Human Subjects Research 101 Revised January 2008

1. Human Subjects Research 101Revised January 2008

2. Presentation Goals • Discuss Human Subjects Research • Definitions • Historical Background • Identify Ethical and Legal Requirements • Belmont Report • 45 CFR 46 – “The Common Rule” • Describe Institutional Review Board • Structure & Policies • Implications For Student Research

3. Why Discuss Human Subjects Research? • Federal guidelines • Messiah College policy regarding all research involving human subjects • Preparation for graduate studies

4. What Is Human Subjects Research? – Part I Federal definition of research A systematic investigation, including research development, testing, and evaluation designed to develop or contribute to generalizable knowledge.

5. What Is Human Subjects Research? – Part II Federal definition of human subject A living individual about whom an investigator (professional or student) conducting research obtains • Data through intervention or interaction with the individual, or • Identifiable private information.

6. Definitions Continued • Intervention includes both physical procedures by which data are gathered and manipulations of subject or subject’s environment that are performed for research purposes. • Interaction includes communication or interpersonal contact between investigator and subject.

7. Definitions Continued • Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public.

8. Historical Background

9. The Nuremberg Trial • Trial of Nazi doctors who experimented on 300 Dachau concentration camp prisoner-subjects, of whom 30% died. • Held from December 9, 1946 to August 20, 1947. • 23 defendants charged with murder, torture, and other atrocities committed in the name of medical science. 15 found guilty.

10. Nuremberg Code - 1947 • Written as part of the judgment of the Nazi trials. • Became the “ethical yardstick” by which the defendants had been measured and guilt determined. • Essential reading for everybody involved in human subject research.

11. Principles of Nuremberg Code • Voluntary informed consent is essential • Research should yield useful results • Risk must be outweighed by importance of research • Base research on prior animal experiments • Avoid physical and mental suffering

12. Principles of Nuremberg Code(continued) • Only qualified scientists may conduct research • Subjects may withdraw from study • Investigators must be willing to withdraw subjects • No expectation of death or disabling injury

13. Effect of Nuremberg Code • Code largely ignored until 1964 because researchers did not see the relevancy to their own work • Hippocratic oath • Missed a lot of important aspects of research • Children and informed consent • People with diminished mental capacity and informed consent

14. Declaration of Helsinki - 1964 • Rules developed by researchers and physicians • Reinterpretation of Nuremberg • Became required for publication in scientific journals to state that the research abided by the Declaration of Helsinki

15. Public Health Service Policy • 1966: All PHS supported research must undergo prior review to: • Protect the rights and welfare of subjects • Assure appropriate informed consent • Determine acceptable risk/benefit balance Beginnings of the IRB (Institutional Review Board)

16. Era of Standards • Standards accepted by researchers • Standards accepted by the media • Standards became the accepted principles for judgment of research • Thalidomide Trial • Jewish Chronic Disease Study • Willowbrook Hepatitis Study • Hidden Recorder Studies • Milgram Study • Tuskegee Study

17. The Tuskegee Study • Purpose: identify the natural history of untreated syphilis • Began in 1932 • Involved 300 black males with syphilis • 1933 – added 300 controls • Was initially supposed to last 1 year • Study stopped in March of 1973 after government investigations and public pressure

18. Syphilis Study Problems • Lack of respect for persons • No informed consent • Deception • Coercion • Lack of good will to subjects • Withholding effective treatment (penicillin) • No continuing review of the research • Unjust • Used an extremely vulnerable population: illiterate, poor farmers in rural Alabama

19. Response to Research Abuses • 1974 – Congress passes the National Research Act • Requirements for informed consent • Necessary review of research by IRB • May 1974 – First version of 45 CFR 46 • April 1979 – The Belmont Report • 1981 – Revision of 45 CFR 46 • 1991 – Common Rule: 56 FR 28003 • 2001 – Latest revision of 45 CFR 46 incorporates Common Rule

20. The Belmont Principles: How They Came About • 1974 – establishment of the National Commission by the federal government • Task • “Identify basic ethical principles that underlie the conduct of human research.” • Develop guidelines to ensure that human research follows these principles • 1979 – The Belmont Report: current set of federal regulations

21. The Belmont Principles • Respect for persons • Beneficence • Justice

22. Respect for Persons • Treat individual as autonomous agents • Do not use people as a means to an end • Allow people to choose for themselves • Give extra protection to those with limited autonomy and have an inability to choose for themselves

23. Beneficence • Do no harm • Prevent harm • Prevent evil • Promote good • Maximize possible benefits and minimize risk • Benefits to individual and/or to society • Risk: consider physical, social, legal, economic, psychological

24. Justice • Fair sharing of burdens and benefits of research • Selection of subjects should not systematically draw from certain classes simply because of their easy availability • Inclusion of diverse populations/groups • Subjects should have a future chance of benefiting personally from the subsequent applications of research findings

25. Rules Derived From Principles • Respect for persons • Informed Consent • Respect for privacy • Confidentiality • Anonymity • Beneficence • Good research design • Competent investigators • Favorable risk/benefit analysis • Justice • Equitable selection of research subjects

