Mixed-Methods to Define Meaningful Change using Exit Interviewand Clinical Trial Data in Patients with Tenosynovial Giant Cell Tumor (TGCT).

backgroundTenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm associated with limited range of motion (ROM), stiffness, joint damage, pain, and reduced physical functioning (PF). The MOTION Phase 3 trial (NCT05059262) was a randomized, placebo-controlled, double-blind study of vimseltinib among patients with TGCT. The objective of the current study was to define meaningful changes in clinical outcome assessments (COAs) measuring active ROM, PF, and stiffness using qualitative and quantitative data from patients in the MOTION trial.

methodsEmbedded exit interviews with patients in MOTION were conducted to explore meaningful changes in Patient Global Impression of Change (PGIC) anchors, active ROM, Patient-Reported Outcomes Measurement Information System (PROMIS)-PF, and Worst Stiffness numeric rating scale (NRS). Anchor- and distribution-based analyses of the MOTION data, informed by the exit interviews, were used to define responder thresholds.

resultsIn the MOTION trial, 96/123 patients (78%) completed an exit interview. Most considered "minimally improved" responses for each question (PGIC-PF: 67%; PGIC-ROM 73%) as meaningful. Responder estimates ranged from 1.45 to 4.9 (PROMIS-PF), from 6.0 to 14.8 (active ROM), and from - 2.3 to - 0.5 (Stiffness). The cumulative distribution function curves show a clear separation between treatment groups at a wide range of values around the proposed thresholds.

conclusionsThe responder definitions were at least a 3-point improvement for PROMIS-PF, a 10% improvement for active ROM, and a 2-point improvement for the Worst Stiffness NRS. Qualitative interviews facilitate integrating the patient perspective in the selection of anchors and defining meaningful change.