Research Ethics and Clinical Care

1. Research Ethics and Clinical Care Jan C. Heller, PhD

2. Presentation Outline • Brief overview of the NIH’s recent clinical and translational science initiative and CTSA grants • Review new ethical “emphases” (rather than new issues), emerging from translational science • Discuss special challenges related to research ethics that won’t go away with translational science • Review research-oriented directives in ERDs • Discussion and questions

3. Clinical and Translational Science • Aim of “basic” biomedical research is new knowledge and aim of “applied” biomedical research is better clinical practice and patient health • Clinical and translational science is a new discipline or a new way of organizing research that is breaking down this older distinction by trying to increase efficiency in moving biomedical research products from “bench to bedside” • NIH funded almost $15 billion in research in 2009, but a study found that… • <25% of promising discoveries resulted in randomized clinical trials • <10% were established in clinical practice after 20 years • BC Droplet and NM Lorenzi, “Translational research: understanding the continuum from bench to bedside,” Translational Research 157, No. 1, January 2011, 1-5.

4. Clinical and Translational Science • This initiative uses “new lexicon” with emphasis on three “translation” periods or “gaps” or “chasms” that are the current focus of attention… • T1: Basic science to clinical efficacy • T2: Clinical efficacy to clinical effectiveness • T3: Clinical effectiveness to health-care delivery • BC Droplet and NM Lorenzi, “Translational research: understanding the continuum from bench to bedside,” Translational Research 157, No. 1, January 2011, 1-5.

5. Clinical and Translational Science • Traditional clinical trials fit into the “gaps” in translational science… • “Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. • Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety. • Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. • Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.” • http://www.nlm.nih.gov/services/ctphases.html • See also http://clinicaltrials.gov/info/resources

6. Clinical and Translational Science • But translational process is also viewed as “bidirectional,” setting up a possible feed-back loop with observational data from patient, community, and public health research • To move this initiative forward, in 2006, the NIH establish the Clinical and Translational Science Awards (CTSA) program to overcome the following barriers… • Increasing complexities of both basic and clinical sciences • Increasing regulatory requirements • Structural impediments in organization of academic health centers • Academic cultural impediments to collaboration • Shortage of translational investigators • Absence of translational mechanisms • Inadequate financial support • SE Reis, et al., “Reengineering the National Clinical and Translational Research Enterprise: The Strategic Plan of the National Clinical and Translational Science Awards Consortium,” Academic Medicine 85, no. 3, March 2010, 463-469.

7. Ethical Emphases • Translational science raises many scientific and organizational challenges for the US research enterprise, but the ethical issues are largely the same as they were for traditional research practices, with perhaps the following differences… • Speed of movement from bench to bedside may exaggerate already blurred lines between research subject and patient, with concerns of… • Safety • Possibility of benefit to subject (vs. clinical treatment) • Experimental design • Informed consent • International research with vulnerable populations • Might also positively affect ethics of research generally as bioethicists get more involved in educating investigators • AR Chapman, “The Potential Contributions of Translational Research and Ethics,” ajob, 8, No. 3, March 2008, 64-66. • C Patrini, “Ethical Issues in Translational Research, Perspectives in Biology and Medicine, 53, No. 4, Autumn 2010, 517-533.

8. Special Challenges • The most heavily regulated part of biomedical ethics, requiring specialized knowledge to maintain competence • 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

9. 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, ethical questions immediately arise… • To whom is our compassion directed? • That is, whose good are we promoting?

10. Special Challenges • Human research subjects certainly qualify as vulnerable • But, with few exceptions, the benefits (if any) of the research will be realized by future patients, many of whom are not currently living • 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 • Also, research diverts resources away from clinical care, per se, making this a stewardship issue

11. 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 (usually) not therapy and subjects are not patients, and this is easily misunderstood by patients or forgotten by clinical researchers • 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

12. 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—again, needs stewardship review (vs. allocation of funds for clinical needs) • Must adhere to Catholic moral principles (some only inferred in ERDs or known from other sources)

13. 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

14. 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 research subjects…

15. 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 • Such constraints are arguably not grounded strictly in moral concerns but rather in political concerns

16. 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?

17. 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 ways constrained by principles governing cooperation • E.g., partner involved in embryonic stem cell research • Seek review by competent ethicist before entering such partnerships

18. Discussion and Questions • Jan C Heller, PhD • Assistant Professor • Clinical Ethicist • Institute for the Medical Humanities • University of Texas Medical Branch • 301 University Blvd., Galveston, TX 77555-1311 • P 409.772.9392 • E jcheller@utmb.edu • W utmb.edu/imh