The goals for successful development of treatment in gastroparesis.

ABSTRACT

BACKGROUND: Gastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical obstruction. There is significant unmet need in its management, and essentially there are no medications approved for its treatment over four decades. PURPOSE: The objectives of this review are to develop an understanding of the goals of treatment, the evidence-based criteria for treatment success based on the current scientific understanding of gastroparesis as well as patient response outcomes, and to propose evidence-based principles for the successful development of treatments for gastroparesis. Specifically, we discuss the pathophysiologic targets in gastroparesis, eligibility criteria for clinical trial participation based on validated gastric emptying studies, and the patient response outcome measures that have been validated to appraise effects of treatment on clinically relevant outcomes. These considerations lead to recommendations regarding eligibility, design, and duration of proof-of-efficacy studies, and to endorsing the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary as a validated patient response outcome and to justification of the shortening of proof-of-efficacy, placebo-controlled clinical trials to 4 weeks treatment duration after a baseline period. We believe that such approaches will increase the likelihood of successful assessment of efficacy of novel approaches to treating patients with gastroparesis.