When is it rational to participate in a clinical trial? A game theory approach incorporating trust, regret and guilt

We employed the trust version of the prisoner’s dilemma since interaction between the patient and researcher in the setting of a clinical trial is inherently based on trust. We also took into account that the patient may have regretted his/her decision to participate in the trial, while a researcher may feel guilty because he/she abused the patient’s trust.We found that under typical circumstances of clinical research, most patients can be expected 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 or standard treatments, respectively. The more that a researcher believes the experimental treatment will be successful, the more incentive the researcher has to abuse trust. The analysis was sensitive to the assumptions about the utilities related to success and failure of therapies that 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, while the patient is inclined to trust the researcher 69% of the time. Under assumptions of our model, enrollment into RCTs represents a rational strategy that can meet both patients’ and researchers’ interests simultaneously 19% of the time.There is an inherent ethical dilemma in the conduct of RCTs. The factors that hamper full co-operation between 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 will be successful, b) improving transparency in the clinical trial system to ensure fulfillment of “the social contract” between patients and researchers.