Protection of Research Participants: The IRB Process and the Winds of Change

Transcription

1 Protection of Research Participants: The IRB Process and the Winds of Change Ethics in Patient-Oriented Research October 12, 2011 Sharon Friend Director, OHRPP

2 Overview Charge and Function of the IRB Quick Guide to IRB Process Winds of Change 2

3 What is an Institutional Review Board (IRB)? An independent internal review committee Composed of institutional members (UCLA faculty) with relevant expertise and at least one nonaffiliated member and at least one nonscientific member Reviews proposed research involving human subjects conducted by UCLA faculty and students regardless of funding source and usually regardless of site Based on federal criteria, IRB has the authority to approve, require changes or disapprove human research. 3

4 What is the mission and charge of UCLA IRBs? Ensure ethical principles are applied to the conduct of research Assure federal criteria for approval of human subjects research and institutional policies are met Promote and facilitate the protection of the rights and welfare of human subjects in research Support and facilitate the conduct of human research at UCLA 4

5 What do both the IRB and the PI consider in applying the ethical principles? Beneficence (Be nice!) Design studies to Minimize risk to the extent possible Maximize benefit (both individual and societal) Respect for Persons (Be respectful!) Obtain informed consent before involving participants (or using private identifiable information) in research Assure confidentiality provisions are in place. Justice (Be fair!) Select participants who are likely to benefit from research participation Do not systematically include or exclude participants for convenience. 5

6 Quick Guide to IRB Process For the Researcher 6

7 Human Research Is any research or clinical investigation that involves people or identifiable data from people. 7

8 Is the project research? #1: Determine if IRB Review is Required DHHS regulations define human research as a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. FDA regulations define a clinical investigation as any experiment that involves a test article and one or more human subjects the results of which are intended to be submitted to the FDA. 8

9 Does the research involve human subjects? DHHS: a living individual about whom an investigator (faculty or student) conducting research obtains data Through an intervention or interaction with the individual, or Access to identifiable, private information. FDA: an individual who becomes a participant in research, either as a recipient of the test article or as a control 9

10 What is not Human Research? The following are types of studies that may not be considered human research at UCLA: Analysis of data or specimens that do not include private or personally identifying information Studies using public data sets 3 or fewer individual case studies Quality improvement/assurance activities Short questionnaire in webirb UCLA OHRPP Guidance and decision trees: ( Determining Which Activities Require UCLA OHRPP/IRB Review Determining When Collection or Use of Data and Specimens for Research Requires IRB Review 10

11 When Is IRB Review Required? All human subjects research requires prior IRB review and approval before initiation (New Studies) All modifications or changes made to an IRBapproved study require IRB approval prior to initiation (Amendments) All continuation of an IRB-approved study beyond its approval period (usually one year) requires IRB approval (Continuing Review) 11

12 #2: Complete Training Required Courses At UCLA, and most academic sites throughout USA: on-line CITI training (Collaborative Institutional Training Initiative) Required every three years at UCLA Additional optional training available 12

13 #3: Assess Risk and Determine Level of Review Identify risks associated with the research: How are risks different than those risks the subject would encounter if not participating in the research? Consider the subject population: Are the research participants particularly sensitive or vulnerable to the risks posed by the research? Do the risk(s) meet the definition of minimal risk? Does research fit into an exempt or expedited category of review or does it require full committee review? 13

14 Definition of Minimal Risk Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life of the general population or during the performance of routine physical or psychological examinations or tests. 14

15 Loss of Confidentiality Which potential risks need to be considered for all levels of IRB review? Has to do with issues surrounding data Data security needs to established and described seek IT help if needed Primary source of complaints to IRBs (beyond why didn t I get paid on time) Loss of Privacy Has to do with personal privacy Important in recruitment and screening as well as practice 15

16 What are the levels of IRB Review? Three levels of IRB Review, depending on level of risk: Full Committee for more than minimal risk Expedited review for minimal risk studies Exempt certification for studies that fall into one of six federal categories 16

17 Expedited Research No more than minimal risk to subjects Expedited protocols are reviewed by an IRB subcommittee Seven federally-defined categories Informed consent or waiver of consent or waiver of signed consent with appropriate justification required 17

18 Full Committee Research Greater than minimal risk to subjects Full committee protocols are reviewed at a convened IRB meeting Informed consent required in almost all cases Includes most clinical trials: studies involving non FDA-approved drugs and devices or medical interventions 18

