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

Quality of Life Research, vol. 35, pp. 57

Abstract

BACKGROUND: Tenosynovial 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. METHODS: Embedded 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. RESULTS: In 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. CONCLUSIONS: The 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.

Authors 12

1. Heather L. Gelhorn corresponding
   Affiliation as printed

   Patient-Centered Research, Evidera, Wilmington, NC, USA. heather.gelhorn@thermofisher.com

2. Katelyn N. Cutts
   Affiliation as printed

   Patient-Centered Research, Evidera, Wilmington, NC, USA

3. Brooke Harrow

   Deciphera Pharmaceuticals (United States)

   Affiliation as printed

   Deciphera Pharmaceuticals, LLC, Waltham, MA, USA

4. Christopher Tait

   Deciphera Pharmaceuticals (United States)

   Affiliation as printed

   Deciphera Pharmaceuticals, LLC, Waltham, MA, USA

5. Amanda Saunders

   Deciphera Pharmaceuticals (United States)

   Affiliation as printed

   Deciphera Pharmaceuticals, LLC, Waltham, MA, USA

6. Tsion Fikre
   Affiliation as printed

   Patient-Centered Research, Evidera, Wilmington, NC, USA

7. Yipin Han
   Affiliation as printed

   Patient-Centered Research, Evidera, Wilmington, NC, USA

8. Nicholas A. Zeringo

   Deciphera Pharmaceuticals (United States)

   Affiliation as printed

   Deciphera Pharmaceuticals, LLC, Waltham, MA, USA

9. Michiel Van De Sande Aachen Department of Orthopedic Surgery

   Leiden University Medical Center

   Affiliation as printed

   Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, Netherlands

10. William Tap

    Memorial Sloan Kettering Cancer Center

    Affiliation as printed

    Memorial Sloan Kettering Cancer Center, New York, NY, USA

11. Hans Gelderblom Aachen Department of Orthopedic Surgery

    Leiden University Medical Center

    Affiliation as printed

    Department of Orthopedic Surgery, Leiden University Medical Center, Leiden, Netherlands

12. Nicholas Bernthal

    University of California, Los Angeles

    Affiliation as printed

    Department of Orthopedic Surgery, University of California Los Angeles, Los Angeles, CA, USA