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WWW.CIOMS.CH December 2018 | Newsletter # 24
International events
Stronger health systems in Asia Pacific The Asia Pacific region is an important hub for collaboration in the quest for universal health coverage. Dr Lembit Rägo, Secretary-General of CIOMS, participated in three events held on 3 October 2018 in Singapore to build regulatory capacity and encourage policy innovation in the region.
ASEAN Regulators’ Roundtable
The ASEAN Regulator’s Roundtable, hosted by the Duke-NUS Centre of Regulatory Excellence (CoRE), focused on good reliance practices (GRP) in regulation of medical products. GRP aims to promote confidence in the integrity of other regulators’ decisions in a more and more complex environment of technological advancement and public health emergencies. It is clear
that regulators have to rely increasingly on the decisions of other regulators, avoiding expensive duplicative efforts that have no added value.
Introductory presentations were given by Dr Neil McAuslane, Centre for Innovation in Regulatory Science (CIRS) and Dr Samvel Azatyan, World Health Organization (WHO). One of the objectives of the roundtable was to get further input for finalizing the WHO GRP guidelines, which focus on accelerating access to quality-assured health products.
CoRE Symposium 2018
The CoRE scientific symposium was centered around the topic of New visions for advancing regulatory science and public health. There were three keynote speakers: Dr Lembit Rägo, Dr Margaret Hamburg and
HIGHLIGHTS Stronger health systems in Asia Pacific 1 First international pharmacovigilance conference in Russia 2 China–CIOMS Forum on DILI 3 ICH Assembly 4 News from the CIOMS Working Groups 5 New translations available 8
From left to right: Professor John Lim (Executive Director of the CoRE Duke-NUS Medical School and Special Advisor to the Ministry of Health Singapore); Professor Sir Alasdair Breckenridge (Chairman of CoRE and former Chair of the UK Medicines and Healthcare products Regulatory Agency, MHRA); Dr Margaret Hamburg (Foreign Secretary of the U.S. National Academy of Medicine, Former Commissioner of the U .S. Food and Drug Administration and President Elect of the American Association for the Advancement of Science), Dr Ronald Piervincenzi, CEO of the United States Pharmacopeial Convention, and Dr Lembit Rägo (Secretary General of CIOMS), at the CoRE Symposium 2018 panel discussion.
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The Moscow pharmacovigilance conference brought together more than 600 experts from regulatory authorities, legislative and executive authorities of the Russian Federation, national and international organisations, medical and pharmaceutical industries and the patient community.
Dr Ronald Piervincenzi. Professor Sir Alasdair Breckenridge introduced the ensuing panel discussion with a presentation on “Advancing regulatory practice to increase patient involvement”.
Strengthening health systems in Asia-Pacific region
The Indo-Pacific Regulatory Strengthening Program (RSP) was launched on 3 October 2018 during a recep-tion at the Australian High Commissioner’s Residence in Singapore. The event was hosted by the Indo-Pacific Centre for Health Security and the Therapeutic Goods Administration (TGA) of Australia. The RSP partnership aims to strengthen registration processes and promote good regulatory practice in the region.
During his visit to Singapore Dr Rägo held discussions on a potential collaboration between CIOMS and CoRE.
First international pharmacovigilance conference in Russia
The International Conference on Pharmacovigilance: Challenges and opportunities was held in Moscow on 10 October 2018. The conference was organised by the regulatory authority of Russia (Roszdrav-nadzor) with sup-port from the Association of Inter-national Pharma-ceutical Manu-facturers (AIPM). At various sessions, workshops, round-table discussion and master classes the participants dis-cussed global trends and best practices to identify the most successful and effective approaches in pharmacovigilance and safety monitoring systems. Professor Hervé Le Louët, President of CIOMS, made a presentation on Global trends of pharmacovigilance in the 21st Century: current challenges and future horizons. He pointed out: “We need to go beyond spontaneous reporting and design systems that provide informed, evidence-based ‘signal anticipation’. This will require a more progressive view of data generated via
social media and other sources that present challenging signal-to-noise obstacles”1.
