Sample Size Requirements for Studies of Treatment Effects on Beta-Cell Function in Newly Diagnosed Type 1 Diabetes
Sample Size Requirements for Studies of Treatment Effects on Beta-Cell Function in Newly Diagnosed Type 1 Diabetes
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DOI：
10.1371/journal.pone.0026471
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发表时间：
2011-11-10
期刊：
影响因子：
3.7
通讯作者：
Skyler, Jay
中科院分区：
文献类型：
--
作者：
Lachin, John M.;McGee, Paula L.;Skyler, Jay
通过刺激的 C 肽测量的 β 细胞功能的保留最近已被接受为新诊断的 1 型糖尿病患者的治疗靶点。在 1 型糖尿病试验网络 (TrialNet) 最近完成的研究中，对 156 名在研究入组时患有 1 型糖尿病病程长达 3 个月的受试者进行了长达 24 个月的重复 2 小时混合膳食耐受性测试 (MMTT)。这些数据提供了更准确地确定未来研究新药对 C 肽值曲线下面积 (AUC) 影响所需的样本量所需的信息。评估了 AUC 的自然 log(x)、log(x+1) 和平方根 (root x) 变换。一般来说，需要对数据进行转换，以更好地满足常用统计检验的正态性假设。对原始数据和转换数据进行统计分析，以估计未经治疗受试者随时间变化的平均水平和残余变异，从而可以在 12 或 24 个月的随访中以及 8-12 岁儿童、青少年（13-17 岁）和成人（18 岁以上）中计算未来研究的样本量。检测治疗组与对照组的给定相对（百分比）差异所需的样本量在 24 个月随访时大于 12 个月随访时，并且不同年龄组之间存在差异。由于 13-17 岁年龄段的剩余变异较大，因此该年龄组需要更大的样本量。还描述了评估不同年龄段受试者混合样本量的方法。提供了统计表达式，用于以原始测量单位 (pmol/ml) 表示 log(x+1) 和 root x 转换值的分析。针对掩蔽抗 CD20（利妥昔单抗）与掩蔽安慰剂的 TrialNet 研究描述了使用不同转换的分析。这些结果提供了准确评估新药研究的样本量所需的信息，以保持新诊断的 1 型糖尿病中的 C 肽水平。
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.