Impact of the COVID-19 Pandemic on the Implementation of Mobile Health to Improve the Uptake of Hydroxyurea in Patients With Sickle Cell Disease: Mixed Methods Study

Abstract

Background Hydroxyurea therapy is effective for reducing complications related to sickle cell disease (SCD) and is recommended by National Health Lung and Blood Institute care guidelines. However, hydroxyurea is underutilized, and adherence is suboptimal. We wanted to test a multilevel mobile health (mHealth) intervention to increase hydroxyurea adherence among patients and improve prescribing among providers in a multicenter clinical trial. In the first 2 study sites, participants were exposed to the early phases of the COVID-19 pandemic, which included disruption to their regular SCD care. Objective We aimed to describe the impact of the COVID-19 pandemic on the implementation of an mHealth behavioral intervention for improving hydroxyurea adherence among patients with SCD. Methods The first 2 sites initiated enrollment 3 months prior to the start of the pandemic (November 2019 to March 2020). During implementation, site A clinics shut down for 2 months and site B clinics shut down for 9 months. We used the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) 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 the proportion 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 PDC change, adjusting for baseline PDC, lockdown duration, and site. We conducted semistructured 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 March 15, 2020 from 86% (n=55) to 70% (n=45). The overall mean PDC increase from baseline to week 12 was 4.5% (P=.32) and to week 24 was 1.5% (P=.70). The mean PDC change was greater at site A (12 weeks: 20.9%; P=.003; 24 weeks: 16.7%; P=.01) than site B (12 weeks: −8.2%; P=.14; 24 weeks: −10.3%; P=.02). After adjustment, PDC change was 13.8% greater in those with increased app use after March 15, 2020. Interview findings indicated that site B’s closure during COVID-19 had a greater impact, but almost all patients reported that the InCharge Health app helped support more consistent medication use. Conclusions We found significant impacts of the early clinic lockdowns, which reduced implementation of the mHealth intervention and led to reduced patient adherence to hydroxyurea. However, disruptions were lower among participants who experienced shorter clinic lockdowns and were associated with higher hydroxyurea adherence. Investigation of added strategies to mitigate the effects of care interruptions during major emergencies (eg, patient coaching and health navigation) may “insulate” the implementation of interventions to increase medication adherence. Trial Registration ClinicalTrials.gov NCT04080167; https://clinicaltrials.gov/ct2/show/NCT04080167 International Registered Report Identifier (IRRID) RR2-10.2196/16319

Recruitment Strategies in the Integration of Mobile Health Into Sickle Cell Disease Care to Increase Hydroxyurea Utilization Study (meSH): Multicenter Survey Study

“…Due to the COVID-19 pandemic restrictions for in-person research activities, virtual enrollment was initiated. The sites most affected by clinic shutdowns were the first 2 sites, as previously reported [ 9 ]. Although clinic lockdowns were no longer in effect when the remaining 5 sites opened enrollment, these sites were also affected by long-term changes related to the pandemic (eg, staff resignation, remote working).…”

“…In March 2020, only 4 months after the study began recruiting providers and 2 months after the initiation of patient recruitment, the global COVID-19 pandemic emerged in the United States. In response to the pandemic, institutions were forced to modify clinical and research procedures by temporarily suspending all nonessential in-person contact [ 9 ]. This rapid procedural change directly impacted all in-person research activities in meSH, which was initially designed to conduct all recruitment in person.…”

Hydroxyurea Adherence for Personal Best in Sickle Cell Treatment (HABIT) efficacy trial: Community health worker support may increase hydroxyurea adherence of youth with sickle cell disease

“…Low participant numbers needing acute healthcare intervention during the trial precluded meaningful comparison of clinical effects by group. While we were unable to assess pandemic‐related effects on HU adherence, a separate US‐based SCD trial demonstrated reduced HU adherence during the public health emergency 38 . Nationally, trial interruption in non‐COVID‐19 studies substantially increased during that period 39 …”

“…While we were unable to assess pandemic-related effects on HU adherence, a separate US-based SCD trial demonstrated reduced HU adherence during the public health emergency. 38 Nationally, trial interruption in non-COVID-19 studies substantially increased during that period. 39 Results from the intervention group suggest a positive impact intervention expressed positive perspectives on the CHW-led intervention.…”

Longitudinal effect of disease‐modifying therapy on left ventricular diastolic function in children with sickle cell anemia

“…Given the low adherence to hydroxyurea as seen in this study, new strategies are needed to achieve full drug benefits. Novel interventions using mobile health are being investigated and may represent a self‐management tool to support medication adherence 50–52 . Finally, our data highlights the need to investigate newer SCA‐approved therapies (e.g., voxelotor, crizanlizumab) and other therapeutic modalities such as curative treatments, that mitigate microvascular ischemic and endothelial injury, and explore their role in potentially preventing the ventricular remodeling that drives the cardiac injury seen in SCA.…”