On the margins of the conference it was agreed to explore ways of strengthening collaboration between CIOMS and the Russian Federation as well as the other countries of the Eurasian Economic Union (EAEU), i.e. Kazakhstan, Kyrgyzstan, Armenia and Belarus.
Second from right: Professor Le Louët, President of CIOMS, at the Pharmacovigilance Conference in Russia.
CIOMS visit to Kyrgyzstan By invitation from the WHO country office Professor Hervé Le Louët and Dr Lembit Rägo visited the medi-cines regulatory authority of Kyrgyzstan. Two work-shops on pharmacovigilance for medical doctors with lectures from CIOMS officials were carried out in the capital city Bishkek and in the country’s second largest city Osh (“Capital of the South”). CIOMS also provided copies of several of its relevant guidelines to the national pharmacovigilance centre. Discussions to explore additional avenues of strengthening the country’s pharmacovigilance system were held with officials of the national regulatory authority to which the pharmacovigilance centre belongs. CIOMS officials emphasised their willingness to help developing pharmacovigilance system in Kyrgyzstan also in the future.
From left: Lembit Rägo and Hervé Le Louët, during their visit to the national medicines regulatory authority of Kyrgyzstan.
1 See also: Pitts PJ, Le Louet H. Advancing Drug Safety Through
Prospective Pharmacovigilance. Therapeutic Innovation & Regulatory Science. 2018; 52(4): 400-402.
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China–CIOMS Forum on DILI In the history of mankind, traditional medicines have made indelible contributions to the prevention and treatment of diseases. However, as traditional medicines are more widely used all over the world, new challenges are arising with their safe use.
The China-CIOMS Forum on Drug-Induced Liver Injury (DILI) was held in Beijing on 5 September 2018. The meeting was co-organised by the Traditional Chinese Medicines Clinical Pharmacology Committee of the China Pharmaceutical Association (CPA), the China National Center for Adverse Drug Reaction Monitoring, the Council for International Organizations of Medical Sciences (CIOMS), the Hepatobiliary Diseases Committee of the China Association of Chinese Medicine (CACM) and the Society of Hepatology of the Chinese Medical Association (CMA). The event aimed to raise awareness of safety challenges with traditional medicines, to strengthen safety research and surveillance, and to promote international collaboration and information-sharing.
It was the first meeting co-hosted by Chinese organisations and CIOMS in this field. The event was co-chaired by three professors and attended by many distinguished experts (see picture below).
Professors Björnsson, Andrade and Navarro presented the epidemiology of DILI and herb-induced liver injury (HILI) based on relevant registries. Professors Hai-bo Song and Jia-bo Wang reported on the risk management of HILI in China based on national
adverse drug reaction monitoring data and the active surveillance system for drug safety. They focused on new challenges posed by traditional medicines-related liver injury in China and proposed solutions for diagnosis and management.
After some spirited discussions the experts reached consensus on several important issues: establishing an international framework for information-sharing and collaboration, developing a search tool for safety information on traditional medicines, working towards internationally unified standards or guidelines for evaluation of traditional medicines-induced liver injury, sharing safety monitoring data and proposing risk minimisation activities. They also endorsed the Beijing Declaration on Safe Use of traditional medicines and discussed a number of action points. Finally, the presenting experts jointly launched the world's first Consortium for Safety Study of Traditional Medicines (CSSTM), which will have its secretariat at the China Military Institute of Chinese Medicine, Beijing 302 Hospital of China.
All experts expressed their interest in working together to speed up collaborative research on diagnosis, evaluation, prevention and control of traditional medicines-induced injuries, to promote international exchange and application of relevant guidelines, to support the safe use of traditional medicines, and to contribute to building a scientific community for their safe use.
