Augmenting Engagement in Decentralized Clinical Trials for Atrial Fibrillation: Development and Implementation of a Programmatic Architecture.

Background: Atrial fibrillation (AF) is a chronic cardiovascular condition that requires long-term adherence to medications and self-monitoring. Clinical trials for AF have had limited diversity by sex, race and ethnicity, and rural residence, thereby compromising the integrity and generalizability of trial findings. Digital technology coupled with remote strategies has the potential to increase recruitment of individuals from underrepresented demographic and geographic populations, resulting in increased trial diversity, and improvement in the generalizability of interventions for complex diseases such as AF.

Objective: This study aimed to summarize the architecture of a research program using remote methods to enhance geographic and demographic diversity in mobile health trials to improve medication adherence.

Methods: We developed a programmatic architecture to conduct remote recruitment and assessments of individuals with AF in 2 complementary randomized clinical trials, funded by the National Institutes of Health, to test the effectiveness of a smartphone-based relational agent on adherence to oral anticoagulation. The study team engaged individuals with either rural or metropolitan residences receiving care for AF at health care settings who then provided consent, and underwent baseline assessments and randomization during a remotely conducted telephone visit. Participants were randomized to receive the relational agent intervention or control and subsequently received a study smartphone with installed apps by mail. Participants received a telephone-based training session on device and app usage accompanied by a booklet with pictures and instructions accessible for any level of health or digital literacy. The program included remote methods by mail and telephone to promote retention at 4-, 8-, and 12-month visits and incentivized return of the smartphone following study participation. The program demonstrated excellent participant engagement and retention throughout the duration of the clinical trials.

Results: The trials enrolled 513 participants, surpassing recruitment goals for the rural (n=270; target n=264) and metropolitan (n=243; target n=240) studies. A total of 62% (319/513) were women; 31% (75/243) of participants in the metropolitan study were African American, Asian, American Indian or Alaskan native or other races or ethnicities, in contrast to 5% (12/270) in the rural study. Among all participants, 56% (286/513) had less than an associate's degree and 44% (225/513) were characterized as having limited health literacy. Intervention recipients receiving the relational agent used the agent median of 95-98 (IQR, 56-109) days across both studies. Retention exceeded 89% (457/513) at 12 months with study phones used for median 3.3 (IQR, 1-5) participants.

Conclusions: We report here the development and implementation of a programmatic architecture for the remote conduct of clinical trials. Our program successfully enhanced trial diversity and composition while providing an innovative mobile health intervention for medication adherence in AF. Our methods provide a model for enhanced recruitment and engagement of diverse participants in cardiovascular trials.