Abstract:

Ethics of clinical research have raised many issues of debate. This, according to Friedman et al., (2010) range from the expected professional obligations of physician, whether clinical research is a worthy cause especially when clinical equipoise is in doubt and what research may imply for patients and societal good. Other such related issues of debate include: which should be an appropriate study design, who should serve as the control group, should placebo be allowed, how well informed is informed consent, equitable conduct of trials among disadvantaged/underprivileged societies, the poor, avoidance of exploitation, how conflict of interest could mar research objectives, protection of subjects confidentiality, right of access to data, control of specimens, and publication ethics.

These general issues of ethical debate are largely based on studies involving subjects who are ill and less on those concerning healthy volunteers. This is perhaps because the concept of medical research ethics is focused on safeguarding the physician-patient relationship which inadvertently comes into question when seeking scientific knowledge for health improvement, (Miller and Rosenstein, 2003). It may be perceived also that the history of ethics emanated from the reckless behaviour of some physicians while dealing with their patients. It is therefore perceived that research involving healthy volunteers is less likely to evoke ethical concern since they are not ill, are not imposed with a condition capable of compromising their autonomy and decision-making capacity, and there is no reason for morbidity in their ability to give informed consent. Yet, research involving volunteers have features that can diminish prospective participants’ ability to exercise free and informed choice and the level of uncertainty characterizing this form of inquiry makes subjects vulnerable to harm.

It is expected that healthy volunteers do not experience “therapeutic misconception” hence should not be confused about the differences between being a research subject and being treated for a health condition, (Appelbaum et al., 1987). They are expectedly not under the control of the study physician hence should not feel pressure to participate in research. This notwithstanding, healthy volunteers possess characteristics that could make them subjects of ethical abuse even though perceived as non-vulnerable. The area of ethical concerns arises mostly from the monetary payment to volunteers for inconvenience and lost time (undue Inducement), risk assessment and inappropriate informed consent procedure.

References:

1.      Appelbaum PS, Roth LH, Lidz CW, Benson P, Winslade W. False hopes and best data: consent to research and the therapeutic misconception. Hastings Cent Rep 1987;17: 20-4.

2.      Apseloff G. Severe neutropenia among healthy volunteers given rifabutin in clinical trials. Clin Pharmacol Ther 2003;74:591-2.

3.      Bentley, J. P., Thacker, P. G., (2004). The influence of risk and monetary payment on the research participation decision making process J Med Ethics;30:293–298. doi: 10.1136/jme.2002.001594

4.      CIOMS, (2002). Council for the International Organisation of Medical Sciences and the World Health Organisation. International ethical guidelines for biomedical research involving human subjects. Geneva

5.      Dickert N, Grady C. What’s the price of a research subject? Approaches to payment for research participation. N Engl J Med 1999;341:198-203

6.      Flexner C, Barditch-Crovo PA. Severe neutropenia among healthy volunteers given rifabutin in clinical trials. Clin Pharmacol Ther 2003;74:592-3.

7.      Franklin G. Miller, (2003). Ethical issues in research with healthy volunteers: Risk-benefit assessment. Clin Pharmacol Ther; 74:513-5. doi:10.1016/j.clpt.2003.08.006

8.      Friedman L. M. et al., (2010). Fundamentals of Clinical Trials, DOI 10.1007/978-1-4419-1586-3_2, © Springer Science+Business Media, LLC

9.      Gilbert S. Trials and Tribulations. Hastings Center Report 2008;38(2):14–18. [PubMed: 18457222]

10.  JAMA, (2000). World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.;284:3043-45

11.  Lemmens T. (2001). Federal Regulation of REB Review of Clinical Trials: A Modest But Easy Step Towards An Accountable REB Review Structure in Canada; Health Law Review Volume 13, Number 2 & 3

12.  Miller FG. Clinical research with healthy volunteers: an ethical framework. J Investig Med 2003;51(Suppl 1): S2-5.

13.  Miller FG, Rosenstein DL. The therapeutic orientation to clinical trials. N Engl J Med 2003;348:1383-6.

14.  Steinbrook R., (2002). Protecting research subjects—the crisis at Johns Hopkins. N Engl J Med;346:716-20.

15.  Steinbrook, R., (2008).The Gelsinger Case. In: Emanuel, E., et al., editors. The Oxford Textbook of Clinical Research Ethics. New York: Oxford University Press; p. 110-120.

16.  Suntharalingam G, et al. Cytokine Storm in a Phase I Trial of the Anti-CD28 Monoclonal Antibody TGN1412. New England Journal of Medicine 2006;355(10):1018–1028. [PubMed: 16908486]