Gastroparesis: FDA Revises Draft Guidance
The US Food and Drug Administration (FDA) on Tuesday updated draft guidance from July 2015 to address public comments and reflect the agency’s current thinking on the development of clinical outcome assessment measures and statistical considerations to assess primary and secondary efficacy endpoints of clinical trials for gastroparesis.The nine-page draft explains: “Until a well-defined and reliable PRO [patient-reported outcome] instrument that measures all the clinically important signs and symptoms of gastroparesis is available, we recommend that the five core signs and symptoms of gastroparesis — nausea, vomiting, postprandial fullness, early satiety, and abdominal pain — be included as endpoints in well-controlled clinical trials.”
As far as the primary efficacy assessment, the draft points to changes in patient-reported signs and symptom scores for idiopathic and diabetic gastroparesis. Changes in gastric emptying time can be measured as a secondary endpoint if desired, but they should not be used as a primary efficacy endpoint “because changes in gastric emptying time are not associated with the changes in the clinically important signs and symptoms in patients with gastroparesis,” the draft adds.
Under the section on statistical considerations, the draft notes: “We recommend that sponsors analyze the primary and secondary endpoints as continuous or ordinal variables; we do not recommend the use of percentage change. In general, a traditional responder analysis would not be appropriate unless the targeted response is complete resolution of signs and symptoms. In addition, we encourage the use of baseline values and other covariates to improve the efficiency of primary and secondary endpoint analyses.”
Gastroparesis: Clinical Evaluation of Drugs for Treatment: Draft Guidance for Industry