PRO95 PSYCHOMETRIC EVALUATION OF A PATIENT-REPORTED OUTCOMES (PRO) INSTRUMENT FOR CONGENITAL THROMBOTIC THROMBOCYTOPENIC PURPURA (CTTP)

Abstract

Congenital thrombotic thrombocytopenic purpura (cTTP, hereditary cTTP) is an ultra-rare, life-threatening disorder where patients experience substantial comorbidity and decreased health-related quality of life (HRQoL). Baxalta (a Takeda company) developed a cTTP-specific patient-reported outcome (PRO) instrument and confirmed its content validity using qualitative cognitive debriefing. This study evaluated the psychometric properties of a newly developed cTTP-specific PRO instrument. This US/UK observational study (NCT03519672) was conducted from July 2018-April 2019 in patients aged ≥18 years receiving treatment for cTTP. Patients were enrolled through investigator sites and direct-to-patient recruitment. Patients completed self-administered PRO measures electronically at baseline and day 14. The cTTP-specific instrument assessed symptoms and impact of cTTP and consists of 5 multiple-item domains (pain/bruising, cognitive impairment, visual impairment, mood, treatment burden) and 3 single-item domains (fatigue, headaches, activity limitation). Convergent and divergent validity were determined by assessing the relationship between cTTP-specific PRO domains and domains of 8 additional PROs using Spearman rank correlation coefficients. Known-groups validity was assessed by comparing two patient-reported impression of severity (PGI-S) groups using t-tests. Internal reliability was assessed using Cronbach’s alpha. Test–retest reliability was assessed using intraclass correlation coefficients (ICC) between the two timepoints. In the 36 patients evaluated, high-to-moderate correlations (r≥0.4) were observed for 10 of 13 pairs of domains and/or total scores, confirming convergent validity. Low correlations (r<0.3) were observed for 7 of 10 hypothesized relationships, confirming divergent validity. Differences in mean cTTP scores between the two PGI-S groups were significant (p≤0.05) for all domains/most items, confirming known-groups validity. Internal Consistency was confirmed with high Cronbach’s alpha (baseline, 0.88; day 14, 0.91). Test-retest reliability was confirmed with a high ICC (0.96). This study provided evidence for the psychometric properties of the newly developed cTTP-specific PRO instrument for use in research and clinical practice to assess HRQoL among cTTP patients.