Chairpersons of the China-CIOMS Forum on DILI (sitting, centre of picture): Professors Xiao-he Xiao (Chair of TCM Clinical Pharmacology Committee of CPA and Director of the China Military Institute of Chinese Medicine, Beijing 302 Hospital of China), Professor Hervé Le Louët (President of CIOMS and Head of the Pharmacovigilance Department of Paris University Hospital) and Victor Navarro (Chair of the AASLD Hepatotoxicity Special Interest Group and Chief of the Department of Digestive Disease & Transplantation of Albert Einstein Medical Center). Among the invited experts were Professors Raúl Andrade (Director of the Spanish DILI Registry and Director of the Department of Medicine at the University of Malaga; Group I Chair of the CIOMS DILI WG,), Einar Björnsson (Chief of Internal Medicine of the National University of Iceland; Group III Chair of the CIOMS DILI WG), Ikhlas Khan (Director of the National Center for Natural Products Research of Mississippi University, USA); Hai-bo Song (National Center for ADR Monitoring, China); Xiu-hui Li (Chair of the Hepatobiliary Diseases Committee of CACM and professor at the Beijing YouAn Hospital of Capital Medical University); Yi-min Mao (Chair, Chinese Society of Hepatology of CMA); Jian-yuan Tang (Chief, Clinical Department of Traditional Chinese Medicine, China National Center for Drug Evaluation); and Jia-bo Wang (Deputy director of the Military Institute of Chinese Medicine, Beijing 302 Hospital of China).
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News from CIOMS partners
ICH Assembly Charlotte, U.S., 17-18 November 2018
Delegates at the recent Assembly of the International Council for Harmonisation (ICH). Dr Lembit Rägo, attended the meeting on behalf of CIOMS, which joined ICH as an observer in 2016.
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is continuing its steady evolution to a more global initiative. The Council now has 16 members and 28 observers. The November Assembly marked the first face-to-face meeting of the expanded Management Committee, which newly includes the regulators of Singapore, Korea and China, as well as two industry members: the Biotechnology Innovation Organization (BIO) and the Internal Generic and Biosimilars Association (IGBA). Dr Theresa Mullin (U.S. FDA, and Member of the CIOMS Working Group on Patient Involvement) was re-elected for another year as ICH Management Committee Chair alongside newly elected Vice-Chair Dr Nobumasa Nakashima (MHLW/ PMDA, Japan).
The Council is considering strategic directions for harmonisation in numerous areas such as quality standards for generics, pharmacoepidemiological studies submitted to regulators for more effective use of real-world data, and a Clinical electronic Structured Harmonized Protocol (CeSHarP). ICH is offering various training activities to support a consistent approach to implementation of its guidelines. The outcomes of a survey on guideline implementation are expected to be published in the second half of 2019.
World Health Organization WHO Programme for International Drug
Monitoring turns 50 In the early 1960s, public reports of children born with underdeveloped limbs led to the discovery that the medicine thalidomide can cause birth defects. This discovery showed that pharmacovigilance – a rigorous system to monitor medical products on the market – is essential to patient safety.
On 5 November 2018 the WHO Programme for International Drug Monitoring (PIDM) celebrated its 50th Anniversary. Dr Lembit Rägo, Secretary-General of CIOMS, attended the event, which was marked on the first day of the 41st Annual Meeting of Representatives of National Pharmacovigilance Centres participating in the WHO PIDM.
From just ten founding members in 1968, the PIDM has grown to 133 full members today, covering more than 90% of the world’s population. Between them the members have submitted more than 12 million indi-vidual case safety reports (ICSRs) of adverse reactions associated with medicinal products to the WHO global database. Named VigiBase, this database is managed by the Uppsala Monitoring Centre (UMC).
A training session on the ICH’s Medical Dictionary for Regulatory Activities (MedDRA) was held as part of the WHO meeting. Close to 190 participants from 82 countries attended this session. (See also page 7 for an update on the CIOMS Implementation Working Group on Standardised MedDRA Queries).
European Medicines Agency (EMA) Good pharmacovigilance practices for the
paediatric population As part of its guidance on good pharmacovigilance practices (GVP) the EMA has published its Product- or Population-Specific Considerations IV: Paediatric Population. This chapter is based on a guideline published before GVP came into existence, and was finalised based on the outcomes of a public consultation held from August to October 2017. It is the first GVP chapter focussing on a specific population group.
