The Division of Medical
Ethics and Humanities
Responsible Conduct of Research - Human Subjects Research
Howard Mann, M.D., Program Associate
Overview  |  Session I  |  Session II  |  Session III  |  Session IV  |  Session V  |  Session VI
   
Session IV

A. Expectations and obligations in the relationship between the investigator and research participant.

B. The ethics of research participant recruitment.

Patients are often recruited for clinical research protocols by physicians in the context of a patient-physician relationship. The fiduciary nature of this relationship is well understood : the physician is expected to advance the medical interests of his patient. The relevant notion is one of therapeutic beneficence. In contrast, it is argued that the nature of the investigator-participant relationship in clinical research is distinctly different. The corresponding obligation involves notions of avoiding undue harm and exploitation. Contentions concerning the salience and weighting accorded these obligations are often at the heart of disputes concerning certain clinical research practices, such as the use of placebos in place of established effective therapy.

The recruitment of patients for clinical research is also an area in which ethical tensions may arise. Physician-investigators (and their institutional employees) may have direct or indirect financial incentives, or interests, in the research, and recuitment should be sensitive to what we understand prospective participants want to know about those interests.

Objectives

  1. To understand role-based differences in the obligations of physicians and physician-investigators to patients.
  2. To explore the salience of these differences in the context of clinical research, using randomized controlled trials (which may employ placebos) as an example.
  3. To explore ethical issues often arising in the recruitment of patients for research, including disclosure of financial interests, recruitment bonuses, and finder's fees.
Required reading for this session

Pimple KD, Pedroni JA. Therapeutic obligation in medical research. February 2003.

Conflict of interest in research, education and patient care, by Trudo Lemmens and Peter A. Singer, from the University of Toronto.

Kim SYH, Millard RW, Nisbet P, Cox C, Caine ED. Potential research participants' views regarding researcher and institutional financial conflicts of interest. Journal of Medical Ethics 2004; 30: 73.


Cases for discussion

Case 1

A sponsor proposes to conduct a multicenter clinical trial to establish the efficacy of a novel anticonvulsant in patients with bipolar I disorder experiencing an acute episode of mania. Eligibility criteria include patients who have been hospitalized at least once previously for mania, and participants will be recruited from otherwise eligible inpatients. Pertinent design features include the following : subjects currently on therapy will undergo a "washout phase" prior to randomization; patients will be randomized to active drug or placebo; participants will be enrolled for a period of three weeks.

Questions
  1. What is the rationale for the use of a placebo arm in the trial?
  2. Is an alternative trial design (active comparator) feasible? If so,would it provide knowledge useful in clinical practice?
  3. Participants are being recruited in the context of a patient- physician relationship, wherein the physician has a duty of therapeutic beneficence. Is the possibility of assignment to the placebo arm consistent with fulfillment of this duty? Or, should the physician explain to a particular patient that he is soliciting her research participation as a scientist, and not offering her personal care directed at her medical interests?
  4. What should potential participants be told about the use of placebo in this trial? What else should potential participants understand about the design aspects of the trial?
Resource for this Case:

Final Report of the National Placebo Working Committee on the Appropriate Use of Placebos in Clinical Trials in Canada - the ethical perspective (July 2004)



Case 2

A university-based physician-investigator has agreed to participate in a multicenter randomized controlled clinical trial sponsored by a pharmaceutical company. The company pays according to a capitated schedule. The negotiated fee incorporates both direct and indirect costs. The investigator has no direct intellectual interest in the clinical trial's scientific objectives. He is not involved as a member of the trial's Steering or Publication committee. He will use the net "income" to support his university-based laboratory research.

Questions

  1. What disclosures (and to whom) does he have to make according to University of Utah policy?
  2. During the process of informed consent, what should he (or a designated individual) tell a prospective participant about his, and the university's, financial interests in the clinical research?
  3. What should he include in the Informed Consent document for the research about these interests?
Additional resources

Miller F. Research ethics and misguided moral intuition. Journal of Law, Medicine and Ethics. 2004; 32: 111.

Lemmens T, Miller PB Avoiding a Jekyll-And-Hyde Approach to the Ethics of Clinical Research and Practice

Final Report of the National Placebo Working Committee on the Appropriate Use of Placebos in Clinical Trials in Canada (July 2004)

Physicians, finder's fees and free, informed consent by Kenneth M. Flegel, in the Canadian Medical Association Journal.

Reports on Individual and Institutional Financial Interest in Human Subjects Research from the Association of American Medical Colleges.

University of Utah's Conflict of Interest policy.