Moral Obligations to Research Subjects

1. Moral Obligations to Research Subjects Jan C. Heller, Ph.D. Office of Ethics and Theology Providence Health and Services

2. Presentation Outline • Introduction • What we hope to accomplish today… • Special challenges in the ethics of human subject research • Selected regulations for IRBs • Implications of relevant Ethical and Religious Directives for Catholic Health Care Services (ERDs) • Discussion and questions

3. Special Challenges • The most heavily regulated part of biomedical ethics, requiring specialized knowledge to maintain competence • Increasingly rapid pace of discovery and movement from laboratory to clinic complicate the ethical challenges • E.g., Human Genome Research in 1990’s (information overload)

4. Special Challenges • Human subject research is also a mission challenge for Catholic health care • E.g., As people of Providence, we reveal God’s love for all, especially the poor and vulnerable, through our compassionate service. • Given this mission, an ethical question immediately arises… • To whom is our compassion directed? • That is, whose good are we promoting?

5. Special Challenges • Human subjects certainly qualify as vulnerable • But, with few exceptions, the benefits (if any) of the research will be realized by future patients • The investigator is seeking new knowledge (basic science) or to test new prophylactic, diagnostic, or therapeutic procedures or devices (applied science), not the direct benefit of the human subjects

6. Special Challenges • Thus, there is a fundamental and inescapable conflict of interest in human subject research between the aims of the research and the needs of the patients who enroll as subjects • Research vs. therapy; Subject vs. patient • Research is not therapy and subjects are not patients, and this is easily misunderstood or forgotten • Does this mean we should not be involved in human subject research? • No, but we must be careful to understand this conflict, always to disclose it, and never to forget it

7. Selected Regulations • General and permanent rules for human subject research are published in the U.S. Code of Federal Regulations (CFR) • Protection of Human Subjects, Title 45, Part 46 • Subpart A, “the Common Rule,” regulates the conduct and support of human subject research • http://www.access.gpo.gov/nara/cfr/waisidx_05/45cfr46_05.html

8. Selected Regulations • Issues to be addressed by IRBs: • The scientific integrity of the research protocol • The level of risk to the study participant [subject] • The quality of the informed consent form • David J Mazur, Evaluating the Science and Ethics of Research on Humans, p. 21 • “The work of the IRB is complicated by this need to focus onboth science and ethics in the decision to approve or reject a study.” • Mazur, p. 23, emphasis added

9. Selected Regulations • (1) Risks to subjects are minimized: (i) By using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes. • Title 45, Part 46, Subpart A, Section 46.111

10. Selected Regulations • (2) Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the IRB should consider only those risks and benefits that may result from the research (as distinguished from risks and benefits of therapies subjects would receive even if not participating in the research). The IRB should not consider possible long-range effects of applying knowledge gained in the research (for example, the possible effects of the research on public policy) as among those research risks that fall within the purview of its responsibility.

11. Selected Regulations • (3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons.

12. Selected Regulations • (4) Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with, and to the extent required by Sec. 46.116. (5) Informed consent will be appropriately documented, in accordance with, and to the extent required by Sec. 46.117. (6) When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.

13. Selected Regulations • (7) When appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data. (b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

14. Selected Regulations • …the IRB shall be able to ascertain the acceptability of proposed research in terms of institutional commitments and regulations, applicable law, and standards of professional conduct and practice. • Title 45, Part 46, Subpart A, Section 46.107, emphasis added • Federal regulations recognize that IRBs should work within constraints of institutional values

15. Relevant Ethical and Religious Directives • Directive 4: A Catholic health care institution, especially a teaching hospital, will promote medical research consistent with its mission of providing health care and with concern for the responsible stewardship of health care resources. Such medical research must adhere to Catholic moral principles. • Research not prohibited, but must be consistent with therapeutic intentions of health care mission • Research and the management of research are expensive—needs good stewardship (vs. allocation of funds for clinical needs) • Must adhere to Catholic moral principles (some not spelled out, but only inferred to in ERDs or known from other sources)

16. Relevant Ethical and Religious Directives • Directive 31: No one should be the subject of medical or genetic experimentation, even if it is therapeutic, unless the person or surrogate first has given free and informed consent… • This may conflict with certain recent emergency related research protocols, but is otherwise consistent with Federal Guidelines

17. Relevant Ethical and Religious Directives • Directive 51: Nontherapeutic experiments [i.e., not intended to benefit the subject] on a living embryo or fetus are not permitted, even with the consent of the parents. Therapeutic experiments are permitted for a proportionate reason with the free and informed consent of the parents or, if the father cannot be contacted, at least of the mother. Medical research that will not harm the life or physical integrity of an unborn child is permitted with parental consent [i.e., research on pregnant women]. • Constraints on certain types of research and subjects…

18. Relevant Ethical and Religious Directives • Directive 66: Catholic health care institutions should not make use of human tissue obtained by direct abortions even for research and therapeutic purposes. • Possible exception: certain vaccines • More constraints, though not grounded strictly in moral concerns but rather in political concerns

19. Relevant Ethical and Religious Directives • Directives 56-57: A person has a moral obligation to use ordinary or proportionate means of preserving his or her life…A person may forgo extraordinary or disproportionate means of preserving life… • A more subtle concern to consider when trying to enroll dying patients in research protocols • E.g., What counts as a “disproportionate means” in cancer research?

20. Relevant Ethical and Religious Directives • Directive 69: If a Catholic health care organization is considering entering into an arrangement with another organization that may be involved in activities judged morally wrong by the Church, participation in such activities must be limited to what is in accord with the moral principles governing cooperation. • In Catholic teaching, one should not do a wrong to bring about a good consequence and should participate in another’s wrongdoing only in very limited ways • E.g., partner involved in embryonic stem cell research • Seek review by competent ethicist before entering such partnerships

21. Discussion and Questions