70 Years – WHO 50 years – WHO-PIDM 40 years – UMC
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The Meds We Can Trust initiative CIOMS signs Oxford statement
CIOMS, along with other organisations, has signed the Oxford statement released in November 2018 on the Meds We Can Trust website. The statement affirms people’s right to safe, quality medicines and calls for collective action by a broad coalition of partners.
WHO estimates that one in every ten medical products circulating in low- and middle-income countries is substandard or falsified. No country is immune or protected. Globally, about US$30 billion are wasted each year on poor-quality medicines, with grave health consequences for hundreds of thousands of people. Left unchecked, poor quality medicines will reverse past progress on infectious and non-communicable diseases, erode trust in health care systems, and increase the threat of antimicrobial resistance.
Patient Solidarity Day 2018 International Alliance of Patients’ Organizations
(IAPO) calls for patient safety
On 7 December 2018, patient advocates from across the world united to call for ‘Global Safe Medication and Healthcare for All’.
Patients are the only ones who directly experience the benefits of medicines and suffer any medication-related harm. Often, they are the first to report unexpected adverse effects.
IAPO patient organizations are working with CIOMS to help ensure that patients have their say on the development and safe use of medicines (see also page 6).
News from the CIOMS Working GroupsClinical Research in Resource-Limited
Settings
3rd Working Group Meeting Tallinn, Estonia, 8-9 October 2018
Creating an environment conducive to clinical research is a must for any country that wishes its people to benefit fully from new therapies and vaccines. The CIOMS Working Group is developing pragmatic, consensus-based recommendations to support meaningful, good quality clinical research in resource-limited settings.
An open pre-meeting was held on the topic of Using electronic health records (EHR) for clinical research: can we do better? Six invited speakers shared their experiences and lessons learned in making use of data from electronic health records – which are designed for daily clinical practice – in research to learn more about the effectiveness of medical products in preventing or treating diseases.
Electronic health records are more and more widely used in health care systems, and yet it remains challenging to transform these healthcare data to into real-world evidence that will make all steps in the
development and use of pharmaceuticals more effective and effi-cient.2 The CIOMS Working Group plans to summarise the lessons learned worldwide in an appendix to its report. This will be useful and timely guidance for countries and donors planning to set up electronic health record systems for the first time.
More about this Working Groups and its meetings is found on the WHO website at https://cioms.ch/working_groups/clinical-research-rls/
2 Eichler HG, Bloechl-Daum B, Broich K et al. Data Rich, Information
Poor: Can We Use Electronic Health Records to Create a Learning Healthcare System for Pharmaceuticals? Clin. Pharmacol. Ther. doi:10.1002/cpt.1226
How should electronic health records be designed so that the data can be used for clinical research? The presentations from the CIOMS pre-meeting are can be accessed from here.
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Patient involvement in the development and safe use of medicines:
2nd Working Group Meeting Berlin, Germany, 23-24 October 2018
Patients are experts in what it is like to live with their conditions. Their voices are now increasingly heard whenever decisions are made in drug development and evaluation. The CIOMS Working Group XI is developing a report which aims to give an overview of patient initiatives globally and to provide guidance in areas where there is a need for consensus principles, notably in the post-marketing phase of medicines. The Working Group members represent patient organisations, companies and regulators with in-depth experience in this area. The U.S. Food and Drug Autho-
rity (FDA) is one of the regulatory authorities with an advanced pro-gramme for patient involvement. At the 2nd Working Group meeting, Dr Theresa Mullin, Associate Director for Strategic Initiatives of the FDA’s Center for Drug Evaluation and Research (CDER), gave some background about the FDA’s initiative to provide
new guidance on patient-focused drug development. The first of four new FDA texts was revised taking into account extensive user feedback. This has resulted in a much clearer guidance that has been well received.
The group agreed on a structure for its report and identified topics to be covered. Input will be sought from ad hoc experts in specific fields during the writing process.
Open pre-meeting to seek wider input
The next Working Group meeting will be held on 1-2 May 2019 in Geneva. It will be preceded by an open pre-meeting on 30 April 2019, during which additional representatives of patient organisations and other stakeholders will be able to provide input and feedback to the group’s work. The pre-meeting will also mark the 70th Anniversary of CIOMS.
