Development and Initial Validation of the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire (ITP-PAQ), a Disease-Specific Health-Related Quality of Life (HRQoL) Questionnaire.
Authors: Mathias Susan D. , Bussel James B. , George James N. , McMillan Robert , Okano Gary J. , Nichol Janet L. 
Published: April 2020

Abstract
Since no validated disease-specific HRQoL questionnaire currently exists to assess the range of issues that impact adult ITP patients, we sought to develop and validate the ITP-PAQ for this population. Information from literature reviews, focus groups, and clinicians were used to develop 50 ITP-PAQ items. Factor analyses were conducted to develop the scales and for item reduction. The final ITP-PAQ contained 44 items (10 scales), assessing Symptoms (S), Bother (B), Fatigue (FT), Activity (A), Fear (FR), Psychological Health (PH), Work (W), Social Activity (SA), Women’s Reproductive Health (RH), and Overall QoL (OQoL). The psychometric properties of the ITP-PAQ were evaluated in two studies. In an initial development study, 73 subjects completed the ITP-PAQ at baseline and 7–10 days later. Later, in an open label study, the ITP-PAQ was administered to 35 subjects at baseline, weeks 4, 12, and 24. Internal consistency, a measure of the extent to which items within each scale correlate with one another, was assessed by Cronbach’sα. Reproducibility was measured by the intra-class correlation coefficient (ICC), which compares scores for each subject over a brief time period. Construct validity was assessed by correlating newly developed ITP-PAQ scales with established measures, such as the SF-36 and the CES-D. Known groups validity, a measure of the questionnaire’s ability to discriminate between groups, was assessed by comparing the groups’ mean scores using ANOVA. Responsiveness, or the questionnaire’s ability to detect changes over time, was measured using Guyatt’s statistic. Internal consistency and reproducibility were acceptable for most scales in both studies (α and ICC&gt;0.70). Construct validity was demonstrated in the development study through moderate correlations between the ITP-PAQ SA and SF-36 Social Function scales (r= 0.67), and between the ITP-PAQ PH and the SF-36 Mental Health scales (r=0.63). In the open-label study, correlations between the ITP-PAQ SA and PH scales and the relevant SF-36 scales were 0.85 and 0.74, respectively. Moderate to strong inter-scale correlations were reported between ITP-PAQ scales and the CES-D, with the exception of the RH scale. In the development study, significant differences (p&lt;0.05) were reported between older (≥45 yrs.) and younger (≤44 yrs.) subjects. In all cases, the mean scale scores for the younger group were higher, indicating fewer negative effects of ITP on HRQoL. In the open label study, significant differences in the S, B, A, PH, and OQoL scales (p&lt;0.05) were found between subjects categorized by durable platelet response, which was found to be a more sensitive clinical marker than platelet response. Responsiveness (only assessed in open label study), was demonstrated for 8 of the 10 scales among durable platelet responders. Results provide preliminary evidence of the reliability, validity, and responsiveness of the ITP-PAQ. The ITP-PAQ, which asks specifically about ITP symptoms, was sensitive to differences in clinical measures such as durable platelet response. Further work should be done to estimate the minimal clinically important difference in ITP-PAQ scale scores to better understand the effects of treatment on HRQoL.