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