity, specificity, proper diagnosis rate, etc.

Associated Analyses Sensitivity analysis Meta-regression Others ( )

Presentation Method of the Results of Meta-Analyses

Effect indicator values and 95% confidence interval Forest plot Funnel plot Others ( )

126

112

References

Reference 1 Systematic Review protocol

Item Entries Note Target Literature Database

PubMed/MEDLINE Ichushi-Web The Cochrane Library Others ( )

Hand Search Not performed Performed Target medical journals: Method:

Grey Literature

Not adopted Adopted Target studies: Abstracts Proceedings Team meeting materials in the MHLW Administrative materials Others ( )

Selection Method Primary screening: Secondary screening: Coping with inconsistency:

Data Extraction Method

Classification of Study Design

RCT, non-randomized controlled trial (non-RCT), cohort study, case-control study, cross-sectional study, case series, case report, others ( )

Risk of Bias Assessed by

Individual Studies and Other

Assessment Items

Selection bias (randomization, concealment) Implementation bias (blinding) Detection bias (blinding) Attrition bias (incomplete outcome reports) Others (selective outcome reports) Indirectness (PICO)

Assessment Method of Each Item and Classification of

Results

For each domain: 3 steps of high, medium/suspected, and low For summary: 3 steps of high, medium, and low

Assessment Items of Body of Evidence

Risk of bias, inconsistency, imprecision, publication bias

Meta-Analysis Method

Randomized effects model, fixed effects model, others (specific names)

Effect Indicators Used

Risk ratio, odds ratio, risk difference (rate difference), NNT, rate, sensitivity, specificity, proper diagnosis rate, etc.

Associated Analyses Sensitivity analysis Meta-regression Others ( )

Presentation Method of the Results of Meta-Analyses

Effect indicator values and 95% confidence interval Forest plot Funnel plot Others ( )

126

113

References

Reference 2 Main database for guidelines search

Database Organization Country URL Browsing requirements

National Guideline Clearinghouse (NGC)

Agency for Healthcare Research and Quality (AHRQ)

The U.S.A. http://guideline.gov/

NICE Evidence Search National Institute for Health and Care Excellence (NICE)

The U.K. http://www.evidence.nhs.uk/

International Guidelines Database

Guidelines International Network (G-I-N)

International organization

http://www.g-i-n.net/ Contract required

MINDS Guidelines Center

Japan Council for Quality Health Care

Japan http://Minds.jcqhc.or.jp/n/

Reference 3 Bibliographic database

Importance Database URL Browsing requirements

Essential

PubMed http://www.ncbi.nlm.nih.gov/pubmed MEDLINE http://gateway.ovid.com/autologin.html Contract

required The Cochrane Library http://www.thecochranelibrary.com/view/0/index.html Contract

required for full-text reference

Ichushi-Web http://www.jamas.or.jp/ Contract required

Important

EMBASE http://www.embase.com/ Contract required

PsycINFOⓇ http://www.apa.org/pubs/databases/psycinfo/index.aspx Contract required

CINAHL http://www.ebscohost.com/ Contract required

JMEDPlus http://jdream3.com/ Contract required

Other information

sources

Grey Literature Report http://www.greylit.org/home (New York Academy of Sciences)

Open Gray http://www.opengrey.eu/ Clinical Trials.gov http://clinicaltrials.gov/ Virtual Health Library http://regional.bvsalud.org/php/index.php?lang=en WHO http://apps.who.int/trialsearch/ UMIN Clinical Trial Register

http://www.umin.ac.jp/ctr/index-j.htm

National Institute of Public Health

http://rctportal.niph.go.jp/ Clinical study (trial) information search

127

113

References

Reference 2 Main database for guidelines search

Database Organization Country URL Browsing requirements

National Guideline Clearinghouse (NGC)

Agency for Healthcare Research and Quality (AHRQ)

The U.S.A. http://guideline.gov/

NICE Evidence Search National Institute for Health and Care Excellence (NICE)

The U.K. http://www.evidence.nhs.uk/

International Guidelines Database

Guidelines International Network (G-I-N)

International organization

http://www.g-i-n.net/ Contract required

MINDS Guidelines Center

Japan Council for Quality Health Care

Japan http://Minds.jcqhc.or.jp/n/

Reference 3 Bibliographic database

Importance Database URL Browsing requirements

Essential

PubMed http://www.ncbi.nlm.nih.gov/pubmed MEDLINE http://gateway.ovid.com/autologin.html Contract

required The Cochrane Library http://www.thecochranelibrary.com/view/0/index.html Contract

required for full-text reference

Ichushi-Web http://www.jamas.or.jp/ Contract required

Important

EMBASE http://www.embase.com/ Contract required

PsycINFOⓇ http://www.apa.org/pubs/databases/psycinfo/index.aspx Contract required

