Characteristics of Randomized Clinical Trials in Surgery From 2008 to 2020: A Systematic Review.

Importance: Randomized clinical trials (RCTs) provide the highest level of evidence to evaluate 2 or more surgical interventions. Surgical RCTs, however, face unique challenges in design and implementation. Objective: To evaluate the design, conduct, and reporting of contemporary surgical RCTs. Evidence Review: A literature search performed in the 2 journals with the highest impact factor in general medicine as well as 6 key surgical specialties was conducted to identify RCTs published between 2008 and 2020. All RCTs describing a surgical intervention in both experimental and control arms were included. The quality of included data was assessed by establishing an a priori protocol containing all the details to extract. Trial characteristics, fragility index, risk of bias (Cochrane Risk of Bias 2 Tool), pragmatism (Pragmatic Explanatory Continuum Indicator Summary 2 [PRECIS-2]), and reporting bias were assessed. Findings: A total of 388 trials were identified. Of them, 242 (62.4%) were registered; discrepancies with the published protocol were identified in 81 (33.5%). Most trials used superiority design (329 [84.8%]), and intention-to-treat as primary analysis (221 [56.9%]) and were designed to detect a large treatment effect (50.0%; interquartile range [IQR], 24.7%-63.3%). Only 123 trials (31.7%) used major clinical events as the primary outcome. Most trials (303 [78.1%]) did not control for surgeon experience; only 17 trials (4.4%) assessed the quality of the intervention. The median sample size was 122 patients (IQR, 70-245 patients). The median follow-up was 24 months (IQR, 12.0-32.0 months). Most trials (211 [54.4%]) had some concern of bias and 91 (23.5%) had high risk of bias. The mean (SD) PRECIS-2 score was 3.52 (0.65) and increased significantly over the study period. Most trials (212 [54.6%]) reported a neutral result; reporting bias was identified in 109 of 211 (51.7%). The median fragility index was 3.0 (IQR, 1.0-6.0). Multiplicity was detected in 175 trials (45.1%), and only 35 (20.0%) adjusted for multiple comparisons. Conclusions and Relevance: In this systematic review, the size of contemporary surgical trials was small and the focus was on minor clinical events. Trial registration remained suboptimal and discrepancies with the published protocol and reporting bias were frequent. Few trials controlled for surgeon experience or assessed the quality of the intervention.

Angiographic Patency of Coronary Artery Bypass Conduits: A Network Meta-Analysis of Randomized Trials.

Background Several randomized trials have compared the patency of coronary artery bypass conduits. All of the published studies, however, have performed pairwise comparisons and a comprehensive evaluation of the patency rates of all conduits has yet to be published. We set out to investigate the angiographic patency rates of all conduits used in coronary bypass surgery by performing a network meta-analysis of the current available randomized evidence. Methods and Results A systematic literature search was conducted for randomized controlled trials comparing the angiographic patency rate of the conventionally harvested saphenous vein, the no-touch saphenous vein, the radial artery (RA), the right internal thoracic artery, or the gastroepiploic artery. The primary outcome was graft occlusion. A total of 4160 studies were retrieved of which 14 were included with 3651 grafts analyzed. The weighted mean angiographic follow-up was 5.1 years. Compared with the conventionally harvested saphenous vein, both the RA (incidence rate ratio [IRR] 0.54; 95% CI, 0.35-0.82) and the no-touch saphenous vein (IRR 0.55; 95% CI, 0.39-0.78) were associated with lower graft occlusion. The RA ranked as the best conduit (rank score for RA 0.87 versus 0.85 for no-touch saphenous vein, 0.23 for right internal thoracic artery, 0.29 for gastroepiploic artery, and 0.25 for the conventionally harvested saphenous vein). Conclusions Compared with the conventionally harvested saphenous vein, only the RA and no-touch saphenous vein grafts are associated with significantly lower graft occlusion rates. The RA ranks as the best conduit. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42020164492.

Robustness of the Comparative Observational Evidence Supporting Class I and II Cardiac Surgery Procedures.

