Effectiveness and Ethics of Incentives for Research Participation: 2 Randomized Clinical Trials

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Hitsman reported nonfinancial support from Pfizer during the conduct of the study. Dr Schnoll reported nonfinancial support from Pfizer during the conduct of the study and consulting fees from Curaleaf and GSK outside the submitted work. Dr Patel reported personal fees from Catalyst Health LLC, Life.io, HealthMine Services, and Holistic Industries outside the submitted work. Dr Volpp reported grants from the National Cancer Institute during the conduct of the study and being a partial owner of VAL Health and grants from Humana, WW, Vitality/Discovery, and HMSA outside the submitted work. Dr Karlawish reported grants from Lilly during the conduct of the study. Dr Stephens-Shields reported grants from National Institutes of Health during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram for the Embedded Recruitment Trials Within the Smoking and Ambulation Trials

RETAIN indicates the Randomized Evaluation of Trial Acceptance by Incentive study. aPostrandomization exclusion reasons: recruiter proceeded to randomization step despite ineligibility (2), ineligibility determined between phone screen and in-person screening (1), participation in conflicting study discovered after randomization (1), and history of falsifying information in other studies (1). bPostrandomization exclusion reasons: recruiter proceeded to randomization step despite inelibigility (2) and phone incompatibility discovered after randomization (2).

Figure 2.. Effect of Income on Relationships Between Incentives and Trial Enrollment

Plots of relationships between incentives and adjusted probability of enrollment in the smoking (A) and ambulation (B) trials using values of income at the 5th, 25th, 50th, 75th, 95th percentiles and mean of its observed distributions. Error bars represent 95% CIs. In the smoking trial, the 5th percentile = less than $10 000, 25th percentile = $10 to $19 000, 50th percentile = $20 to $29 000, 75th percentile = $30 to $49 000, 95th percentile = $100 000 or more, and mean = $20 to $29 000. In the ambulation trial, the 5th percentile = $10 to $19 000, 25th percentile = $30 to $49 000, 50th and 75th percentiles both = $50 to $99 000, 95th percentile = $100 000 or more, and mean = $30 to $49 000. There was no significant effect modification by income in either trial.

Figure 3.. Effect of Financial Well-being on Relationships Between Incentives and Trial Enrollment

Plots of relationships between incentive and adjusted probability of enrollment in the smoking (A) and ambulation (B) trials using values of financial well-being at the 5th, 25th, 50th, 75th, 95th percentiles, and mean of its observed distributions. Error bars represent 95% CIs. There was no significant effect modification by financial well-being in either trial.