Abstract
Introduction
Gallstone disease is a common gastrointestinal disorder in industrialised societies. The prevalence of gallstones in the adult population is estimated to be approximately 10-15%, and around 80% remain asymptomatic. At present cholecystectomy is the default option for people with symptomatic gallstone disease.
Objective
To assess the clinical and cost-effectiveness of observation/conservative management compared with laparoscopic cholecystectomy for preventing recurrent symptoms and complications in adults presenting with uncomplicated symptomatic gallstones in secondary care.
Methods
Parallel group, multicentre patient randomised superiority pragmatic trial with up to 24 months follow-up and embedded qualitative research. Within trial cost utility and 10-year Markov model analyses. Development of a core outcome set for uncomplicated symptomatic gallstone disease. Adults with symptomatic uncomplicated gallstone disease referred to a secondary care setting were considered for inclusion. Participants were randomised 1:1 at clinic to receive
either laparoscopic cholecystectomy or observation/conservative management.
The primary outcome was quality of life measured by area under the curve over 18 months using the SF-36 bodily pain domain. Secondary outcomes included the Otago gallstones’ condition-specific questionnaire, SF-36 domains (excluding bodily pain), area under the curve over 24 months for SF-36 bodily pain domain, persistent symptoms, complications and need for further treatment. No outcomes were blinded to allocation.
Results
Between August 2016 to November 2019, 434 participants were randomised (217 in each group) from 20 UK centres. By 24 months, 64 (29.5%) in the observation/conservative management group and 153 (70.5%) in the laparoscopic cholecystectomy group had received surgery, median time to surgery of 9.0 months (IQR, 5.6-15.0) and 4.7 months (IQR 2.6-7.9), respectively.
At 18 months, the mean SF-36 norm-based bodily pain score was 49.4 (SD 11.7) in the observation/conservative management group and 50.4 (SD 11.6) in the laparoscopic cholecystectomy group. The mean AUC over 18 months was 46.8 for both groups with no difference: mean difference (MD) -0.0, 95% CI (-1.7, 1.7); p-value 0.996; n=203 observation/conservative, n=205 cholecystectomy).
There was no evidence of differences in quality of life, complications or need for further treatment at up to 24 months follow-up. Condition specific quality of life at 24 months favoured cholecystectomy: MD 9.0, 95% CI (4.1, 14.0), p-value Within-trial cost utility analysis found observation/conservative management over 24 months was less costly than cholecystectomy (mean difference -£1, 033). A non-significant QALY difference of -0.019 favouring cholecystectomy resulted in an incremental cost-effectiveness ratio of £55,235. The Markov model continued to favour observation/conservative management, but some scenarios reversed the findings due to uncertainties in longer-term quality of life. The core outcome set included 11 critically important outcomes from both patients and healthcare professionals.
Conclusion
The results suggested that in the short-term (up to 24 months) observation/conservative management may be a cost-effective use of NHS resources in selected patients but subsequent surgeries in the randomised groups and differences in quality of life beyond 24 months could reverse this finding. Future research should focus on longer-term follow-up data and identification of the cohort of patients that should be routinely offered surgery
Gallstone disease is a common gastrointestinal disorder in industrialised societies. The prevalence of gallstones in the adult population is estimated to be approximately 10-15%, and around 80% remain asymptomatic. At present cholecystectomy is the default option for people with symptomatic gallstone disease.
Objective
To assess the clinical and cost-effectiveness of observation/conservative management compared with laparoscopic cholecystectomy for preventing recurrent symptoms and complications in adults presenting with uncomplicated symptomatic gallstones in secondary care.
Methods
Parallel group, multicentre patient randomised superiority pragmatic trial with up to 24 months follow-up and embedded qualitative research. Within trial cost utility and 10-year Markov model analyses. Development of a core outcome set for uncomplicated symptomatic gallstone disease. Adults with symptomatic uncomplicated gallstone disease referred to a secondary care setting were considered for inclusion. Participants were randomised 1:1 at clinic to receive
either laparoscopic cholecystectomy or observation/conservative management.
