Ethical Issues for Human Subjects Research

1. Ethical Issues for Human Subjects Research Role of IRBs

2. I. Purpose of Human Subjects Research • Understand Disease • Validate New Therapies • Understand Physiological Processes • Study Human Behavior • Evaluate Curricular Changes • Evaluate New Teaching Methods

3. Ethical Issues in Research • When using humans or animals for research, important ethical issues must be addressed • Historically, these issues were addressed by the professional code of ethics • Codes of conduct have evolved and now have been codified into law.

4. Ethical Issues in Research • World War II—The Nuremburg Trial • Joseph Mengele and unethical experiments performed by Nazi doctors

5. Ethical Issues in Research • World War II-The Nuremburg Trial • 20 doctors were charged with War Crimes and Crimes against humanity • Joseph Mengele fled and was not tried • Lead to Nuremburg Code of 10 Principles

6. Nuremburg Code • Requires voluntary consent • Experiments must be rational • Experiments must be based on animal studies and knowledge of the disease • Experiments should avoid suffering • No experiment should involve excessive risks, except in those studies where physical experimental physicians also serve as subjects

7. Nuremburg Code • Degree of risks should be determined by importance of the problem • Precautions should be taken to avoid against even remote possibilities of injury, disability, or death • Experiment should be conducted only by scientifically qualified persons • Subjects should be able to end experiment at any time • The scientist in charge must be prepared to terminate the experiment at any stage, if they believe the experiment is likely to result in injury, disability, or death to the subject

8. Ethical Issues in Research • Unfortunately, codes were not always followed: • Tuskegee Syphilis Study-USPHS-1930’s • Not treated even after penicillin discovered • Jewish Chronic Disease Hospital • Patients injected with cancer cells • Midgeville State Hospital • Investigational drugs used without consent

9. Ethical Issues in Research • Willowbrook State Hospital-1970 • Retarded injected with viral hepatitis • US Department of Energy-1950s-60s • Studies on radioactive fallout • University of Iowa-1940s • Research on stuttering in orphans home • Johns Hopkins-2001 • Asthma study with hexamethonium

10. National Research Act • Increased Public concern led to congressional action and National Research Act of 1974 • President Nixon then established National Commission for the Protection of Human Subjects of Biomedical and Behavioral research • Commission charged to consider: • Boundaries between practice and research • Assessment of role of risk vs. benefit in research • Guidelines for selection of subjects • Informed Consent

11. Belmont Report • National Commission submitted the Belmont Report to President in 1979 • Led to 1981 revision of 1974 guidance (45 CFR 46) for human research committees • 45 CFR 46-has become the bible for reviewing research funded by DHHS • Required appointment of Institutional Review Boards or IRB’s to review human subject studies • Provided standards for appointment of IRBs, record-keeping and oversight in research

12. 45 CFR 46 • Revised in 1983 and 1991 • In 1991 revisions referred to as Common Rule • Adopted by 15 federal agencies, not just DHHS • Institutions with NIH funding must submit assurance of compliance to OHRP, DHHS • After February 28, 2001-assurances must cover all research at institution, not just NIH

13. II. Institutional Review Boards • Makeup of IRB • At least 5 members • Male/Female • Professionals/laypersons • External “non-affiliated” member • Must represent community • Lay person must be at meeting for reviews

14. II. Institutional Review Boards • IRB’S must be guided by principles outlined in Belmont Report: • Respect for persons: respect for patient autonomy • Beneficence: maximize benefits and minimize harm • Justice: Equitable distribution of research burdens and benefits

15. III. IRB Review of Research • Three categories of Review: • Exempt • Expedited • Full Review

16. IRB Review of Research • Exempt-by Chair or Administrator • Research in educational settings involving normal educational practices • Instructional strategies • Effectiveness of instructional techniques • Comparison of techniques or curricula, etc.

