Ethical Principles of Clinical Research Trials

Whether or not you choose to participate in clinical trial is an intensely personal decision.  Many patients evaluate both the ethics of participating in a trial, as well as their own sense of moral values. 

Ethics is the study of a society’s discipline between right and wrong; morality is an individual’s personal judgment between right and wrong.  While an individual has the right to judge human research as immoral and decide not to volunteer in research trials, as a society, we have accepted and benefited from clinical research trials based on the following ethical principles:

“Equipoise” requires that the medical expert community be “equally poised” or genuinely uncertain of the superiority between medical treatment options (treatment arms) in each arm of the research trial.  The tenant of equipoise is also referred to as the “uncertainty principle.”  In other words, before performing the trial, physicians must be uncertain of which treatment is better.  For example, in a trial involving chemotherapy drug A in one arm and a different chemotherapy in trial arm B, physicians enrolling patients should have no medical preference for either drug in arm A or B of the trial.  It is unethical to perform a trial if an alternative medical treatment is superior, or to design a trial with a known inferior treatment arm.  This way, research-participating patients can be assured that the trial will always include at least the current best standard of care, and the trial is attempting to improve upon this “best standard of care”. 

Based on equipoise, one can therefore not assume that an experimental drug has any therapeutic benefit until the trial has been completed.  In many trials, they have found that the older standard drug may still remain superior to the newer experimental agent. For example, many drugs that cure cancer in mice have no activity in humans when tested.  Patients considering clinical trials must understand this common “therapeutic misconception.”   Experimental drugs on trial are not therapeutic until proven so after trial completion and accepted by the medical community as valid.   The clinical medicine doctrine that “best equals standard” reflects the paradox of scientific advancement that “uncertainty equals progress.”  The uncertainty of clinical trial results is the cutting edge of medicine. 

In structuring a clinical trial, the ethical principle of beneficence, or “do good” must also be weighed against non-malfeasance, or “do no harm”.  In attempting to maximize benefits and minimize harm, clinical cancer research trials must be both scientifically reviewed for their rationale, and peer reviewed by multiple physicians for their clinical significance and safety.

1. “Autonomy” is the ethical principle that patients may make their own decisions about medical treatments.  Cancer patients volunteer to enroll in clinical trials by giving informed consent – or understanding and agreeing to the trial protocol treatments. Patients have the right to choose their physician, make choices about treatment options, or refuse intervention altogether.  During the clinical trial, patients maintain autonomy and may withdraw at any time without consequences.   Certain aspects of autonomy, such as patient drug preference are lost because the protocol may randomly assign (randomize) which treatment arm is given.  Further narrowing of autonomy in a research trial may occur due to the need to outline in advance the schedule of treatments. For example, patients in the midst of a trial may need to arrange their vacations around the protocol schedule, instead of the protocol changing for their vacations.    However, the overlying principle that a patient autonomously can accepts or refuse a research protocol is upheld. 

The last ethical principle supporting clinical trials is “Justice.”  Justice requires that the benefit and burden of human research be shared without bias.  As an example, if the burden of AIDS drug research is laid upon impoverished African patient volunteers with the benefit of a discovered cure available only to patients in richer nations, there would be an outcry against such bias and injustice.  Physicians share a covenant of justice with all patients who participate in clinical research trials. The burden of disease that they bear will benefit all equally.