Psychometric evaluation of the Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) in a phase 2 clinical study

Brad Padilla, Alan L Shields, Fiona Taylor, Xiaoran Li, Jeffrey Mcdonald, Tanya Green, Anthony L Boral, Hui-Min Lin, Cem Akin, Frank Siebenhaar, Brenton Mar, Brad Padilla, Alan L Shields, Fiona Taylor, Xiaoran Li, Jeffrey Mcdonald, Tanya Green, Anthony L Boral, Hui-Min Lin, Cem Akin, Frank Siebenhaar, Brenton Mar

Abstract

Background: Indolent systemic mastocytosis (ISM) is a rare, clonal mast cell neoplasm characterized by severe, unpredictable symptoms. The Indolent Systemic Mastocytosis Symptom Assessment Form (ISM-SAF) items compose a Total Symptom Score (TSS), Gastrointestinal Symptom Score (GSS), and Skin Symptom Score (SSS) to assess symptom severity. This study evaluated the psychometric performance of ISM-SAF among ISM patients.

Methods: In PIONEER, a Phase 2 trial evaluating safety and efficacy of selective kinase inhibitor avapritinib in patients with ISM, the 12-item ISM-SAF was administered daily. Psychometric evaluation of score reliability, validity, and clinical interpretation was conducted using the trial data.

Results: Thirty-eight patients contributed to analyses (78.9% female; mean age = 49). Baseline internal consistency reliability (α) for bi-weekly TSS, GSS, and SSS was 0.86, 0.83, and 0.82, respectively. Test-retest reliability among patients exhibiting no change in Patient Global Impression of Symptom Severity (PGIS) between Baseline and Day 15 exceeded 0.74 universally. Construct validity and known-groups analysis showed moderate to strong ISM-SAF score correlation (r = 0.382-0.881) to supportive patient-reported questionnaires (e.g., PGIS and Mastocytosis Quality of Life Questionnaire) symptom and skin scores, and ability to distinguish among clinically unique groups. Correlations of ISM-SAF and other assessment change scores reflect evidence of score sensitivity. Clinically important difference and response estimates were 7-10 and 19, respectively.

Discussion: ISM-SAF produced reliable, construct-valid, sensitive scores when administered in PIONEER to patients in the target population. Results of this study support the use of the ISM-SAF as a reliable and valid measure to evaluate disease symptomology in ISM patients. Trial registration ClinicalTrials.gov, NCT03731260. Registered 10 October 2018, https://ichgcp.net/clinical-trials-registry/NCT03731260 .

Keywords: Indolent systemic mastocytosis; Instrument development; Patient-reported outcomes; Psychometric evaluation.

Conflict of interest statement

BP, ALS, FT, XL, and JM are, or were at the time of the research, employees of Adelphi Values, which conducted research on behalf of Blueprint Medicines. TG, ALB, H-ML, and BM are employees of Blueprint Medicines and own stock in the company. CA received research funding and consultancy fees from Blueprint Medicines. FS is or recently was a speaker and/or advisor for and/or has received research funding from Allakos, Blueprint, Celldex, Genentech, Moxie, Novartis, and Uriach.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
BLU-285-2203 Part 1 study design. BSC best supportive care, GI gastrointestinal, ISM indolent systemic mastocytosis, PRO patient-reported outcome, RP2D recommended phase 2 dose, TSS total symptom score. aAll subjects were randomized at the beginning of the study to one of three avapritinib doses or placebo in Part 1

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Source: PubMed

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