Objectives: We describe the feasibility of embedding PROs for chemotherapy-induced peripheral neuropathy (CIPN) and cost effectiveness (CEA) in a randomized, multi-institutional Phase III study (NCT02166463), evaluating the efficacy of the novel agent, Brentuximab vedotin, for advanced cHL in children and adolescents. Methods: Recruitment for PROs of interest is targeted for 250 of the planned 600 trial participants. Participation in the trial includes prospective collection of patient- and parent proxy-reported outcomes. CIPN is evaluated with the 11- item FACT-GOG-NTX and paired with the 9-item CHRIs-Global to serially evaluate health-related quality of life (HRQL) consequences of CIPN from initial diagnosis to 12 months off therapy. For CEA, US-based participants are queried from diagnosis through 36 months off therapy with the 4-item Stanford Healthcare Utilization Questionnaire (parent-report), the Health Utilities Index (HUI) 2/3, and the 23-item Caregiver Work Limitations Questionnaire (parent-report) as a measure of productivity loss. A study-designated research assistant is charged with contacting site personnel at study entry and at each scheduled assessment. All data are tracked for completion and uploaded into a web-based relational database for future analysis. Units of healthcare utilization will be monetized with unit costs from US-based administrative databases, including claims from public and private payers, based on site of care and diagnostic and/or procedure codes. Total costs will be calculated by study arm and expressed as cost per quality-adjusted life year, derived from the HUI 2/3.
Results: The clinical trial, activated in March 2015, has enrolled 137 participants; accrual is ongoing at 170 participating institutions. Among participants 95% have completed the baseline CIPN and CEA assessments and > 90% have completed subsequent measures. Monetization of significant adverse events and utilization is in progress. Discussion: We demonstrate feasibility of embedding PROs evidenced by high acceptance and completion rates of assessments for prospective evaluation of CIPN, HRQL, and healthcare utilization in a multi-institutional trial of children with advanced HL. Our experience serves as a proof of principle to cooperative groups regarding the resources and the feasibility of incorporating necessary PRO and health utilization outcomes into Phase III clinical trials as a component of cancer care delivery research.