For children with systemic lupus erythematosus (SLE), there are significant advantages to direct-to-family clinical trials compared with traditional approaches; however, there are still design and implementation challenges to overcome, according to findings from a pilot trial published in Lupus Science & Medicine.
The Individual Patient Exposure and Response in Pediatric Lupus (iPERSONAL) trial, a single-arm, self-controlled, unblinded, direct-to-family pilot trial (ClinicalTrials.gov Identifier: NCT04358302) was conducted to determine the effects of a medication management device for supporting patient adherence to self-administration of hydroxychloroquine. The device, an electronic pill bottle cap containing an electronic sensor, recorded the date and time of bottle opening and provided automated reminders (via visual and auditory alerts, along with optional alerts including text messages and/or automated phone calls) related to taking the hydroxychloroquine pills.
Data were collected from 26 pediatric patients with SLE at 4 in-home visits over a 6-month period, including a physician-guided teleresearch examination that was conducted at the first visit. Eligible participants were aged between 5 years and 17.5 years, were enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry with a diagnosis of SLE, had received hydroxychloroquine for at least 3 months, and had internet access.
The primary study outcome was hydroxychloroquine adherence, which was defined as the proportion of dispensed doses as measured by the electronic pill bottle cap. Secondary outcomes were medication adherence using the Medication Adherence Self-Reported Inventory, plasma hydroxychloroquine concentrations, manual pill counts, and disease activity measured by the SLE Disease Activity Index-2K (SLEDAI) and the Systemic Lupus Activity Questionnaire.
Study authors explained that remote physicians and in-home nurses conducting the SLE disease activity assessment were trained in virtual examination (via video) of gait and musculoskeletal condition, as well as a teleresearch SLEDAI.
Results of iPERSONAL suggested that poor adherence to hydroxychloroquine was positively associated with poor outcomes in pediatric SLE. Researchers aimed to overcome this challenge by choosing a low-risk intervention that could be evaluated from the patients’ homes.
One challenge associated with direct-to-family trials the logistics of prescribing and administering investigational medical products and ensuring appropriate safety monitoring outside of the research facility. Another challenge is considering the accessibility of outcome measures in a remote setting.
Noting that enrollment and engagement in the trial exceeded expectations, the researchers have called for additional research to characterize the effects of the study design in different patient populations.
In conclusion, the study authors cited the “many potential benefits” of direct-to-family trials, in terms of enrollment, engagement, retention, cost-savings, and feasibility but emphasized that the study design posed several unique challenges. Nevertheless, they added, “These challenges provide valuable insight into [family-centered] clinical research, which may ultimately provide more robust and meaningful research.”
Disclosure: Multiple study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Randell RL, Singler L, Cunningham A, et al for the CARRA Registry. Delivering clinical trials at home: protocol, design and implementation of a direct-to-family paediatric lupus trial. Lupus Sci Med. 2021;8(1):e000494. doi:10.1136/lupus-2021-000494