StATS: More thoughts on equipoise (January 17, 2005)

Vital to the ethical conduct of a clinical trial is the concept of equipoise, that a researcher is clinically indifferent or genuinely uncertain, as to whether a new therapy is better than the standard therapy.

Stephen Senn is a harsh critic of the concept of equipoise and points out the reality that most researchers go into a study with a belief that the new therapy being tested is better.

Equipoise is an irrelevance. Patients are entered onto the trial because the trialists believe that the experimental treatment is better. The control group treatment should be as good as that available outside the trial. Experimentation continues until either the trialists are convinced they are wrong (equipoise is reached) or they convince Society they are right. -- Senn (2000).

The FDA comments on equipoise are less extreme than Dr. Senn's but still echo the same sentiment.

Indeed, true neutrality is rarely present at the start of an investigation; in the absence of expectation that an intervention may represent an improvement, or a belief that a standard therapy might not work, there is little incentive to proceed. The experienced clinical investigator, however, also knows that expectations are not the same as knowledge and that disappointments are too common to ignore. Therefore, despite optimistic expectations, one can be in the state of equipoise needed to allow a clinical investigation to be conducted. -- www.fda.gov/opacom/morechoices/fed996.html.

I had included both of these quotes before in a web page about placebos, but I did not realize until just now that this is in diametric opposition to a claim by Djulbegovic

FINDINGS: Trials funded solely or in part by 35 profit-making organisations had a trend toward higher quality scores (mean 2.94 [SD 1.3]; median 3) than randomised trials supported by 95 governmental or other non-profit organisations (2.4 [0.8]; 2; p=0.06). Overall, the uncertainty principle was upheld, with 44% of randomised trials favouring standard treatments and 56% innovative treatments (p=0.17); mean and median preference evaluation scores were 3.7 (1.0) and 4. However, when the analysis was done according to the source of funding, studies funded by non-profit organisations maintained equipoise favouring new therapies over standard ones (47% vs 53%; p=0.608) to a greater extent than randomised trials supported solely or in part by profit-making organisations (74% vs 26%; p=0.004). INTERPRETATION: The reported bias in research sponsored by the pharmaceutical industry may be a consequence of violations of the uncertainty principle. Sponsors of clinical trials should be encouraged to report all results and to choose appropriate comparative controls. Djulbegovic 2000.

Perhaps this 74/26 split is a reflection, not of publication bias, not of choice of inappropriate controls, but rather the intelligence of the research planners who work for commercial sponsors. This is not to say that publication bias does not exist, or that bad controls are not sometimes deliberately chosen. It's just that if I were a drug company, I would want to hire people who, because of their intuition and good sense, investigate new drugs that have a good chance of actually working.

This page was written by Steve Simon while working at Children's Mercy Hospital. Although I do not hold the copyright for this material, I am reproducing it here as a service, as it is no longer available on the Children's Mercy Hospital website. Need more information? I have a page with general help resources. You can also browse for pages similar to this one at Category: Equipoise in research.