Mismatch of populations between randomised controlled trials of perioperative interventions in major abdominal surgery and current clinical practice

BACKGROUND: Demographics of patients undergoing major abdominal surgery are changing. External validity of relevant RCTs may be limited by participants not resembling patients encountered in clinical practice. We aimed to characterise differences in age, weight, BMI, and ASA grade between participants in perioperative trials in major abdominal surgery and patients in a reference real-world clinical practice sample. The secondary aim was to investigate whether time since trial publication was associated with increasing mismatch between these groups. METHODS: MEDLINE and Embase were searched for multicentre RCTs from inception to September 2022. Studies of perioperative interventions in adults were included. Studies that limited enrolment based on age, weight, BMI, or ASA status were excluded. We compared trial cohort age, weight, BMI, and ASA distribution to those of patients undergoing major abdominal surgery at our tertiary referral hospital during September 2021 to September 2022. We used a local, single-institution reference sample to reflect the reality of clinical practice (i.e. patients treated by a clinician in their own hospital, rather than averaged nationally). Mismatch was defined using comparison of summary characteristics and ad hoc criteria based on differences relevant to predicted mortality risk after surgery. RESULTS: One-hundred and six trials (44,499 participants) were compared to a reference cohort of 2792 clinical practice patients. Trials were published a median (IQR [range]) 13.4 (5-20 [0-35]) years ago. A total of 94.3% of trials were mismatched on at least one characteristic (age, weight, BMI, ASA). Recruitment of ASA 3 + participants in trials increased over time, and recruitment of ASA 1 participants decreased over time (Spearman's Rho 0.58 and - 0.44, respectively). CONCLUSIONS: Patients encountered in our current local clinical practice are significantly different from those in our defined set of perioperative RCTs. Older trials recruit more low-risk than high-risk participants-trials may thus 'expire' over time. These trials may not be generalisable to current patients undergoing major abdominal surgery, and meta-analyses or guidelines incorporating these trials may therefore be similarly non-applicable. Comparison to local, rather than national cohorts, is important for meaningful on-the-ground evidence-based decision-making.