Abstract
BACKGROUND: 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.
OBJECTIVES: 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.
DESIGN: 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.
SETTING: Secondary care elective settings.
PARTICIPANTS: Adults with symptomatic uncomplicated gallstone disease referred to a secondary care setting were considered for inclusion.
INTERVENTIONS: Participants were randomised 1: 1 at clinic to receive either laparoscopic cholecystectomy or observation/conservative management.
MAIN OUTCOME MEASURES: The primary outcome was quality of life measured by area under the curve over 18 months using the Short Form-36 bodily pain domain. Secondary outcomes included the Otago gallstones' condition-specific questionnaire, Short Form-36 domains (excluding bodily pain), area under the curve over 24 months for Short Form-36 bodily pain domain, persistent symptoms, complications and need for further treatment. No outcomes were blinded to allocation.
RESULTS: Between August 2016 and November 2019, 434 participants were randomised (217 in each group) from 20 United Kingdom 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 (interquartile range, 5.6-15.0) and 4.7 months (interquartile range 2.6-7.9), respectively. At 18 months, the mean Short Form-36 norm-based bodily pain score was 49.4 (standard deviation 11.7) in the observation/conservative management group and 50.4 (standard deviation 11.6) in the laparoscopic cholecystectomy group. The mean area under the curve over 18 months was 46.8 for both groups with no difference: mean difference -0.0, 95% confidence interval (-1.7 to 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: mean difference 9.0, 95% confidence interval (4.1 to 14.0), p < 0.001 with a similar pattern for the persistent symptoms score. Within-trial cost-utility analysis found observation/conservative management over 24 months was less costly than cholecystectomy (mean difference -£1033). A non-significant quality-adjusted life-year 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.
CONCLUSIONS: The results suggested that in the short term (up to 24 months) observation/conservative management may be a cost-effective use of National Health Service 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.
TRIAL REGISTRATION: This trial is registered as ISRCTN55215960.
FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/71) and is published in full in Health Technology Assessment; Vol. 28, No. 26. See the NIHR Funding and Awards website for further award information.
| Original language | English |
|---|---|
| Pages (from-to) | 1-151 |
| Number of pages | 184 |
| Journal | Health Technology Assessment |
| Volume | 28 |
| Issue number | 26 |
| DOIs | |
| Publication status | Published - Jun 2024 |
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
Data Availability Statement
All data requests should be submitted to the corresponding author for consideration. Access to availableanonymised data may be granted following review.
Funding
This report presents independent research funded by the National Institute for Health and Care Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care The authors wish to thank the men and women who participated in C-GALL. We also thank the CHaRT data co-ordinators and trial managers who helped support the study: Zoe Batham, Louise Campbell, Janice Cruden, Dianne Dejean, Jackie Ellington, Andrea Fraser and Bev Smith (Data Co-ordinators), 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 also go to the Research Governance team (Louise King, Stacey Dawson, Lynn McKay) at the University of Aberdeen for their advice and support during the study. Funding:\u2002This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/71) and is published in full in ealth H eT chnology Assessment Vol. 28, No. 26. See the NIHR Funding and Awards website for further award information. ertChap 7 ore Outcome SetB? This work was also supported by NHS Grampian Endowment (project grant no. 16/11/006). KG held a Medical Research Council UK Methodology Fellowship during the delivery of this project (MR/L01193X/1).
| Funders | Funder number |
|---|---|
| National Institute for Health and Care Research | 14/192/71 |
| NHS Grampian Endowment | 16/11/006 |
| Medical Research Council | MR/L01193X/1 |
Keywords
- Randomised controlled trial
- gallstones
- cholecystectomy
- conservative treatment
- cholelithiasis
- Quality-Adjusted Life Years
- Markov Chains
- Humans
- Cholecystectomy, Laparoscopic
- Middle Aged
- Male
- Conservative Treatment
- United Kingdom
- Technology Assessment, Biomedical
- Cost-Benefit Analysis
- Quality of Life
- Female
- Adult
- Aged
- Gallstones/surgery
Access to Document
- Innes_etal_HTA_Laparoscopic_Cholecystectomy_Versus_VoR
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