19 Examples of Expedited or Full Committee Research or Research Not Requiring IRB Review Randomized double-blind study for the safety and efficacy of investigational drug XYZ Review of medical records of patients in hospital from 1990 to present to study correlation of Alzheimer s and heart disease Randomized study to compare two approved treatment regimens for cervical cancer Comparison of psychotherapy vs medication for the treatment of depression 19

20 Examples continued Study of elder abuse among caregivers Skin samples collected via punch biopsy for SCNT (somatic cell nuclear transfer) study Skin samples sent from UCSF with or without PHI (private health information) Collection of saliva samples from people who developed a cold and cough within the last 48 hours to study the genes related to asthma 20

21 #4 Allow Sufficient Time for IRB Process From time of complete submission to time of full IRB approval: Full Committee: ~ 4 to 8 weeks Expedited: No Subject Contact ~ 2 weeks Subject Contact ~ 4 weeks Continuations: Expedited < two weeks Full Committee ~4 weeks 21

22 What are the Special Issues for Industry-Sponsored Clinical Trials? Need to coordinate IRB approval and contract Sponsor pays IRB Review Fees Consent form needs to be revised to Use UCLA standard requirements for indemnification and ownership of tissue Be in lay language and not overly legal Data Safety Monitoring Boards usually required IRB cannot require a major change in the science and expect the company to revise the protocol it s either thumbs up or thumbs down 22

23 #5: Apply for via webirb On-Line Application Web-based system for IRB submission, review and tracking All levels of review use the same webirb application with branching based on responses to questions Help text and links within application Uploads of supporting materials required 23

24 How does it support PIs and Research Staff? Homepage with access to information on all studies 24

25 How does it support PIs and Research Staff? Track status of submissions Receive feedback and approvals online 25

26 #2 Writing Musts Consider the audience Not all IRB members are scientists Avoid acronyms Use lay language for recruitment and consent documents Be consistent Within the application Make sure that study aims, methods, risks, benefits and alternatives are consistent Between application and consent documents Between application and sponsor protocols or grants Use the same name for the study drugs throughout the submission 26

27 #6: Understand the IRB Review Process Administrative pre-review by staff to check for completeness IRB review (UCLA does not include researchers present) Post Review communication of IRB actions via webirb, including Approval Accepted pending modification Deferral Disapproval 27

28 #7: Understand Your Responsibilities Obtain prospective IRB approval for modifications Obtain IRB continuing review approval at least annually Submit post-approval reports of events that are unanticipated problems that may adversely affect the safety of participants Submit closure report 28

29 #8: Ask Questions; Refer to OHRPP Website Medical IRBs Telephone: (310) webirb Help Desk OHRPP Website: 29

30 Bonus Tips! Bonus Tips: Do not group related full committee studies into a complicated application. Submit a separate application for each study or phase of study. Do group data analysis or retrospective chart reviews into one study when useful for your purposes. 30

31 "The Winds of Change are Coming... Winds of Change DHHS Advance Notice of Proposed Rulemaking (ANPRM): Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators Responses due 10/26/11 31

32 Summary of Aspects of Common Rule Being Re-Examined Two overarching goals with respect to the revisions it is considering to the Common Rule: To enhance the protection of research subjects and To improve the efficiency of the IRB review process 19 proposed revisions See DHHS Summary Table 32

33 Areas of Revisions Data Security and Privacy Reporting of Unanticipated Problems to a Central Database Simplifying Informed Consent Full Committee Reivew Expedited Review Exempt Review Extension of Federal Regulations Harmonization of Regulatory Requirements 33

34 Proposed Revisions Specified data security protections would apply to human research, calibrated to level of identifiability of data Written consent required for research use of biospecimens even when stripped of identifiers. Allowance for use of standard short form consent for biospecimen collection that might be collected at a particular hospital 34

35 Proposed Revisions Eliminating continuing review for expedited protocols Eliminating continuing review for full committee protocols after all subjects have completed protocol interventions Clarifying exempt categories Allowing registration of exempt studies with an administrative body, not necessarily IRB but auditing would be required 35

36 Proposed Revisions Creation of a single website for electronic reporting of unanticipated problems Greater specificity about how consent forms should be written and what information they should contain All US sites in a multi-site study would be required to use a single IRB. 36

37 Historic Opportunity DHHS regulations in place since August 1979 Basic protections revised in 1981, 1991 and 2005 Common Rule issued by 15 departments and agencies in 1991 FDA regulations issues in 1980 and revised and amended > a dozen times after that 37

38 How to comment on the ANPRN UCLA OHRPP ANPRM Survey Summary Tables: DHHS and UCLA Human Research News: