Sample size requirements for studies of treatment effects on Beta-Cell function in newly diagnosed type 1 diabetes

John M. Lachin, Paula L. McGee, Carla J. Greenbaum, Jerry Palmer, Mark D. Pescovitz, Peter Gottlieb, Jay S Skyler

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Preservation of β-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(x), log(x+1) and square-root (√x) 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(x+1) and √x 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.

Original languageEnglish
Article numbere26471
JournalPLoS One
Volume6
Issue number11
DOIs
StatePublished - Nov 10 2011

Fingerprint

insulin-dependent diabetes mellitus
Medical problems
Type 1 Diabetes Mellitus
Sample Size
C-Peptide
peptides
cells
sampling
Area Under Curve
Units of measurement
Statistical tests
statistical analysis
Therapeutics
Statistical methods
Time and Motion Studies
placebos
preserves
Meals
Age Groups
Placebos

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sample size requirements for studies of treatment effects on Beta-Cell function in newly diagnosed type 1 diabetes. / Lachin, John M.; McGee, Paula L.; Greenbaum, Carla J.; Palmer, Jerry; Pescovitz, Mark D.; Gottlieb, Peter; Skyler, Jay S.

In: PLoS One, Vol. 6, No. 11, e26471, 10.11.2011.

Research output: Contribution to journalArticle

Lachin, John M. ; McGee, Paula L. ; Greenbaum, Carla J. ; Palmer, Jerry ; Pescovitz, Mark D. ; Gottlieb, Peter ; Skyler, Jay S. / Sample size requirements for studies of treatment effects on Beta-Cell function in newly diagnosed type 1 diabetes. In: PLoS One. 2011 ; Vol. 6, No. 11.
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