CINAHL http://www.ebscohost.com/ Contract required

JMEDPlus http://jdream3.com/ Contract required

Other information

sources

Grey Literature Report http://www.greylit.org/home (New York Academy of Sciences)

Open Gray http://www.opengrey.eu/ Clinical Trials.gov http://clinicaltrials.gov/ Virtual Health Library http://regional.bvsalud.org/php/index.php?lang=en WHO http://apps.who.int/trialsearch/ UMIN Clinical Trial Register

http://www.umin.ac.jp/ctr/index-j.htm

National Institute of Public Health

http://rctportal.niph.go.jp/ Clinical study (trial) information search

127

114

References

Reference 4 Plan of benefit search

Examples of search on the outcome of benefit are shown below:

CQ: Is rt-PA administration (intervention) within 6 hours of onset recommended in patients younger than 80 years with acute cerebral embolism 3 hours or more after onset?

PubMed search examples <benefit search> Date of search: 2013/11/02

#1 “acute ischemic stroke” [TIAB] 6,037 #2 “acute ischaemic stroke” [TIAB] 1,144 #3 “Brain Ischemia” [Mesh] 78,210 #4 “Stroke” [Mesh] 78,704 #5 #1 OR #2 OR #3 OR #4 120,577 #6 “Tissue Plasminogen Activator” [Mesh] 14,657 #7 rt-pa [TIAB] 1,918 #8 alteplase [TW] 1,139 #9 #6 OR #7 OR #8 15,508 #10 #5 AND #9 3,476 #11 #10 AND (Meta-Analysis [PT] OR systematic [SB]) 185 #12 #10 AND “Randomized Controlled Trial” [PT] 174 #13 #11 OR #12 354

128

114

References

Reference 4 Plan of benefit search

Examples of search on the outcome of benefit are shown below:

CQ: Is rt-PA administration (intervention) within 6 hours of onset recommended in patients younger than 80 years with acute cerebral embolism 3 hours or more after onset?

PubMed search examples <benefit search> Date of search: 2013/11/02

#1 “acute ischemic stroke” [TIAB] 6,037 #2 “acute ischaemic stroke” [TIAB] 1,144 #3 “Brain Ischemia” [Mesh] 78,210 #4 “Stroke” [Mesh] 78,704 #5 #1 OR #2 OR #3 OR #4 120,577 #6 “Tissue Plasminogen Activator” [Mesh] 14,657 #7 rt-pa [TIAB] 1,918 #8 alteplase [TW] 1,139 #9 #6 OR #7 OR #8 15,508 #10 #5 AND #9 3,476 #11 #10 AND (Meta-Analysis [PT] OR systematic [SB]) 185 #12 #10 AND “Randomized Controlled Trial” [PT] 174 #13 #11 OR #12 354

128

115

References

Reference 5 Revision review sheet

Key clinical issues

Review items

Is there any change in the items below? Evidence on benefit and harm of intervention Important outcome Change in possible interventions Evidence showing that the current clinical practice is optimal Value toward the outcome Resources available for healthcare *If any of the above items is checked, enter the reason(s) below:

Necessity of revision

Revision required Revision not required *If any of the above items is checked, enter the reason(s) below:

129

115

References

Reference 5 Revision review sheet

Key clinical issues

Review items

Is there any change in the items below? Evidence on benefit and harm of intervention Important outcome Change in possible interventions Evidence showing that the current clinical practice is optimal Value toward the outcome Resources available for healthcare *If any of the above items is checked, enter the reason(s) below:

Necessity of revision

Revision required Revision not required *If any of the above items is checked, enter the reason(s) below:

129

130 130

Index

131

Index

131

118

INDEX

A

academic COI, 5, 11 AGREE II (The Appraisal of

Guidelines for Research & Evaluation II), 67

applicability, 75 Attrition bias, 36

B

balance between benefits and harms, 5, 53

Basic characteristics of the health topic, 20

Bias of selective outcome report, 36

Bias of trial stopping, 36 body of evidence, 5, 34

C

CINAHL®, 32 clinical practice flowchart, 21 clinical question, 3, 22 cost, 54

D

Database for literature search, 32 Delphi method, 55 Detection bias, 36

E

effectiveness assessment, 78 EMBASE, 32 evaluation of the body of

evidence, 34 evaluation sheet, 34

expert panel, 55 External review, 66 External Review Committee, 10

F

finalization, 62 financial COI, 5, 11 fixed effects model, 38 Formal consensus method, 55 funds to develop clinical

