Study protocol for ADHERE (Applying Directly observed therapy to HydroxyurEa to Realize Effectiveness): Using small business partnerships to deliver a scalable and novel hydroxyurea adherence solution to youth with sickle cell disease

Background: Sickle cell disease (SCD) is an inherited blood disorder that affects approximately 100,000 Americans, primarily from underrepresented racial minority populations, and results in costly, multi-organ complications. Hydroxyurea, the primary disease-modifying therapy for SCD, is effective at reducing most complications; however, adherence to hydroxyurea remains suboptimal and is the primary barrier to clinical effectiveness.

Objective: Given prior challenges and the need for a successful and scalable hydroxyurea adherence solution to improve outcomes, the primary aim of this study is to assess retention and sustained engagement during a pilot randomized controlled trial (RCT) comparing VDOT for hydroxyurea delivered by Scene Health to attention control among youth with SCD. The secondary aim of this study is to use a novel adherence monitoring device to measure hydroxyurea adherence and explore needs and preferences for longer-term adherence monitoring and intervention.

Methods: This study was initially approved by a single Institutional Review Board on 08/15/2023 (STUDY00003303) and is registered with the National Institutes of Health

(NCT06264700). All participants will provide consent/assent. Relevant data will be made available at the conclusion of this study upon request. This trial includes all items on the Standard Protocol Items: Recommendations for Interventional Trials Checklist.

Anticipated outcomes and future directions: This study's anticipated outcomes are that VDOT will be acceptable and result in sustained retention and engagement with a centrally delivered adherence intervention. These results will be used to inform the definitive efficacy RCT of VDOT for hydroxyurea.

‍Funding: This research is supported by funding awarded from the National Heart, Lung, and Blood Institute of the National Institutes of Health (1 R44 HL169085) (https://www.nhlbi.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.