exempt expedited rev

Dr. Julie LoweryDr. Julie LoweryAssociate Director, VA Health Services ResearchAssociate Director, VA Health Services Research

Ann Arbor, MIAnn Arbor, MI

andand

Dr. Joan P. PorterDr. Joan P. PorterDeputy Chief OfficerDeputy Chief Officer

Office of Research OversightOffice of Research OversightDepartment of Veterans AffairsDepartment of Veterans Affairs

November 15, 2006 November 15, 2006 Washington, DCWashington, DC

ORO

HumanSubjectProtection

ResearchMisconduct

LaboratoryAnimal Welfare

ResearchLaboratorySafety/Security

A brief review of regulator A brief review of regulator requirements in the Common Rule requirements in the Common Rule (38CFR16 for VA) for exempt and (38CFR16 for VA) for exempt and expedited reviewexpedited review

Case “snippets” for discussionCase “snippets” for discussion

Questions and your advice on where Questions and your advice on where more help is neededmore help is needed

Unless otherwise required by Unless otherwise required by department or agency heads, department or agency heads, research activities in which the only research activities in which the only involvement of human subjects will be involvement of human subjects will be in one or more of the following in one or more of the following categories exemptcategories exempt from this policy.from this policy.

(1)(1) Research conducted in established or Research conducted in established or commonly accepted educational settings, commonly accepted educational settings, involvinginvolving normal educational practicesnormal educational practices such as:such as:

(i)(i) Research on regular and special education Research on regular and special education strategies, orstrategies, or

(ii)(ii) Research in the effectiveness of or Research in the effectiveness of or comparison among instructional techniques, comparison among instructional techniques, curricula, or classroom management methodscurricula, or classroom management methods

(2)(2) Research involving the use ofResearch involving the use of educational educational teststests (cognitive, diagnostic, aptitude, (cognitive, diagnostic, aptitude, achievement), achievement), survey procedures, interview survey procedures, interview procedures or observation of public behaviorprocedures or observation of public behavior, , unlessunless::(i)(i) Information obtained is recorded in such a manner that Information obtained is recorded in such a manner that

human subjects can be identified, directly or through human subjects can be identified, directly or through identifiers linked to the subjects andidentifiers linked to the subjects and

(ii)(ii) Any disclosure of the human subjects’ responses outside the Any disclosure of the human subjects’ responses outside the research could reasonable place the subjects at risk or research could reasonable place the subjects at risk or criminal or civil liability or be damaging to the subjects’ criminal or civil liability or be damaging to the subjects’ financial standing, employability, or reputationfinancial standing, employability, or reputation

(3)(3) Research involving the use of Research involving the use of educational testseducational tests (cognitive, diagnostic, aptitude, achievement), (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or survey procedures, interview procedures, or observation of public behaviorobservation of public behavior that is not exempt that is not exempt under paragraph (b)(2) or this section, under paragraph (b)(2) or this section, if:if:

(i)(i) The human subjects are elected or appointed public The human subjects are elected or appointed public officials or candidates for public office; orofficials or candidates for public office; or

(ii)(ii) Federal statute(s) require(s) without exception that Federal statute(s) require(s) without exception that the confidentiality of the personally identifiable the confidentiality of the personally identifiable information will be maintained throughout the information will be maintained throughout the research and thereafter.research and thereafter.

(4)(4) Research involving the collection or study Research involving the collection or study of of existing data, documents, records, existing data, documents, records, pathological specimens, or diagnostic pathological specimens, or diagnostic specimensspecimens, if these sources are publicly , if these sources are publicly available or if the information is recorded available or if the information is recorded by the investigator in such a manner that by the investigator in such a manner that subjects cannot be identified, directly or subjects cannot be identified, directly or through identifiers linked to the subjects.through identifiers linked to the subjects.

(5)(5) Research and demonstration projectsResearch and demonstration projects which which are conducted by or subject to the approval are conducted by or subject to the approval of department or agency heads, and which of department or agency heads, and which are designed to study, evaluate, or otherwise are designed to study, evaluate, or otherwise examine:examine:

(i)(i) Public benefit or service programsPublic benefit or service programs;;

(ii)(ii) Procedures for obtaining benefits or services under those Procedures for obtaining benefits or services under those programs;programs;

(iii)(iii) Possible changes in or alternatives to those programs or Possible changes in or alternatives to those programs or procedures; orprocedures; or

(iv)(iv) Possible changes in methods or levels of payment for Possible changes in methods or levels of payment for benefits or services under those programs.benefits or services under those programs.

(6)(6) Taste and food quality evaluation and Taste and food quality evaluation and consumer acceptance studiesconsumer acceptance studies

(i)(i) If wholesome foods without additives are consumers orIf wholesome foods without additives are consumers or

(ii)(ii) If a food is consumed that contains a food ingredient at or If a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Safety and Inspection Service of the U.S. Department of Agriculture.Agriculture.

