Participant recruitment and attrition in surgical randomised trials with placebo controls versus non-operative controls: a meta-epidemiological study and meta-analysis

Abstract

Objective: To compare differences in recruitment and attrition between placebo control randomised trials of surgery, and trials of the same surgical interventions and conditions that used non-operative (non-placebo) controls.

Design: Meta-epidemiological study.

Data sources: Randomised controlled trials were identified from an electronic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from their inception date to 21 November 2018.

Study selection: Placebo control trials evaluating efficacy of any surgical intervention and non-operative control trials of the same surgical intervention were included in this study. 25 730 records were retrieved from our systemic search, identifying 61 placebo control and 38 non-operative control trials for inclusion in analysis.

Outcome measures: Primary outcome measures were recruitment and attrition. These were assessed in terms of recruitment rate (number of participants enrolled, as a proportion of those eligible) and overall attrition rate (composite of dropout, loss to follow-up and cross-overs, expressed as proportion of total sample size). Secondary outcome measures included participant cross-over rate, dropout and loss to follow-up.

Results: Unadjusted pooled recruitment and attrition rates were similar between placebo and non-operative control trials. Study characteristics were not significantly different apart from time to primary timepoint which was shorter in studies with placebo controls (365 vs 274 days, p=0.006). After adjusting for covariates (follow-up duration and number of timepoints), the attrition rate of placebo control trials was almost twice as high compared with non-operative controlled-trials (incident rate ratio (IRR) (95% CI) 1.8 (1.1 to 3.0), p=0.032). The incorporation of one additional follow-up timepoint (regardless of follow-up duration) was associated with reduced attrition in placebo control surgical trials (IRR (95% CI) 0.64 (0.52 to 0.79), p<0.001).

Conclusions: Placebo control trials of surgery have similar recruitment issues but higher attrition compared with non-operative (non-placebo) control trials. Study design should incorporate strategies such as increased timepoints for given follow-up duration to mitigate losses to follow-up and dropout.

Prospero registration number: CRD42019117364.

Keywords: Follow-Up Studies; Randomized Controlled Trial; SURGERY.