Approach to patient reported outcome measures selection and implementation in a chronic norovirus clinical efficacy trial for patients after solid organ transplant.

Abstract

Norovirus is the second most common cause of diarrhea among solid organ transplant recipients. There are currently no approved therapies for Norovirus, which can substantially impact quality of life, particularly in an immunocompromised patient population. In order to establish clinical efficacy and support any medication claims related to a patient's symptoms or function, the Food and Drug Administration requires that a trial's primary endpoints be derived from patient reported outcome measures- an outcome that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else. In this paper, we describe our study team's approach to the definition, selection, measurement and evaluation of patient reported outcome measures as part of establishing clinical efficacy of Nitazoxanide for acute and chronic Norovirus in solid organ transplant recipients. We specifically describe our approach to measuring the primary efficacy endpoint- days to cessation of vomiting and diarrhea after randomization through 160 days, measured through daily symptom diaries as well as the impact of treatment on exploratory efficacy endpoints, particularly change in the impact of norovirus on psychological function and quality of life.