In VA:In VA: Investigators submit the proposed research and the Investigators submit the proposed research and the request for exemption. The IRB Chair, or an IRB member request for exemption. The IRB Chair, or an IRB member designated by the Chair, must review all requests in a designated by the Chair, must review all requests in a timely manner and make a determination based on Section timely manner and make a determination based on Section 6.101, and record the decision. The decision must be 6.101, and record the decision. The decision must be communicated in writing to the investigator and the IRB communicated in writing to the investigator and the IRB Documentation must include the specific categories Documentation must include the specific categories justifying exemption. The Research and Development justifying exemption. The Research and Development Committee review regulations even though exempt.Committee review regulations even though exempt.

*.102(f) Human subject means a living individual about when an *.102(f) Human subject means a living individual about when an investigator investigator

(whether professional or student conducting research (whether professional or student conducting research obtains:obtains:

(1)(1) Data through intervention or interaction with the Data through intervention or interaction with the individual, orindividual, or

(2)(2) Identifiable private information . . . Identifiable private information . . .

Expedited review procedures for Expedited review procedures for certain kinds of research involving certain kinds of research involving no more than minimal risk, and for no more than minimal risk, and for minor changes in approved minor changes in approved researchresearch

38 CFR 16.11038 CFR 16.110

(a) The Secretary, HHS, has established, and The Secretary, HHS, has established, and published as a Notice in the published as a Notice in the Federal Register,Federal Register, a a list of categories of researchlist of categories of research that may be that may be reviewed by the IRB through an expedited reviewed by the IRB through an expedited review procedures. The list will be amended, as review procedures. The list will be amended, as appropriate, after consultation with other appropriate, after consultation with other departments and agencies, through periodic departments and agencies, through periodic republication by the Secretary, in the FEDERAL republication by the Secretary, in the FEDERAL REGISTER. A copy of the list is available from REGISTER. A copy of the list is available from the Office for Human Research Protections, HHS, the Office for Human Research Protections, HHS, or any successor office.or any successor office.

(b)(b) An IRB may use the expedited review procedure An IRB may use the expedited review procedure to review either or both of the following:to review either or both of the following:

(1)(1) Some or all of the research appearing on Some or all of the research appearing on the list and found by the reviewer(s) to the list and found by the reviewer(s) to involve no more than minimal risk,involve no more than minimal risk,

(2)(2) Minor changesMinor changes in previously approved in previously approved research during the period (of one year or research during the period (of one year or less) for which approval is authorized. less) for which approval is authorized. (Note that if approved, the continuing (Note that if approved, the continuing review date does not change and if the review date does not change and if the change involves biosafety or ionizing change involves biosafety or ionizing radiation, the appropriate committee must radiation, the appropriate committee must be consulted prior to approving the change; be consulted prior to approving the change; the consultation must be documented in the the consultation must be documented in the

IRB file.IRB file.

Also Note:Also Note:

An IRB (or Privacy Board) may use the An IRB (or Privacy Board) may use the expedited review process to reviewexpedited review process to review

(3) waiver or alteration of authorization for (3) waiver or alteration of authorization for the use and/or disclosure of Protected the use and/or disclosure of Protected Health Information.Health Information.

The IRB Chair may carry out the review or The IRB Chair may carry out the review or delegate the review to one or more delegate the review to one or more experienced reviewers from among IRB experienced reviewers from among IRB members.members.

(1) In reviewing the research, the reviewers In reviewing the research, the reviewers may exercise all of the authorities of the may exercise all of the authorities of the IRB except that the reviewer may not IRB except that the reviewer may not disapprove the research. A research disapprove the research. A research activity may be disapproved only after activity may be disapproved only after review in accordance with the full-review review in accordance with the full-review procedures.procedures.

(2) If a proposal has been initially approved through the full review procedure, the continuing review may not be done by the expedited review procedure

Continuing review of research previously approved Continuing review of research previously approved by the convened IRB as follows:by the convened IRB as follows:

(a) Research in which the enrollment of a new (a) Research in which the enrollment of a new subject is permanently closed; all subjects have subject is permanently closed; all subjects have completed all research-related interventions, and completed all research-related interventions, and the research remains active only for long-term the research remains active only for long-term follow-up of subjects; orfollow-up of subjects; or

(b) Research in which no subject have been enrolled (b) Research in which no subject have been enrolled and no additional risks have been identified, orand no additional risks have been identified, or

(c) Research in which the remaining research (c) Research in which the remaining research activities are limited to data analysis.activities are limited to data analysis.

Each IRB that uses an expedited Each IRB that uses an expedited review process must adopt a review process must adopt a method for keeping all members method for keeping all members advised of research proposals that advised of research proposals that have been approved under this have been approved under this process.process.

The minutes and/or the protocol The minutes and/or the protocol files must reflect the expedited files must reflect the expedited review eligibility category that the review eligibility category that the research meets.research meets.

