Psychometric Evaluation of the Mastocytosis Symptom Severity Daily Diary (MS2D2) Instrument in Patients with Nonadvanced Systemic Mastocytosis (NonAdvSM)
Author(s)
James Marcus, PhD1, Cem Akin, MD2, Ralph Turner, PhD1, Jenna Zhang, PhD3, Rachael Easton, MD3, Michelle Lim-Watson, PhD4, Marcus Carden, MD3, Frank Siebenhaar, MD5;
1IQVIA, New York, NY, USA, 2University of Michigan, Ann Arbor, MI, USA, 3Cogent Biosciences, Waltham, MA, USA, 4MCPHS University, Boston, MA, USA, 5Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin and Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
1IQVIA, New York, NY, USA, 2University of Michigan, Ann Arbor, MI, USA, 3Cogent Biosciences, Waltham, MA, USA, 4MCPHS University, Boston, MA, USA, 5Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin and Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany
Presentation Documents
OBJECTIVES: The psychometric properties of the MS2D2, a 17-item electronic measure and daily diary used to evaluate symptom severity in patients with NonAdvSM, including smoldering systemic mastocytosis, bone marrow mastocytosis, and indolent systemic mastocytosis subtypes, were assessed in Part 1 (n=54) of a multi-part, randomized, double-blind, placebo-controlled, Phase 2 clinical study (SUMMIT) of patients with moderate to severe NonAdvSM.
METHODS: Structural validity (confirmatory factor) analyses refined the composition of the MS2D2’s domains and total symptom score (TSS). The measures were evaluated for internal consistency, test-retest reliability, construct validity, sensitivity to change, and to determine clinically meaningful change thresholds (MCTs).
RESULTS: Structural validity analyses (2nd order CFA model) supported an 11-item MS2D2 with four domains - Dermatological (4), Other (GI and Pain) (4), Neurocognitive (2), and Fatigue (1) - all contributing to TSS. The MS2D2 demonstrated excellent internal consistency (α= 0.84-0.92) and test-retest reliability (ICC=0.86-0.97). Convergent validity was high, with TSS having r=0.90 with Mastocytosis Activity Score and r=0.57 with the Mastocytosis Quality of Life Questionnaire. Known-groups validity was supported, with MS2D2 scores distinguishable based on patient global impression of severity (PGIS). The MS2D2 was sensitive to changes in patient status, e.g., at Week 12 TSS had r=-0.55 with patient global impression of change (PGIC) and r=0.71 with PGIS. Anchor-based analyses yielded MCTs of 1.5-2.0 change on a 0-10 scale, exceeding distribution-based measurement error; values corresponded to 34-45% of baseline for TSS.
CONCLUSIONS: The MS2D2 is a reliable and valid instrument for capturing the NonAdvSM patient experience, fulfilling FDA’s patient-focused drug development guidance to a greater extent than other measures of NonAdvSM symptom severity, particularly regarding structural validity. The study provides evidence for use of MS2D2 in clinical trials and it is currently being used as the primary endpoint in a larger (n=179) placebo-controlled, second phase of the study (Summit Part 2) currently underway.
METHODS: Structural validity (confirmatory factor) analyses refined the composition of the MS2D2’s domains and total symptom score (TSS). The measures were evaluated for internal consistency, test-retest reliability, construct validity, sensitivity to change, and to determine clinically meaningful change thresholds (MCTs).
RESULTS: Structural validity analyses (2nd order CFA model) supported an 11-item MS2D2 with four domains - Dermatological (4), Other (GI and Pain) (4), Neurocognitive (2), and Fatigue (1) - all contributing to TSS. The MS2D2 demonstrated excellent internal consistency (α= 0.84-0.92) and test-retest reliability (ICC=0.86-0.97). Convergent validity was high, with TSS having r=0.90 with Mastocytosis Activity Score and r=0.57 with the Mastocytosis Quality of Life Questionnaire. Known-groups validity was supported, with MS2D2 scores distinguishable based on patient global impression of severity (PGIS). The MS2D2 was sensitive to changes in patient status, e.g., at Week 12 TSS had r=-0.55 with patient global impression of change (PGIC) and r=0.71 with PGIS. Anchor-based analyses yielded MCTs of 1.5-2.0 change on a 0-10 scale, exceeding distribution-based measurement error; values corresponded to 34-45% of baseline for TSS.
CONCLUSIONS: The MS2D2 is a reliable and valid instrument for capturing the NonAdvSM patient experience, fulfilling FDA’s patient-focused drug development guidance to a greater extent than other measures of NonAdvSM symptom severity, particularly regarding structural validity. The study provides evidence for use of MS2D2 in clinical trials and it is currently being used as the primary endpoint in a larger (n=179) placebo-controlled, second phase of the study (Summit Part 2) currently underway.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
PCR173
Topic
Patient-Centered Research
Topic Subcategory
Instrument Development, Validation, & Translation, Patient-reported Outcomes & Quality of Life Outcomes
Disease
SDC: Rare & Orphan Diseases, SDC: Systemic Disorders/Conditions (Anesthesia, Auto-Immune Disorders (n.e.c.), Hematological Disorders (non-oncologic), Pain)