More information on the patient involvement group including past meeting minutes, is found on the CIOMS website at https://cioms.ch/working_groups/working-group-xi-patient-involvement/
Drug-Induced Liver Injury (DILI) 4th Working Group Meeting
Aix-en-Provence, France, 27-28 November 2018
The CIOMS Working Group on Drug-Induced Liver Injury (DILI) includes some of the world’s foremost experts from regulatory authorities, academia and industry. The group is making good progress in developing pragmatic, consensus-based recommenda-tions for investigators and clinicians on what to look out for when their patients present with liver damage, which might or might not be caused by the medicines they are taking. In these cases it is important to ask the right questions and to record accurate, reliable data to determine the cause and prevent further harm.
An earlier CIOMS Working group had recommended using the RUCAM scale3 to determine whether liver injury is likely to have been caused by a patient’s medicines. Much has been learned since then, and the field of DILI is rapidly expanding as new types of cancer medicines and other novel treatments are coming to market. The CIOMS DILI Working Group will provide updated guidance for investigators, clinicians, regulatory authorities and the pharmaceutical industry on how to prevent, detect and diagnose drug-induced liver injury during drug development and in the postmarketing phase.
Find the group’s past meeting minutes on the CIOMS website at https://cioms.ch/working_groups/dili/.
3 “Launched in 1993 and partially based on the results of an
international consensus meeting organised under the auspices of the Council of International Organizations of Medical Sciences (CIOMS), the Roussel Uclaf Causality Assessment Method (RUCAM) is the most used causality assessment tool worldwide for the diagnosis of drug-induced liver injury (DILI) and herb-induced liver injury (HILI) in a large number of epidemiological studies, case reports, and case series.” (Danan G, Teschke R, 2018)
Above: A subgroup working at the 4
th DILI WG meeting, held
in the very room where the painter Paul Cézanne observed the card players depicted in some of his works. (left).
The CIOMS Working Group on Patient Involve-ment, at its 2
nd Meeting
in Berlin, Germany
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New Working Group on MedDRA labelling groupings (MLGs) emerges
Expertise to be used from the CIOMS Standardised MedDRA Query (SMQ) Implementation Working
Group (IWG)
The Medical Dictionary for Regulatory Activities (MedDRA®) is widely used for coding of information of medicines. However, when it comes to listing adverse effects in the reference safety information approved by regulators and supplied with each medicinal product, the MedDRA terminology is sometimes too detailed. Users are therefore creating their own “labelling groupings” of MedDRA terms for product labelling.
There is currently no standardised approach to MedDRA Labelling Groupings (MLGs). The differences can affect the information provided to doctors and patients, as shown in this illustrative example:
Product A
Adverse effects: Abdominal pain*
* Includes these MedDRA Preferred Terms (PTs):
– Abdominal pain – Upper abdominal pain – Lower abdominal pain – Abdominal tenderness – Gastrointestinal pain – Abdominal discomfort
Product B
Adverse effects: Abdominal pain**
** Includes these MedDRA PTs:
– Abdominal pain – Upper abdominal pain – Lower abdominal pain – Abdominal tenderness – Abdominal rigidity – Acute abdomen – Esophageal pain
The above differences would also affect the calculation of frequencies of suspected adverse reactions from clinical trial data, making it more difficult for health care professionals and patients to compare safety profiles between products.
CIOMS lecture held at the 2018 ISoP meeting
From left to right: Victoria Rollason (ISoP), Ilona Große-Michaelis (Bayer), Sonja Brajovic (U.S. FDA), Hervé le Louët (CIOMS President), and Judith Jones (PharmaLex) at the CIOMS lecture held during the ISoP 2018 Annual Meeting
Three members of the CIOMS Implementation Working Group (IWG) on Standardised MedDRA queries (SMQs) gave presentations and led a panel discussion on MLGs at the 18th Annual Meeting of the International Society of Pharmacovigilance (ISoP), held in Geneva on 11-14 November 2018 (see above).