Remember:Remember: (1) Research activities that present no (1) Research activities that present no more than minimal risk and (2) involve only more than minimal risk and (2) involve only procedures listed in one or more categories on the procedures listed in one or more categories on the expedited review lists.expedited review lists.

Remember:Remember: Expedited review procedures may not be Expedited review procedures may not be used where identification of the subjects and/or their used where identification of the subjects and/or their responses would reasonably place them at risk of responses would reasonably place them at risk of criminal or civil liability or be damaging to the subjects criminal or civil liability or be damaging to the subjects (e.g. employability, insurability, reputation), unless (e.g. employability, insurability, reputation), unless protectiions are in place to minimize invasion of protectiions are in place to minimize invasion of privacy and breach of confidentiality so risks are no privacy and breach of confidentiality so risks are no greater than minimal.greater than minimal.

(Paraphrased)(Paraphrased)

(1)(1) Clinical studies of drugs and medical devices only when Clinical studies of drugs and medical devices only when condition (a) or (b) is met.condition (a) or (b) is met.

(a)(a) Research on drugs for which an investigational new Research on drugs for which an investigational new drug application (21 CFR Part 312) is not required. drug application (21 CFR Part 312) is not required. (Note: Research on marketed drugs that (Note: Research on marketed drugs that significantly increases the risks or decreases the significantly increases the risks or decreases the acceptability of the risk associated with the use of acceptability of the risk associated with the use of the product is not eligible for expedited review.)the product is not eligible for expedited review.)

(b)(b) Research on medical devices for which (i) an Research on medical devices for which (i) an investigational device exemption application (21 investigational device exemption application (21 CFR Part 812) is not required; or (ii) the medical CFR Part 812) is not required; or (ii) the medical device is cleared/approved for marketing and the device is cleared/approved for marketing and the medical device is being used in accordance with its medical device is being used in accordance with its cleared/approved labeling.cleared/approved labeling.

(2)(2) Collection of blood samples by finger stick heel Collection of blood samples by finger stick heel stick, ear stick, or venipuncture as follows:stick, ear stick, or venipuncture as follows:

(a)(a) From healthy, non-pregnant adults who weigh From healthy, non-pregnant adults who weigh at least 110 pounds. For these subjects, the at least 110 pounds. For these subjects, the amounts drawn may not exceed 550 ml in an 8 amounts drawn may not exceed 550 ml in an 8 week period and collection may not occur week period and collection may not occur more frequently than two times per week; ormore frequently than two times per week; or

(b)(b) From other adults and children, considering From other adults and children, considering the age, weight, and health of the subjects, the age, weight, and health of the subjects, the collection procedure, the amount of blood the collection procedure, the amount of blood collected, and the frequency with which it will collected, and the frequency with which it will be collected. For these subjects the amount be collected. For these subjects the amount drawn may not exceed the lesser of 50 ml or 3 drawn may not exceed the lesser of 50 ml or 3 ml per kg in an 8 week period and collection ml per kg in an 8 week period and collection may not occur more frequently than two times may not occur more frequently than two times per week.per week.

(3)(3) Prospective collection of biological specimens for each Prospective collection of biological specimens for each research purposes by noninvasive means.research purposes by noninvasive means.Examples: Examples: (a)(a) hair and nail clippings in a non-disfiguring hair and nail clippings in a non-disfiguring manner; manner; (b)(b) deciduous teeth at time of exfoliation or if deciduous teeth at time of exfoliation or if routine patient care indicates a need for extraction; routine patient care indicates a need for extraction; (c)(c) permanent teeth if routine patient care indicates a need for permanent teeth if routine patient care indicates a need for extraction; extraction; (d)(d) excreta and external secretions (including sweat); excreta and external secretions (including sweat); (e)(e) uncannulated saliva collected either in an unstimulated uncannulated saliva collected either in an unstimulated fashion or stimulated by chewing gumbase or wax or by fashion or stimulated by chewing gumbase or wax or by applying a dilute citric solution to the tongue; applying a dilute citric solution to the tongue; (f)(f) placenta placenta removed at delivery; removed at delivery; (g)(g) amniotic fluid obtained at the time amniotic fluid obtained at the time of rupture of the membrane prior to or during labor; of rupture of the membrane prior to or during labor; (h)(h) supra- and subgingival dental plaque and calculus, provided supra- and subgingival dental plaque and calculus, provided the collection procedure is not more invasive than routine the collection procedure is not more invasive than routine prophylactic scaling of the teeth and the process is prophylactic scaling of the teeth and the process is accomplished in accordance with accepted prophylactic accomplished in accordance with accepted prophylactic techniques; techniques; (i)(i) mucosal and skin cells collected by buccal mucosal and skin cells collected by buccal scraping or swab, skin swab, or mouth washings; scraping or swab, skin swab, or mouth washings; (j)(j) sputum sputum collected after saline mist nebulization.collected after saline mist nebulization.

