PMID- 34190996
OWN - NLM
STAT- MEDLINE
DCOM- 20220105
LR  - 20220105
IS  - 2574-3805 (Electronic)
IS  - 2574-3805 (Linking)
VI  - 4
IP  - 6
DP  - 2021 Jun 1
TI  - Characteristics of Randomized Clinical Trials in Surgery From 2008 to 2020: A 
      Systematic Review.
PG  - e2114494
LID - 10.1001/jamanetworkopen.2021.14494 [doi]
LID - e2114494
AB  - 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.
FAU - Robinson, N Bryce
AU  - Robinson NB
AD  - Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.
FAU - Fremes, Stephen
AU  - Fremes S
AD  - Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, 
      Toronto, ON, Canada.
FAU - Hameed, Irbaz
AU  - Hameed I
AD  - Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.
AD  - Division of Cardiothoracic Surgery, Yale University School of Medicine, New 
      Haven, Connecticut.
FAU - Rahouma, Mohamed
AU  - Rahouma M
AD  - Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.
FAU - Weidenmann, Viola
AU  - Weidenmann V
AD  - Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.
FAU - Demetres, Michelle
AU  - Demetres M
AD  - Samuel J. Wood Library and C.V. Starr Biomedical Information Centre, Weill 
      Cornell Medicine, New York, New York.
FAU - Morsi, Mahmoud
AU  - Morsi M
AD  - Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.
FAU - Soletti, Giovanni
AU  - Soletti G
AD  - Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.
FAU - Di Franco, Antonino
AU  - Di Franco A
AD  - Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.
FAU - Zenati, Marco A
AU  - Zenati MA
AD  - BHS Department of Cardiothoracic Surgery, West Roxbury, Massachusetts.
FAU - Raja, Shahzad G
AU  - Raja SG
AD  - Department of Cardiac Surgery, Harefield Hospital, London, United Kingdom.
FAU - Moher, David
AU  - Moher D
AD  - Ottawa Methods Centre, Ottawa Hospital Research Institute, Ottawa, Ontario, 
      Canada.
FAU - Bakaeen, Faisal
AU  - Bakaeen F
AD  - Department of Thoracic Surgery, Heart and Vascular Institute, Cleveland Clinic, 
      Cleveland, Ohio.
AD  - Department of Cardiovascular Surgery, Heart and Vascular Institute, Cleveland 
      Clinic, Cleveland, Ohio.
FAU - Chikwe, Joanna
AU  - Chikwe J
AD  - Department of Cardiac Surgery, Smidt Heart Institute, Cedars-Sinai Medical 
      Center, Los Angeles, California.
FAU - Bhatt, Deepak L
AU  - Bhatt DL
AD  - Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, 
      Massachusetts.
FAU - Kurlansky, Paul
AU  - Kurlansky P
AD  - Department of Surgery, Columbia University Medical Center, New York, New York.
FAU - Girardi, Leonard N
AU  - Girardi LN
AD  - Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.
FAU - Gaudino, Mario
AU  - Gaudino M
AD  - Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Systematic Review
DEP - 20210601
PL  - United States
TA  - JAMA Netw Open
JT  - JAMA network open
JID - 101729235
SB  - IM
CIN - JAMA Netw Open. 2021 Jun 1;4(6):e2115456. PMID: 34191001
MH  - General Surgery/*trends
MH  - Humans
MH  - Randomized Controlled Trials as Topic/*classification/*statistics & numerical 
      data
MH  - Time Factors
PMC - PMC8246313
COIS- 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.
EDAT- 2021/07/01 06:00
MHDA- 2022/01/06 06:00
PMCR- 2021/06/30
CRDT- 2021/06/30 12:26
PHST- 2021/06/30 12:26 [entrez]
PHST- 2021/07/01 06:00 [pubmed]
PHST- 2022/01/06 06:00 [medline]
PHST- 2021/06/30 00:00 [pmc-release]
AID - 2781512 [pii]
AID - zoi210437 [pii]
AID - 10.1001/jamanetworkopen.2021.14494 [doi]
PST - epublish
SO  - JAMA Netw Open. 2021 Jun 1;4(6):e2114494. doi: 
      10.1001/jamanetworkopen.2021.14494.