Induced Bias Due to Crossover Within Randomized Controlled Trials in Surgical Oncology: A Meta-regression Analysis of Minimally Invasive versus Open Surgery for the Treatment of Gastrointestinal Cancer.

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Title: Induced Bias Due to Crossover Within Randomized Controlled Trials in Surgical Oncology: A Meta-regression Analysis of Minimally Invasive versus Open Surgery for the Treatment of Gastrointestinal Cancer.
Authors: Garas, G
Markar, SR
Malietzis, G
Ashrafian, H
Hanna, GB
Zacharakis, E
Jiao, LR
Argiris, A
Darzi, A
Athanasiou, T
Item Type: Journal Article
Abstract: BACKGROUND: Randomized controlled trials (RCTs) inform clinical practice and have provided the evidence base for introducing minimally invasive surgery (MIS) in surgical oncology. Crossover (unplanned intraoperative conversion of MIS to open surgery) may affect clinical outcomes and the effect size generated from RCTs with homogenization of randomized groups. OBJECTIVES: Our aims were to identify modifiable factors associated with crossover and assess the impact of crossover on clinical endpoints. METHODS: A systematic review was performed to identify all RCTs comparing MIS with open surgery for gastrointestinal cancer (1990-2017). Meta-regression analysis was performed to analyze factors associated with crossover and the influence of crossover on endpoints, including 30-day mortality, anastomotic leak rate, and early complications. RESULTS: Forty RCTs were included, reporting on 11,625 patients from 320 centers. Crossover was shown to affect one in eight patients (mean 12.6%, range 0-45%) and increased with American Society of Anesthesiologists score (β = + 0.895; p = 0.050). Pretrial surgeon volume (β = - 2.344; p = 0.037), composite RCT quality score (β = - 7.594; p = 0.014), and site of tumor (β = - 12.031; p = 0.021, favoring lower over upper gastrointestinal tumors) showed an inverse relationship with crossover. Importantly, multivariate weighted linear regression revealed a statistically significant positive correlation between crossover and 30-day mortality (β = + 0.125; p = 0.033), anastomotic leak rate (β = + 0.550; p = 0.004), and early complications (β = + 1.255; p = 0.001), based on intention-to-treat analysis. CONCLUSIONS: Crossover in trials was associated with an increase in 30-day mortality, anastomotic leak rate, and early complications within the MIS group based on intention-to-treat analysis, although our analysis did not assess causation. Credentialing surgeons by procedural volume and excluding high comorbidity patients from initial trials are important in minimizing crossover and optimizing RCT validity.
Issue Date: 6-Nov-2017
Date of Acceptance: 27-Jul-2017
URI: http://hdl.handle.net/10044/1/54541
DOI: 10.1245/s10434-017-6210-y
ISSN: 1068-9265
Publisher: Springer Verlag
Start Page: 221
End Page: 230
Journal / Book Title: Annals of Surgical Oncology
Volume: 25
Issue: 1
Copyright Statement: © The Author(s) 2017. This article is an open access publication
Keywords: 1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Appears in Collections:Division of Surgery
Faculty of Medicine



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