(4)(4) Collection of data through noninvasive Collection of data through noninvasive proceduresprocedures (not involving general (not involving general anesthesia or sedation) routinely anesthesia or sedation) routinely employed in clinical practice, excluding employed in clinical practice, excluding procedures involving x-rays or procedures involving x-rays or microwaves. Where medical devices are microwaves. Where medical devices are employed, they must be employed, they must be cleared/approved for marketing. (Studies cleared/approved for marketing. (Studies intended to evaluate the safety and intended to evaluate the safety and effectiveness of the medical device are effectiveness of the medical device are not generally eligible for expedited not generally eligible for expedited review, including studies of cleared review, including studies of cleared medical devices for new indications.)medical devices for new indications.)

(5)(5) Research involving materialsResearch involving materials (data, (data, documents, records, or specimens) that documents, records, or specimens) that have been collected, or will be collected have been collected, or will be collected solely solely for non-research purposesfor non-research purposes (such (such as medical treatment or diagnosis).as medical treatment or diagnosis).

(6)(6) Collection of data from voice, video, Collection of data from voice, video,

digital, or image recordings made for digital, or image recordings made for

research purposes.research purposes.

(7)(7) Research on individual or group Research on individual or group characteristics or behaviorcharacteristics or behavior (including, but (including, but not limited to, research on perception, not limited to, research on perception, cognition, motivation, identity, language, cognition, motivation, identity, language, communication, cultural beliefs or communication, cultural beliefs or practices, and social behavior) or practices, and social behavior) or research research employing survey, interview, oral history, employing survey, interview, oral history, focus group, program evaluation, human focus group, program evaluation, human factors evaluation, or quality assurance factors evaluation, or quality assurance methodologiesmethodologies. (NOTE: Some research in . (NOTE: Some research in this category may be exempt from the HHS this category may be exempt from the HHS regulations for the protection of human regulations for the protection of human subjects, 45 CFR 46.101 (b)(2) and (b)(3). subjects, 45 CFR 46.101 (b)(2) and (b)(3). This listing refers only to research that is This listing refers only to research that is not exempt.)not exempt.)

(8)(8) Continuing review of research previously Continuing review of research previously approved by the convened IRB as follows:approved by the convened IRB as follows:

(a)(a) Where (i) the research is permanently Where (i) the research is permanently closed to the enrollment of new subjects; closed to the enrollment of new subjects; (ii) all subjects have completed all (ii) all subjects have completed all research-related interventions; and (iii) research-related interventions; and (iii) the research remains actively only for the research remains actively only for long-term follow-up of subjects; orlong-term follow-up of subjects; or

(b)(b) Where no subjects have been enrolled Where no subjects have been enrolled and no additional risks have been and no additional risks have been identified; oridentified; or

(c)(c) Where the remaining research activities Where the remaining research activities are limited to data analysis.are limited to data analysis.

(9)(9) Continuing review of research, not conducted Continuing review of research, not conducted under an investigational new drug under an investigational new drug application or investigational device application or investigational device exemptionexemption where categories (2) through (8) where categories (2) through (8) do not apply but the IRB has determined and do not apply but the IRB has determined and documented at a convened meeting that the documented at a convened meeting that the research involves no greater than minimal research involves no greater than minimal risk and no additional risks have been risk and no additional risks have been identified.identified.

OPRR Guidance on .101 (6)(5)OPRR Guidance on .101 (6)(5)Exemption for Research and Demonstration on Exemption for Research and Demonstration on

Public Benefit and Service ProgramPublic Benefit and Service Program

http://www.hhs.gov/ohrp/humansubjects/guidance/exmpt-pb.htm

Office of Human Research Protections (OHRP)Office of Human Research Protections (OHRP)Guidance on the Use of Expedited Review ProceduresGuidance on the Use of Expedited Review Procedures

http://www.hhs.gov/ohrp/humansubjects/guidance/exprev.htm

Categories of Research that May be Reviewed by the Categories of Research that May be Reviewed by the Institutional Review Board (IRB) through Expedited Review Institutional Review Board (IRB) through Expedited Review

ProceduresProcedures

http://www.hhs.gov/ohrp/humansubjects/guidance/expedited98.htm

Case Study 1Case Study 1Investigator Chew is a dentist working as a WOC. He would Investigator Chew is a dentist working as a WOC. He would

like to collect photographs, dental plaque, and saliva from all like to collect photographs, dental plaque, and saliva from all his patients to see if there are characteristics of dental decay his patients to see if there are characteristics of dental decay and ulcerations that can help predict HIV infection. He will:and ulcerations that can help predict HIV infection. He will:

Test the saliva and plaque for the presence of HIV.Test the saliva and plaque for the presence of HIV.Obtain informed consent from his subjects.Obtain informed consent from his subjects.Keep the results of his findings in a locked cabinet in his office Keep the results of his findings in a locked cabinet in his office

at the university.at the university.

