Human Research: Consent, Assent, and Permission

1. Human Research: Consent, Assent, and Permission John DeBoer, M.Div, MSW Paul J. Reitemeier, Ph.D. Human Research Review Committee Grand Valley State University

2. What is Ethics? • A sustained conversation about what one ought to do in a given situation, all things considered, and why.

3. The Protection of Human Subjects • Research using human subjects is intended to benefit them and/or society, but also imposes risks on research subjects. • To help ensure that the research risks do not outweigh the benefits, human subjects research is carefully regulated. • Regulated research must comply with • 1) federal regulations • 2) state and local laws • 3) institutional policies & ethics standards • 4) codes formulated by professional groups.

4. The Protection of Human Subjects • Researchers must meet a variety of oversight responsibilities. This requires: • 1) knowing what research is subject to regulation • 2) understanding and following the rules & regs • 3) obtaining training in subject protection • 4) acceptingresponsibility for full compliance

5. Federal Regulations • Research preceded the regulations, at society’s peril and harm to individuals. • Following WWII discoveries widespread concerns arose re: atrocities committed in the name of medical research. • Legal defense at Nuremburg Doctor’s trial focused on absence of regulations or laws governing medical experimentation • International codes & guidelines for ethical human subjects research were formulated • the Nuremburg Code (1947) • The Declaration of Helsinki (1964)

6. Federal Regulations • The codes & guidelines did not end unethical human subjects research. Many examples exist. • 1950-60s  Tuskegee AL deceptive research on rural males with untreated active syphilis • Cold War era  radiation tests on hospital patients, soldiers, & children w/o consent or permission. • Leo Alexander, MD, NEJM article (1949;241:39-47)Medical Science Under Dictatorship • Henry Beecher, MD, NEJM article (6/16/1966;274;24:1354-1360) Ethics and Clinical Research. • Media story re: Tuskeegee 1972 government regulation • 1974 Congress required the DHEW (now HHS) to develop rules for the use of human subjects research 45 CFR 46

7. How often did it Happen? • 17 published clinical studies were originally identified, expanded to 50 from the studies’ own references. • The 50 studies included 186 references to further problematic studies. Pappworth (U.K.) claimed to have identified 500 papers based upon unethical experimentation. • Beecher reported on 22 of the 50 studies due to space limits. An experiment is ethical or not at its inception; it does not become ethical post hoc—ends do not justify means. There is no ethical distinction between ends and means. -- Henry Beecher, 1966

8. How did it Happen? During ten years of study of these matters it has become apparent that thoughtlessness and carelessness, not a willful disregard of the patient’s rights, account for most of the cases encountered … A far more dependable safeguard than consent is the presence of a truly responsible (sic)investigator. -- Henry Beecher, 1966

9. Federal Regulations • 22 federal agencies issued individual rules • 1991 most federal agencies & departments adopted a common set of regulations: “The Common Rule” (45 CFR 46) • Three especially vulnerable populations were given additional protections: • Subpart B – pregnant women, fetuses & neonates(<1mo) • Subpart C – prisoners • Subpart D – children • Subpart E – cognitively impaired (was never adopted)

10. Definitions • Researchers must obtain appropriate approval from the subject or guardian before conducing research. • Three key considerations: • 1) whether the activity qualifies as research • 2) whether it involves live human subjects • 3) whether it is covered research or exempt

11. 1st Question:Is it Research? • 45 CFR 46.102(d): Definition of Research • A systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. • A project or study is research if it: • is conducted with the intention of drawing conclusions that have some general applicability [dissemination], and • uses a commonly accepted scientific method

12. 2nd Question:Does it concern human subjects? • Definition of Human Subject 45 CFR 46.102(f) • living individual(s) about whom an investigator (whether professional or student) conducting research obtains: • (1) data through intervention or interaction with the individual, or • (2) identifiable private information

13. 3rd Question:Is the research exempt? • Definition of Exempt 45 CFR 46.102(i) • Research that fall into the following categories may qualify for exemption: • Research conducted in established or commonly accepted educational settings involving normal educational practices • Research involving the use of educational tests, surveys, interviews (#3: involving public officials or candidates) • Research involving the collection or study of previously existing data, documents, records, specimens, if publicly available or personally unidentifiable • Research conducted by or subject to the approval of federal department or agency heads • taste and food quality evaluation and consumer acceptance studies.

14. Who makes these determinations? • That it is research  the investigator • That it is covered research  the IRB • That it is in compliance with the regulations  the IRB • An Institutional Review Board (IRB) shall review and have authority to approve, require modifications in, or disapprove all research activities covered by this policy. 45 CFR 46.109(a) • The determination about whether particular research activities are exempt from the regulations must be made by an IRB, not by the individual investigator.

