Incorporating Objective Behavioral and Biological Measures in a Large-Scale Decentralized Mobile Health Trial for...

Decentralized (ie, fully remote) clinical trials (DCTs) offer a scalable and ecologically valid approach to evaluating digital mental health interventions (DMHIs). Yet, incorporating objective measures of well-being within DCTs poses novel methodological and feasibility challenges that can limit the rigor and precision of data collection in the field.

We recently conducted the Behavior, Biology, and Well-being (BeWell) Study, a large-scale, 3-arm randomized DCT evaluating the Healthy Minds Program app (Humin)-a self-guided DMHI that includes didactic well-being information and meditation components. The current paper's objective is to describe the methodological approach to collecting and processing a multimodal battery of psychological (questionnaires and structured clinical interview), biological (blood and stool assays), and behavioral (stimulus-elicited affect [SEA] task, video log, and Mnemonic Similarity Task [MST]) measures, longitudinally across baseline, the 4-week intervention period, and 17-week follow-up. Secondarily, we evaluate its feasibility.

The BeWell Study methodology is described. Descriptive statistics characterized recruitment and retention, as well as data completion and data quality. Binary logistic regressions evaluated whether recruitment sources, demographics, and depression severity predicted measure completion and data quality.

From June 1, 2022, through July 15, 2024, 52,052 individuals started the screening questionnaire. Of these, 2.22% (n=1156 participants; mean age 38.69, SD 12.14 years; women=75.50%; non-Hispanic White=68.88%) completed the screener, met eligibility criteria (including elevated depressive symptoms [Patient Health Questionnaire-9 [PHQ-9] score≥5]), completed baseline measures, were enrolled, and were randomized. Participants were recruited from Craigslist (694/1154, 60.14%), a US-based advertisement website, and university email messages (107/1154, 9.27%); participants were enrolled from every US state. Across the study, 84% (971/1156) of participants were retained (completed ≥1 measure at 17-week follow-up). Across time points, ≥81.40% (941/1156) of participants completed questionnaires and ≥75.17% (869/1156) completed biological samples. Of those completing questionnaires, ≥84.14% (796/946) completed SEA and video log tasks and ≥91.75% (868/946) completed the MST. Of completed assessments, high-quality or analyzable data rates across all time points were ≥97.89% (926/946) for questionnaires, ≥90.20% (773/857) for SEA, ≥84.60% (725/857) for video logs, ≥94.20% (1056/1121) for the MST, ≥98.84% (849/859) for dried blood spots, and ≥99.43% (865/870) for microbiome samples. Greater depressive symptoms at screening, but not age, predicted completion of baseline measures (odds ratios 0.96-0.99; P<.001). For enrolled participants, recruitment sources and baseline depressive symptoms were not predictive of data completion or quality. Older age and having a college degree predicted significantly higher rates of data completion across all data types (questionnaire, behavioral, and biological) at week 4 or week 17 follow-ups.

This methodological approach offers one model of incorporating objective measures of well-being into DCTs testing DMHIs. Implications and limitations of our approach are discussed.