Conceptual Framework for Patient-Reported Outcome Measures in Clinical Trials of Skeletal Muscle Cramping Experienced in Dialysis: A Kidney Health Initiative Workgroup Report.

Skeletal muscle cramping is a common and bothersome symptom for patients on maintenance dialysis therapy, regardless of modality, and it has not been prioritized for innovative assessments or treatments. Research to prevent or treat skeletal muscle cramping in patients receiving dialysis is hindered by poorly understood pathophysiology, lack of an accepted definition, and the absence of a standardized measurement method. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a multidisciplinary workgroup to define a set of patient-reported outcome measures for use in clinical trials to test the effect of new dialysis devices, new KRTs, lifestyle/behavioral modifications, and medications on skeletal muscle cramping. Upon determining that foundational work was necessary, the workgroup undertook a multistep process to elicit concepts central to developing the basis for demonstrating content validity of candidate patient-reported outcome measures for skeletal muscle cramping in patients on dialysis. The workgroup sought to () create an accepted, patient-endorsed definition for skeletal muscle cramping that applies to all dialysis modalities, () construct a conceptual model for developing and evaluating a skeletal muscle cramping-specific patient-reported outcome measure, and () identify potential questions from existing patient-reported outcome measures that could be modified or adapted and subsequently tested in the dialysis population. We report the results of the workgroup's efforts, provide our recommendations, and issue a call to action to address the gaps in knowledge and research needs we identified. These action steps are urgently needed to quantify skeletal muscle cramping burden, assess the effect, and measure meaningful changes of new interventions to improve the experience of patients receiving dialysis and suffering from skeletal muscle cramping.