26. Conflict in Belmont Principles • Conflict is expected • Sometimes decisions that are made utilizing the principles may yield different outcomes, depending on which principle is being considered: one decision is to approve the research, one to limit the research, one to deny the research • Remember: all 3 principles are on equal footing with equal moral force. • Consider each situation individually • Carefully review the principles • Avoid the tendency to always put one principle above another

27. Code of Federal Regulations45 CFR 46

28. Title 45 of CFR Part 46 • Codified by the government in 1991 • Based on Belmont Principles, 56 FR 28003 • Title 45: Public Welfare and Human Services • Part 46: Protection of Human Subjects • Last revised in November 2001 • Supporting agencies • Department of Health & Human Services • National Institutes of Health • Office for Human Research Protections

29. Title 45 of CFR Part 46 • Subpart A – Basic DHHS Policy for the Protection of Human Research Subjects • Subpart B – Pregnant Women, Human Fetuses and Neonates Involved in Research • Subpart C – Prisoners • Subpart D - Children

30. Institutional Review Board (IRB)

31. Institutional Review Board • DHHS requirement for all human subjects research sponsored by federal agencies • Regulations for IRB found in 45 CFR 46.107-123

32. IRB Structure • Minimum of 5 members with varying academic backgrounds • Every nondiscriminatory effort will be made to ensure diversity (e.g., race, gender, cultural) • One member who primary training is in nonscientific areas • One member whose primary training is in scientific areas • One member from the community

33. Primary Duties of IRB • Protect human subjects from undue risk & deprivation of human rights and dignity • Ensure confidentiality and voluntary participation of subjects • Balance potential benefits with risks • Determine appropriateness of research design & study methods • Assist researcher through peer review and institutional approval • Ensure research compliance with DHHS regulations & other funding agencies

34. Is Any Research Exempt From Review? Yes, if the research involves no more than minimal risk to subjects, no ethical concerns, does not involve vulnerable subjects, and meets at least one of the exempt research categories established by the government regulations. IRB chair can make this determination.

35. ExpeditedReview • Nine governmentally designated research categories that allow for expedited review • Proposal distributed to all IRB members and all must agree on expedited review • Approval by one designated reviewer • Reviewer cannot disapprove research. Must go to full IRB for rejection. • Decision reported to IRB at next meeting

36. Informed Consent

37. InformedConsent • “Informedconsent is a process of information exchange that takes place between the prospective subject and the investigator, before, during, and sometimes after the study.” Dunn & Chadwick (1999), Protecting Study Volunteers in Research • Information • Comprehension • Voluntariness

38. Research Purpose/Duration Procedures Experimental Risks Benefits Alternatives Confidentiality Compensation for injury Whom to contact re: Study, subject’s rights, event of injury Right to refuse or withdrawn Essential Basic Elements

39. Additional Elements • Currently unforeseeable risks • Termination of participation • Additional costs to subjects • Consequence of withdrawal • Informing of new findings • Number of subjects

40. Other Considerations • There are situations where DHHS regulations allow for waiver of informed consent. • There are also situations where DHHS regulations allow for exception to providing written documentation of informed consent.

41. Informed Consent Process • Sufficient time to make decision • Sufficient opportunity to ask questions • Strategies to minimize coercion • Avoid overstating benefits • Ensure an understanding of risks/benefits • Be sensitive to subject’s needs

42. Informed Consent Process • Train individuals obtaining consent • Fully explain use of technology or innovative approaches • Make adjustments in process, as necessary • Obtain IRB approval for changes

43. Implications For Faculty and Student Research

44. WhatDoesThisMeanForMe? • MC policy applies only to research in certain cases; determination can be made by IRB in consultation with IRB chair. • Approval must be obtained from the IRB prior to beginning research, including any research that will be disseminated beyond the classroom, including public presentations and publications. • Student projects that will not be disseminated beyond the classroom are considered course assignments and not subject to regulations. • However, all research must be done with due consideration of Messiah’s ethical and legal responsibility to protect subjects.

45. Research Likely Exempt From Review - #1 Educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior, if minimal risk, no correlation between subjects/responses, and no vulnerable population included. (Category #2)

46. Anonymous Versus Confidential • Anonymous: No way to trace responses to an individual person. Will not use any coding system or be able to trace responses to a person (e.g., ethnicity, gender, etc.) • Confidential: Can trace responses to an individual, even though this may not be revealed beyond the investigative team.

47. Research Likely Exempt From Review - #2 Research involving the collection or study of existing data, documents, records, or specimensif these sources are publicly available or the information is recorded in such a way that subjects cannot be identified, indirectly or through identifiers linked to the subjects. (Category #4)

48. Research Likely Exempt From Review - #3 Taste and food quality evaluation and consumer acceptance studiesifwholesome foods without additives are consumed or food contains ingredients approved by FDA, EPA, or USDA. (Category #6)

49. If You Plan on Conducting a Research Study • Complete Form 100 – Request for Review of Faculty Project • If a student: Work with course professor to complete Form 050 – Request for Review of Student Project • Submit application and proposal to Provost’s Office, Box 3016. • If you have questions, contact Jenny Dose, IRB Chair (ext. 2320).