title: Quantification of the External Validity of Randomized Controlled Trials Supporting Clinical Care Guidelines: The Case of Thromboprophylaxis.
abstract: BACKGROUND
  Clinical guidelines are based on the results of several randomized controlled trials. However, due to the stringent exclusion criteria of these trials, their external validity may be low. We aimed to evaluate the external validity of the randomized controlled trials cited in the American College of Chest Physicians guidelines for the use of pharmacological thromboprophylaxis in hospitalized medical patients.
  
  
  METHODS
  We conducted a cross-sectional, chart-review study of a random sample of patients admitted between July 1, 2013 and June 30, 2014 to the Internal Medicine ward of a large Canadian teaching university hospital. We identified the proportion of our population presenting exclusion criteria used in the randomized controlled trials cited in support of clinical care guidelines on thromboprophylaxis in the medical setting.
  
  
  RESULTS
  Nine trials were identified for a total of 28,793 included patients following 23 distinct exclusion criteria. We included 429 patients. Median age was 65 years (interquartile ratio 51-77 years), and 236 (55%) were males. Of those not already anticoagulated at admission (n = 351), between 26% and 67% (weighted average, 51%) of our population presented at least one exclusion criterion, making them ineligible to be enrolled in randomized controlled trials. When restricting our population to patients with an indication for thromboprophylaxis based on a Padua risk score at admission ≥4, 21% to 76% (weighted average 55%) were ineligible to be enrolled in individual trials.
  
  
  CONCLUSIONS
  Our cross-sectional study illustrates that the external validity of randomized controlled trials cited in the guidelines was low in our population, and lower when applying the risk-stratification tool recommended by guidelines. This can bias the clinicians toward treating patients that were not represented in the supporting evidence.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Sami
authors.initials: S
authors.lastname: Morin-Ben Abdallah
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Aurore
authors.initials: A
authors.lastname: Dutilleul
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Valérie
authors.initials: V
authors.lastname: Nadon
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Ji Wei
authors.initials: JW
authors.lastname: Yang
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Xavier
authors.initials: X
authors.lastname: Marchand-Sénécal
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Van Nguyen
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Lamarre-Cliche
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Wistaff
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Christophe
authors.initials: C
authors.lastname: Kolan
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada. Electronic address: mikhael.laskine.chum@ssss.gouv.qc.ca.
authors.forename: Mikhael
authors.initials: M
authors.lastname: Laskine
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Durand
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D004608:Eligibility Determination; D019317:Evidence-Based Medicine; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D015203:Reproducibility of Results; D054556:Venous Thromboembolism / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants
keywords: American College of Chest Physicians guidelines; Exclusion criteria; External validity; Medical hospitalized patients; Padua score; Pharmacological thromboprophylaxis; Risk scores