The Institutional Review Board

1. The Institutional Review Board Monica B. Spaulding, M.D. Chair-Health Sciences IRB Professor of Medicine

2. Outline • What is an IRB? • Why does it exist • What do we do • IRB Reviews • Full • Expedited • HIPAA • Its impact on your research

3. What is an Institutional Review Board? • An administrative body established to protect the rights of welfare of human research subjects recruited to participate in research activities • Independent of other committees and independent of the needs of the institution • All research involving human subjects (or their records) must be reviewed by an IRB

4. Why do IRBs exist? • Historical context • Nuremburg trials • Atrocious trials done in the name of science • Tuskegee syphilis trial • 1932 -1972 study designed to look at the natural history of untreated syphilis • Willowbrook Hepatitis study • Retarded children were deliberately fed a solution including the feces of children with hepatitis

5. Rules governing IRB activity • After the Tuskegee studies were reported in The NY Times and The Washington Post, Congress acted • National Research Act of 1974 • Established IRBs • Code of Federal regulations contains broad outlines of what an IRB should do • New rules can be written or rules can be modified generally in response to bad events, such as those occurring in 1999-2000

6. Major research problems occurred between 1999-2001 • Death of a research participant in a gene therapy trial at the University of Pennsylvania • First suit against a University for clinical research • Death of a normal volunteer At JHH • Closed research activities at Johns Hopkins, the medical school with the largest federal research budget at the time • Investigations of research conduct closed research at 10 major research universities because of misconduct

7. Death of a normal subject at Johns Hopkins (1) • An investigator was studying the physiology of asthma and reactive airways • He recruited normal volunteers to inhale a drug formerly used for ↑BP • The drug had been taken off the market when better drugs were available • Since it could no longer be purchased, he made the drug in his lab

8. Death of a normal subject at Johns Hopkins (2) • The subject, a regular volunteer in research studies, developed respiratory distress about 24 hours post participation and subsequently died • Massive literature searches turned out rare reports of pulmonary problems from the drug when it was being used clinically • The FDA investigated, denied all responsibility, although they had reviewed the project • The Office for Human Research Protection investigated, found fault with the IRB and shut down all research • OHRP then reviewed the IRB activities at other institutions and faulted the system

9. Problems discovered with IRB activities across the country • Insufficient project review by the IRBs • Casual review of research projects • Lack of attention to regulations • Lack of knowledge about research regulations by those doing research • Financial conflicts of interest by those doing research

10. IRB changes since 2001 • Requirement for each researcher to complete an educational program • We use CITI, a web-based program • Potential for audits by the Office of Human Research Protection • HIPAA rules

11. Types of IRB Review • Full review • More than minimal risk • Requires review and approval (by vote) of a full IRB committee • Expedited • < minimal risk • Approved by IRB chair and designated representatives • Usually approved relatively rapidly

12. Expedited projects • Most residents will be doing expedited projects • Non invasive studies include: • Review of charts, old x-rays or other imaging studies, lab values • Or invasive studies which use simple blood draws • Approval is generally rapid • If changes are needed, we usually communicate them by e-mail • Nevertheless, give your self enough time to deal with the IRB minutiae

13. Categories of expedited review • Clinical studies on drugs and devices as long as the study does not increase risk • Blood tests, within limits • From healthy adults >110 pounds • The amount drawn may not exceed 550 mls over an 8 week period and less than 2Xs/week • Different rules for children • Biologic specimens collected by non-invasive means (scaling of teeth, nail clippings, sputum etc.)

14. Categories of Expedited Review (2) • Collection of data through non-invasive procedures routinely employed in clinical practice (excludes x-ray and microwaves) • Study of materials collected for non-research purposes • Medical record information (confidentiality important) • Collection of data by voice recordings, etc. • IRB must assure that confidentiality is assured

15. The phenomenon of continuing review • All studies must be re-reviewed at least yearly • The IRB sends a reminder • Information desired • Number enrolled • Problems encountered • Is the study still appropriate (literature review) • If the investigator does not respond to our reminder, the study will be suspended and will be closed

