A Randomized Trial of Incentives for Research Participation

 描述（由申请人提供）：随机临床试验（RCT）中的患者招募不足是评估新医疗干预措施的最大障碍。调查人员通常会提供经济激励措施来促进入学和保留，但这些做法变化很大，基本上不受监管，并且一直存在争议。鼓励研究参与的最常见的伦理问题是，它们可能（1）通过削弱人们对研究风险的看法，从而防止完全知情同意，从而构成不正当的诱惑;（2）通过鼓励优先在穷人中注册，构成不公平的诱惑;（3）减少可能阻止进入研究的信息披露，从而威胁参与者的安全和科学完整性。 这些问题都没有表现在研究中使用假设的激励参与假设的随机对照试验。但是，没有证据表明真实的激励如何影响真实的随机对照试验的决策，实践的可变性仍然存在。一些研究者在机构审查委员会（IRB）批准下使用的激励措施是否阻碍了自主决策和/或违反了公正原则？或者，其他研究者和IRB是否严重利用了一种可以提高医疗创新有效性和效率而不会引发这些意外后果的方法？研究激励措施是否能通过提醒参与者注意研究风险来促进自主性？激励措施的成本效益是否足以证明使用这些措施的合理性？我们提出的研究将提供 迄今为止对这些问题最明确的答案。 我们将进行一项随机试验，有3种真实的激励（0美元、500美元或1,500美元）参与比较常规放射治疗与质子束治疗肺癌的母RCT。在患者审查知情同意文件（包括分配给他们的激励措施）后，我们将评估他们的研究态度、人口统计学特征、感知的研究风险、审查知情同意文件所花的时间、区分研究与个性化患者护理的能力以及对关键试验特征的理解。这些定量评估将辅以半结构化访谈，更深入地探讨患者参与试验的动机，以及激励措施对这些选择的相对影响。在患者决定是否入组母RCT后，我们将向患者汇报激励措施的随机分配情况。该研究将有足够的权力，以排除，使用正式的“非劣效性”测试，激励规模和风险感知之间的相互作用（即，不适当的诱导）和激励规模与收入之间（即，不公平的诱惑）。我们还将探讨激励措施的潜在好处，例如激励措施通过使人们更彻底地关注研究风险来改善知情同意的可能性，以及它们加快招募足以节省成本的可能性。这项研究将首次对真实的研究激励措施的预期和非预期后果进行测试，从而为研究法规提供信息，并指导这种方法的使用，从而加快医学创新和改善健康。

 DESCRIPTION (provided by applicant): 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.