practice guidelines, 10 future research question, 39

G

GRADE, 39 guideline development group, 3,

9 Guideline Executive Committee,

3, 9 Guideline summary, 62

I

Ichushi-Web, 32 Identifying the Evidence, 32 Implementation, 75 Imprecision, 36 Inconsistency, 36 Indirectness, 36 Informal consensus method, 56 integration of the body of

evidence, 37

J

JMEDPlus, 32

K

Key clinical issues, 22

L

Literature management, 33

M

MEDLINE, 32 meta-analysis, 30, 38 metafor, 38

N

NIH consensus development conferences, 55

Nominal group technique (NGT) method, 55

O

Organizational COI, 12 outcome, 23 Outcome Importance, 24 Overview of Systematic Review,

30

P

Performance bias, 35 Personal COI, 11 PICO, 23 Primary screening, 33 PRISMA, 33 procedure for the external review, 67 PROSPERO, 32 PsycINFO®, 32 public comment, 66

132

118

INDEX

A

academic COI, 5, 11 AGREE II (The Appraisal of

Guidelines for Research & Evaluation II), 67

applicability, 75 Attrition bias, 36

B

balance between benefits and harms, 5, 53

Basic characteristics of the health topic, 20

Bias of selective outcome report, 36

Bias of trial stopping, 36 body of evidence, 5, 34

C

CINAHL®, 32 clinical practice flowchart, 21 clinical question, 3, 22 cost, 54

D

Database for literature search, 32 Delphi method, 55 Detection bias, 36

E

effectiveness assessment, 78 EMBASE, 32 evaluation of the body of

evidence, 34 evaluation sheet, 34

expert panel, 55 External review, 66 External Review Committee, 10

F

finalization, 62 financial COI, 5, 11 fixed effects model, 38 Formal consensus method, 55 funds to develop clinical

practice guidelines, 10 future research question, 39

G

GRADE, 39 guideline development group, 3,

9 Guideline Executive Committee,

3, 9 Guideline summary, 62

I

Ichushi-Web, 32 Identifying the Evidence, 32 Implementation, 75 Imprecision, 36 Inconsistency, 36 Indirectness, 36 Informal consensus method, 56 integration of the body of

evidence, 37

J

JMEDPlus, 32

K

Key clinical issues, 22

L

Literature management, 33

M

MEDLINE, 32 meta-analysis, 30, 38 metafor, 38

N

NIH consensus development conferences, 55

Nominal group technique (NGT) method, 55

O

Organizational COI, 12 outcome, 23 Outcome Importance, 24 Overview of Systematic Review,

30

P

Performance bias, 35 Personal COI, 11 PICO, 23 Primary screening, 33 PRISMA, 33 procedure for the external review, 67 PROSPERO, 32 PsycINFO®, 32 public comment, 66

132

119

Publication bias, 36 PubMed, 32

Q

QI, 78 Qualitative systematic review,

30, 37 quality indicators (QIs), 78 Quantitative systematic review,

30, 38

R

random effects model, 38 Revision, 79 RevMan, 35, 38 Risk of bias, 35

S

scope, 20 scoping search, 32 Screening, 33 Secondary screening, 33 Secretariat of Guideline

Development, 9 Selection bias, 35 Software for meta-analysis, 38 strength of evidence, 38 Summary for the public, 56 summary of the body of evidence,

52 surrogate, 78 Systematic Review protocol, 112 Systematic Review Report, 39 Systematic Review Team (SR

Team), 3, 10

T

the Cochrane Library, 32 the strength of recommendation, 52

U

Unbiasedness of Development Process, 4

V

Values, preferences, and burden of patients, 54

133

119

Publication bias, 36 PubMed, 32

Q

QI, 78 Qualitative systematic review,

30, 37 quality indicators (QIs), 78 Quantitative systematic review,

30, 38

R

random effects model, 38 Revision, 79 RevMan, 35, 38 Risk of bias, 35

S

scope, 20 scoping search, 32 Screening, 33 Secondary screening, 33 Secretariat of Guideline

Development, 9 Selection bias, 35 Software for meta-analysis, 38 strength of evidence, 38 Summary for the public, 56 summary of the body of evidence,

52 surrogate, 78 Systematic Review protocol, 112 Systematic Review Report, 39 Systematic Review Team (SR

Team), 3, 10

T

the Cochrane Library, 32 the strength of recommendation, 52

U

Unbiasedness of Development Process, 4

V

Values, preferences, and burden of patients, 54

133

134

134