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. 2024 Jun;28(26):1–151. doi: 10.3310/MNBY3104

Laparoscopic cholecystectomy versus conservative management for adults with uncomplicated symptomatic gallstones: the C-GALL RCT.

Karen Innes, Irfan Ahmed, Jemma Hudson, Rodolfo Hernández, Katie Gillies, Rebecca Bruce, Victoria Bell, Alison Avenell, Jane Blazeby, Miriam Brazzelli, Seonaidh Cotton, Bernard Croal, Mark Forrest, Graeme MacLennan, Peter Murchie, Samantha Wileman, Craig Ramsay
PMCID: PMC11228691  PMID: 38943314

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.

Plain language summary

The C-GALL study assessed the benefits, in terms of symptoms, quality of life and costs, of cholecystectomy versus observation (conservative management: by the patient and general practitioner that might include dietary advice and pain management and surgery if needed). Four hundred and thirty-four patients with symptomatic gallstones were randomly allocated surgery or conservative management. The main symptom of ongoing bodily pain and some other quality-of-life measures were assessed over the next 2 years using postal questionnaires. After 2 years, 70% of those allocated to surgery had been operated on and 37% of the observation group either had an operation or were waiting for one. There was no difference in bodily pain or overall quality of life between the groups. However, participants in the surgery group reported fewer ongoing problems related to their gallstone disease or after surgery than those in the conservative management group. Surgery was, however, more costly than conservative management. The C-GALL study has shown that for some patients, a conservative management approach may be a sufficient and less costly way of managing their gallstone symptoms rather than going straight on the waiting list for surgery. More research is needed to identify which patients benefit most from surgery.

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References

  1. Ahmed I, Innes K, Brazzelli M, Gillies K, Newlands R, Avenell A, et al. Protocol for a randomised controlled trial comparing laparoscopic cholecystectomy with observation/conservative management for preventing recurrent symptoms and complications in adults with uncomplicated symptomatic gallstones (C-Gall trial). BMJ Open 2021;11(3):e039781. doi: 10.1136/bmjopen-2020-039781. [DOI] [PMC free article] [PubMed]
  2. American College of Physicians. Guidelines for the treatment of gallstones. Ann Intern Med 1993;119(7 Pt. 1):620–2. doi: 10.7326/0003-4819-119-7_part_1-199310010-00011. [DOI] [PubMed]
  3. Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone disease. Lancet 2006;368(9531):230–9. doi: 10.1016/S0140-6736(06)69044-2. [DOI] [PubMed]
  4. Shaffer EA. Gallstone disease: epidemiology of gallbladder stone disease. Best Pract Res Clin Gastroenterol 2006;20(6):981–96. doi: 10.1016/j.bpg.2006.05.004. [DOI] [PubMed]
  5. Stinton LM, Myers RP, Shaffer EA. Epidemiology of gallstones. Gastroenterol Clin North Am 2010;39(2):157–69, vii. doi: 10.1016/j.gtc.2010.02.003. [DOI] [PubMed]
  6. Bateson MC. Gallstones and cholecystectomy in modern Britain. Postgrad Med J 2000;76(901):700–3. doi: 10.1136/pmj.76.901.700. [DOI] [PMC free article] [PubMed]
  7. Barbara L, Sama C, Morselli Labate AM, Taroni F, Rusticali AG, Festi D, et al. A population study on the prevalence of gallstone disease: the Sirmione study. Hepatology 1987;7(5):913–7. doi: 10.1002/hep.1840070520. [DOI] [PubMed]
  8. Everhart JE, Khare M, Hill M, Maurer KR. Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology 1999;117(3):632–9. doi: 10.1016/s0016-5085(99)70456-7. [DOI] [PubMed]
  9. Heaton KW, Braddon FE, Mountford RA, Hughes AO, Emmett PM. Symptomatic and silent gall stones in the community. Gut 1991;32(3):316–20. doi: 10.1136/gut.32.3.316. [DOI] [PMC free article] [PubMed]
  10. Williams JG, Roberts SE, Ali MF, Cheung WY, Cohen DR, Demery G, et al. Gastroenterology services in the UK: the burden of disease, and the organisation and delivery of services for gastrointestinal and liver disorders: a review of the evidence. Gut 2007;56(Suppl. 1):1–113. doi: 10.1136/gut.2006.117598. [DOI] [PMC free article] [PubMed]
  11. Festi D, Dormi A, Capodicasa S, Staniscia T, Attili AF, Loria P, et al. Incidence of gallstone disease in Italy: results from a multicenter, population-based Italian study (the MICOL project). World J Gastroenterol 2008;14(34):5282–9. doi: 10.3748/wjg.14.5282. [DOI] [PMC free article] [PubMed]
  12. Festi D, Reggiani MLB, Attili AF, Loria P, Pazzi P, Scaiolo E, et al. Natural history of gallstone disease: expectant management or active treatment? Results from a population‐based cohort study. J Gastroenterol Hepatol 2010;25(7):719–24. doi: 10.1111/j.1440-1746.2009.06146.x. [DOI] [PubMed]
