Fast Takes

Ezekiel J. Emanuel, David Wendler, and Christine Grady.  What makes clinical research ethical?  JAMA 283:2701-2711, 2000. Complete Text

These authors, from the Clinical Bioethics department at the National Institutes of Health, attempt a new reformulation of the essential aspects of the ethics of research.  They are prompted to do so in part because of the tendency in recent times to view research ethics as the functional equivalent of informed consent.  They argue, to the contrary, that adequate informed consent is neither necessary nor sufficient for research to be ethical.

Emanuel et al. first review the major codes of ethics and official guidelines produced around the world between 1947 and 1999.  From these documents they distil a set of 7 requirements for ethical research which reflect the underlying moral values which inform the codes and guidelines:

Requirement Explanation Justifying ethical values
Social or scientific value Results must improve health and well-being or increase knowledge Scarce resource

Nonexploitation

Scientific validity Study must use accepted scientific techniques so that results are reliable and valid Scarce resources

Nonexploitation

Fair subject selection Avoid targeting stigmatized and vulnerable groups for risky research or powerful groups for special benefits Justice
Favorable risk-benefit ratio Subject's risks should be minimized and benefits maximized, proportionate to benefits to society Nonmaleficence

Beneficence

Nonexploitation

Independent review Disinterested individuals should review study design and methods Public accountability

Minimize conflicts of interest

Informed consent Subjects must have full information and be able to make voluntary decision to enroll or not Respect for subject autonomy
Respect for enrolled and potential subjects Permit withdrawal from research; protect privacy; inform of new data; inform of results; maintain welfare Respect for subject autonomy

Beneficence

Nonmaleficence

The authors state, "[T]he fulfillment of each of these 7 requirements ensures that research is socially valuable and subjects are not exploited, that subjects are treated fairly and with respect, and that their interests are protected.  As a result, these requirements should be sufficient to ensure that the vast majority of clinical research is ethical."   They go on to argue that the requirements should be regarded as universal, though what it would mean in practice to fulfill each requirement might well vary from nation to nation and from culture to culture.   They give the example of a culture in which "treating one with respect" requires that one approach the community elders for permission first, before individuals are asked to give consent.  They also argue that different risk-benefit ratios in different countries may make a research project ethical in one setting and unethical in another, and this does not automatically equate with exploitation.

If there is a central word in this essay, it seems to be "nonexploitation."  (Even the squares in the table under  "justifying ethical values" which currently do not include this word could easily have it added.  For instance, informed consent is arguably a feature of nonexploitation.)  The authors naturally wish to avoid the charge that their essay is merely a reaction to specific research scandals in the past rather than a sober analysis of the ethical dictates of good research in the future.  But, if there is a summary statement of past research scandals like Tuskegee that seems to provide valid general guidance, it is that these unethical studies were unethical because they exploited human subjects, and the investigators appeared to be blinded to the nature and degree of the exploitation because they could see only the presumed benefits of the research to society as a whole.  For this reason, ethical principles that address exploitation head on, and practical review strategies which are designed to avoid the potential blindness of the research zealot, seem primarily to be called for.  In this regard the authors seem fully correct, that an overreliance on informed consent as the sole arbiter of ethical or unethical research misses the basic ethical point and provides poor practical safeguards for the interests of subjects and the public.

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