Psychometric Validation of the CLN2 Quality of Life Questionnaire in Participants with CLN2 Disease Treated with Cerliponase Alfa

Objectives: This study evaluated the psychometric properties of the ceroid lipofuscinosis type 2 Quality of Life (CLN2 QoL) questionnaire. Methods: Data from children with CLN2 disease aged 3-16 years receiving cerliponase alfa in the BMN 190-201 and BMN 190-202 clinical studies, collected via purposive sampling, were used to assess convergent and divergent validity, internal consistency and reliability. The clinically important difference (CID) was estimated with distribution- and anchor-based methods. Descriptive and inferential statistical analyses were conducted using IBM SPSS. Results: CLN2 QoL data of 22 participants were analysed. Ceiling effects were observed in 22 items (35% threshold); no floor effects were observed. Internal consistency analysis showed good reliability (Cronbach's alpha and Omega reliability >0.7) for four domains at study completion; only one domain had good reliability at baseline. All domains had good test-retest reliability (correlation >0.5) except Feeding With G-Tube and Seizures. Convergent and divergent correlation analysis showed moderate-strong correlations (>0.4) between PedsQL and CLN2 QoL total scores, between the Pediatric Quality of Life Inventory (PedsQL) total score and most CLN2 QoL domains at baseline, and between CLN2 QoL total score and most PedsQL domains at week 97. Known groups validity showed a significant difference in means for the Behaviour domain (p = 0.05) for reasons that could not be clarified. CID was 6.79-12.94 for domains; total score CID was 6.91 using distribution-based and 6.13-13.05 using anchor-based methods. Conclusions: This study is the first to validate the CLN2 QoL and to estimate the CID of this instrument in CLN2 patients. Our results show good validity and reliability of this tool.