  13. Sakorafas GH, Milingos D, Peros G. Asymptomatic cholelithiasis: is cholecystectomy really needed? A critical reappraisal 15 years after the introduction of laparoscopic cholecystectomy. Dig Dis Sci 2007;52(5):1313–25. doi: 10.1007/s10620-006-9107-3. [DOI] [PubMed]
  14. Beckingham I. ABC of diseases of liver, pancreas, and biliary system: gallstone disease. BMJ 2001;322:91–4. doi: 10.1136/bmj.322.7278.91. [DOI] [PMC free article] [PubMed]
  15. Friedman GD, Raviola CA, Fireman B. Prognosis of gallstones with mild or no symptoms: 25 years of follow-up in a health maintenance organization. J Clin Epidemiol 1989;42(1986):127–36. doi: 10.1016/0895-4356(89)90086-3. [DOI] [PubMed]
  16. Thistle J, Cleary P, Lachin J, Tyor M, Hersh T. The natural history of cholelithiasis: the National Cooperative Gallstone Study. Ann Intern Med 1984;101:171–5. doi: 10.7326/0003-4819-101-2-171. [DOI] [PubMed]
  17. Attili AF, De Santis A, Capri R, Repice AM, Maselli S. The natural history of gallstones: the GREPCO experience. The GREPCO Group. Hepatology 1995;21(3):655–60. doi: 10.1002/hep.1840210309. [DOI] [PubMed]
  18. McSherry CK, Ferstenberg H, Calhoun WF, Lahman E, Virshup M. The natural history of diagnosed gallstone disease in symptomatic and asymptomatic patients. Ann Surg 1985;202(1):59–63. doi: 10.1097/00000658-198507000-00009. [DOI] [PMC free article] [PubMed]
  19. Berhane T, Vetrhus M, Hausken T, Olafsson S, Sondenaa K. Pain attacks in non-complicated and complicated gallstone disease have a characteristic pattern and are accompanied by dyspepsia in most patients: the results of a prospective study. Scand J Gastroenterol 2006;41(1):93–101. doi: 10.1080/00365520510023990. [DOI] [PubMed]
  20. Schmidt M, Dumot JA, Soreide O, Sondenaa K. Diagnosis and management of gallbladder calculus disease. Scand J Gastroenterol 2012;47(11):1257–65. doi: 10.3109/00365521.2012.704934. [DOI] [PubMed]
  21. CholeS Study Group. West Midlands Research Collaborative: population-based cohort study of outcomes following cholecystectomy for benign gallbladder diseases. Br J Surg 2016;103(12):1704–15. doi: 10.1002/bjs.10287. [DOI] [PubMed]
  22. Larsen TK, Qvist N. The influence of gallbladder function on the symptomatology in gallstone patients, and the outcome after cholecystectomy or expectancy. Dig Dis Sci 2007;52(3):760–3. doi: 10.1007/s10620-006-9498-1. [DOI] [PubMed]
  23. Jorgensen T, Teglbjerg JS, Wille-Jorgensen P, Bille T, Thorvaldsen P. Persisting pain after cholecystectomy: a prospective investigation. Scand J Gastroenterol 1991;26(1):124–8. doi: 10.3109/00365529108996493. [DOI] [PubMed]
  24. Ahmed R, Freeman JV, Ross B, Kohler B, Nicholl JP, Johnson AG. Long term response to gallstone treatment: problems and surprises. Eur J Surg 2000;166(6):447–54. doi: 10.1080/110241500750008754. [DOI] [PubMed]
  25. Lamberts MP, Lugtenberg M, Rovers MM, Roukema AJ, Drenth JP, Westert GP, van Laarhoven CJHM. Persistent and de novo symptoms after cholecystectomy: a systematic review of cholecystectomy effectiveness. Surg Endosc 2013;27(3):709–18. doi: 10.1007/s00464-012-2516-9. [DOI] [PubMed]
  26. Girometti R, Brondani G, Cereser L, Como G, Del Pin M, Bazzocchi M, Zuiani C. Post-cholecystectomy syndrome: spectrum of biliary findings at magnetic resonance cholangiopancreatography. Br J Radiol 2010;83(988):351–61. doi: 10.1259/bjr/99865290. [DOI] [PMC free article] [PubMed]
  27. Luman W, Adams WH, Nixon SN, Mcintyre IM, Hamer-Hodges D, Wilson G, Palmer KR. Incidence of persistent symptoms after laparoscopic cholecystectomy: a prospective study. Gut 1996;39(6):863–6. doi: 10.1136/gut.39.6.863. [DOI] [PMC free article] [PubMed]
  28. Schmidt M, Sondenaa K, Dumot JA, Rosenblatt S, Hausken T, Ramnefjell M, et al. Post-cholecystectomy symptoms were caused by persistence of a functional gastrointestinal disorder. World J Gastroenterol 2012;18(12):1365–72. doi: 10.3748/wjg.v18.i12.1365. [DOI] [PMC free article] [PubMed]
  29. Bisgaard T, Rosenberg J, Kehlet H. From acute to chronic pain after laparoscopic cholecystectomy: a prospective follow-up analysis. Scand J Gastroenterol 2005;40(11):1358–64. doi: 10.1080/00365520510023675. [DOI] [PubMed]
  30. van Dijk AH, de Reuver PR, Besselink MG, van Laarhoven KJ, Harrison EM, Wigmore SJ, et al. Assessment of available evidence in the management of gallbladder and bile duct stones: a systematic review of international guidelines. HPB (Oxford) 2017;19(4):297–309. doi: 10.1016/j.hpb.2016.12.011. [DOI] [PubMed]
  31. NHS England. 2019/20 National Cost Collection for the NHS data (Version 2). URL: www.england.nhs.uk/publication/2019-20-national-cost-collection-data-publication/?msclkid=a717fabdba4111ecae08168a6a0b8189 (accessed 1 December 2021).
