Sample Size Requirements for Studies of Treatment Effects on Beta-Cell Function in Newly Diagnosed Type 1 Diabetes
Open Access
- 10 November 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (11), e26471
- https://doi.org/10.1371/journal.pone.0026471
Abstract
Preservation of -cell function as measured by stimulated C-peptide 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 2-hour 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 2-hour area under the curve (AUC) of the C-peptide values. The natural log( ), log( +1) and square-root 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 follow-up 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 follow-up, 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 anti-CD20 (rituximab) versus masked placebo. These results provide the information needed to accurately evaluate the sample size for studies of new agents to preserve C-peptide levels in newly diagnosed type 1 diabetes.Keywords
This publication has 16 references indexed in Scilit:
- Failure to Preserve β-Cell Function With Mycophenolate Mofetil and Daclizumab Combined Therapy in Patients With New- Onset Type 1 DiabetesDiabetes Care, 2010
- Rituximab, B-Lymphocyte Depletion, and Preservation of Beta-Cell FunctionNew England Journal of Medicine, 2009
- GAD Treatment and Insulin Secretion in Recent-Onset Type 1 DiabetesNew England Journal of Medicine, 2008
- Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in Therapeutic Trials in Type 1 DiabetesDiabetes Care, 2008
- Insulin Needs after CD3-Antibody Therapy in New-Onset Type 1 DiabetesNew England Journal of Medicine, 2005
- Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes MellitusNew England Journal of Medicine, 2002
- β-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trialThe Lancet, 2001
- The Pathogenesis of Insulin-Dependent Diabetes MellitusNew England Journal of Medicine, 1994
- The Box-Cox Transformation Technique: A ReviewJournal of the Royal Statistical Society: Series D (The Statistician), 1992
- A Heteroskedasticity-Consistent Covariance Matrix Estimator and a Direct Test for HeteroskedasticityEconometrica, 1980