title: Islet cell transplantation in type 1 diabetes: an analysis of efficacy outcomes and considerations for trial designs.
abstract: To estimate treatment effect size and other parameters required for planning the designs and analyses of future phase 3 islet transplant trials, we analyzed key clinical and laboratory outcomes of 347 allogeneic islet transplant recipients, using data from the Collaborative Islet Transplant Registry (CITR). At 1 year, approximately 59% of all transplant recipients were free of severe hypoglycemic events and maintained hemoglobin A1c (HbA1c) level of ≤ 6.5%. The Kaplan-Meier (KM) survival analyses showed that 69%, 54% and 44% of these 1-year responders maintained this composite endpoint at 2, 3 and 4 years, respectively. Ninety-one percent of all recipients were free of severe hypoglycemic episodes at 1 year. Furthermore, the KM survival estimates showed that 91%, 85% and 80% of these subjects maintained this clinical benefit at 2, 3 and 4 years, respectively. These results can be very useful in developing framework for study designs, sample size estimates, and statistical analysis plans for future pivotal trials of islet cell transplantation in type 1 diabetes.
authors.affiliation: Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA. jawahar.tiwari@fda.hhs.gov
authors.forename: J L
authors.initials: JL
authors.lastname: Tiwari
authors.forename: B
authors.initials: B
authors.lastname: Schneider
authors.forename: F
authors.initials: F
authors.lastname: Barton
authors.forename: S A
authors.initials: SA
authors.lastname: Anderson
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D016381:Islets of Langerhans Transplantation; D008297:Male; D012042:Registries; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human