A novel Bayesian adaptive design incorporating both primary and secondary endpoints for randomized IIB chemoprevention study of women at increased risk for breast cancer.
A novel Bayesian adaptive design incorporating both primary and secondary endpoints for randomized IIB chemoprevention study of women at increased risk for breast cancer.
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DOI：
10.1186/s13063-022-06930-5
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发表时间：
2022-12-05
期刊：
影响因子：
2.5
通讯作者：
Fabian, Carol J. J.
中科院分区：
文献类型：
--
作者：
Gajewski, Byron J. J.;Kimler, Bruce F. F.;Koestler, Devin C. C.;Mudaranthakam, Dinesh Pal;Young, Kate;Fabian, Carol J. J.
关键词：
我们的随机对照临床试验将探索巴多昔芬加结合雌激素调节乳腺组织风险生物标志物作为降低乳腺癌风险的替代品的潜力。本文探讨了试验的统计设计特点和最终选择试验设计的依据。成组序贯设计是一种流行的设计方法，允许试验因成功或无效而提前停止，与固定试验设计相比，可能节省时间和金钱。虽然贝叶斯自适应设计具有与成组序贯设计相同的属性，但它们具有使用先验信息以及以数据为条件的推理解释的额外好处。无论是频率论还是贝叶斯试验，大多数适应性设计都有中期分析，允许提前停止，通常只使用主要终点。这种方法的一个缺点是，研究可能没有足够的数据来充分比较单个关键次要终点。例如，如果次要终点的影响小于主要终点，则可能发生这种情况。在本文中，我们研究了一种称为双终点自适应的试验设计，只有在满足主要和次要终点的标准时才会提前停止。该方法将最终分析的重点放在主要终点上，但确保有足够的数据用于次要分析。我们的研究有两组，主要终点（乳腺摄影纤维腺体体积的变化）和次要终点（乳腺组织Ki-67的变化）。我们目前的操作特性，包括功率，试验持续时间，和I型错误率，并讨论了建模贝叶斯组序贯设计的主要和次要终点的价值和风险，与替代设计进行比较。结果表明，如果关注关键次要终点的充分信息，则双终点自适应设计比竞争设计具有更好的操作特征。我们的方法平衡了试验速度和对单个关键次要终点信息的需求。
Our randomized controlled clinical trial will explore the potential of bazedoxifene plus conjugated estrogen to modulate breast tissue-based risk biomarkers as a surrogate for breast cancer risk reduction. This paper investigates the statistical design features of the trial and the rationale for the final choice of its design. Group sequential designs are a popular design approach to allow a trial to stop early for success or futility, potentially saving time and money over a fixed trial design. While Bayesian adaptive designs enjoy the same properties as group sequential designs, they have the added benefit of using prior information as well as inferential interpretation conditional on the data. Whether a frequentist or Bayesian trial, most adaptive designs have interim analyses that allow for early stopping, typically utilizing only the primary endpoint. A drawback to this approach is that the study may not have enough data for adequate comparisons of a single, key secondary endpoint. This can happen, for example, if the secondary endpoint has a smaller effect than the primary endpoint. In this paper, we investigate a trial design called two-endpoint adaptive, which stops early only if a criterion is met for primary and secondary endpoints. The approach focuses the final analysis on the primary endpoint but ensures adequate data for the secondary analysis. Our study has two arms with a primary (change in mammographic fibroglandular volume) and secondary endpoint (change in mammary tissue Ki-67). We present operating characteristics including power, trial duration, and type I error rate and discuss the value and risks of modeling Bayesian group sequential designs with primary and secondary endpoints, comparing against alternative designs. The results indicate that the two-endpoint adaptive design has better operating characteristics than competing designs if one is concerned about having adequate information for a key secondary endpoint. Our approach balances trial speed and the need for information on the single, key secondary endpoint.
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影响因子：
2.7
作者：
Komm, Barry S.;Mirkin, Sebastian;Jenkins, Simon N.
通讯作者：
Jenkins, Simon N.
影响因子：
1.5
作者：
Zhou, Heng;Chen, Cong;Yuan, Ying
通讯作者：
Yuan, Ying
DOI：
10.1097/gme.0b013e318252e46d
发表时间：
2012-11
期刊：
Menopause (New York, N.Y.)
影响因子：
--
作者：
Ethun KF;Wood CE;Register TC;Cline JM;Appt SE;Clarkson TB
通讯作者：
Clarkson TB
DOI：
10.1093/annonc/mdv590
发表时间：
2016-04
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Smith SG;Sestak I;Forster A;Partridge A;Side L;Wolf MS;Horne R;Wardle J;Cuzick J
通讯作者：
Cuzick J
影响因子：
1.5
作者：
Dmitrienko, Alex;Tamhane, Ajit C.
通讯作者：
Tamhane, Ajit C.