Discussion
gallstone disease, pain
GALLSTONE DISEASE, SECONDARY, RECRUITMENT, COMPLICATIONS
The C-GALL trial is a multicentre, pragmatic trial to evaluate the clinical and cost effectiveness of conservative management compared with laparoscopic cholecystectomy to prevent recurrent symptoms and complications in adults with uncomplicated symptomatic gallstone disease in a secondary care setting. The trial was conducted across 20 secondary care sites in the UK NHS. The trial found no differences in overall bodily pain (primary outcome), quality of life, complications, or the need for further treatment between the two management strategies up to 18 months of follow-up. There was statistically significant evidence that gallbladder specific quality of life measures (condition specific questionnaire total score and condition specific questionnaire persistent symptoms)improved in the randomised cholecystectomy group at 18 months.Before the trial, the C-GALL group envisaged that clinicians would be reluctant to recruit patients because of a bias towards surgery. Moreover, it was assumed that patients might be unwilling to consent to recruitment, as surgery is usually the only option discussed to relieve symptoms, and alternatives are probably not considered at both primary and secondary care level. During the trial, many patients opted for non-surgical treatment after the C-GALL team provided detailed information on the alternative option. Almost one third of patients randomised to receive conservative management subsequently received surgery, and 30% of those randomised to receive cholecystectomy had not undergone surgery by 24 months. It was also interesting to note the number of patients that opted not to take part in the trial, accepting conservative management over surgery during the trial when alternative treatments were discussed.Prespecified sensitivity analyses showed that adherence to treatment allocation, missing data, and perceived potential impact of covid-19 (when national elective surgery was suspended for many months), did not change findings. Cost analysis showed that conservative management was less costly than cholecystectomy. The trial did not find a statistically significant difference in QALYs between the groups. The incremental cost effectiveness ratio was high, meaning important potential savings to the NHS with limited QALY loss by following a conservative management approach in the short term (up to 24 months). Longer term modelling suggested that a conservative management approach might be cost effective, but uncertainty was higher owing to limited information on subsequent surgeries in the randomised groups and quality of life beyond 24 months.The within trial economic analysis indicated that intention to treat with conservative management was less costly than cholecystectomy over 24 months (mean difference £1033). Consistent with the primary outcome results of the C-GALL trial, a non-significant QALY difference of 0.019 favouring cholecystectomy was observed. The significant cost difference favouring conservative management and a small non-significant QALY difference favouring cholecystectomy resulted in an incremental cost effectiveness ratio of £55 235. That is, moving from the standard practice of intention to treat with laparoscopic cholecystectomy to conservative management would on average result in lower costs and QALYs, with a saving of £55 235 per QALY lost. Moreover, at a conventional cost effectiveness threshold of £20 000 per QALY used in the UK, the probabilistic analysis showed conservative management to have a 97% probability of being cost effective.