Seven requirements for ethical clinical research?

by Anne Meade, senior manager for website and social media

Each member of the PRIM&R staff is responsible for making sure that PRIM&R runs smoothly, whether their job is answering calls and planning programs, or updating the website and talking to members. No matter which job function we fulfill, it’s important that we stay informed about research ethics, and so we periodically review pertinent articles during our staff meetings. At last month’s meeting we discussed “What Makes Clinical Research Ethical?,” by Ezekiel Emanuel, David Wendler, and Christine Grady, and published in the May 2000  issue of the Journal of the American Medical Association.

In this article, which has become a seminal piece in the field, the authors propose seven requirements that a clinical research study needs to fulfill in order to be considered ethical: social or scientific value, scientific validity, fair subject selection, favorable risk-benefit ratio, independent review, informed consent, and respect for potential or enrolled subjects.

While these requirements may seem obvious, the suggestion that all seven conditions must be met is novel. The authors reference examples of where some of the principles presented have previously appeared (such as The Belmont Report and the Nuremberg Code), but each of those examples exclude a relevant requirement. They argue that only when all seven requirements are addressed can a clinical trial be considered ethical.

Of note, these requirements presented by Emanual et al. also expand on informed consent as presented in The Belmont Report. There, the principle of respect for persons is operationalized primarily by the procedure of  asking for informed consent, but for the authors of this piece, respect for subjects must be broader, and includes respect before, during, and after a trial, and also respecting the right of subjects to change their mind.

Scientific validity brought up a lot of questions for the PRIM&R staff.  In order for research to be considered scientifically valid, “there must be some controversy within the scientific community about whether the new intervention is better than standard therapy (p. 2704).” However, there has been increasing evidence that study results can be incorrect, which raises the question, is there value in running a study again in order to validate earlier results, even if there isn’t a controversy about whether those results are valid?

Additionally, does requiring scientific validity stifle the scientific process? For example, suppose there is a proven treatment used as the standard of care in Western medicine. But suppose there is also a treatment from Eastern medicine for that same condition. Assuming that most clinicians and researchers are involved in Western medicine, one might think that a study comparing the two treatment  is not scientifically valid, since there is no controversy within this scientific community; however, it seems possible that the Eastern treatment could provide an alternative that proves to be superior.

There was consensus among the PRIM&R staff that this article was compelling and served to expand on the ethical principles introduced in the The Belmont Report. PRIM&R’s executive director, Joan Rachlin, explained she felt this article was a testament to how far the field has evolved, specifically regarding the  concept of informed consent (which at one point only consisted of signing on the dotted line), to fully encompass ethics and value over legality.