Residual Disease After Primary Surgical Treatment for Advanced Epithelial Ovarian Cancer, Part 2: Network Meta-analysis Incorporating Expert Elicitation to Adjust for Publication Bias

Abstract

Background: 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.

Areas of uncertainty: 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.

Data sources: 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.

Therapeutic advances: 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.

Conclusions: 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.