Background:
Randomized controlled trials (RCTs) remain an indispensable form of humanexperimentation as a vehicle for discovery of new treatments. However, since their inceptionRCTs have raised ethical concerns. The ethical tension has revolved around "duties toindividuals" vs. "societal value" of RCTs. By asking current patients "to sacrifice for thebenefit of future patients" we risk subjugating our duties to patients’ best interest to theutilitarian goal for the good of others. This tension creates a key dilemma: when is it rational,from the perspective of the trial patients and researchers (as societal representatives of futurepatients), to enroll in RCTs?
Methods:
We employed the trust version of the prisoner’s dilemma since interaction between thepatient and researcher in the setting of a clinical trial is inherently based on trust. We alsotook into account that the patient may have regretted his/her decision to participate in thetrial, while a researcher may feel guilty because he/she abused the patient’s trust.
Results:
We found that under most typical circumstances of clinical research, most patients can beexpected not to trust researchers, and most researchers can be expected to abuse the patients’trust. The most significant factor determining trust was the success of experimental orstandard treatments, respectively. The more that a researcher believes the experimentaltreatment will be successful, the more incentive the researcher has to abuse trust. The analysiswas sensitive to the assumptions about the utilities related to success and failure of therapiesthat are tested in RCTs. By varying all variables in the Monte Carlo analysis we found that,on average, the researcher can be expected to honor a patient’s trust 41% of the time, whilethe patient is inclined to trust the researcher 69% of the time. Under assumptions of ourmodel, enrollment into RCTs represents a rational strategy that can meet both patients’ andresearchers’ interests simultaneously 19% of the time.
Conclusions:
There is an inherent ethical dilemma in the conduct of RCTs. The factors that hamper full cooperationbetween patients and researchers in the conduct of RCTs can be best addressed by:a) having more reliable estimates on the probabilities that new vs. established treatments willbe successful, b) improving transparency in the clinical trial system to ensure fulfillment of"the social contract" between patients and researchers.