COVID-19 Pandemic Impact on Implementation of mHealth to Improve Uptake of Hydroxyurea in Sickle Cell Disease: A Mixed-Methods Evaluation (Preprint)

BACKGROUND Hydroxyurea therapy is effective in reducing sickle cell disease (SCD)-related complications and is recommended by NHLBI care guidelines. However, hydroxyurea is underutilized, and adherence is suboptimal. We are testing a multi-level mobile health (mHealth) intervention to increase hydroxyurea adherence among patients and prescribing among providers in a multi-center clinical trial. In the first two study sites, participants were exposed to the early phases of the COVID-19 pandemic, which included disruption to their regular SCD care. The contextual changes that occurred as part of the pandemic response can affect implementation of new interventions. OBJECTIVE We aimed at describing the impact of COVID-19 pandemic on implementation of an mHealth behavioral intervention aimed at improving hydroxyurea adherence among patients with SCD. METHODS The first two sites initiated enrollment three months prior to the start of the pandemic (11/2019-3/2020). During implementation, Site A clinics shut down for 2 months and Site B clinics for 9 months. We used the Reach Effectiveness Adoption Implementation and Maintenance framework to evaluate the implementation and effectiveness of the intervention. mHealth implementation was assessed based on patients’ daily app use. Adherence to hydroxyurea was calculated as Percentage of Days Covered (PDC) from prescription records over the first 12- and 24-weeks after implementation. A linear model examined the relationship between app usage and change in PDC, adjusting for baseline PDC, lock down duration, and site. We also conducted semi-structured interviews with patients, health care providers, administrators and research staff to identify factors associated with mHealth implementation and effectiveness. We used a mixed-methods approach to investigate the convergence of qualitative and quantitative findings. RESULTS The percentage of patients accessing the app decreased after 3/15/2020 (85.9% to 70.3%). The overall mean increase in PDC from baseline to week 12 was 4.5% (p=0.32) and to week 24 was 1.5% (p=0.70). Mean change in PDC was greater at Site A (12 weeks: 20.9%, p=0.0029; 24 weeks: 16.7%, p=0.0139) compared to Site B (12 weeks: -8.2%, p=0.14; 24 weeks: -10.3%, p=0.0151). After adjusting for other predictors, change in PDC was 13.8% greater in those with increased app use after 3/15/20. Interview findings indicated Site B’s closure during COVID-19 had a greater impact on patients, but almost all patients reported InCharge Health helped support more consistent medication use. CONCLUSIONS We found significant impacts of the early clinic lock downs, which reduced implementation of the mHealth intervention. This disruption led to reduced patient adherence to hydroxyurea. However, disruptions to mHealth implementation were lower among participants who experienced shorter clinic lock downs and were associated with higher hydroxyurea adherence. Investigation of added strategies to mitigate effects of care interruptions during major emergencies (e.g., patient coaching, health navigation) may “insulate” the implementation of interventions to increase medication adherence. CLINICALTRIAL ClinicalTrials.gov NCT04080167; https://clinicaltrials.gov/ct2/show/NCT04080167 INTERNATIONAL REGISTERED REPORT RR2-10.2196/16319