Bayesian methods for the design and interpretation of clinical trials in very rare diseases.
Bayesian methods for the design and interpretation of clinical trials in very rare diseases.
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DOI：
10.1002/sim.6225
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发表时间：
2014-10-30
影响因子：
2
通讯作者：
Brogan, Paul
中科院分区：
文献类型：
--
作者：
Hampson, Lisa V.;Whitehead, John;Eleftheriou, Despina;Brogan, Paul
本文考虑了临床试验的设计和解释，这些临床试验比较了非常罕见的疾病的治疗方法，以至于全球范围内的招募工作可能会产生50个或更少的总样本量，即使患者招募了几年。对于此类研究，满足传统频率论功效要求所需的样本量显然不可行。相反，对任何此类试验的期望都必须限于对治疗方案的更好理解。我们提出了一种贝叶斯方法进行罕见病试验比较实验性治疗与对照患者的反应被归类为成功或失败。一个系统的启发，从临床医生的信念，他们的治疗效果是用来建立贝叶斯先验未知的模型参数。确定先验的过程中描述，包括正式考虑相关试验的结果的可能性。由于样本量较小，因此可以计算两种成功率的所有可能的后验分布。可以考虑两个治疗组之间的许多分配比率，以最大化试验得出结论推荐新治疗的先验概率，而实际上它不劣于对照。考虑到意见可以改变的程度，即使是最佳可行设计的数据，也可以帮助确定这样的试验是否值得。© 2014作者。出版社：John Wiley & Sons，Ltd
This paper considers the design and interpretation of clinical trials comparing treatments for conditions so rare that worldwide recruitment efforts are likely to yield total sample sizes of 50 or fewer, even when patients are recruited over several years. For such studies, the sample size needed to meet a conventional frequentist power requirement is clearly infeasible. Rather, the expectation of any such trial has to be limited to the generation of an improved understanding of treatment options. We propose a Bayesian approach for the conduct of rare-disease trials comparing an experimental treatment with a control where patient responses are classified as a success or failure. A systematic elicitation from clinicians of their beliefs concerning treatment efficacy is used to establish Bayesian priors for unknown model parameters. The process of determining the prior is described, including the possibility of formally considering results from related trials. As sample sizes are small, it is possible to compute all possible posterior distributions of the two success rates. A number of allocation ratios between the two treatment groups can be considered with a view to maximising the prior probability that the trial concludes recommending the new treatment when in fact it is non-inferior to control. Consideration of the extent to which opinion can be changed, even by data from the best feasible design, can help to determine whether such a trial is worthwhile. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd.
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影响因子：
3.7
作者：
HOGARTH, RM
通讯作者：
HOGARTH, RM
影响因子：
1.9
作者：
Morita, Satoshi;Thall, Peter F.;Mueller, Peter
通讯作者：
Mueller, Peter
DOI：
10.3899/jrheum.100632
发表时间：
2011-03-01
期刊：
The Journal of rheumatology
影响因子：
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作者：
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通讯作者：
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影响因子：
105.7
作者：
Lilford, RJ;Thornton, JG;Braunholtz, D
通讯作者：
Braunholtz, D
影响因子：
2
作者：
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通讯作者：
Rhame, FS