Strengths of this study
The strengths of the C-GALL trial include the pragmatic randomised controlled design and methodological rigour. The benefit of the sample size is reflected in the precision with which outcomes were estimated. The multicentre nature of the trial improves confidence in the generalisability of findings to the NHS. The recruited sample had a mean age of 50-51 years (slightly older than those who declined to take part (mean 48 years)). Among the population sample, participants were predominantly female (79%), white (86%) with Asian/Asian British and black/African/Caribbean/ black British participants comprising 7% and 3% of the sample, respectively. This is similar to national statistics for England and Wales for ethnicity (86%, 9%, and 3%, respectively),This trial was pragmatic, where patients in the UK may not always receive the treatment they are offered and waiting lists for surgical treatment exist. We carefully tracked treatment after randomisation and monitored adherence. A major strength of the trial was the inclusion of sensitivity analyses, with adherence analysis, imputation for missing data, and potential impact of the covid-19 pandemic. Our findings remained unchanged after these analyses.The study was designed as a superiority trial rather than a non-inferiority trial. We considered the study to be, in essence, a de-adoption study (removing cholecystectomy). When considering de-adopting cholecystectomy, the NHS would need strong, clear evidence that surgery is superior or inferior to conservative management. Performing the study to show that conservative management was non-inferior to surgery would be unlikely to provide strong enough evidence to change surgical practice. The randomised controlled design allowed unbiased, prospective collection of data on resource use and quality of life for comparable groups. This is a strength of the cost effectiveness analysis.