The IRB: Friend or Foe?

1. The IRB:Friend or Foe? Margaret J. Neff, MD MSc Assistant Professor of Medicine Pulmonary & Critical Care Medicine

2. Getting things through the IRB • Why does it matter? • Basic requirements • Lay-out of the UW IRB • Specific scenarios • Screening, consent, database reviews • Helpful tips

3. Past Research • 1930s-40s: Nazi war • crimes & experiments • 1971 Stanford Prison • Experiment • 1932-1972 Tuskegee • Syphilis Experiment

4. Recent Research • 1999 U Penn gene transfer study (Jesse Gelsinger); followed incl/excl criteria?, safety monitoring?, informed consent?, conflict of interest? • 2001 Johns Hopkins asthma study (Ellen Roche); hexamethonium; who is responsible for researching safety?

5. Common Themes • Lack of informed consent • Risk >>>>> benefit • Risk assessment not complete • Vulnerable populations • Students; employees • Poor safety oversight • Conflict of interest

6. Penn Duke Johns Hopkins U of Illinois-Chicago U Colorado West LA VA Rush Presbyterian Virginia Not a list we want to join…… Troubled Waters

7. Ethical Codes Guiding Clinical Research (Human Research) • Nuremberg Code: 1947 • Declaration of Helsinki: 1964 • The Belmont Report: 1979

8. Regulations Pertaining to Clinical Research • U.S. Code of Federal Regulations • Health and Human Services • 45 CFR 46 (protection of human subjects) • Food and Drug Administration • 21 CFR 50 (protection of human subjects) • 21 CFR 56 (institutional review boards) • State Law • Washington Administrative Code (WAC) • Institutional policies, sponsor

9. Criteria for approval of research • Risks minimized and reasonable in relation to anticipated benefits • Subject selection is equitable • Informed consent sought • Informed consent documented • Plan data safety monitoring • Provisions for privacy/ confidentiality • Additional safeguards for vulnerable populations www.access.gpo.gov/nara/cfr

10. Design of IRB • At least 5 members • Varying backgrounds, gender • At least 1 scientist & 1 non-scientist • At least 1 not affiliated with institution • No conflict of interest with study reviewing • May invite consultants to review www.access.gpo.gov/nara/cfr

11. Univ. of Washington IRB • Multidisciplinary membership • MDs, RNs, pharmacists, lawyers, students, community members • 6500 protocols reviewed/year • 10 committees • 3 biomedical, 3 behavioral, 3 minimal risk, 1 VA • Full-time staff but other members are primarily volunteering their time • Western IRB: now used for all industry-sponsored trials

12. When do you need IRB approval? • When you’re conducting “human subjects research” • Any study where results are intended for dissemination as research (vs QI) • Patient info or patient samples • Waiver of consent possible in some instances: • De-identified data • 18 specific data points removed • Limited data set • Meet specific criteria (emerg research; records review, etc)

13. Types of Review • Full committee review • Most studies • Expedited review • Generally only for database/registry work • No patient contact, no interventions • Using data already available • May qualify for certificate of exemption

14. General Issues Prior to Review • Do you have the resources to do it? • Coordinator? Funds? Enough time? • Any financial conflict of interest? • Taken ethics/IRB training? • Required for NIH and VA studies; soon for all UW studies • Clinical Research Budget & Billing • Made contact

15. The IRB Submission Process • Complete application, get dept signatures • Submit application (include a cover letter with a “howdy, here’s what we’re doing” and address any anticipated problem points; brief) • Once at the IRB: • Pre-screening • Full review with deferral or approval • Committee letter • Your response • Re-evaluated in sub-committee • Back to full committee, hopefully to approve

16. Who is it you’re hearing from? • Each committee: • Chair, members, administrator, and coordinators • The administrator pre-screens the study and often contacts you for clarifications prior to first review • Get to know this person • If complex study, go and meet • Offer to come to the committee meeting (or be available by phone) if anticipated questions/problems • Be nice and not defensive

17. Some common pitfalls • Application should be understandable to an educated, lay audience (the IRB members) • Avoid lots of cutting and pasting of text • Be organized! Be consistent. • Make it easy to read (not tiny font) • Think of it like a grant you’re submitting • Be thorough and follow the instructions • Appropriate # copies, answer all questions • If you don’t know what they mean, ask!

18. Screening/Recruitment • Screening for potential subjects • Waiver of consent for screening • Confidentiality agreement • Need to report each time access chart • Recruitment • Include any flyers or website notices • Generally try to allow potential subjects to call you rather than “cold calls.”

19. Subject approach • Avoid any appearance of coercion • Initial introduction by non-research personnel • Ideally have clinical personnel separate from research personnel

20. Privacy/Confidentiality • Minimize identifiable information on data collection forms; no names • No identifiable elements on screened, non-enrolled (non-consented) subjects • Describe mechanism for safeguarding data • Plan for destruction of any links and the data as soon as possible (but feasible)

21. Risks and Benefits • Don’t exaggerate the benefits • Be honest about the risks • Usually “death” is always a risk in any intervention study • Often useful to group by common and rare risks • How you’ll deal with any adverse events • Who pays? • Who pays for research studies? • In most cases, it’s the sponsor • For NIH or investigator initiated: UW Compensation plan

22. Consent • Utilize the consent template (some standard wording and sections) • Assent form for children as well • Language: • 8th grade reading level • “Subject” not “patient” • Go through consent checklist

23. Obtaining Consent • Subject needs adequate time and information to make a decision • Competency must be assessed • If limited, at minimum need assent • Consent is invalid if subject is pressured or coerced • Ideally assess comprehension

24. Who Can Consent? • Subject him or herself • Legally authorized representative • This varies state-to-state whether allowed and what order is followed • In Washington, it’s based on WAC guiding clinical decision making, extrapolated to research • Guardian, Subject, DPOA-HC, spouse, adult children, parents, adult siblings • Who consents for clinical procedures may vary but for research, this order is strictly adhered to • Recent changes clinically for domestic partners

25. Waived Consent for Emergency Research • “Should the needs of the many ever outweigh the needs of the one?” • Waived consent (e.g. pre-hospital, MI, stroke) • Specific criteria must be met and documented • If criteria for waived consent are met • No more than minimal risk • Will not adversely affect rights of subjects • Research not practical without waiver • Provide info to subjects at later date • May require survey and notification of community

26. Other Issues • Federal Certificate of Confidentiality • If “sensitive” questions about drug and alcohol abuse • Vulnerable subjects • Prisoners, pregnant women, children • Registration of clinical trials

27. Tips for Interacting with the IRB • They are there to help you and to protect the subjects and the ability to do research here at all! • Research is a privilege, not a right • Be prompt in responses • Be cordial

28. May not be consistent committee to committee • Each is independent but this is improving; moving towards sending all of 1 type of specialized study to 1 committee

29. There may be delays and lots of questions that seem not relevant • They’re trying to best understand the study • If you don’t understand what they’re getting at, call them. Maybe they didn’t understand something you’re trying to do. • Offer to meet the administrator or go to the meeting. Resolve the problems up front. • Try to explain your intent

30. Resources • IRB website: • http://www.washington.edu/research/hsd/ • Clinical Research Budget & Billing: • http://www.uwmedicine.org/Research/ ResearchBudgetBilling/ • HIPPA resources: • http://privacyruleandresearch.nih.gov/ • http://www.hhs.gov/ocr/hipaa/ • Me: mneff@u.washington.edu