It is envisaged that a new CIOMS Working Group will be convened to develop principles and points to consider type guidance for defining MLGs. The current CIOMS SMQ IWG works under a Memorandum of Understanding (MoU) between the ICH MedDRA Management Committee and CIOMS. The MoU was renewed for another year at the ICH Meeting held in Charlotte, U.S., in November 2018. The new CIOMS Working Group on MLGs will emerge using expertise from the existing CIOMS SMQ IWG, and several new members who have not been part of the IWG may also join. As a first step, the group aims to reach consensus on an international approach to MLGs, for voluntary consideration by institutions.
News from the CIOMS Secretariat CIOMS 85th Executive Committee Meeting
11 December 2018, Geneva, Switzerland
At its 85th Meeting the CIOMS Executive Committee Committee heard a report from the Secretariat on progress achieved in strengthening the organisation itself, its global outreach and communication. Through its 40 member organisations CIOMS represents a large part of the world’s health professionals, and its four active Working Groups include some of the leading experts in their respective fields. (See the News from the CIOMS Working Groups on page 5 onwards.)
The Committee members made a number of decisions on the strategic directions for CIOMS and
congratulated the Secretariat for driving some significant achievements during 2018.
In remembrance: Professor Jaroslav Blahoš
Professor Jaroslav Blahoš, past President of WMA and member of the CIOMS Executive Committee, passed away on 27 November 2018 at 88 years of age. Professor Blahoš was a renowned Czech endocrinologist and an inspirational leader who always emphasised the high responsibility of physicians. He will be missed by his family, friends and colleagues.
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New translations available
International ethical guidelines for health-related research involving humans (2016),
in Portuguese
International ethical guidelines for health-related research involving humans (2016),
in Ukrainian
Development and Rational Use of Standardised MedDRA Queries (SMQs): Retrieving Adverse Drug Reactions with
MedDRA (Second Edition 2016), in Japanese
Sale now on Get reduced prices on some selected publications until end of January 2019.
See more at: https://cioms.ch/shop/
CIOMS IN THE MEDIA Where available, articles about CIOMS can be accessed through our website at:
http://www.cioms.ch/cioms-in-the-media/
In: Bioethics. Special issue: Research Ethics Revised (Four additional articles from this special issue were listed in the CIOMS Newsletter # 23):
Van der Graaf R, van der Zande ISE, van Delden JJ. How the CIOMS guidelines contribute to fair inclusion of pregnant women in research. https://doi.org/10.1111/bioe.12520.
Douglass A, Ballantyne A. From protectionism to inclusion: A New Zealand perspective on health-related research involving adults incapable of giving informed consent. https://doi.org/10.1111/bioe.12509.
Slack C, Wilkinson A, Salzwedel J, Ndebele P. Strengthening stakeholder engagement through ethics review in biomedical HIV prevention trials: opportunities and complexities. Journal of the International AIDS Society 2018, 21 (S7):e25172. https://doi.org/10.1002/jia2.25172.
Chokevivat V. International Ethical Guidelines for Health-related Research Involving Humans, 2016. Journal of Thai Traditional & Alternative Medicine 16(2), May-August 2018: 303-311. (In Thai, with an abstract in English).
CIOMS SECRETARIAT
Secretary-General Dr Lembit Rägo Tel: +41 22 791 6410 [email protected]
Administrative Assistant Ms Sue Le Roux Tel: +41 22 791 6439 [email protected]
Technical Writer Ms Monika Zweygarth Tel : +41 22 791 6497 [email protected]
UPCOMING MEETINGS
4th
meeting of the CIOMS Working Group on Clinical Research in Resource-Limited Settings
27-28 February 2019, Geneva, Switzerland
15th
Meeting of the Implementation Working Group on SMQs
2-3 April 2019, Geneva, Switzerland
3rd
Meeting of the CIOMS Working Group on Patient Involvement in the Development and Safe Use of Medicines
Open pre-meeting, 30 April 2019, Geneva, Switzerland Closed Working Group meeting: 1-2 May 2019, Geneva