He must have his proposal reviewed by the IRB and the R&D He must have his proposal reviewed by the IRB and the R&D committee within 2 weeks to meet the deadline for funding. committee within 2 weeks to meet the deadline for funding. He requests that the IRB Chair expedite the project since he He requests that the IRB Chair expedite the project since he will be merely collecting dental plaque by routine methods will be merely collecting dental plaque by routine methods that he would be doing anyway and he will collect sputum that he would be doing anyway and he will collect sputum after saline mist nebulization.after saline mist nebulization.

Case Study 1 Case Study 1 ContinuedContinued

Is Dr. Chew’s study Expeditable? Why or why not?Is Dr. Chew’s study Expeditable? Why or why not?

If not, can the IRB and R&D committee approve it If not, can the IRB and R&D committee approve it tentatively by expedited means so that he can get tentatively by expedited means so that he can get the funding that would otherwise be “swept”?the funding that would otherwise be “swept”?

Case Study 2Case Study 2Dr. Curio is going to look at medical records in the Dr. Curio is going to look at medical records in the

VA to determine if veterans with psoriasis have a VA to determine if veterans with psoriasis have a high rate of diabetes and he wants to check high rate of diabetes and he wants to check records from May 2004 to May 2007. He will:records from May 2004 to May 2007. He will:

Be using the medical records at three sites in his Be using the medical records at three sites in his VISN to see if there is any correlationVISN to see if there is any correlation

Contact each of the medical centers, rather than Contact each of the medical centers, rather than using a VISN or central data baseusing a VISN or central data base

Not be recording nay names when he looks at the Not be recording nay names when he looks at the records from each site.records from each site.


At his VA facility, the IRB chair says that the project is At his VA facility, the IRB chair says that the project is exempts, and because he is not recording any information by exempts, and because he is not recording any information by name or other identifiers, the IRB need not review the projectname or other identifiers, the IRB need not review the project

The IRB in the second facility indicates that the project is not The IRB in the second facility indicates that the project is not exempt, but that it could be expedited, but informed consent exempt, but that it could be expedited, but informed consent must be obtained to do an expedited project that has must be obtained to do an expedited project that has prospective data.prospective data.

The third IRB indicated that the project could be expedited and The third IRB indicated that the project could be expedited and that informed consent can be waived by the RIB consultant that informed consent can be waived by the RIB consultant who is doing the expedited review.who is doing the expedited review.

Who is right?Who is right?


Answer. All three responses have regulatory issues.Answer. All three responses have regulatory issues.

For IRB 1: The project is not exempt. Some of the data will be For IRB 1: The project is not exempt. Some of the data will be collected prospectively.collected prospectively.

For IRB 2: Waiver of consent can be given if appropriately For IRB 2: Waiver of consent can be given if appropriately justified in accordance with Section .116 of the regulations.justified in accordance with Section .116 of the regulations.

For IRB 3: The reviewer must be the Chair or a member or For IRB 3: The reviewer must be the Chair or a member or members of the IRB appointed by the Chair. A non-IRB members of the IRB appointed by the Chair. A non-IRB member cannot do the expedited review.member cannot do the expedited review.

Case Study 3- Analysis of Case Study 3- Analysis of Patient Data from Patient Data from

Secondary SourcesSecondary SourcesThis study includes analysis of patient data from existing VA This study includes analysis of patient data from existing VA databases (originally established for patient care and databases (originally established for patient care and administrative purposes- not research) to compare statistical administrative purposes- not research) to compare statistical models of risk adjustment and mortality prediction. There is models of risk adjustment and mortality prediction. There is no direct patient contact, and scrambled patient identifiers are no direct patient contact, and scrambled patient identifiers are used to link data from various sources.used to link data from various sources.

Data are collected on 5,000 VA patients with ICU admissions. Data are collected on 5,000 VA patients with ICU admissions. Subjects are to be identified from VA databases using Subjects are to be identified from VA databases using diagnostic criteria.diagnostic criteria.


Data collection:Data collection:

Patient data to be collected include demographic Patient data to be collected include demographic information, date of birth, zip code, gender, information, date of birth, zip code, gender, ethnicity, ICU admissions, diagnoses, lab results, ethnicity, ICU admissions, diagnoses, lab results, inpatient treatment information, mortality data, and inpatient treatment information, mortality data, and other outcomes.other outcomes.

These data are collected via database search (e.g., These data are collected via database search (e.g., Austin data, Pharmacy Benefits Management data, Austin data, Pharmacy Benefits Management data, DSS data) and will be used to test and compare risk DSS data) and will be used to test and compare risk adjustment methods.adjustment methods.