17. IRB Review of Research • Exempt-by Chair or Administrator • Research involving educational tests (cognitive, diagnostic, aptitude) • Unless • Names or identifiers are recorded and • Disclosure could put subject at risk of criminal liability or affect employability

18. IRB Review of Research • Exempt-by Chair or Administrator • Survey research without identifiers; interviews, observation of public behavior • Unless • Names or identifiers are recorded and • Disclosure could put subject at risk of criminal liability or affect employability

19. IRB Review of Research • Exempt-by Chair or Administrator • Collection or study of existing data, documents, records, pathological or diagnostic specimens • If the sources are publicly available, or • If information is recorded so that the subject cannot be identified, directly or indirectly

20. IRB Review of Research • Exempt-by Chair or Administrator • Research and demonstration projects conducted by or subject to approval by DHHS to study, evaluate or examine: • Public benefit or service programs • Procedures for obtaining benefits or services from these programs • Other changes in these programs • Taste and food quality evaluation and consumer acceptance studies

21. IRB Review of Research • Expedited Review • Research activities reviewed by Chair or designee • Two cautions however: • Only for activities involving minimal risk-i.e., no more risks than those in everyday life • Cannot be used if subject responses might pose civil or criminal risk to subject, unless • Reasonable protections can be implemented so that risks related to invasion of privacy and breach of confidentiality are minimal

22. IRB Review of Research • Expedited Review-Categories eligible • Some studies of approved drugs or devices • Collection of blood from adults • Not to exceed 550mL in 8 weeks • Not more often than 2 times per week • Collection of specimens by non-invasive means: sweat, excreta, amniotic fluid, hair, teeth, plaque

23. IRB Review of Research • Expedited Review-Categories eligible • Collection of data through non-invasive means, excluding X-ray and microwave • EKG, ECG, MRI, weighing, thermography, ultrasound, doppler blood flow, exercise, flexibility testing, etc. • Research involving data, records, specimens collected, or that will be collected solely for non-research purposes • Collection of voice, video, digital, or images made for research purposes

24. IRB Review of Research • Expedited Review-Categories eligible • Research on individual or group characteristics or behavior including: • Perception, cognition, motivation, identity, language, communication, beliefs or practices, etc. • Research involving surveys, interview focus groups, program evaluations, or quality assurance methods • Continuing reviews for previously approved projects • Minor changes in previously approved research

25. IRB Review of Research • Full Review-Full Committee • Investigational drugs, devices, invasive techniques (PET scan), implants, etc. • Higher risk research • NOTE-research not approved by IRB cannot be approved by higher authorities, however approved research may be disapproved by higher authorities

26. IV. IRB Approval • To be approved: • Risks must be minimized by sound research design • Risks must be reasonable in relation to benefits • Selection of subjects must be equitable • Informed consent will be sought from each subject

27. IRB Approval • To be approved-continued: • Informed consent will be appropriately documented • When appropriate, research plan must ensure continued safety of subjects • Where appropriate, provisions made to protect privacy of subjects and data • When working with subjects vulnerable to coercion, must consider added safeguards

28. Continuing Review • For research continuing more than one year, an annual review is required • New standards under review: • Will probably require IRB monitoring of some clinical trials • Constant assessment of conflict of interest of the investigators

29. Informed Consent • Not needed for exempt studies • Required for Expedited Review-but may be simplified for low risk studies • Rigorous consent for Full Review projects • May be waived by IRB for emergency Medicine research-controversial issue

30. Informed Consent • Consent must address critical elements or points outlined by Federal Law • Consent signed by subject or legal representative and investigator • Subject must be given copy of consent • No exculpatory language may be used in the written consent

31. Basic Elements of Consent • Explanation of purpose and duration • Description of risks • Description of benefits • Disclosure of alternatives to participation

32. Basic Elements of Consent • Explanation of Confidentiality of Records • Who to contact regarding patient rights • For research with more than minimal risks, comment on compensation and care for injury • Right to withdraw without prejudice • Statement regarding unforeseen risks, especially to unborn child

33. Additional Elements for Consent • Statement that investigator may terminate patient participation • Information regarding any costs • Statement regarding consequences of withdrawing-especially for drug studies • Number of subjects in study

34. Special Populations-Children • Special Considerations • Children are persons who have not attained the legal age for consent to treatments or procedures involved in research • Research not involving greater than minimal risk may be approved: • With assent of the child and permission of parents

