Bringing the Patient Voice to Drug Development

Challenge

When Deciphera Pharmaceuticals developed vimseltinib (ROMVIMZA™) to treat patients with Tenosynovial Giant Cell Tumor (TGCT), demonstrating improvement in how patients functioned, not just tumor shrinkage, was essential. TGCT is a rare disease that can cause pain and stiffness and severely impair physical function.. Because patients can have tumors in different locations in their bodies, they experience varied impacts on their physical function.  Deciphera needed a valid, sensitive measure that could be used across patients with tumors in different locations and could garner regulatory approval from the Food and Drug Administration (FDA).

The measure needed to:

• Capture the full range of real-world impact of TGCT on physical function
• Capture unique impacts of lower and upper extremity tumors  using scoring that would allow the team to analyze data from all clinical trial patients together regardless of tumor location
• Provide compelling evidence of treatment benefit
• Meet FDA expectations for a rigorous and relevant patient-reported outcome measure

Solution

Across one qualitative study, two trials, two investigational TGCT treatments and multiple pharmaceutical sponsors, the PRO focused study team set out to create a custom PROMIS Physical Function short form tailored to people with TGCT (Tap et al., 2019; Gelderblom et al., 2024) direct patient input on the ways in which TGCT impacted their physical functioning and triangulated this with item-level psychometric information to select 15 Physical Function items (Gelhorn et al., 2016). This was separated into an 11-item measure tailored to people with upper extremity tumors and a 13-item measure tailored to people with lower extremity tumors (Gelhorn et al., 2019).

The new custom short forms were targeted to:

• Apply to the wide range of impacts TGCT can have depending on tumor location
• Reflect the changes in function that are meaningful to patients
• Align with regulatory expectations

Built on item response theory, PROMIS item banks allow for this approach of selecting specific patient-relevant items while keeping the resultant Physical Function scores on the PROMIS metric. Thus, scores for patients with upper and lower extremity tumors are interpretable and comparable and can be analyzed together.

The custom short form was administered electronically at multiple points during the trial, including baseline and week 25, to capture vimseltinib’s impact on physical function. Deciphera consulted with HealthMeasures scientists to accurately calculate PROMIS T-scores and provide necessary support material about item response theory scoring for the FDA.

Results

PROMIS Physical Function data played a key role in establishing the functional benefits of vimseltinib. In the Phase 3 trial supporting FDA approval, the higher proportion of patients treated with vimseltinib experienced a clinically meaningful improvement in physical function compared to placebo (43% vs 25%), as measured by PROMIS Physical Function (Gelderblom et al., 2024).

Clinically meaningful improvement was defined using a pre-specified responder threshold of ≥3 T-score points, established through anchor- and distribution-based analyses linking changes in PROMIS scores to patient-reported improvement in physical function.

In addition:

• The mean PROMIS Physical Function score increased (improved) by 4.6 points at Week 25 in the vimseltinib group, versus 1.3 points in the placebo group. Earlier research found that a change of 3 or more points for physical functioning was considered meaningful for patients with TGCT (Speck et. al, 2020).
• PROMIS-PF facilitated quantifiable and interpretable assessment of treatment benefit, grounded in changes that are meaningful to patients’ daily functioning.

Impact

Including PROMIS in the clinical trial helped Deciphera:

• Differentiate vimseltinib in a rare disease space where treatment options are limited and often insufficient to address functional impairment
• Grounded their regulatory submission in meaningful patient outcomes
• Earn credibility with regulators, clinicians, and patients

For HealthMeasures, this milestone underscores the growing value of PROMIS tools in advancing patient-centered drug development and regulatory innovation.

Takeaways

• FDA acceptance of PROMIS –Physical Function short forms in the vimseltinib label claim reinforces its value as rigorous and fit-for-purpose measures (or endpoints).
• PROMIS item banks facilitate tailoring measures to specific patient populations while retaining the ability to reliably score and interpret findings.
• Demonstrating improvement in patient physical function, not just tumor response, builds a compelling, patient-centered value story.
• Consultation with HealthMeasures ensures accurate scoring, interpretation, and presentation of PROMIS data for the FDA.