Appraisal of Patient-Reported Outcome Measures in Analogous Diseases and Recommendations for Use in Phase II & III Clinical Trials of Pyruvate Kinase Deficiency

Abstract

Pyruvate kinase deficiency (PKD) is regarded as a rare disease and understanding of the epidemiology and burden associated with PKD remains limited, due to the low incidence of the condition. Clinical manifestations of PKD can be life threatening, and there is currently no curative therapy. The condition is generally clinically managed by maintaining adequate hemoglobin levels through transfusion and subsequent transfusion support, but with frequent complications. The treatment goal for PKD is to maintain/improve the patient’s quality of life. With the advancement of new therapies, there is a need to identify reliable, valid and relevant patient reported outcome (PRO) tools for use in planned clinical trials. This paper presents a systematic search of the literature to identify current PRO tools that may be used to capture/measure the impact of PKD and its treatment in clinical trials. It identifies appropriate PRO instruments and compares psychometric properties and strengths and weakness of each selected PRO instrument, and provides recommendations for the choice of PRO tools for use in future clinical trials. In the adult population, the use of EORTC QLQ C30 and SF-36v2 are recommended, the former being a basic minimum, particularly because this measure covers all key impacts as well as symptom concepts in the hypothesized psychosocial model, including generic HRQoL, as well as core symptoms such as fatigue. In the pediatric population, the use of PedsQL Generic Core Scale and the PedsQL MFS scale are recommended. The PedsQL Generic Core Scale is recommended as a measure of HRQoL, over the CHQ. The PedsQL MFS scale is recommended as a measure of fatigue over the pedsFACIT. It is likely that some symptoms/life impacts in PKD are unique to the disease, and are not observable in analogous conditions. Therefore, to fully capture the impact of PKD a 'Physico-Psychosocial Model' derived from the ‘Medical Model’ is proposed to form the basis for a hypothesised conceptual framework to address the need for development of a PKD specific PRO instrument.