  32. National Institute for Health and Care Excellence. Adult laparoscopic cholecystectomy 01/09/2010-31/10/2020. https://doi.org/10.5061/dryad.k9q7h
  33. Somasekar K, Shankar PJ, Foster ME, Lewis MH. Costs of waiting for gall bladder surgery. Postgrad Med J 2002;78(925):668–9. doi: 10.1136/pmj.78.925.668. [DOI] [PMC free article] [PubMed]
  34. Schmidt M, Hausken T, Glambek I, Schleer C, Eide GE, Sondenaa K. A 24-year controlled follow-up of patients with silent gallstones showed no long-term risk of symptoms or adverse events leading to cholecystectomy. Scand J Gastroenterol 2011;46(7–8):949–54. doi: 10.3109/00365521.2011.571710. [DOI] [PubMed]
  35. Brazzelli M, Cruickshank M, Kilonzo M, Ahmed I, Stewart F, McNamee P, et al. Clinical effectiveness and cost-effectiveness of cholecystectomy compared with observation/conservative management for preventing recurrent symptoms and complications in adults presenting with uncomplicated symptomatic gallstones or cholecystitis: a systematic review and economic evaluation. Health Technol Assess 2014;18(55):1–101, v. doi: 10.3310/hta18550. [DOI] [PMC free article] [PubMed]
  36. StataCorp. Stata Statistical Software: Release 16. College Station, TX: StataCorp LLC; 2019.
  37. Zou G. A modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol 2004;159(7):702–6. doi: 10.1093/aje/kwh090. [DOI] [PubMed]
  38. WHO. WHO Director-General’s opening remarks at the media briefing on COVID-19: 11 March 2020. URL: www.who.int/director-general/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020 (accessed 4 November 2022).
  39. Treweek S, Gillies K, Innes K, MacLennan G. Sending Christmas cards to trial participants to improve retention. Trials 2017;18:406. URL: www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,846275,en.pdf (accessed 4 November 2022).
  40. Coleman E, Arundel C, Clark L, Doherty L, Gillies K, Hewitt C, et al. Bah humbug! Association between sending Christmas cards to trial participants and trial retention: randomised study within a trial conducted simultaneously across eight host trials. BMJ 2021;375:e067742. doi: 10.1136/bmj-2021-067742. [DOI] [PMC free article] [PubMed]
  41. Duncan A, Innes K, Goulao B, Ramsay C. SWAT 145: The sticker SWAT: does a trial logo sticker placed on the outside of the envelope encourage the return of postal questionnaires. URL: www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,1140958,en.pdf (accessed 4 November 2022).
  42. Drummond M, Sculpher M, Claxton K, Stoddart G, Torrance G. Methods for the Economic Evaluation of Health Care Programmes. 4th edn. Oxford: Oxford University Press; 2015.
  43. Glick HA, Doshi JA, Sonnad SS, Polsky D. Economic Evaluation in Clinical Trials. 2nd edn. Oxford: Oxford University Press; 2014.
  44. Husereau D, Drummond M, Augustovski F, de Bekker-Grob E, Briggs AH, Carswell C, et al. Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations. Appl Health Econ Health Policy 2022;20(2):213–21. doi: 10.1007/s40258-021-00704-x. [DOI] [PMC free article] [PubMed]
  45. Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from the SF-36. J Health Econ 2002;21(2):271–92. doi: 10.1016/s0167-6296(01)00130-8. [DOI] [PubMed]
  46. School of Health and Related Research. Measuring and Valuing Health. URL: www.sheffield.ac.uk/scharr/research/themes/valuing-health (accessed 4 November 2022).
