A meta-epidemiological study of bias in randomized clinical trials of open and laparoscopic surgery

Abstract

Background Blinding, random sequence generation, and allocation concealment are established strategies to minimize bias in RCTs. Meta-epidemiological studies of drug trials have demonstrated exaggerated treatment effects in RCTs where such methods were not employed. As blinding is more difficult in surgical trials it is important to determine whether this applies to them. The study aimed to investigate this using systematic meta-epidemiological methods. Method The Cochrane Database of Systematic Reviews was searched for systematic reviews of RCTs that compared laparoscopic and open abdominal surgical procedures. Each review was then scrutinized to determine whether at least one of the included trials was blinded. Eligible reviews were updated and individual RCTs retrieved. Extracted data included the primary outcomes of interest (length of stay and complications), secondary outcomes and a risk of bias assessment. A multistep meta-regression analysis was then performed to obtain an overall difference in the reported outcome differences between trials that employed each bias-minimization strategy, and those that did not. Results Some 316 RCTs were included, reporting on eight different procedures. Patient-blinded RCTs reported a smaller difference in length of stay between laparoscopic and open groups (difference of standardized mean differences –0·36 (95 per cent c.i. –0·73 to 0·00)) and complications (ratio of odds ratios 0·76 (95 per cent c.i. 0·61 to 0·93)). Blinding of postoperative carers and outcome assessors had similar effects. Conclusion Lack of blinding significantly altered the treatment effect estimates of RCTs comparing laparoscopic and open surgery. Blinding should be implemented in surgical RCTs where possible to avoid systematic bias.

The impact of blinding on trial results: A systematic review and meta-analysis

“…Twenty-three studies addressed the effects of blinding of outcome assessors/adjudicators (30, 33-35, 37-39, 41, 42, 44, 51-53, 55, 57, 58, 61-63, 71-73).…”

“…Twelve studies addressed the effects of blinding of patients (31, 33-35, 41, 44, 47, 48, 55, 62, 71, 73).…”

“…The strengths of our systematic review include a priori methods, a systematic search for eligible studies, duplicate screening and data extraction, and assessment of the role of blinding across a range of clinical areas. Our review improves on previous reviews by performing an assessment of risk of bias and the certainty of evidence and including several recently published studies not included in previous reviews (10, 15, 18, 19, 33, 40, 44).…”

Association of Preoperative High-Intensity Interval Training With Cardiorespiratory Fitness and Postoperative Outcomes Among Adults Undergoing Major Surgery

“…Statistical heterogeneity was due to a need for additional calculations based on the data as described in the Methods and summarized in the eAppendix in Supplement 1. While participant masking is an unavoidable limitation in prehabilitation studies, as participants cannot be masked to their exercise intervention, assessor masking was not mentioned in 4 of the 12 studies, potentially limiting the assessment of clinical outcomes . For these reasons, when using GRADE, we determined the certainty of the evidence to be moderate (for V̇ o 2 peak and complications) to very low for our outcomes (eTable 4 in Supplement 1).…”

Has network meta‐analysis resolved the controversies related to bowel preparation in elective colorectal surgery?

“…Another issue is the potential impact of lack of blinding on iSSI results. A review of blinding in surgical RCTs comparing laparoscopic and open surgery showed a significant reduction in the differences in length of stay and complications when participant or assessor blinding was achieved [30]. While patient blinding is not possible with MBP, assessor blinding can still be achieved.…”