The primary outcome was quality of life measured by area under the curve over 18 months using the SF-36 bodily pain domain. Secondary outcomes included the Otago gallstones’ condition-specific questionnaire, SF-36 domains (excluding bodily pain), area under the curve over 24 months for SF-36 bodily pain domain, persistent symptoms, complications and need for further treatment. No outcomes were blinded to allocation.
Results
Between August 2016 to November 2019, 434 participants were randomised (217 in each group) from 20 UK centres. By 24 months, 64 (29.5%) in the observation/conservative management group and 153 (70.5%) in the laparoscopic cholecystectomy group had received surgery, median time to surgery of 9.0 months (IQR, 5.6-15.0) and 4.7 months (IQR 2.6-7.9), respectively.
At 18 months, the mean SF-36 norm-based bodily pain score was 49.4 (SD 11.7) in the observation/conservative management group and 50.4 (SD 11.6) in the laparoscopic cholecystectomy group. The mean AUC over 18 months was 46.8 for both groups with no difference: mean difference (MD) -0.0, 95% CI (-1.7, 1.7); p-value 0.996; n=203 observation/conservative, n=205 cholecystectomy).
There was no evidence of differences in quality of life, complications or need for further treatment at up to 24 months follow-up. Condition specific quality of life at 24 months favoured cholecystectomy: MD 9.0, 95% CI (4.1, 14.0), p-value Within-trial cost utility analysis found observation/conservative management over 24 months was less costly than cholecystectomy (mean difference -£1, 033). A non-significant QALY difference of -0.019 favouring cholecystectomy resulted in an incremental cost-effectiveness ratio of £55,235. The Markov model continued to favour observation/conservative management, but some scenarios reversed the findings due to uncertainties in longer-term quality of life. The core outcome set included 11 critically important outcomes from both patients and healthcare professionals.
Conclusion
The results suggested that in the short-term (up to 24 months) observation/conservative management may be a cost-effective use of NHS resources in selected patients but subsequent surgeries in the randomised groups and differences in quality of life beyond 24 months could reverse this finding. Future research should focus on longer-term follow-up data and identification of the cohort of patients that should be routinely offered surgery
| Original language | English |
|---|---|
| Journal | Health and Social Care Delivery Research |
| Publication status | Accepted/In press - 14 Feb 2023 |
Bibliographical note
AcknowledgementsThe authors wish to thank the men and women who participated in C-GALL. We also thank the CHaRT data coordinators and trials managers who helped support the study: Zoe Batham, Louise Campbell, Janice Cruden, Dianne Dejean, Jackie Ellington, Andrea Fraser and Bev Smith (data coordinators), Tracey Davidson and Alison McDonald (Trial managers).
We are grateful to Kirsty McCormack and John Norrie for their help and advice in developing the grant proposal, to the Programming Team in CHaRT for developing and maintaining the study website. We thank Juliette Snow and Rachael West for their help with contracting, and Louise Cotterell, Kerry Duffus and Anne Buckle for their assistance in managing the budget. Our thanks go also to the Research Governance team (Louise King, Stacey
Dawson, Lynn McKay) at the University of Aberdeen for their advice and support during the study.
Thanks to Jamie McAllister (NHS Grampian) for providing unit cost data for the within trial economic analysis.
Thanks to the Chen et al. for allowing the C-GALL group the use of the Otago ConditionSpecific Questionnaire (OCSQ) for gallstone disease, developed by Chen et al. in the University of Otago, New Zealand.1,2
1. Chen TY, Landmann MG, Potter JC, van Rij AM. Questionnaire to aid priority and outcomes assessment in gallstone disease. ANZ J Surg. 2006;76(7):569-74.
2. Chen TY. A novel set of condition-specific quality of life questionnaires in elective general surgical patient prioritization and outcome assessment [dissertation]. Dunedin (NZ): University of Otago; 2012. Retrieved from
http://hdl.handle.net/10523/2588 Members of the PMG for their ongoing support and advice. The independent members of the TSC and DMC, and the staff at the recruiting sites (listed below) who facilitated recruitment, treatment and follow up of trial participants.
Trial funding
This project was funded by the National Institute for Health Research (NIHR) XXX
programme and will be published in full in HTA journal; Vol. XX, No. XX
Keywords
- Randomised controlled trial
- gallstones
- cholecystectomy
- conservative treatment
- cholelithiasis