Quantification of the External Validity of Randomized Controlled Trials Supporting Clinical Care Guidelines: The Case of Thromboprophylaxis

• Published in: The American journal of medicine Vol. 129; no. 7; pp. 740 - 745
• Main Authors: Morin-Ben Abdallah, Sami, MD, Dutilleul, Aurore, MD, Nadon, Valérie, MD, Yang, Ji Wei, MD, Marchand-Sénécal, Xavier, MD, Van Nguyen, Paul, MD, Lamarre-Cliche, Maxime, MD, MSc, Wistaff, Robert, MD, Kolan, Christophe, MD, Laskine, Mikhael, MD, MSc, Durand, Madeleine, MD, MSc
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2016; Elsevier Sequoia S.A
• Subjects: Aged; American College of Chest Physicians guidelines; Anticoagulants - therapeutic use; Clinical trials; Cross-Sectional Studies; Eligibility Determination; Evidence-Based Medicine; Exclusion criteria; External validity; Female; Hospitalization; Humans; Internal Medicine; Male; Medical hospitalized patients; Middle Aged; Padua score; Patient admissions; Pharmacological thromboprophylaxis; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Reproducibility of Results; Risk factors; Risk scores; Vein & artery diseases; Venous Thromboembolism - prevention & control; Exclusion criteria; Medical hospitalized patients; American College of Chest Physicians guidelines; Pharmacological thromboprophylaxis; External validity; Padua score; Risk scores
• ISSN: 0002-9343; 1555-7162
• DOI: 10.1016/j.amjmed.2016.02.016

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.