Poor patient accrual in randomized clinical trials (RCTs) is the greatest barrier to evaluating new medical interventions. Investigators commonly offer financial incentives to promote enrollment and retention, but these practices are highly variable, largely unregulated, and persistently controversial. The most common ethical concerns with incentives for research participation are that they may (1) represent undue inducements by blunting peoples' perceptions of research risks, thereby preventing fully informed consent; (2) represent unjust inducements by encouraging enrollment preferentially among the poor; and (3) reduce disclosure of information that would preclude entry into studies, thereby threatening participant safety and scientific integrity. None of these concerns have been shown to manifest in studies using hypothetical incentives for participating in hypothetical RCTs. But without evidence of how real incentives influence decision-making for real RCTs, practice variability remains. Are the incentives that some investigators use with institutional review board (IRB) approval thwarting autonomous decision-making and/or violating principles of justice? Or are other investigators and IRBs grossly underutilizing a method that can enhance the validity and efficiency of medical innovation without inciting these unintended consequences? Might research incentives actually promote autonomy by alerting participants to research risks? And are incentives sufficiently cost-effective to justify using them? The study we propose will provide the most definitive answers to date to these questions. We will conduct a randomized trial of 3 real incentives ($0, $500, or $1,500) to participate in a parent RCT comparing conventional radiation therapy with proton beam therapy for lung cancer. After patients review informed consent documents including their assigned incentive, we will assess their research attitudes, demographic characteristics, perceived research risks, time spent reviewing informed consent documents, ability to distinguish research from individualized patient care, and comprehension of key trial features. These quantitative assessments will be supplemented by semi-structured interviews that more deeply explore patients' motivations for participating in trials, and the relative influence of incentives on those choices. After patients decide to enroll or not in the parent RCT, we will debrief patients about the random assignment of the incentives. The study will have adequate power to rule out, using formal non-inferiority tests, interactions between incentive size and risk perception (i.e., undue inducement) and between incentive size and income (i.e., unjust inducement). We also will explore potential benefits of incentives, such as the possibilities that incentives improve informed consent by making people attend more thoroughly to research risks, and that they expedite recruitment enough to be cost-saving on balance. This study will provide the first-ever tests of a broad range of intended and unintended consequences of real research incentives, thereby informing research regulations and guiding the use of this method that could expedite medical innovation and improve health.
Paying patients to enroll in randomized clinical trials could dramatically improve the pace and scientific validity with which new interventions for cancer and other diseases are tested, but the practice raises important ethical concerns. To inform the regulation of research incentives and reduce undue variability in their use, we will conduct a randomized trial of 3 real incentives for patients with lung cancer to participate in a real trial comparing two forms of radiation therapy. The trial's innovative design will enable definitive test of how patients make research decisions in the face of money, and will provide the best possible evidence regarding the scientific and ethical pros and cons of incentives for research participation.
| VanEpps, Eric M; Volpp, Kevin G; Halpern, Scott D (2016) A nudge toward participation: Improving clinical trial enrollment with behavioral economics. Sci Transl Med 8:348fs13 |