Data Confidentiality:Data Confidentiality:The patient cohort will be obtained from existing VA databases The patient cohort will be obtained from existing VA databases

using diagnostic criteria.using diagnostic criteria.Some of the databases contain real SSNs, others contain Some of the databases contain real SSNs, others contain

scrambled SSNs.scrambled SSNs.After the study data, including SSNs and scrambled SSNs are After the study data, including SSNs and scrambled SSNs are

pulled, all real SSNs will be converted to scrambled SSNs, pulled, all real SSNs will be converted to scrambled SSNs, using a file linking scrambled SSNs with the real SSNs using a file linking scrambled SSNs with the real SSNs obtained from a separate Austin database. Thus, as study obtained from a separate Austin database. Thus, as study files with patient data will include only scrambled SSNs.files with patient data will include only scrambled SSNs.

The file linking scrambled SSNs with real SSNs will be The file linking scrambled SSNs with real SSNs will be maintained by the research team as a separate file, in a maintained by the research team as a separate file, in a password protected drive that is separate from the drive password protected drive that is separate from the drive containing the study data.containing the study data.


What type of review should this application receive What type of review should this application receive and why?and why?


Chart 2: Is the research involving human subjects eligible for Chart 2: Is the research involving human subjects eligible for exemption under 45 CFR 46.101(b)?exemption under 45 CFR 46.101(b)?

Will the only involvement of human subjects be in one or more Will the only involvement of human subjects be in one or more of the following research categories?of the following research categories?

Research conducted in established or commonly accepted Research conducted in established or commonly accepted educational settings, involving education practices?educational settings, involving education practices?

Research involving the use of educational tests, survey Research involving the use of educational tests, survey procedures, interview procedures, or observation of public procedures, interview procedures, or observation of public behavior?behavior?

Research involving the collection of existing data, documents, Research involving the collection of existing data, documents, records, or pathological or diagnostic specimens?records, or pathological or diagnostic specimens?

Research studying, evaluating, or examining public benefits or Research studying, evaluating, or examining public benefits or service programs?service programs?

Research involving taste and food quality evaluation or Research involving taste and food quality evaluation or consumer acceptance studies?consumer acceptance studies?


YES: Research involving collection or study of YES: Research involving collection or study of existing data, documents, records, or pathological existing data, documents, records, or pathological or diagnostic specimens.or diagnostic specimens.

Exemption 45 CFR 46.101(b) may apply. Go to Exemption 45 CFR 46.101(b) may apply. Go to Chart 5.Chart 5.


Are these sources publicly available? (No.)Are these sources publicly available? (No.)

Will information be recorded by the investigator in Will information be recorded by the investigator in such a manner that the subjects cannot be such a manner that the subjects cannot be identified, directly or through identifiers linked to identified, directly or through identifiers linked to the subjects?the subjects?

If no, research is not exempt. Go to Chart 8.If no, research is not exempt. Go to Chart 8.


Has the research been previously reviewed and Has the research been previously reviewed and approved by the IRB? (No.)approved by the IRB? (No.)

Does the research present no more than minimal Does the research present no more than minimal risk to the human subjects? ANDrisk to the human subjects? AND

Does the research involve only procedure indicated Does the research involve only procedure indicated in categories 1-7 on the list of categories that may in categories 1-7 on the list of categories that may be reviewed though an expedited review be reviewed though an expedited review procedure? [45 CFR 46 110 (b)(1)]procedure? [45 CFR 46 110 (b)(1)]


YES (category 5): Research involving materials YES (category 5): Research involving materials (data, documents, records, or specimens) that have (data, documents, records, or specimens) that have been collected, or will be collected, solely for non-been collected, or will be collected, solely for non-research purposes (such as medical treatment or research purposes (such as medical treatment or diagnosis).diagnosis).

Is this research classified? (No.)Is this research classified? (No.)

Research is eligible for IRB review through Research is eligible for IRB review through expedited procedures. [45 CFR 46.110(d)]expedited procedures. [45 CFR 46.110(d)]

Case Study 3- Case Study 3- Modification AModification A

Data Confidentiality:Data Confidentiality:

Data obtained from these databases will include scrambles Data obtained from these databases will include scrambles SSNs, which are needed to link patients across time and SSNs, which are needed to link patients across time and across multiple databases. The scrambled SSN for a given VA across multiple databases. The scrambled SSN for a given VA patient is the same across all Austin databases; so, the patient is the same across all Austin databases; so, the scrambled identifier can be used to link data for a given scrambled identifier can be used to link data for a given patient across databases.patient across databases.

All study files with patient data will include only scrambled All study files with patient data will include only scrambled SSNs. The file linking scrambled SSNs with real SSNs is in a SSNs. The file linking scrambled SSNs with real SSNs is in a database maintained in Austin.database maintained in Austin.

Case Study 3- Case Study 3- Modification BModification B

Data Confidentiality:Data Confidentiality:

The SSNS of eligible patients are obtained are used to identify The SSNS of eligible patients are obtained are used to identify the patients’ electronic medical records, from which relevant the patients’ electronic medical records, from which relevant clinical data for the study are obtained.clinical data for the study are obtained.

