Sample Size Requirements for Studies of Treatment Effects on Beta-Cell Function in Newly Diagnosed Type 1 Diabetes

被引:36
作者
Lachin, John M. [1 ]
McGee, Paula L. [1 ]
Greenbaum, Carla J. [2 ]
Palmer, Jerry [3 ]
Pescovitz, Mark D. [4 ]
Gottlieb, Peter [5 ]
Skyler, Jay [6 ]
机构
[1] George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA
[2] Benaroya Res Inst, Seattle, WA USA
[3] Univ Washington, Dept Med, Seattle, WA USA
[4] Indiana Univ, Med Ctr, Dept Surg & Microbiol Immunol, Indianapolis, IN USA
[5] Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO 80262 USA
[6] Univ Miami, Sch Med, Diabet Res Inst, Miami, FL USA
来源
PLOS ONE | 2011年 / 6卷 / 11期
基金
美国国家卫生研究院;
关键词
THERAPY;
D O I
10.1371/journal.pone.0026471
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Preservation of beta-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 (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 root 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.
引用
收藏
页数:14
相关论文
共 23 条
  • [1] [Anonymous], 1996, Applied Linear Regression Models
  • [2] [Anonymous], GUID IND DIAB MELL D
  • [3] ATKINSON MA, 1994, NEW ENGL J MED, V331, P1428
  • [4] THE USE OF TRANSFORMATIONS
    BARTLETT, MS
    [J]. BIOMETRICS, 1947, 3 (01) : 39 - 52
  • [5] AN ANALYSIS OF TRANSFORMATIONS
    BOX, GEP
    COX, DR
    [J]. JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1964, 26 (02) : 211 - 252
  • [6] RANK TRANSFORMATIONS AS A BRIDGE BETWEEN PARAMETRIC AND NONPARAMETRIC STATISTICS
    CONOVER, WJ
    IMAN, RL
    [J]. AMERICAN STATISTICIAN, 1981, 35 (03) : 124 - 129
  • [7] Demidenko E., 2004, MIXED MODELS THEORY
  • [8] Failure to Preserve β-Cell Function With Mycophenolate Mofetil and Daclizumab Combined Therapy in Patients With New-Onset Type 1 Diabetes
    Gottlieb, Peter A.
    Quinlan, Scott
    Krause-Steinrauf, Heidi
    Greenbaum, Carla J.
    Wilson, Darrell M.
    Rodriguez, Henry
    Schatz, Desmond A.
    Moran, Antoinette M.
    Lachin, John M.
    Skyler, Jay S.
    [J]. DIABETES CARE, 2010, 33 (04) : 826 - 832
  • [9] Mixed-Meal Tolerance Test Versus Glucagon Stimulation Test for the Assessment of β-Cell Function in Therapeutic Trials in Type 1 Diabetes
    Greenbaum, Carla J.
    Mandrup-Poulsen, Thomas
    Friedenberg, Paula
    Battelino, Tadej
    Haastert, Burkhard
    Ludvigsson, Johnny
    Pozzilli, Paolo
    Lachin, John M.
    Kolb, Hubert
    [J]. DIABETES CARE, 2008, 31 (10) : 1966 - 1971
  • [10] Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus
    Herold, KC
    Hagopian, W
    Auger, JA
    Poumian-Ruiz, E
    Taylor, L
    Donaldson, D
    Gitelman, SE
    Harlan, DM
    Xu, DL
    Zivin, RA
    Bluestone, JA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (22) : 1692 - 1698