Novel approach for assessing outcomes of type 1 diabetes prevention trials over a fixed time interval

Abstract

We evaluated whether a binary metabolic end point for change (A) from baseline to 1-year postrandomization could be useful in type 1 diabetes (T1D) prevention trials. Using 2-h oral glucose tolerance testing data from the stage 1 participants in the recent abatacept prevention trial and similar participants in the observational TrialNet Pathway to Prevention (PTP) study, we assessed Ametabolic measures, plotted glucose and C-peptide response curves, and categorized vectors for A from baseline to 1 year as metabolic treatment failure versus success. Analyses were validated using the teplizumab prevention study. PTP participants with Aglucose >0 and AC-peptide <0 from baseline to 1 year were at substantially higher risk for stage 3 T1D than those with Aglucose <0 and AC-peptide >0 (P < 0.0001). Based on this, we compared placebo versus treatment groups in both trials for failure (Dglucose >0 with DC-peptide <0) versus success (Dglucose <0 with AC-peptide >0) after 1 year. Using this end point, a favorable metabolic impact of abatacept was found after 12 months of treatment. An analytic approach using a binary metabolic end point of failure versus success at a fixed time interval appears to detect treatment effects at least as well as standard primary end points with shorter follow-up.