Background Current cardiac surgery guidelines give Class I and II recommendations to valve-sparing root replacement over the Bentall procedure, mitral valve (MV) repair over replacement, and multiple arterial grafting with bilateral internal thoracic artery based on observational evidence. We evaluated the robustness of the observational studies supporting these recommendations using the E value, an index of unmeasured confounding. Methods and Results Observational studies cited in the guidelines and in the 3 largest meta-analyses comparing the procedures were evaluated for statistically significant effect measures. Two E values were calculated: 1 for the effect-size estimate and 1 for the lower limit of the 95% CI. Thirty-one observational studies were identified, and E values were computed for 75 effect estimates. The observed effect estimates for improved clinical outcomes with valve-sparing root replacement versus the Bentall procedure, MV repair versus replacement, and grafting with bilateral internal thoracic artery versus single internal thoracic artery could be explained by an unmeasured confounder that was associated with both the treatment and outcome by a risk ratio of more than 16.77, 4.32, and 3.14, respectively. For MV repair versus replacement and grafting with bilateral internal thoracic artery versus single internal thoracic artery, the average E values were lower than the effect sizes of the other measured confounders in 33.3% and 60.9% of the studies, respectively. For valve-sparing root replacement versus the Bentall procedure, no study reported effect sizes for associations of other covariates with outcomes. Conclusions The E values for observational evidence supporting the use of valve-sparing root replacement, MV repair, and grafting with bilateral internal thoracic artery over the Bentall procedure, MV replacement, and grafting with single internal thoracic artery are relatively low. This suggests that small-to-moderate unmeasured confounding could explain most of the observed associations for these procedures.

Diagnostic dilemma of perioperative myocardial infarction after coronary artery bypass grafting: A review.

Coronary artery bypass grafting (CABG) is one of the most commonly performed cardiac procedures in the United States (US) and Europe. In the US, perioperative morbidity and mortality related to CABG are below 5%. One of the most significant complications following CABG, however, is perioperative myocardial infarction (PMI). Cardiac biomarkers, intra- and post-operative echocardiography, and electrocardiography are routinely used to monitor for evidence of PMI. In this review, we seek to summarize how each of these modalities is used in the clinical setting to differentiate PMI from expected procedure-related changes, and how these findings impact patients' outcomes. We conclude that while no perfect diagnostic test for the detection of clinically meaningful PMI exists, using a combination of existing modalities with knowledge of expected post-procedure changes allows for early and reliable detection. Future development is needed to create more sensitive and specific modalities for the detection of PMI in patients undergoing CABG.

Characteristics, results, and reporting of contemporary surgical trials: A systematic review and analysis.

INTRODUCTION: The complexities and risks inherent to the field of surgery and surgical interventions present unique challenges to the design and analysis of surgical randomized controlled trials (RCT). Prior studies have investigated the practical and methodologic challenges posed by surgical RCTs. To date, however, a comprehensive analysis of the contemporary literature across multiple surgical subspecialties does not exist. In this descriptive analysis, we set out to characterize surgical RCTs over the past 10 years across six major surgical specialties. METHODS AND ANALYSIS: A literature search by a medical librarian will be performed to identify all surgical randomized clinical trials published between January 2009 and December 2019 in the two journals with the highest impact factor for six surgical specialties as well as two large general medicine journals. Two reviewers will independently screen the citations retrieved from the literature search and extract data according to a previously described protocol via a pre-defined data collection form. Categorical variables will be reported as counts and percentages. Following assessment of normality, continuous variables will be reported as mean (standard deviation) or median (inter-quartile range). Based on normality of data, independent t-test or the Mann-Whitney U test will be used to compare continuous variables and chi-square and Fisher's exact tests to compare categorical variables. Comparisons across multiple sets will be performed using ANOVA or Kruskak-Wallis tests. Two-sided significance testing will be used and a p-value <0.05 will be considered significant without adjustment for multiple testing. All analyses will be performed using SPSS version 24 and R within RStudio. PROSPERO (ID number: 162797). ETHICS AND DISSEMINATION: There are no ethical concerns directly pertinent to this systematic review. The retrieved data will be made available upon request. The study will be written in English and submitted for publication in a peer-reviewed journal.