Discussion
anemia, PK deficiency
K DEFICIENCY, DISEASE, RECRUITMENT, ANEMIA
This analysis assessed the psychometric performance of the first two PK deficiency-specific PRO instruments, the PKDD and PKDIA, using blinded data from the phase 3 ACTIVATE trial of mitapivat [Both the PKDD and PKDIA performed well across the psychometric analyses applied. Internal consistency was high for both the PKDD and PKDIA (ω = 0.86 and 0.90, respectively), with excellent test–retest reliability (Baseline PGIS was selected for use as the known-groups set as it is a widely employed PRO that provides a simple 1-item outcome measure specifically focused on patient perception of the severity of their condition, with clearly defined categories of severity. A linear model for known-groups validity demonstrated PGIS-stratified PKDD and PKDIA means increased with increased PGIS score, as expected, with large effect sizes for both assessments. As both the PKDD and PKDIA also correlated well with PGIS, these results suggest that PGIS is a reasonable criterion measure for known-groups validity. These analyses provide evidence that the PKDD and PKDIA are valid and reliable PRO tools to measure disease impact, signs, and symptoms in adults with PK deficiency. Therefore, these are very likely to represent appropriate measures for the capture of relevant and informative feedback from patients on the severity of their disease and impact of treatment on their quality of life and symptoms. As such, the PKDD and PKDIA represent the first validated PK deficiency-specific PRO measures.This analysis has several limitations. Validation was performed in-trial, which may restrict the spectrum of latent traits under investigation due to the selection criteria necessary in recruitment of a study population. Although the study population was substantial for this rare anemia, the small overall patient population does represent a limitation of this analysis despite high response rates to the surveys at the assessed timepoints. The known-groups validity analysis is somewhat limited by the use of a single known-groups set (PGIS) based on patient self-reports, and future research may examine additional sets that focus on other relevant patient characteristics to enhance the current psychometric analyses. It is also of note that the PKDD and PKDIA instruments were also designed for use in a clinical trial setting, which may limit their utility in a real-world clinical setting due to the complex scoring algorithms required, the expectation that the PKDD is completed at the end of the day (which may not align with patients’ clinician visits), the need for completion of the PKDD on at least four days of a seven-day period for stable scoring estimates, and the use of electronic deployment of the instruments throughout the trial which may not be available as part of standard care and may thus have enhanced the likelihood of reliable data capture in the trial. However, there may be utility in the use of the simple sum scores in a clinical setting, as while these do not provide a validated estimate, they may serve to give specialist clinicians an approximation of patient status [