  47. NHS Digital. Hospital Admitted Patient Care Activity 2020–21: Procedures and interventions. URL: https://digital.nhs.uk/data-and-information/publications/statistical/hospital-admitted-patient-care-activity/2020-21 (accessed 4 November 2022).
  48. Cooper K, Breeman S, Scott NW, Scotland G, Hernández R, Clark TJ, et al. Laparoscopic supracervical hysterectomy compared with second-generation endometrial ablation for heavy menstrual bleeding: the HEALTH RCT. Health Technol Assess 2019;23(53):1–108. doi: 10.3310/hta23530. [DOI] [PMC free article] [PubMed]
  49. Public Health Scotland. Data and Intelligence. URL: https://beta.isdscotland.org/topics/finance/file-listings-fy-2019-to-2020/ (accessed 4 November 2022).
  50. NHS Institute for Innovation and Improvement. Improving Quality and Efficiency in the Operating Theatre. URL: https://alesi-surgical.com/wp-content/uploads/2019/09/Improving-quality-and-efficiency-in-the-operating-theatre.pdf (accessed 4 November 2022).
  51. NHS Improvement. Archived Reference Costs. URL: https://webarchive.nationalarchives.gov.uk/ukgwa/20200501111106/https://improvement.nhs.uk/resources/reference-costs/ (accessed 4 November 2022).
  52. Curtis L, Burns A. Unit Costs of Health and Social Care 2020. 2020th edn. Canterbury: Personal Social Services Research Unit, University of Kent; 2020.
  53. National Institute for Health and Care Excellence. British National Formulary. URL: http://bnf.nice.org.uk/drug/ (accessed 4 November 2022).
  54. Cooper K, Breeman S, Scott NW, Scotland G, Clark J, Hawe J, et al.; HEALTH Study Group. Laparoscopic supracervical hysterectomy versus endometrial ablation for women with heavy menstrual bleeding (HEALTH): a parallel-group, open-label, randomised controlled trial. Lancet 2019;394(10207):1425–36. doi: 10.1016/S0140-6736(19)31790-8. [DOI] [PMC free article] [PubMed]
  55. EUROQOL. URL: https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/faqs-2/ (accessed September 2022).
  56. StataCorp. Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC; 2021.
  57. Rubin DB. Multiple Imputation for Nonresponse in Surveys. New York: Wiley; 1987.
  58. Brand J, van Buuren S, le Cessie S, van den Hout W. Combining multiple imputation and bootstrap in the analysis of cost-effectiveness trial data. Stat Med 2019;38(2):210–20. doi: 10.1002/sim.7956. [DOI] [PMC free article] [PubMed]
  59. National Institute for Health and Care Excellence. Technology Appraisal Processes. URL: www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-technology-appraisal-guidance/process (accessed 4 November 2022).
  60. Schmidt M, Sondenaa K, Vetrhus M, Berhane T, Eide GE. A randomized controlled study of uncomplicated gallstone disease with a 14-year follow-up showed that operation was the preferred treatment. Dig Surg 2011;28(4):270–6. doi: 10.1159/000329464. [DOI] [PubMed]
  61. National Institute for Health and Care Excellence. Guide to the Methods of Technology Appraisal. National Institute for Health and Care Excellence, 2013. URL: www.nice.org.uk/process/pmg9/resources/guide-to-the-methods-of-technology-appraisal-2013-pdf-2007975843781?msclkid=015aa049ba4211eca67d6ef9d3815df7 (accessed December 2017). [PubMed]
  62. Gary A, Clarke P, Wolstenholme S, Wordsworth S. Applied Methods of Cost-effective Analysis in Health Care. Oxford: Oxford University Press; 2011.
  63. Office for National Statistics. National Life Tables – Life Expectancy in the UK: 2018 to 2020. 23 September 2021. URL: www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/lifeexpectancies/bulletins/nationallifetablesunitedkingdom/2018to2020?msclkid=599e4de4ba4211ec9b9ec1408d1c6ed5/peoplepopulationandcommunity/birthsdeathsandmarriages/lifeexpectancies/bulletins/nationallifetablesunitedkingdom/2018to2020 (accessed 12 November 2022).
  64. van den Berg B. Sf-6D population norms. Health Econ 2012;21(12):1508–12. doi: 10.1002/hec.1823. [DOI] [PubMed]
  65. Ara R, Brazier JE. Populating an economic model with health state utility values: moving toward better practice. Value Health 2010;13(5):509–18. doi: 10.1111/j.1524-4733.2010.00700.x. [DOI] [PubMed]
  66. National Institute for Health and Care Excellence. Gallstone Disease: Diagnosis and Management [CG188]. 2014. URL: www.nice.org.uk/guidance/cg188 (accessed 4 November 2022).
