Messaging Informed by Behavioral Economics and Representativeness in Clinical Research Enrollment

Importance: Prospective clinical research studies are challenged by low enrollment rates and underrepresentation of individuals from racial and ethnic minority groups. Objective: To determine the effect of electronic message content on study enrollment among racial and ethnic groups. Design, Setting, and Participants: Four sequential randomized clinical trials (RCTs) were conducted between October 30, 2023, and November 13, 2024, in which University of Pennsylvania Health System patients (aged ≥18 years) were contacted electronically via email, text message, or both. The most effective arm from each RCT served as the control in the subsequent observational study. This analysis of all 4 RCTs was performed on the intention-to-treat principle from December 2024 through September 2025. Intervention: Messages varied by method, source, framing, and incentive structure. Main Outcomes and Measures: The primary outcome was enrollment fraction (number enrolled divided by total contacted) among Black and Hispanic participants. Overall enrollment fraction was a secondary outcome. Results: Overall, 26 215 patients were contacted and 26 029 were offered enrollment in the Penn Medicine BioBank; 63.2% were Black and 7.2% were Hispanic. Their mean (SD) age was 60.5 (17.9) years, and 60.1% were female. In the first recruitment RCT (RCT 1) (n = 8038), the enrollment fraction among 4581 Black and Hispanic patients was 0% with email, 0.5% with text, and 0.2% with email plus text (P = .06 for text vs email; P = .20 for email plus text vs email). Due to technical issues, more than 80% of participants who attempted to consent in RCT 1 failed; consent attempts were higher with text (4.8%) and email plus text (4.4%) than email alone (0.6%) (P < .001 for text vs email and email plus text vs email). In RCT 2 (n = 4271), the enrollment fraction among 1902 Black and Hispanic patients was 1.0% with research team outreach and 1.8% with clinical team outreach (P = .12). In RCT 3 (n = 3217 Black and Hispanic patients), the enrollment fraction was 3.2% with a control message, 3.6% with an appeal to altruism, and 4.1% with an appeal to social proof (P > .05 for all comparisons). In RCT 4 (n = 10 689), the enrollment fraction among 8629 Black and Hispanic patients was 2.5% with no incentive, 6.8% with $25, 5.5% with $15 plus a 5% chance at $200, 5.8% with a 5% chance at $500, and 6.5% with a 1% chance at $2500 (P < .001 for each incentive vs no incentive; P > .05 for each incentive compared with another). Conclusions and Relevance: In this series of RCTs, the enrollment fraction among Black and Hispanic patients was improved with outreach by text message and with an incentive. Trial Registration: ClinicalTrials.gov Identifier: NCT05827718.