Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom.
Pan-Birmingham Gynaecological Oncology Cancer Centre, Birmingham, United Kingdom.
Am J Ther. 2023;30(1):e56-e71. doi: 10.1097/MJT.0000000000001548. Epub 2022 Nov 1.
Previous work has identified a strong association between the achievements of macroscopic cytoreduction and improved overall survival (OS) after primary surgical treatment of advanced epithelial ovarian cancer. Despite the use of contemporary methodology, resulting in the most comprehensive currently available evidence to date in this area, opponents remain skeptical.
We aimed to conduct sensitivity analyses to adjust for potential publication bias, to confirm or refute existing conclusions and recommendations, leveraging elicitation to incorporate expert opinion. We recommend our approach as an exemplar that should be adopted in other areas of research.
We conducted random-effects network meta-analyses in frequentist and Bayesian (using Markov Chain Montel Carlo simulation) frameworks comparing OS across residual disease thresholds in women with advanced epithelial ovarian cancer after primary cytoreductive surgery. Elicitation methods among experts in gynecology were used to derive priors for an extension to a previously reported Copas selection model and a novel approach using effect estimates calculated from the elicitation exercise, to attempt to adjust for publication bias and increase confidence in the certainty of the evidence.
Analyses using data from 25 studies (n = 20,927 women) all showed the prognostic importance of complete cytoreduction (0 cm) in both frameworks. Experts accepted publication bias was likely, but after adjustment for their opinions, published results overpowered the informative priors incorporated into the Bayesian sensitivity analyses. Effect estimates were attenuated but conclusions were robust in all analyses.
There remains a strong association between the achievement of complete cytoreduction and improved OS even after adjustment for publication bias using strong informative priors formed from an expert elicitation exercise. The concepts of the elicitation survey should be strongly considered for utilization in other meta-analyses.
先前的研究已经确定，在对晚期上皮性卵巢癌进行初次手术治疗后，实现大体减瘤术的效果与提高总生存期（OS）之间存在很强的关联。尽管采用了当代方法，得出了迄今为止该领域最全面的现有证据，但反对者仍然持怀疑态度。
我们旨在进行敏感性分析，以调整潜在的发表偏倚，确认或反驳现有结论和建议，并利用启发式方法纳入专家意见。我们建议采用我们的方法作为范例，应在其他研究领域采用。
我们在频繁主义和贝叶斯（使用马尔可夫链蒙特卡罗模拟）框架中进行了随机效应网络荟萃分析，比较了在初次细胞减瘤手术后患有晚期上皮性卵巢癌的女性中，残留疾病阈值对 OS 的影响。利用妇科专家的启发式方法，为先前报道的 Copas 选择模型的扩展和使用从启发式练习中计算出的效应估计值的新方法提供了先验，以尝试调整发表偏倚并增加对证据确定性的信心。
使用来自 25 项研究（n = 20,927 名女性）的数据进行的分析在两个框架中均显示了完全细胞减瘤术（0 cm）的预后重要性。专家们认为发表偏倚很可能存在，但在调整了他们的意见后，发表的结果超过了纳入贝叶斯敏感性分析的信息性先验。尽管效应估计值有所减弱，但在所有分析中结论都是稳健的。
即使使用从专家启发式调查中形成的强有力信息性先验来调整发表偏倚，完全细胞减瘤术的效果与提高 OS 之间仍然存在很强的关联。启发式调查的概念应强烈考虑用于其他荟萃分析。