  67. Lawrie L, Duncan E, Dunsmore J, Newlands R, Gillies K. Using a behavioural approach to explore the factors that affect questionnaire return within a clinical trial: a qualitative study based on the theoretical domains framework. 2021. URL: https://bmjopen.bmj.com/content/11/4/e048128 (accessed 4 November 2022).
  68. Tunji-Ajayi P, Duncan EM, Gillies K. An embedded mixed-methods study highlighted a lack of discussions on retention in clinical trial consultations. J Clin Epidemiol 2020;123:49–58. doi: 10.1016/j.jclinepi.2020.03.011. [DOI] [PubMed]
  69. Abrams P, Shearer K. The MASTER trial: artificial urinary sphincter versus male sling. Trends Urol Men’s Health. 2015;6(2):37–8.
  70. Donovan J, Mills N, Smith M, Brindle L, Jacoby A, Peters T, et al. Quality improvement report: improving design and conduct of randomised trials by embedding them in qualitative research: ProtecT (prostate testing for cancer and treatment) study. Commentary: presenting unbiased information to patients can be difficult. BMJ 2002;325(7367):766–70. doi: 10.1136/bmj.325.7367.766. [DOI] [PMC free article] [PubMed]
  71. Rogers CA, Welbourn R, Byrne J, Donovan JL, Reeves BC, Wordsworth S, et al. The By-Band study: gastric bypass or adjustable gastric band surgery to treat morbid obesity: study protocol for a multi-centre randomised controlled trial with an internal pilot phase. Trials 2014;15:53. doi: 10.1186/1745-6215-15-53. [DOI] [PMC free article] [PubMed]
  72. Donovan JL, Rooshenas L, Jepson M, Elliott D, Wade J, Avery K, et al. Optimising recruitment and informed consent in randomised controlled trials: the development and implementation of the Quintet Recruitment Intervention (QRI). Trials 2016;17(1):283. doi: 10.1186/s13063-016-1391-4. [DOI] [PMC free article] [PubMed]
  73. Gillies K, Brehaut J, Coffey T, Duncan EM, Francis JJ, Hey SP, et al. How can behavioural science help us design better trials? Trials 2021;22(1):882. doi: 10.1186/s13063-021-05853-x. [DOI] [PMC free article] [PubMed]
  74. Cane J, O’Connor D, Michie S. Validation of the theoretical domains framework for use in behaviour change and implementation research. Implement Sci 2012;7:37. doi: 10.1186/1748-5908-7-37. [DOI] [PMC free article] [PubMed]
  75. Newlands R, Duncan E, Presseau J, Treweek S, Lawrie L, Bower P, et al. Why trials lose participants: a multitrial investigation of participants’ perspectives using the theoretical domains framework. J Clin Epidemiol 2021;137:1–13. doi: 10.1016/j.jclinepi.2021.03.007. [DOI] [PubMed]
  76. Lalu MM, Foster M, Presseau J, Dowlatshahi D, Castillo G, Cardenas A, et al. What are potential barriers and enablers to patient and physician participation in Canadian cell therapy trials for stroke? A stakeholder interview study. BMJ Open 2020;10(3):e034354. doi: 10.1136/bmjopen-2019-034354. [DOI] [PMC free article] [PubMed]
  77. Castillo G, Lalu MM, Asad S, Foster M, Kekre N, Fergusson DA, et al. Navigating choice in the face of uncertainty: using a theory informed qualitative approach to identifying potential patient barriers and enablers to participating in an early phase chimeric antigen receptor T (CAR-T) cell therapy trial. BMJ Open 2021;11(3):e043929. doi: 10.1136/bmjopen-2020-043929. [DOI] [PMC free article] [PubMed]
  78. Lawrie L, Duncan EM, Jansen JO, Campbell MK, Brunsdon D, Skea Z, et al. Behavioural Optimisation to Address Trial Conduct Challenges: Case Study in the UK-REBOA Trial (Under Review with Trials). URL: www.researchsquare.com/article/rs-1166980/v1 (accessed 4 November 2022). doi: 10.1186/s13063-022-06341-6. [DOI] [PMC free article] [PubMed]
  79. Atkins L, Francis J, Islam R, O’Connor D, Patey A, Ivers N, et al. A guide to using the theoretical domains framework of behaviour change to investigate implementation problems. Implement Sci 2017;12(1):77. doi: 10.1186/s13012-017-0605-9. [DOI] [PMC free article] [PubMed]
