Current Issues in Conduct and Reporting of Noninferiority Randomized Controlled Trials in Surgical Management of Cancer Patients.

ABSTRACT

BACKGROUND: Serious concerns regarding quality of conduct and reporting of noninferiority trials (NITs) have been raised. Systematic analysis of the quality of the surgical NITs is lacking. Assessing the quality of conduct, reporting, and interpretation of surgical NITs in cancer patients is critical given their potential clinical impact. We aim to assess the quality of conduct, reporting, and interpretation of NITs that investigate the effects of surgical management in cancer patients. METHODS: A cross-sectional analysis of papers identified through a comprehensive literature database search was performed. Forty papers employing a phase III noninferiority (NI) randomized trial design to study effects of surgical methodology or sequencing of surgery in patients with solid cancers were included. Papers were assessed for type of analysis, justification of the noninferiority margin (NIM), consistency of type I error with confidence intervals (CIs), ability to achieve the predefined sample size, and interpretations regarding NI. RESULTS: Only half of the papers used both intention-to-treat and per protocol analyses; 62.5% provided no or poor justification for the NIM; 42.5% showed inconsistency of the type I error rate with CIs; 52.5% were deemed poor or fair quality, and 60.0% did not achieve the predefined sample size. One-fifth of the papers provided interpretation of the NI hypothesis that was not in concordance with the CONSORT guidelines. CONCLUSIONS: The quality of conduct, reporting, and interpretation of surgical NITs is suboptimal, requiring further improvements through adherence to guidelines and rigorous assessment at the stages of the study approval, funding, and the peer-review process.