These clinical data are entered into the study database, which These clinical data are entered into the study database, which doesn't contain any SSNs or linkages to patient identifiers.doesn't contain any SSNs or linkages to patient identifiers.

A file containing the list of SSNs of eligible patients- but no A file containing the list of SSNs of eligible patients- but no linkages and no other data- is temporarily maintained until all linkages and no other data- is temporarily maintained until all of the medical record data are obtained.of the medical record data are obtained.

Case Study 4Case Study 4Observational Study Using Patient Interviews and Observational Study Using Patient Interviews and

QuestionnairesQuestionnaires

This study examines health related quality of life (QOL) for This study examines health related quality of life (QOL) for individuals in the VA health care system with a specific, non-individuals in the VA health care system with a specific, non-sensitive chronic illness. Investigator propose to administer sensitive chronic illness. Investigator propose to administer two QOL measures to patients at baseline and a follow-up two QOL measures to patients at baseline and a follow-up structured interview every month for a 1-year study period. structured interview every month for a 1-year study period. They will use written informed consent, which will include a They will use written informed consent, which will include a HIPAA authorization form.HIPAA authorization form.

The subjects are 500 patients at 8 VAMCs. They are identified The subjects are 500 patients at 8 VAMCs. They are identified via VA databases and initially contracted and invited by letter via VA databases and initially contracted and invited by letter to participate in the project. Interested patients are scheduled to participate in the project. Interested patients are scheduled to meet with project staff at an upcoming clinic appointment to meet with project staff at an upcoming clinic appointment to go over requirements for participation and sign the consent to go over requirements for participation and sign the consent form.form.


Data Collection and Confidentiality:Data Collection and Confidentiality:

Baseline interviews are conducted in person at a regularly Baseline interviews are conducted in person at a regularly scheduled clinic appointment, and follow-up interviews are scheduled clinic appointment, and follow-up interviews are conducted over the telephone.conducted over the telephone.

Data collected from patients include demographics/SES, Data collected from patients include demographics/SES, general health information, and QOL data.general health information, and QOL data.

Data are confidential but not anonymous- linkages are Data are confidential but not anonymous- linkages are maintained in a crosswalk file to facilitate the monthly maintained in a crosswalk file to facilitate the monthly follow-up.follow-up.

The crosswalk file linking patient identifying data to study The crosswalk file linking patient identifying data to study identification numbers will be maintained as a separate file, identification numbers will be maintained as a separate file, in a password-protected drive that is separate from the drive in a password-protected drive that is separate from the drive containing study data.containing study data.

No study data will be maintained with the patient identifying No study data will be maintained with the patient identifying data.data.


YES: Research involving the use of educational YES: Research involving the use of educational tests, survey procedures, interview procedures, or tests, survey procedures, interview procedures, or observation of public behavior.observation of public behavior.

Exemption 45 CFR 46.101(b)(2) or (b)(3) may apply. Exemption 45 CFR 46.101(b)(2) or (b)(3) may apply. Go to chart 4. Go to chart 4.


Is the information recorded in such a manner that Is the information recorded in such a manner that human subjects can be identified, directly or human subjects can be identified, directly or through identifiers linked to the subjects; ANDthrough identifiers linked to the subjects; AND

Could any disclosures of the human subject’s Could any disclosures of the human subject’s responses outside the research reasonably place responses outside the research reasonably place the subjects at risk of criminal or civil liability or be the subjects at risk of criminal or civil liability or be damaging to the subjects’ financial standing, damaging to the subjects’ financial standing, employability or reputation?employability or reputation?

If yes, research is not exempt. Go to Chart 8.If yes, research is not exempt. Go to Chart 8.



Does the research present no more than minimal Does the research present no more than minimal risk to human subjects? ANDrisk to human subjects? AND

Does the research involve only procedure included Does the research involve only procedure included in categories 1-7 on the list of categories that may in categories 1-7 on the list of categories that may be reviewed through an expedited review be reviewed through an expedited review procedures? [45 CFR 46 110(b)(1)]procedures? [45 CFR 46 110(b)(1)]


YES (Category 7): Research on individual or group YES (Category 7): Research on individual or group characteristics (including but not limited to, research on characteristics (including but not limited to, research on perception, cognition, motivation, identity, language, perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies.evaluation, or quality assurance methodologies.


Research is eligible for IRB review through expedited Research is eligible for IRB review through expedited procedures. [45 CFR 46 110(d)]procedures. [45 CFR 46 110(d)]

Case Study 5Case Study 5Observational Study Using Provider Interviews and Observational Study Using Provider Interviews and

QuestionnairesQuestionnaires

This study will use provider interviews and written This study will use provider interviews and written surveys to assess how a new clinical reminder surveys to assess how a new clinical reminder system is working at 8 VAMCs. (This study is an system is working at 8 VAMCs. (This study is an investigator initiated research project, not a quality investigator initiated research project, not a quality improvement project initiated by medical center improvement project initiated by medical center management.)management.)

