Diabetes and Endocrinology  Mathematics  Science Policy

Sample Size Requirements for Studies of Treatment Effects on BetaCell Function in Newly Diagnosed Type 1 Diabetes
Published:
Thursday, November 10, 2011
Author:
John M. Lachin et al.
by John M. Lachin, Paula L. McGee, Carla J. Greenbaum, Jerry Palmer, Mark D. Pescovitz, Peter Gottlieb, Jay Skyler, Type 1 Diabetes Trial Network
Preservation of cell function as measured by stimulated Cpeptide has recently been accepted as a therapeutic target for subjects with newly diagnosed type 1 diabetes. In recently completed studies conducted by the Type 1 Diabetes Trial Network (TrialNet), repeated 2hour Mixed Meal Tolerance Tests (MMTT) were obtained for up to 24 months from 156 subjects with up to 3 months duration of type 1 diabetes at the time of study enrollment. These data provide the information needed to more accurately determine the sample size needed for future studies of the effects of new agents on the 2hour area under the curve (AUC) of the Cpeptide values. The natural log(), log(+1) and squareroot transformations of the AUC were assessed. In general, a transformation of the data is needed to better satisfy the normality assumptions for commonly used statistical tests. Statistical analysis of the raw and transformed data are provided to estimate the mean levels over time and the residual variation in untreated subjects that allow sample size calculations for future studies at either 12 or 24 months of followup and among children 8–12 years of age, adolescents (13–17 years) and adults (18+ years). The sample size needed to detect a given relative (percentage) difference with treatment versus control is greater at 24 months than at 12 months of followup, and differs among age categories. Owing to greater residual variation among those 13–17 years of age, a larger sample size is required for this age group. Methods are also described for assessment of sample size for mixtures of subjects among the age categories. Statistical expressions are presented for the presentation of analyses of log(+1) and transformed values in terms of the original units of measurement (pmol/ml). Analyses using different transformations are described for the TrialNet study of masked antiCD20 (rituximab) versus masked placebo. These results provide the information needed to accurately evaluate the sample size for studies of new agents to preserve Cpeptide levels in newly diagnosed type 1 diabetes.
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