Ethics and Clinical Research

Abstract & Commentary

Synopsis: Informed consent is the cornerstone of the ethics of clinical research; however, more subtle but equally important considerations are value, scientific validity, fair subject selection, favorable risk-benefit ratio, independent review, and respect for enrolled subjects.

Source: Emanuel EJ, et al. What makes clinical research ethical? JAMA 2000;283:2701-2711.

Informed consent is generally considered to be the factor that renders research involving human subjects ethical. Emanuel and associates assert that although informed consent is necessary in most but not all cases, in no case is it sufficient for ethical clinical research. Some of the most contentious contemporary ethical controversies in clinical research raise questions of the ethics of subject selection, appropriate risk-benefit ratios, and the value of research to society. Since obtaining informed consent does not ensure ethical research, it is necessary to have a systematic and coherent framework for evaluating clinical studies that incorporates all relevant ethical considerations.

Emanuel et al delineate seven requirements that provide a framework synthesizing traditional codes, declarations, and relevant literature on the ethics of human subject-based research. The objective of clinical research is to develop generalizable knowledge to improve health and increase understanding of human biology. That knowledge can be gained by having subjects participate. Ethical requirements minimize the possibility of exploitation of subjects. Seven tenets of ethical research are proposed.

Value

The research must evaluate a diagnostic or therapeutic intervention that could lead to improvements in health or well-being. The research is an etiological, pathophysiological, or epidemiological study to develop such an intervention, or tests a hypothesis that can generate important knowledge about structure or function. The evaluation of clinical research should ensure that the results will be disseminated. Comparative evaluation of value is necessary in considering finite scientific resources.

Scientific Validity

Research is conducted in a methodologically rigorous manner. For a clinical research protocol to be ethical, the methods must be valid and practically feasible. The research must have a clear scientific objective. The study must definitively test the objective and offer a plausible data analysis plan.

Fair Subject Selection

Selection requires decisions about who will be included and the strategy for recruiting subjects. The scientific goals of the study drive fair selection. Groups or individuals should not be excluded without scientific reason. Subject selection cannot affect the risks and benefits of the study.

Favorable Risk-Benefit Ratio

Uncertainty about the risks and benefits of drugs, devices, and procedures must be justified by the planned research. Requirements are that the potential risks to individual subjects are minimized, the potential benefits are enhanced, and the potential benefits to individual subjects and society are proportionate to or outweigh the risks. If the benefits do not outweigh the risks, the subjects are being exploited.

Independent Review

Multiple interests of investigators include conducting high-quality research, completing the research expeditiously, protecting subjects, obtaining funding, and advancement of career. These diverse interests generate conflicts and may distort judgment. With research with little or no risk, the review may be expedited, but for much of clinical research, review should be done by a committee with a full range of expertise and with the authority to approve, amend, or terminate a study.

Informed Consent

This requirement has received the most explication. The purpose is to ensure that individuals control whether or not they enroll in clinical research and participate only when the research is consistent with their values, interests, and preferences. It also indicates that individuals are accurately informed of the purpose, methods, risks, benefits, and alternatives to the research.

Respect for Potential and Enrolled Subjects

Individuals must be treated with respect throughout their participation and after their participation in a study. This issue includes privacy, permission to change their minds, and provision of new information relating to the study.

The tenets listed above are all necessary elements of the ethical requirements of clinical research. They must be adjusted and balanced in different types of research. They are necessary requirements that could be challenged and serve as protection of individuals who are subjects of studies as well as protecting investigators.

Comment by Beverly P. Wood, MD

Informed consent is not enough in planning, designing, and recruiting individual participants in a clinical research study. These ethical requirements emphasize the training and skills needed for clinical investigators and those reviewing proposals for investigations. Potential investigators must recognize, affirm, and implement these ethical requirements, and review committees should consist of persons with scientific training, statistics, ethics, law, and reflective persons who are aware of social values, priorities, and vulnerabilities. We should be sure to train our young researchers in these requirements.