The subjects are 70 VA primary care physicians at 8 The subjects are 70 VA primary care physicians at 8 VAMCs.VAMCs.


Data Collection and Confidentiality:Data Collection and Confidentiality:Data collected will include perceptions of barriers and Data collected will include perceptions of barriers and

facilitators to implementation of the system, provider self-facilitators to implementation of the system, provider self-efficacy, satisfaction with the system, and data about efficacy, satisfaction with the system, and data about organizational structure.organizational structure.

Data are confidential, but are not anonymous, since providers Data are confidential, but are not anonymous, since providers are interviewed in person and data from interviews and are interviewed in person and data from interviews and surveys must be linked.surveys must be linked.

The crosswalk file linking provider identifying data to study The crosswalk file linking provider identifying data to study identification numbers will be maintained as a separate file, identification numbers will be maintained as a separate file, in a password-protected drive that is separate from the drive in a password-protected drive that is separate from the drive containing the study data.containing the study data.

No study data will be maintained with the provider identifying No study data will be maintained with the provider identifying data.data.


YES: Research involving the use of educational YES: Research involving the use of educational tests, survey procedures, interview procedures, or tests, survey procedures, interview procedures, or observation of public behavior.observation of public behavior.

Exemption 45 CFR 46.101(b)(2) or (b)(3) may apply. Exemption 45 CFR 46.101(b)(2) or (b)(3) may apply. Go to chart 4. Go to chart 4.


Is the information recorded in such a manner that Is the information recorded in such a manner that human subjects can be identified, directly or though human subjects can be identified, directly or though identifiers linked to the subjects; ANDidentifiers linked to the subjects; AND

Could any disclosure of the human subjects’ Could any disclosure of the human subjects’ responses outside the research reasonably place responses outside the research reasonably place the subjects at risk of criminal or civil liability or be the subjects at risk of criminal or civil liability or be damaging to the subject’s financial standing, damaging to the subject’s financial standing, employability, or reputation?employability, or reputation?

If yes, research is not exempt. Go to Chart 8.If yes, research is not exempt. Go to Chart 8.



Does the research present no more than minimal Does the research present no more than minimal risk to human subjects? ANDrisk to human subjects? AND

Does the research involve only procedure included Does the research involve only procedure included in categories 1-7 on the list of categories that may in categories 1-7 on the list of categories that may be reviewed though an expedited review be reviewed though an expedited review procedure? [45 CFR 46 110(b)(1)]procedure? [45 CFR 46 110(b)(1)]


YES (Category 7): Research on individual or group YES (Category 7): Research on individual or group characteristics (including but not limited to, research on characteristics (including but not limited to, research on perception, cognition, motivation, identity, language, perception, cognition, motivation, identity, language, communication, cultural beliefs or practices, and social communication, cultural beliefs or practices, and social behavior) or research employing survey, interview, oral behavior) or research employing survey, interview, oral history, focus group, program evaluation, human factors history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies.evaluation, or quality assurance methodologies.


Research is eligible for IRB review through expedite Research is eligible for IRB review through expedite procedures. [45 CFR 46 110(d)]procedures. [45 CFR 46 110(d)]

Case Study 5 Case Study 5 ModificationModification

Data Collection:Data Collection:

Data collected will include information on how Data collected will include information on how providers were education in the use of the system, providers were education in the use of the system, and data about organizational structure.and data about organizational structure.

The providers will not be asked about their The providers will not be asked about their satisfaction with the system or their opinions on satisfaction with the system or their opinions on how the system could be improved.how the system could be improved.


Chart 1: Is an activity research involving human Chart 1: Is an activity research involving human subjects covered by 45 CFR Part 46?subjects covered by 45 CFR Part 46?

Is the study a systematic investigation designed to Is the study a systematic investigation designed to develop or contribute to generalizable knowledge? develop or contribute to generalizable knowledge? (Yes.)(Yes.)

Activity is research. Does the research involve Activity is research. Does the research involve obtaining information about living individuals?obtaining information about living individuals?

If no, the research is not research involving human If no, the research is not research involving human subjects.subjects.

www.va.gov/annarbor-hsrd/irb/subjectsreview.htm

Guidelines for Human Subjects ReviewGuidelines for Human Subjects Review of Health Service Research Studies of Health Service Research Studies

Dr. Julie LoweryDr. Julie LoweryAssociate DirectorAssociate Director

VA Health Services Research VA Health Services Research Phone: (734) 769-7100 (ext. 6222)Phone: (734) 769-7100 (ext. 6222)

[email protected]

Dr. Joan P. PorterDr. Joan P. PorterDeputy Chief OfficerDeputy Chief Officer

Office of Research Oversight (10R)Office of Research Oversight (10R)Phone: (202) 565-7197Phone: (202) 565-7197

[email protected]

exempt expedited rev

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