  80. Michie S, Richardson M, Johnston M, Abraham C, Francis J, Hardeman W, et al. The behavior change technique taxonomy (v1) of 93 hierarchically clustered techniques: building an international consensus for the reporting of behavior change interventions. Ann Behav Med 2013;46(1):81–95. doi: 10.1007/s12160-013-9486-6. [DOI] [PubMed]
  81. Wilson C, Rooshenas L, Paramasivan S, Elliott D, Jepson M, Strong S, et al. Development of a framework to improve the process of recruitment to randomised controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised) framework. Trials 2018;19(1):50. doi: 10.1186/s13063-017-2413-6. [DOI] [PMC free article] [PubMed]
  82. Rooshenas L, Elliott D, Wade J, Jepson M, Paramasivan S, Strong S, et al.; ACST-2 Study Group. Conveying equipoise during recruitment for clinical trials: qualitative synthesis of clinicians’ practices across six randomised controlled trials. PLOS Med 2016;13(10):e1002147. doi: 10.1371/journal.pmed.1002147. [DOI] [PMC free article] [PubMed]
  83. Donovan JL, Paramasivan S, de Salis I, Toerien M. Clear obstacles and hidden challenges: understanding recruiter perspectives in six pragmatic randomised controlled trials. Trials 2014;15:5. doi: 10.1186/1745-6215-15-5. [DOI] [PMC free article] [PubMed]
  84. Paramasivan S, Strong S, Wilson C, Campbell B, Blazeby JM, Donovan JL. A simple technique to identify key recruitment issues in randomised controlled trials: Q-QAT – quanti-qualitative appointment timing. Trials 2015;16:88. doi: 10.1186/s13063-015-0617-1. [DOI] [PMC free article] [PubMed]
  85. Malterud K, Siersma VD, Guassora AD. Sample Size in Qualitative Interview Studies: Guided by Information Power. Qual Health Res 2016;26(13):1753–60. doi: 10.1177/1049732315617444. [DOI] [PubMed]
  86. Goulao B, Duncan A, Floate R, Clarkson J, Ramsay C. Three behavior change theory-informed randomized studies within a trial to improve response rates to trial postal questionnaires. J Clin Epidemiol 2020;122:35–41. doi: 10.1016/j.jclinepi.2020.01.018. [DOI] [PubMed]
  87. Kearney A, Rosala-Hallas A, Bacon N, Daykin A, Shaw ARG, Lane AJ, et al. Reducing attrition within clinical trials: the communication of retention and withdrawal within patient information leaflets. PLOS ONE 2018;13(10):e0204886. doi: 10.1371/journal.pone.0204886. [DOI] [PMC free article] [PubMed]
  88. Innes K, Cotton S, Campbell MK, Elliott J, Gillies K. Relative importance of informational items in participant information leaflets for trials: a Q-methodology approach. BMJ Open 2018;8(9):e023303. doi: 10.1136/bmjopen-2018-023303. [DOI] [PMC free article] [PubMed]
  89. Cruickshank M, Newlands R, Blazeby J, Ahmed I, Bekheit M, Brazzelli M, et al. Identification and categorisation of relevant outcomes for symptomatic uncomplicated gallstone disease: in-depth analysis to inform the development of a core outcome set. BMJ Open 2021;11(6):e045568. doi: 10.1136/bmjopen-2020-045568. [DOI] [PMC free article] [PubMed]
  90. Williamson PR, Altman DG, Blazeby JM, Clarke M, Devane D, Gargon E, Tugwell P. Developing core outcome sets for clinical trials: issues to consider. Trials 2012;13:132. doi: 10.1186/1745-6215-13-132. [DOI] [PMC free article] [PubMed]
  91. Davis K, Gorst SL, Harman N, Smith V, Gargon E, Altman DG, et al. Choosing important health outcomes for comparative effectiveness research: an updated systematic review and involvement of low and middle income countries. PLOS ONE 2018;13(2):e0190695. doi: 10.1371/journal.pone.0190695. [DOI] [PMC free article] [PubMed]
  92. Comet Initiative. Development of Core Outcome Set for Symptomatic Uncomplicated Gallstone Disease. URL: www.comet-initiative.org/Studies/Details/927 (accessed 4 November 2022).
