1 / 49

IRB review and assessment of risks / benefits

IRB review and assessment of risks / benefits. Bernard Lo, M.D. August 6, 2009. Overview of today. Why do we have IRBs? What are the federal requirements for human subjects research? What risks are acceptable in research? Case examples. Nazi “experiments”.

rosine
Download Presentation

IRB review and assessment of risks / benefits

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. IRB review andassessment of risks / benefits Bernard Lo, M.D. August 6, 2009

  2. Overview of today • Why do we have IRBs? • What are the federal requirements for human subjects research? • What risks are acceptable in research? • Case examples

  3. Nazi “experiments” • Cause intentional and lethal harm • No consent • Use vulnerable subjects who were coerced into participating

  4. Tuskegee study 1932 Study started 1936 Journal told that local MDs asked not to treat subjects 1940 Subjects not treated in military 1947 USPHS Rapid Treatment Centers

  5. Tuskegee study 1968 Whistleblower Peter Buxtun 1969 CDC, local chapters of AMA and NMA reaffirm support 1970 News coverage

  6. Tuskegee study 1974 DHEW issues regulations on funded research 1974 Tuskegee Benefit Program

  7. Fundamental tension in research • Primary goal is generalizable knowledge, benefit to society • Participants experience risks but benefit to others

  8. Ethical violations in Tuskegee • Serious harm to participants • Deliberately withholding treatment • Consent not informed • Deception during consent process • Unfair selection of participants • Take advantage of vulnerable population

  9. Regulations respond to Tuskegee • Beneficence • Risks must be acceptable in light of benefits • Risks must be minimized • Interventions that offer benefit? • Psychosocial risks?

  10. Regulations respond to Tuskegee • Respect for persons • Informed and voluntary consent • How much to participants need to understand? • Not capable of consent (children, adults who lack decision-making capacity) • Impracticable to obtain consent

  11. Regulations respond to Tuskegee • Justice • Equitable selection of subjects • Protections for vulnerable subjects • Populations susceptible to condition? • Access to benefits of research?

  12. Topics to cover • What risks must we consider? • Biomedical interventions • Secondary analysis of existing data • Survey and interview research • How to decrease risks

  13. HIV vaccine trial • Vaccine to induce cellular immunity to HIV • Subjects at high risk for HIV • Injection drug users • Multiple sexual partners • Commercial sex workers

  14. Biomedical risks of study • Injection-related adverse effects • False + HIV test

  15. Psychosocial risks of study • Behavioral disinhibition • May increase high-risk behaviors • Stigma and discrimination if confidentiality breached

  16. Measures to reduce risk • At every visit, risk reduction counseling, condoms • Monitoring of high-risk behaviors • No difference in placebo and vaccine groups • Cards, letters to explain false + HIV test

  17. Outcomes of trial • No reduction in HIV incidence • Higher incidence in men with Ad5 antibodies, uncircumcised • Research intervention may have serious unexpected adverse effect

  18. Birmingham VA research • 1.3 million MDs • SSN • Not encrypted, not password protected • Employee not authorized to have data

  19. Letter from VA • “We at the VA take information security and privacy very seriously. We apologize for any inconvenience or concern this situation may cause, but we believe it is important for you to be fully informed of any potential risk to you”

  20. How to decrease risk • Exclude persons susceptible to risk • Protect confidentiality • Train staff • Use coded or de-identified data

  21. How to decrease risk • Protect confidentiality • Security for identifiable data • No laptops or portable storage devices • Password • Encrypt files • Certificate of confidentiality

  22. How to decrease risk • Monitor for adverse events • Respond to serious adverse event

  23. Study 1: effects of cocaine on memory and attention • Subjects • Chronic cocaine users • Healthy persons • Study interviews are psychological tests

  24. Study 1: risks • If confidentiality breached • Legal risk: illegal activities • Social harm: stigma, disruption of relationships • Economic harm: loss of employment

  25. Question for audience • How to minimize risks?

  26. Study 1: How to minimize risks? • Protect confidentiality • Staff training • Use coded or de-identified data • Payment without identifiers • Data security • Locked files • Password protection

  27. Study 1: How to minimize risks? • Data security • Do not store identified data on laptops, removable devices • Encrypt files • Certificate of confidentiality

  28. Certificates of confidentiality • May withhold names and identifiers in case of subpoena or court order • Issued by NIH • Need not be NIH-funded study

  29. Certificates of confidentiality • Limitations • Not apply to audits, state reporting laws • Not definitively tested in court • Language in consent form • Exceptions are longer than protections

  30. Study 2: New HIV vaccine study • DNA plasmids express gag, pol, nef • Adenovirus vector booster that encodes for gag, pol, env • Clinical effects • More balanced CD4 and CD8 response • More immunity to HIV rather than Ad

  31. Question for audience • Do you regard benefit / risk balance as acceptable? • Yes • No • Unsure

  32. Study 2: New HIV vaccine study • How to reduce risks of study? • Is the balance of benefits to risks acceptable?

  33. How to reduce risks of study? • Exclude persons at increased risk • Adverse effects of study drug • Monitor adverse effects carefully

  34. How to reduce risks of study? • Stop trial if significantly increased infections in vaccine group • Data and Safety Monitoring Committee • Independent of sponsor and investigators • Statistical stopping rules

  35. Questions regarding Study 2 • How to combine risks and benefits into overall assessment?

  36. Federal regulations • Risks must be reasonable compared to potential knowledge gained • Risks must be minimized (consistent with valid research design)

  37. Framework for analyzing study • Underlying condition/prognosis is serious • Foregoing trial has costs • Potential benefit of study is high • Likelihood and magnitude of benefit requires in-depth scientific review

  38. Framework for analyzing study • Risk of study intervention is high • DSMB decided that any statistically significant increase in HIV incidence would terminate the study

  39. Take home message • Risks can be serious, even in secondary analysis and questionnaire research • Assessment of benefits and risks made by IRB independent of investigators

  40. Definition of minimal risk • Probability and magnitude of harm or discomfort • Not greater than encountered in daily life or routine physical exam

  41. Significance of minimal risk • May be eligible for • Expedited IRB review • Waiver of informed consent • In pediatrics, different categories of review and approval

  42. Looking ahead • When is informed consent not necessary? • Not research • Exempt from federal regulations • Waiver of consent

  43. Looking ahead • When is IRB review not necessary? • Not research • Certain survey, interview research • Certain research with existing data and biological specimens

  44. Looking ahead • When may IRB review be expedited? • Minimal risk in technical sense • On list approved by DHHS • Venipuncture • Noninvasive • Not XRs • Minor changes • Continuing review

  45. Practical IRB tips on 8/14 • Bring your questions!

More Related