PMU101 MOST BOTHERSOME SYMPTOM MEASUREMENT STRATEGIES: CONSIDERATIONS FOR REGULATED CLINICAL TRIALS

Increasingly, sponsors are developing patient-centric measurement strategies to evaluate treatment benefit. In conditions with heterogenous symptoms, tracking improvements in each patient’s self-identified most bothersome symptom (MBS) may be useful, as relevant symptoms can vary among individuals. This research reviews current approaches for measuring patient-reported MBS in regulated clinical trials. Clinical trials reporting an MBS measurement strategy were identified and reviewed. Trial characteristics were extracted and aggregated. To supplement this review, a targeted literature search was conducted. Findings documented existing practices and challenges/opportunities associated with MBS measurement strategies. Thirty-nine trials using MBS measurement strategies primarily in adult populations initiated between 2005-2018 were reviewed. MBS assessments informed secondary (n=17, 43.6%), co-primary (n=14, 35.9%), primary (n=5, 12.8%), and co-primary/primary and secondary combination (n=3, 7.7%) endpoints in these trials. Most were Phase 3 studies (61.5%) and the majority of trials were in genitourinary conditions (GU, 46.2%) or migraine (41.0%). Most primary endpoints informed by MBS assessments were in GU (n=4/5, 80.0%) and most co-primary endpoints using MBS assessments were in migraine (n=11/14, 78.6%). Various response scales (e.g., binary or Likert scales), dimensions (e.g., severity), and timepoints (e.g., hours, months) were employed to measure MBS change. MBS was generally assessed by providing respondents with a pre-specified list of symptoms. Considerations for employing an MBS measurement strategy include analytic (e.g., defining/scoring the MBS), operational (e.g., administering the MBS assessment) and regulatory (e.g., referencing existing guidance) factors. MBS endpoints promote patient-centric drug development by measuring what matters most to patients. This novel approach, supported by regulatory guidance in migraine and GU conditions, can be applied to other therapeutic areas characterized by heterogenous symptoms. An MBS measurement strategy requires thoughtful consideration from sponsors, including input from patients, regulators, and measurement experts, to effectively evaluate and support treatment benefit claims substantiated via MBS assessments.