  93. Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST, et al. The COMET Handbook: version 1.0. Trials 2017;18(Suppl. 3):280. doi: 10.1186/s13063-017-1978-4. [DOI] [PMC free article] [PubMed]
  94. Gurusamy KS, Samraj K, Fusai G, Davidson BR. Early versus delayed laparoscopic cholecystectomy for biliary colic. Cochrane Database Syst Rev 2008;2008(4):CD007196. doi: 10.1002/14651858.CD007196.pub2. [DOI] [PubMed]
  95. Gurusamy KS, Koti R, Fusai G, Davidson BR. Early versus delayed laparoscopic cholecystectomy for uncomplicated biliary colic. Cochrane Database Syst Rev 2013;2013(6):CD007196. doi: 10.1002/14651858.CD007196.pub3. [DOI] [PMC free article] [PubMed]
  96. Gurusamy KS, Davidson C, Gluud C, Davidson BR. Early versus delayed laparoscopic cholecystectomy for people with acute cholecystitis. Cochrane Database Syst Rev 2013;2013(6):CD005440. doi: 10.1002/14651858.CD005440.pub3. [DOI] [PubMed]
  97. Gurusamy KS, Samraj K, Fusai G, Davidson BR. Robot assistant versus human or another robot assistant in patients undergoing laparoscopic cholecystectomy. Cochrane Database Syst Rev 2012;2012(9):CD006578. doi: 10.1002/14651858.CD006578.pub3. [DOI] [PMC free article] [PubMed]
  98. Gurusamy KS, Vaughan J, Ramamoorthy R, Fusai G, Davidson BR. Miniports versus standard ports for laparoscopic cholecystectomy. Cochrane Database Syst Rev 2013;2013(8):CD006804. doi: 10.1002/14651858.CD006804.pub3. [DOI] [PubMed]
  99. Hsieh HF, Shannon SE. Three approaches to qualitative content analysis. Qual Health Res 2005;15(9):1277–88. doi: 10.1177/1049732305276687. [DOI] [PubMed]
  100. Hewitt-Taylor J. Use of constant comparative analysis in qualitative research. Nurs Stand 2001;15(42):39–42. doi: 10.7748/ns2001.07.15.42.39.c3052. [DOI] [PubMed]
  101. Thomas J, Harden A. Methods for the thematic synthesis of qualitative research in systematic reviews. BMC Med Res Methodol 2008;8:45. doi: 10.1186/1471-2288-8-45. [DOI] [PMC free article] [PubMed]
  102. Macefield RC, Jacobs M, Korfage IJ, Nicklin J, Whistance RN, Brookes ST, et al. Developing core outcomes sets: methods for identifying and including patient-reported outcomes (PROs). Trials 2014;15:49. doi: 10.1186/1745-6215-15-49. [DOI] [PMC free article] [PubMed]
  103. Hopkins JC, Howes N, Chalmers K, Savovic J, Whale K, Coulman KD, et al.; By-Band Trial Management Group. Outcome reporting in bariatric surgery: an in-depth analysis to inform the development of a core outcome set, the BARIACT study. Obes Rev 2015;16(1):88–106. doi: 10.1111/obr.12240. [DOI] [PubMed]
  104. Coulman KD, Hopkins J, Brookes ST, Chalmers K, Main B, Owen-Smith A, et al.; BARIACT Working Group. A core outcome set for the benefits and adverse events of bariatric and metabolic surgery: the BARIACT project. PLOS Med 2016;13(11):e1002187. doi: 10.1371/journal.pmed.1002187. [DOI] [PMC free article] [PubMed]
  105. Comet Initiative. DelphiManager. URL: www.comet-initiative.org/delphimanager/ (accessed 4 November 2022).
  106. Okoli C, Pawlowski SD. The Delphi method as a research tool: an example, design considerations and applications. Inform Manag 2004;42(1):15–29.
  107. Murphy MK, Black NA, Lamping DL, McKee CM, Sanderson CF, Askham J, et al. Consensus development methods, and their use in clinical guideline development. Health Technol Assess 1998;2(3):i1–iv88. [PubMed]
  108. Aprea G, Coppola Bottazzi E, Guida F, Masone S, Persico G. Laparoendoscopic single site (LESS) versus classic video-laparoscopic cholecystectomy: a randomized prospective study. J Surg Res 2011;166(2):e109–12. doi: 10.1016/j.jss.2010.11.885. [DOI] [PubMed]
  109. Artis T, Kucuk C, Akay A, Zararsiz G, Sozuer E. Prospective Randomized Study Comparing Single Incision vs. Standard Laparoscopic Cholecystectomy. URL: www.cochranelibrary.com/central/doi/10.1002/central/CN-01063839/full# (accessed 4 November 2022).
  110. UMIN-CTR Clinical Trial. Randomized Controlled Trial to Evaluate the Superiority of the Single Port Chlecystectomy (SPC) on Reduction of Postoperative Pain, Compared with the Conventional Laparoscopic Cholecystectomy at the Single Institution. URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000003103 (accessed 4 November 2022).
  111. ClinicalTrials.gov. Single Port Laparoscopic Cholecystectomy Versus Four Port Laparoscopic Cholecystectomy: Impact on Postoperative Pain. URL: https://clinicaltrials.gov/ct2/show/ NCT01348620 (accessed 4 November 2022).
