Generalisability of randomised trials evaluating perioperative ß-blocker therapy in noncardiac surgery.

ABSTRACT

BACKGROUND: The limited applicability of evidence from RCTs in real-word practice is considered a potential bottleneck for evidence-based practice but rarely systematically assessed. Using our failure to recruit patients into a perioperative beta-blocker trial, we set out to analyse the restrictiveness and generalisability of trial eligibility criteria in a real-world cohort. METHODS: We prospectively included adult patients (≥18 yr) scheduled for elective noncardiac surgery at an academic tertiary care facility who were screened for inclusion in a planned perioperative beta-blocker RCT, which was terminated owing to recruitment failure. The primary outcome was the proportion of screened patients who matched the eligibility criteria of 36 published RCTs included in a large Cochrane meta-analysis on perioperative beta-blocker therapy. The pragmatic/explanatory level of each RCT was assessed using the PRagmatic-Explanatory Continuum Indicator Summary 2 (PRECIS-2) score, which ranges from 9 points (indicating a very explanatory study) to 45 points (indicating a very pragmatic study). RESULTS: A total of 2241 patients (54% female, n=1215; 52 [standard deviation, 20] yr) were included for the assessment of trial eligibility between October 2015 and January 2016. Only a small proportion of patients matched the inclusion and exclusion criteria for each of the 36 RCTs, ranging from 53% to 0%. The average proportion of patients who did match the eligibility criteria of all 36 RCTs was 6.5% (n=145; 95% confidence interval, 6.3-6.6). A higher PRECIS-2 score was associated with a higher proportion of matching patients (P<0.001). CONCLUSIONS: Trial eligibility criteria in perioperative beta-blocker therapy trials are overly restrictive and not generalisable to a real-world surgical population. CLINICAL TRIAL REGISTRATION EudraCT# 2015-002366-23.