Importance Incentivizing research participation is controversial and variably regulated because of uncertainty regarding whether financial incentives serve as undue inducements by diminishing peoples' sensitivity to research risks or unjust inducements by preferentially increasing enrollment among underserved individuals. Objective To determine whether incentives improve enrollment in real randomized clinical trials (RCTs) or serve as undue or unjust inducements. Design, Setting, and Participants Two RCTs of incentives that were embedded in 2 parent RCTs, 1 comparing smoking cessation interventions (conducted at smoking cessation clinics in 2 health systems) and 1 evaluating an ambulation intervention (conducted across wards of the Hospital of the University of Pennsylvania) included all persons eligible for the parent trials who did not have prior knowledge of the incentives trials. Recruitment occurred from September 2017 to August 2019 for the smoking trial and January 2018 through May 2019 for the ambulation trial; data were analyzed from January 2020 to July 2020. Interventions Patients were randomly assigned to incentives of $0, $200, or $500 for participating in the smoking cessation trial and $0, $100, or $300 for the ambulation trial. Main Outcomes and Measures The primary outcome of each incentive trial was the proportion of people assigned to each recruitment strategy that consented to participate. Each trial was powered to test the hypotheses that incentives served neither as undue inducements (based on the interaction between incentive size and perceived research risk, as measured using a 10-point scale, on the primary outcome), nor unjust inducements (based on the interaction between incentive size and participants' self-reported income). Noninferiority methods were used to test whether the data were compatible with these 2 effects of incentives and superiority methods to compare the primary and other secondary outcomes. Results There were a total of 654 participants (327 women [50.0%]; mean [SD] age, 50.6 [12.1] years; 394 Black/African American [60.2%], 214 White [32.7%], and 24 multiracial individuals [3.7%]) in the smoking trial, and 642 participants (364 women [56.7%]; mean [SD] age, 46.7 [15.6] years; 224 Black/African American [34.9%], 335 White [52.2%], and 5 multiracial individuals [0.8%]) in the ambulation trial. Incentives significantly increased consent rates among those in the smoking trial in 47 of 216 (21.8%), 78 of 217 (35.9%), and 104 of 221 (47.1%) in the $0, $200, and $500 groups, respectively (adjusted odds ratio [aOR] for each increase in incentive, 1.70; 95% CI, 1.34-2.17; P < .001). Incentives did not increase consent among those in the ambulation trial: 98 of 216 (45.4%), 102 of 212 (48.1%), and 92 of 214 (43.0%) in the $0, $100, and $300 groups, respectively (aOR, 0.88; 95% CI, 0.64-1.22; P = .45). In neither trial was there evidence of undue or unjust inducement (upper confidence limits of ORs for undue inducement, 1.15 and 0.99; P < .001 showing noninferiority; upper confidence limits of ORs for unjust inducement, 1.21 and 1.26; P = .01 and P < .001, respectively). There were no significant effects of incentive size on the secondary outcomes in either trial, including time spent reviewing the risk sections of consent forms, perceived research risks, trial understanding, perceived coercion, or therapeutic misconceptions. Conclusions and Relevance In these 2 randomized clinical trials, financial incentives increased trial enrollment in 1 of 2 trials and did not produce undue or unjust inducement or other unintended consequences in either trial. Trial Registration ClinicalTrials.gov Identifier: NCT02697799.

中文翻译：

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研究参与激励措施的有效性和伦理：2 项随机临床试验。

重要性 激励研究参与是有争议的，并且由于不确定性，财政激励是通过降低人们对研究风险的敏感性而作为不正当的诱因，还是通过优先增加服务不足的个体的入学率来作为不公平的诱因。目的 确定激励措施是否可以提高真实随机临床试验 (RCT) 的注册率，或者是否可以作为不正当或不公正的诱因。设计、设置和参与者 嵌入在 2 个父 RCT 中的两个激励机制的 RCT，1 比较戒烟干预（在 2 个卫生系统的戒烟诊所进行）和 1 评估步行干预（在宾夕法尼亚大学医院的病房中进行）包括所有符合父母试验条件但事先不了解激励试验。吸烟试验招募时间为 2017 年 9 月至 2019 年 8 月，步行试验招募时间为 2018 年 1 月至 2019 年 5 月；对 2020 年 1 月至 2020 年 7 月的数据进行分析。干预 患者被随机分配到参与戒烟试验的 0 美元、200 美元或 500 美元的奖励以及步行试验的 0 美元、100 美元或 300 美元的奖励中。主要结果和措施 每个激励试验的主要结果是分配到每个招聘策略的同意参与的人的比例。每项试验都旨在检验以下假设，即激励既不是不正当诱因（基于激励规模和感知研究风险之间的交互作用，使用 10 分制测量主要结果），也不是不公正诱因（基于激励规模与参与者自报收入之间的相互作用）。非劣效性方法用于测试数据是否与激励和优势方法的这 2 种影响相一致，以比较主要和其他次要结果。结果共有 654 名参与者（327 名女性 [50.0%]；平均 [SD] 年龄，50.6 [12.1] 岁；394 名黑人/非裔美国人 [60.2%]，214 名白人 [32.7%] 和 24 名多种族个体 [3.7%]），以及 642 名参与者（364 名女性 [56.7%]；平均 [SD] 年龄，46.7 [15.6] 岁；224 名黑人/非裔美国人 [ 34.9%]、335 名白人 [52.2%] 和 5 名多种族个体 [0.8%]）在步行试验中。在 0 美元、200 美元和 500 美元组中，奖励措施分别显着提高了 216 人中的 47 人（21.8%）、217 人中的 78 人（35.9%）和 221 人中的 104 人（47.1%）的同意率（调整后的几率）每次激励增加的比率 [aOR]，1.70；95% CI，1.34-2.17；P < .001）。激励措施并未增加步行试验参与者的同意：在 0 美元、100 美元和 300 美元组中，分别有 216 人中的 98 人（45.4%）、212 人中的 102 人（48.1%）和 214 人中的 92 人（43.0%）（aOR， 0.88；95% CI，0.64-1.22；P = .45)。在这两项试验中都没有不正当或不正当诱导的证据（不正当诱导的 OR 置信上限为 1.15 和 0.99；P < .001 表明非劣效性；不正当诱导的 OR 置信上限为 1.21 和 1.26；P = .01 和P < .001，分别）。在这两项试验中，激励规模对次要结果没有显着影响，包括审查同意书风险部分的时间、感知的研究风险、对试验的理解、感知的强迫或治疗误解。结论和相关性 在这 2 项随机临床试验中，经济激励措施增加了 2 项试验中 1 项的试验注册，并且在任一试验中都没有产生不正当或不公正的诱因或其他意外后果。试验注册 ClinicalTrials.gov 标识符：NCT02697799。