Optimizing Sample Size Determinations for Phase 3 Clinical Trials in Type 2 Diabetes.

IF 1.3 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Alexander C Cambon, James Travis, Liping Sun, Jada Idokogi, Anna Kettermann
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Abstract

An informed estimate of subject-level variance is a key determinate for accurate estimation of the required sample size for clinical trials. Evaluating completed adult Type 2 diabetes studies submitted to the FDA for accuracy of the variance estimate at the planning stage provides insights to inform the sample size requirements for future studies. From the U.S. Food and Drug Administration (FDA) database of new drug applications containing 14,106 subjects from 26 phase 3 randomized studies submitted to the FDA in support of drug approvals in adult type 2 diabetes studies reviewed between 2013 and 2017, we obtained estimates of subject-level variance for the primary endpoint-change in glycated hemoglobin (HbA1c) from baseline to 6 months. In addition, we used nine additional studies to examine the impact of clinically meaningful covariates on residual standard deviation and sample size re-estimation. Our analyses show that reduced sample sizes can be used without interfering with the validity of efficacy results for adult type 2 diabetes drug trials. This finding has implications for future research involving the adult type 2 diabetes population, including the potential to reduce recruitment period length and improve the timeliness of results. Furthermore, our findings could be utilized in the design of future endocrinology clinical trials.

优化 2 型糖尿病 3 期临床试验的样本量确定。
对受试者水平差异的知情估计是准确估计临床试验所需样本量的关键因素。在计划阶段对提交给美国食品药品管理局的已完成的成人 2 型糖尿病研究进行评估,以确定方差估计的准确性,从而为未来研究的样本量要求提供启示。从美国食品药品管理局(FDA)的新药申请数据库中,我们获得了主要终点--糖化血红蛋白(HbA1c)从基线到6个月的变化--的受试者水平方差估计值。此外,我们还使用了另外九项研究来考察具有临床意义的协变量对残差标准差和样本量再估计的影响。我们的分析表明,缩小样本量不会影响成人 2 型糖尿病药物试验疗效结果的有效性。这一发现对未来涉及成人 2 型糖尿病人群的研究具有重要意义,包括有可能缩短招募期和提高结果的及时性。此外,我们的发现还可用于未来内分泌学临床试验的设计。
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来源期刊
Pharmaceutical Statistics
Pharmaceutical Statistics 医学-统计学与概率论
CiteScore
2.70
自引率
6.70%
发文量
90
审稿时长
6-12 weeks
期刊介绍: Pharmaceutical Statistics is an industry-led initiative, tackling real problems in statistical applications. The Journal publishes papers that share experiences in the practical application of statistics within the pharmaceutical industry. It covers all aspects of pharmaceutical statistical applications from discovery, through pre-clinical development, clinical development, post-marketing surveillance, consumer health, production, epidemiology, and health economics. The Journal is both international and multidisciplinary. It includes high quality practical papers, case studies and review papers.
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