Effects of sceptical priors on the performance of adaptive clinical trials with binary outcomes.
Effects of sceptical priors on the performance of adaptive clinical trials with binary outcomes.
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DOI：
10.1002/pst.2387
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发表时间：
2024-03-29
影响因子：
1.5
通讯作者：
Kaas-Hansen，Benjamin Skov
中科院分区：
文献类型：
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作者：
Granholm，Anders;Lange，Theis;Kaas-Hansen，Benjamin Skov
目前尚不清楚怀疑先验如何影响适应性试验。我们使用不同临床场景下的二元结果评估了表达一系列怀疑的先验对几种贝叶斯、多阶段、适应性临床试验设计性能的影响。使用固定停止规则和经过校准的停止规则进行模拟，以将 1 类错误率保持在大约 5%。我们评估了总样本量、事件发生率、事件计数、结论性概率和选择最佳组、所选组中估计治疗效果的均方根误差 (RMSE) 以及理想设计百分比 (IDP；它结合了组选择概率、功效和选择较差组的后果)，仅在结论性试验中以及在非结论性试验中选择对照组后估计 RMSE 和 IDP。使用固定的停止规则，越来越多的怀疑先验导致更大的样本量、更多的事件、以优越性结束的模拟中更高的 IDP，以及更低的 RMSE、更低的结论性/选择最佳臂的概率，以及在非结论性模拟中选择控制时更低的 IDP。通过校准停止规则，增加的怀疑对样本量和事件计数的影响被减弱，并且增加的怀疑增加了在不显着增加样本量的情况下在非结论性模拟中选择对照时得出结论/选择最佳组和 IDP 的概率。具有温和适应和非信息性先验的试验设计的结果类似于使用弱到中度怀疑先验的更积极适应的设计。总之，在同时考虑多个性能指标时，在具有二元结果的自适应试验设计中使用有些怀疑的先验似乎是合理的。
It is unclear how sceptical priors impact adaptive trials. We assessed the influence of priors expressing a spectrum of scepticism on the performance of several Bayesian, multi‐stage, adaptive clinical trial designs using binary outcomes under different clinical scenarios. Simulations were conducted using fixed stopping rules and stopping rules calibrated to keep type 1 error rates at approximately 5%. We assessed total sample sizes, event rates, event counts, probabilities of conclusiveness and selecting the best arm, root mean squared errors (RMSEs) of the estimated treatment effect in the selected arms, and ideal design percentages (IDPs; which combines arm selection probabilities, power, and consequences of selecting inferior arms), with RMSEs and IDPs estimated in conclusive trials only and after selecting the control arm in inconclusive trials. Using fixed stopping rules, increasingly sceptical priors led to larger sample sizes, more events, higher IDPs in simulations ending in superiority, and lower RMSEs, lower probabilities of conclusiveness/selecting the best arm, and lower IDPs when selecting controls in inconclusive simulations. With calibrated stopping rules, the effects of increased scepticism on sample sizes and event counts were attenuated, and increased scepticism increased the probabilities of conclusiveness/selecting the best arm and IDPs when selecting controls in inconclusive simulations without substantially increasing sample sizes. Results from trial designs with gentle adaptation and non‐informative priors resembled those from designs with more aggressive adaptation using weakly‐to‐moderately sceptical priors. In conclusion, the use of somewhat sceptical priors in adaptive trial designs with binary outcomes seems reasonable when considering multiple performance metrics simultaneously.