16. Some studies are exempt from IRB continuing review • Exempt studies are reviewed by the IRB chair, designated as exempt and a letter is sent indicating that and the applicable federal Regulation • Exempt studies do not require continuing review • Six exempt categories • Surveys, publicly available tissues or samples, food evaluations, educational tests • Note that any study done in minors, prisoners or other special populations cannot be exempt

17. Full review projects • These are generally invasive studies or utilize a new drug or drugs. • In most cases, residents are not involved as a PI in such a study • Such studies are reviewed monthly, but by the committee • The studies are reviewed closely by at least three committee members and are discussed by the full committee. • Approval takes much longer, just because of the processes involved

18. What do we review for both fulll and expedited projects? • Research design • Are the objectives clear with sufficient background information to justify the study? • Is there a reasonable statistical plan? • Does it require more subjects than can reasonably be enrolled • Are risks minimized and reasonable in relationship to any potential benefit • The informed consent • Are HIPAA requirements met

19. Informed consent • If a consent is required, there are a number of required elements • The IRB provides a template at their web site which includes the required elements • The informed consent must be written so that a 10th grader can understand it • This is very hard!

20. How should this be reviewed? • The PI is a physical therapist who wants to investigate the effect of a controlled exercise program on osteoarthritis of the knee • Eligible subjects have osteoarthritis and will be randomized to their usual activities or a program which requires supervised exercise 3 Xs/ week • All subjects have permission from their MD to participate. All will have an x-ray of their knee as part of the study and will answer weekly questionnaires about quality of life • Can this be expedited?

21. How should this study be reviewed? • A dentist is interested in why students chose to have oral piercings • He develops a survey in which high school students will be asked a variety of questions incl. • Do you have any oral piercings? • Have you ever considered having one? • Did you have any hesitation about a piercing. If so, what were your concerns? • The survey is anonymous, without an IC • What kind of review should this be?

22. What should be in the IC? • Clear indication that this is research • Description of what will be done • Description of risks and benefits • Indicate that participation is ‘voluntary’ • alternatives to participation and what these are? • A statement about compensation for potential injury is needed. • Usually the statement says that there is no compensation

23. IRB decisions • Approval without any changes • Approval pending minor changes • Most common • For expedited projects those revisions are usually handled by e-mail • Tabled • Major questions have been raised about the study design, but the study is believed to be worthwhile • Disapproved (rare)

24. Other IRB communication • Once approved, the study must be done as described • Changes to the study or to the informed consent need to be approved by the IRB • Ads must be approved • Deviations from the proposal need to be sent to the IRB

25. IRB Committees at UB • Social and Behavioral • Studies which are not invasive • Usually cover studies done on the Amherst campus • Womens and Childrens Hospital • For those <18 unless emancipated adults • All studies on pregnancy come to HS-IRB • Health Sciences IRB • Invasive studies • Medical records • Studies which may have HIPAA issues

26. HIPAA – Health Insurance Portability and Accountability • The law was written to protect individuals from losing insurance with a job change • Congress was supposed to define and establish guidelines for medical privacy but didn’t get around to it • Thus the law was written by the Department of Health and Human Services • Clearly it has far reaching effects, particularly in research

27. HIPAA authorization • Researchers can create PHI, access and receive PHI by reviewing records • If this is being done prospectively, the patient must authorize the release of information • The authorization may be included in the whole informed consent or be a separate document

28. Waiver from an authorization • Retrospective medical record review • If possible, consents from the involved individuals are needed • This is impossible in many cases • Subject has died or has moved • A waiver allows you to access that information, providing that • There is a plan to protect the information • It is coded or somehow secured • Statement that the research cannot be done without it • You indicate why obtaining a consent is impossible

29. De-identified data • Data that is de-identified, according to 18 identifiers, is not subject to HIPAA rules • But the investigator must get the data when it has been de-identified • Removing identifiers and storing data under a secure code doesn’t fulfill the letter of the law

30. Conclusion • Institutional Review Boards exist to protect participants in research • IRBs also protect researchers • Second opinion about research quality • Is the question worth asking? • Is the study being done in the safest way? • Can the question be answered? • Can it be statistically justified? • HIPAA concerns are so far manageable, although an added burden for many

31. Questions • Health sciences IRB • 150 Parker Hall • Phone 829-2752 • Contact: IRB office • Website: • www.research.buffalo.edu/humansubjects/IRB/healthsciences