35. Special Populations-Children • Special Considerations • Research involving greater than minimal risk and the prospect of direct benefit to the child may be approved: • If the risk is justified by the anticipated benefit • The relation of the benefit to risk is at least as favorable to subjects as the alternative approaches • With assent of the child and permission of parents

36. Special Populations-Children • Special Considerations • Research involving greater than minimal risk and no prospect of direct benefit to the child may be approved: • If the risk represents a minor risk over minimal risk • If the intervention presents experiences that are reasonably similar to those in actual medical, dental, social, psychological, or educational situations • If the intervention is likely to yield generalizeable knowledge about the disorder or condition • With assent of the child and permission of parents

37. Special Populations-Children • Special Considerations • Assent of the child • Usually verbal-confirmed by parents • “Assent” cam usually be provided by children over six years of age-but varies based on maturity and psychological state • Failure to object should not, absent affirmative agreement, be construed as assent

38. Special Populations-Prisoners • Special Considerations • IRB membership • Majority of members must have no association with the prison • Must include a prisoner, or prisoner representative with experience to serve in this capacity

39. Special Populations-Prisoners • Special Considerations • The research may be approved if: • The advantages of participation are not “enticing” or prohibit good judgment • Risks are similar to those for non-prisoner research • Consent is understandable to prison population • Decision to participate will not affect parole

40. Special Populations-Prisoners • Special Considerations • Permitted Research: • Study of causes, effects, or processes involving incarceration • Study of prisons as institutional structures or of prisoners as incarcerated persons • Study of conditions affecting prisoners as a class • Vaccine trials for diseases prevalent in prisons • Study of social behavior of prison population

41. VI. Federal Oversight • FDA spot checks IRBs to monitor compliance with drug and device studies • Recent problems at Rush, Duke, UIC, U of Colorado, U of Oklahoma, and Hopkins have prompted calls for greater scrutiny of IRBs

42. VI. Federal Oversight • New 2000/2001 DHHS guidelines require: • Training of investigators and “key” personnel in human research protection • Certification by investigators that they have received training (NIH offers on web) • Certification that investigator has no conflict of interest • Monitoring of clinical trials by IRB

43. VI. Federal Oversight • Education on “Responsible Conduct of Research” • Nine Areas: • Data acquisition, management, sharing, ownership • Mentor, trainee practices and responsibilities • Publication practices and responsible ownership • Peer review

44. VI. Federal Oversight • Education on “Responsible Conduct of Research” • Nine Areas: • Collaborative science • Human subjects • Research involving animals • Research misconduct • Conflict of interest and commitment

45. VII. New HIPAA regulations • Health Insurance Portability and Accountability Act of 1996 • Privacy Rules effective April 14th, 2001 • Health insurers must safeguard personal health information • May not disclose to employers for employment-related decisions • However, information can be used for research approved by a properly convened IRB • http://www.hipadvisory.com/regs/finaladvisory/gresearch.htm

46. HIPAA allows research with conditions • If material has been or can be de-identified, no conflict with HIPAA regulations • Appropriate if records custodian uses data • Often not practical to disclose since records custodian may simply state this is too difficult

47. HIPAA allows research with conditions • To use or disclose data without patient authorization: • Discloser (records custodian) must document that waiver (of consent) has been obtained from an IRB or • Researcher must represent in writing or orally, that disclosure is preparatory to research, and no records will be removed or • Researcher must represent in writing or orally that the disclosure is for research on decedents • Document of death may be required by disclosure

48. Laboratory Research Animals

49. Laboratory Research Animals • All NIH funded research with animals requires IACUC approval • IACUC or Institutional Animal Care and Use Committee must meet NIH standards • Scientist • Non-scientist • Non-affiliated member • Veterinarian

50. Laboratory Research Animals • Functions of the IACUC • Review animal care and use program every six months • Inspect facilities for housing animals every six months • Prepare reports o reviews for Institutional Official • Review concerns involving animals at institution • Make recommendations regarding program to Official