15. What are the levels of review ? • Exempt review – Research does not fall under HHS or FDA required review categories. Still subject to GVSU ethics standards. • Expedited review – Research subject to HHS and/or FDA required review categories. Reviewed by 2 HRRC members, ongoing review schedule. All regulation review elements apply. • Full Board Review– 12 committee members review, analyze and discuss toward consensus to assure that • All research subjects’ interests are protected • risk of harm is minimized, • full compliance with federal regulations & ethics standards

16. Moral wisdom is exercised not by those who stick to a single principle come what may, absolutely and without exception …but rather by those who understand that in the long run, no principle, however absolute, can avoid running up against another equally absolute principle. The key virtue therefore is practical wisdom or judgment (phronesis); the ability to discern the right and good thing to do in a given situation in terms of a particular moral choice. --- Aristotle

17. What ethical principles guide these determinations? • Nuremberg Code (1947) • Rules for permissible medical experimentation • voluntary consent • benefits outweigh risks • Subject able to terminate participation at any time without penalty or loss of privileges

18. What ethical principles guide these determinations? • The National Commission’s Belmont Report (1979) • 1. Respect for Persons • the right to make decisions about themselves (consent) without undue influence or coercion from someone else • 2. Beneficence/Nonmaleficence • the obligation to maximize benefits & reduce risks of harm to the subject • 3. Justice • the obligation to distribute benefits & risksequally and without prejudice to individuals or groups, e.g. the mentally disadvantaged or members of a particular race or gender.

19. Respect for Persons • Autonomy: self-directed living. Freedom, power & authority to make choices that are important to oneself. • Autonomy is respected & supported via process of Informed Consent: sufficient information about the research to determine whether it is in one’s interests to participate, all things considered.

20. Informed Consent • IC is aprocess:not an outcome, not a document, not a signature. • IC refers to the ongoing process of exchanging information (subject researcher) to effect a shared understandingof the research project in all matters of material relevance. • Requires positive/meaningful input from both parties.

21. Informed Consent • Material relevance: information that might reasonably be expected to make a differenceto the subject concerning whether or not to participate in the research. • Most common categories of materially relevant information include:

22. Informed Consent • It is expected that ALL research subjects will be fully informed about research in which they participate and will give their consent before they enroll. • Some subjects cannot give ethically valid consent due to age (children) or temporary or permanent cognitive impairment (mentally ill or impaired, intoxicated, extreme emotional upset, etc). • It may not be easy to decide when an individual should be allowed to give consent or how it should best be obtained.

23. Informed Consent • Only competent adults can give CONSENT • Children 7-17 years can give ASSENT • Parents or Guardians give PERMISSION • Consent and Permission are usually required to be documented in writing • Assent is usually required, but not its documentation

24. Informed Consent • Some waivers of consent, assent or permission, or alterations to the usual requirements, are allowed under 45 CFR 46.116 • Some waivers of documentation or use of alternate forms of information re: consent or permission are allowed under 45 CFR 46.117

25. Informed Consent • Waivers & alterations of IC elements require 4 separate findings by the HRRC in response to a request from the investigator: • Research involves no more than minimal risk • Subjects’ rights & welfare will not be adversely affected • Could not practicably be carried out without the waiver or alteration • When appropriate, subjects will be provided pertinent information after participation

26. General Requirements for Informed Consent Legally effective informed consent shall: • Be obtained directly from the subject or the subject’s legally authorized representative; • Be in a language understandable to the subject or representative; • Be obtained under circumstances that provide subject opportunity to consider whether to participate, and that minimizes coercion influences • Not include language waiving subjects’ legal rights or which releases investigator, sponsor or institution from liability for negligence.

27. 8 Basic Elements of Informed Consent • Statement that study involves research; explanation of purposes of research & expected duration of subject’s participation; description of procedures to be followed and identification of any procedure that are experimental.

28. 8 Basic Elements of Informed Consent • Description of the potential risks or discomforts to the subject. • Description of the potential benefits to subject or others, including society (general welfare). • Disclosure of alternative procedures, if appropriate. • Description of the extent to which confidentiality will be maintained.

29. 8 Basic Elements of Informed Consent • For research involving more than minimal risk, explanation as to whether compensation & medical treatments are available if injury occurs. • Explanation of whom to contact if questions arise about the research, the subject’s rights or whom to contact if research-related injury occurs.

30. 8 Basic Elements of Informed Consent • Statement that participation is voluntary, that refusal to participate or decision to withdraw involves no penalty or loss of benefits.

31. Additional Elements of Informed Consent 45 CFR 46.116(b) When required by the HRRC, one or more of the following elements shall be provided to each subject: • Statement that procedure may involve unforeseeable risks; • Description of circumstances under which subject’s participation may be terminated by the investigator without subject’s consent;

32. Additional Elements of Informed Consent 45 CFR 46.116(b) • Additional costs to subject resulting from participation in research; • Consequences of subject’s decision to withdraw from research; • Statement that significant new findings developed during research which may relate to subject’s willingness to continue will be provided to subject; • Approximate number of subjects involved in study

33. How do I start? • GVSU home page: Search term: HRRC • Human Subjects Review • Special forms, links, etc. • The Faculty Research and Development Center 301-C DeVos • 331-3197 or hrrc@gvsu.edu • Ms. Kelly Snyder, Grad Asst.