  112. Bignell M, Lewis MP, Cheong EC, Rhodes M. A prospective, randomized, single-blind trial of 5-mm versus 3-mm ports for laparoscopic cholecystectomy: is smaller better? Surg Endosc 2013;27(10):3616–21. doi: 10.1007/s00464-013-2933-4. [DOI] [PubMed]
  113. Bingener J, Skaran P, McConico A, Novotny P, Wettstein P, Sletten DM, et al. A double-blinded randomized trial to compare the effectiveness of minimally invasive procedures using patient-reported outcomes. J Am Coll Surg 2015;221(1):111–21. doi: 10.1016/j.jamcollsurg.2015.02.022. [DOI] [PMC free article] [PubMed]
  114. Russell ML, Preshaw RM, Brant RF, Bultz BD, Page SA. Disease-specific quality of life: the Gallstone Impact Checklist. Clin Invest Med 1996;19(6):453–60. [PubMed]
  115. 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. doi: 10.1111/j.1445-2197.2006.03777.x. [DOI] [PubMed]
  116. Eypasch E, Wood-Dauphinée S, Williams JI, Ure B, Neugebauer E, Troidl H. The Gastrointestinal Quality of Life Index: a clinical index for measuring patient status in gastroenterologic surgery. Chirurg 1993;64(4):264–74. [PubMed]
  117. Kleinbeck SV, Hoffart N. Outpatient recovery after laparoscopic cholecystectomy. AORN J 1994;60(3):394–402. doi: 10.1016/s0001-2092(07)62774-4. [DOI] [PubMed]
  118. Urbach DR, Harnish JL, McIlroy JH, Streiner DL. A measure of quality of life after abdominal surgery. Qual Life Res 2006;15(6):1053–61. doi: 10.1007/s11136-006-0047-3. [DOI] [PubMed]
  119. Lindseth GN, Denny DL. Patients’ experiences with cholecystitis and a cholecystectomy. Gastroenterol Nurs 2014;37(6):407–14. doi: 10.1097/SGA.0000000000000072. [DOI] [PMC free article] [PubMed]
  120. Psaila J, Agrawal S, Fountain U, Whitfield T, Murgatroyd B, Dunsire MF, et al. Day-surgery laparoscopic cholecystectomy: factors influencing same-day discharge. World J Surg 2008;32(1):76–81. doi: 10.1007/s00268-007-9225-x. [DOI] [PubMed]
  121. Comet Initiative. Advanced Search. URL: www.comet-initiative.org/Studies (accessed 12 November 2021).
  122. Remus A, Smith V, Gutke A, Mena JJS, Mørkved S, Wikmar LN, et al. A core outcome set for research and clinical practice in women with pelvic girdle pain: PGP-COS. PLOS ONE 2021;16(2):e0247466. doi: 10.1371/journal.pone.0247466. [DOI] [PMC free article] [PubMed]
  123. Chiarotto A, Ostelo RW, Turk DC, Buchbinder R, Boers M. Core outcome sets for research and clinical practice. Braz J Phys Ther 2017;21(2):77–84. doi: 10.1016/j.bjpt.2017.03.001. [DOI] [PMC free article] [PubMed]
  124. Daliya P, Gemmill EH, Lobo DN, Parsons SL. A systematic review of patient reported outcome measures (PROMs) and quality of life reporting in patients undergoing laparoscopic cholecystectomy. Hepatobiliary Surg Nutr 2019;8(3):228–45. doi: 10.21037/hbsn.2019.03.16. [DOI] [PMC free article] [PubMed]
  125. Alexander HC, Nguyen CH, Moore MR, Bartlett AS, Hannam JA, Poole GH, Merry AF. Measurement of patient-reported outcomes after laparoscopic cholecystectomy: a systematic review. Surg Endosc 2019;33(7):2061–71. doi: 10.1007/s00464-019-06745-7. [DOI] [PubMed]
  126. Comet Initiative. Identification and Categorisation of Relevant Outcomes for Symptomatic Uncomplicated Gallstone Disease: In-Depth Analysis to Inform the Development of a Core Outcome Set. URL: www.comet-initiative.org/Studies/Details/1909 (accessed 4 November 2022). doi: 10.1136/bmjopen-2020-045568. [DOI] [PMC free article] [PubMed]
  127. SWORD Methods. SWORD Database Accessed Through AUGIS Website (Due to Lack of Funding This Database Closed in 2020). 2019.
  128. GOV.UK. Population of England and Wales. URL: www.ethnicity-facts-figures.service.gov.uk/uk-population-by-ethnicity/national-and-regional-populations/population-of-england-and-wales/latest (accessed 8 March 2022).
  129. Sacks GD, Dawes AJ, Ettner SL, Brook RH, Fox CR, Maggard-Gibbons M, et al. Surgeon perception of risk and benefit in the decision to operate. Ann Surg 2016;264(6):896–903. doi: 10.1097/SLA.0000000000001784. [DOI] [PubMed]

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