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. 2021 Jun 1;4(6):e2114494.
doi: 10.1001/jamanetworkopen.2021.14494.

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

N Bryce Robinson  1 , Stephen Fremes  2 , Irbaz Hameed  1   3 , Mohamed Rahouma  1 , Viola Weidenmann  1 , Michelle Demetres  4 , Mahmoud Morsi  1 , Giovanni Soletti  1 , Antonino Di Franco  1 , Marco A Zenati  5 , Shahzad G Raja  6 , David Moher  7 , Faisal Bakaeen  8   9 , Joanna Chikwe  10 , Deepak L Bhatt  11 , Paul Kurlansky  12 , Leonard N Girardi  1 , Mario Gaudino  1
Affiliations

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

N Bryce Robinson et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Bhatt reported receiving grants from Amarin, grants from AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company, other support from FlowCo, grants and other support from PLx Pharma and Takeda, personal fees from Duke Clinical Research Institute, Mayo Clinic, Population Health Research Institute, personal fees, nonfinancial support and other support from American College of Cardiology, personal fees from Belvoir Publications, Slack Publications, WebMD, Elsevier, other support from Medscape Cardiology, Regado Biosciences, Boston VA Research Institute, and personal fees and nonfinancial support from Society of Cardiovascular Patient Care, nonfinancial support from American Heart Association, personal fees from HMP Global, grants from Roche, personal fees from Harvard Clinical Research Institute (now Baim Institute for Clinical Research), other support from Clinical Cardiology, personal fees from Journal of the American College of Cardiology, other support from VA, grants from Pfizer, Forest Laboratories/AstraZeneca, Ischemix, and other support from St. Jude Medical (now Abbott) and Biotronik, grants and other support from Cardax and Boston Scientific, grants from Amgen, Lilly, Chiesi, Ironwood, personal fees from Cleveland Clinic, Mount Sinai School of Medicine, other support from Merck, grants from Abbott and Regeneron, other support from Svelte, grants and other support from PhaseBio, grants from Idorsia andSynaptic, personal fees from TobeSoft, grants, personal fees, and other support from Boehringer Ingelheim, personal fees from Bayer, other support from Novo Nordisk, grants from Fractyl, personal fees from Medtelligence/ReachMD, personal fees from CSL Behring, other support from Cereno Scientific, grants from Afimmune, personal fees from Ferring Pharmaceuticals, other support from CSI, grants from Lexicon, personal fees from MJH Life Sciences, Level Ex, Contego Medical, CellProthera, K2P, Canadian Medical and Surgical Knowledge Translation Research Group, grants and other support from MyoKardia, grants from Owkin, grants from HLS Therapeutics, outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Randomized Clinical Trials During the Study Period
A-C, By year, outcome, and study design.
Figure 2.
Figure 2.. Evaluation of Randomized Clinical Trials
A, Evaluation using the Pragmatic Explanatory Continuum Index Summary 2 (PRECIS-2) Tool. B, Evaluation using the Fragility Index. C, Evaluation with reporting bias.
See this image and copyright information in PMC

Comment in

References

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