Original Title: Efectividad, seguridad y coste-efectividad de la colecistectomía frente al tratamiento conservador para la colelitiasis sintomática no complicada o colecistitis aguda

Authors' objectives: The aim of the present assessment is to evaluate the clinical effectiveness and safety, and cost-effectiveness of cholecystectomy compared with observation/conservative management for preventing recurrent symptoms and complications in adults presenting initially with uncomplicated symptomatic gallstones (biliary pain or acute cholecystitis) for whom surgery is considered a treatment option.

Authors' results and conclusions: RESULTS: CLINICAL EFFECTIVENESS AND SAFETY: The literature searches identified 3,823 potentially relevant citations, of which 91 reports were selected for full-text eligibility screening. Two RCTs published in six reports and involving 201 participants were subsequently deemed suitable for inclusion. Both trials, conducted in Norway, were considered to be at low risk of bias for all assessed quality domains. The results showed that participants randomized to observation were significantly more likely to experience gallstone-related complications (RR= 6.69; 95% CI: 1.57 to 28.51; P= 0.01), particularly acute cholecystitis (RR= 9.55; 95% CI: 1.25 to 73.27; P= 0.03), and less likely to undergo surgery (RR= 0.50; 95% CI: 0.34 to 0.73; P= 0.0004). They also experienced fewer surgery-related complications (RR= 0.36; 95% CI: 0.16 to 0.81; P= 0.01), with a significant reduction in minor surgery-related complications (RR= 0.11; 95% CI: 0.02 to 0.56; P= 0.008) compared to those randomized to surgery. Among participants with an initial diagnosis of uncomplicated symptomatic gallstones (biliary pain only) rather than cholecystitis, those randomized to observation were significantly more likely to experience pain attacks after randomization (χ2 = 9.10; P= 0.0026) and to be admitted to hospital for gallstone-related pain (χ2 = 7.79; P= 0.0053) compared to those randomized to surgery. Mortality risk was greater (but not significantly greater) among participants randomized to surgery. Fifty-five percent of people randomized to observation did not require surgery during the 14-year follow-up period, indicating that there is probably a subgroup of people with uncomplicated symptomatic gallstones who could benefit from conservative management. COST-EFFECTIVENESS: The base case results of the economic evaluation showed that, on average, the cost of surgery is higher than observation/conservative management (around 600 € per patient treated) and less effective, at a 5-year modeling time horizon. Therefore, observation/conservative management is dominant compared to cholecystectomy in patients with symptomatic gallstones. The probabilistic sensitivity analysis showed that the probability of accepting observation as a cost-effective treatment strategy is 80% at a willingness to pay of 5,000 €/QALY. However, these results are sensitive to the utility value assigned to patients who remain asymptomatic after observation, as well as the cost of the hospital stay for these patients. CONCLUSIONS: The results of this assessment, although associated with some uncertainty, allow the following conclusions about the treatment of uncomplicated symptomatic gallstones or acute cholecystitis: • Available evidence on the clinical effectiveness and safety of cholecystectomy compared with observation/conservative treatment is scarce: an RCT on patients with uncomplicated symptomatic gallstones (only biliary pain) and another one on patients with acute cholecystitis. • Combined results of these 2 RCTs show that participants assigned to cholecystectomy experienced more complications related to surgery and showed a slight, although statistically non-significant, increase in all-cause mortality rate than those assigned to be conservatively. In contrast, participants assigned to observation experienced more episodes of acute cholecystitis but few other complications related to gallstones. About half of those in the observation group did not require surgery in the long term which indicates that there is probably a subset of people with symptomatic gallstones who could benefit from observation/conservative treatment. • Cholecystectomy is a more expensive alternative for the NHS than observation/conservative treatment due to the increased number of healthcare resources associated with surgery and the costs related to the treatment of post-surgery complications. This alternative is also less effective (in terms of QALY) if there is no risk of recurrent symptoms or complications requiring emergency surgery. • Conservative treatment may be an option in patients with uncomplicated symptomatic gallstones and low risk of recurrent symptoms. Furthermore, as symptoms are usually not urgent, it may be reasonable to consider first this non-surgical option, taking into account personal preference and comfort of people.

Authors' recommendations: With the available evidence at the time of preparation of this report and using the more usual willingness to pay used to assess the results of such studies in Spain, it is suggested not to consider cholecystectomy as the first choice treatment for symptomatic gallstones in patients with low risk of recurrent symptoms. (Strength of recommendation: weak)

Authors' methods: Mixed methodology of development-adaptation-update of a previous Health Technology Assessment (HTA) report. A Systematic review of published literature from 1980 to February 2015. MEDLINE Y PREMEDLINE, EMBASE, SCI, CENTRAL and CRD EED were searched. A comprehensive search strategy that included controlled vocabulary and free text terms was used. In addition, a manual search was performed with the references of articles included. Evidence was considered from randomized controlled trials (RCTs) or non-randomized comparative studies in which people received either cholecystectomy or observation/conservative management. The population was adults with first episode of symptomatic gallstone disease (biliary pain or cholecystitis) being considered for surgical treatment in a secondary care setting. The intervention considered was cholecystectomy (open or laparoscopic). The comparator was observation and/or conservative management. For the cost-effectiveness evaluation, full economic evaluations, that are those studies in which costs and benefits of at least two alternatives are compared by one of the following techniques: cost-effectiveness analysis, cost-utility analysis and cost benefit analysis, were selected Methodological limitations of the included RCTs or non-randomized comparative studies were assessed according to the criteria of Scottish Intercollegiate Guidelines Network (SIGN). Economic evaluations were assessed using the criteria of Drummond et al. Data are presented through narrative synthesis and tables. Standard meta-analysis techniques were used to combine results from included studies Pooled estimates of effect size were obtained for studies with methodological homogeneity using meta-analysis (RevMan software). Results were risk ratios (RR) and confidence intervals (CI) at 95% were analyzed by the Mantel-Haenszel method. The methodology of the international working group Grading of Recommendations Assessment, Development and Evaluation (GRADE) was follow to assess the quality of evidence and to grade the strength of the recommendations. A full economic evaluation through a Markov model was developed to compare the costs and health outcomes of two treatment strategies for symptomatic gallstones: 1) observation/conservative management versus cholecystectomy. Costs were considered from a health services perspective and were discounted at 3% per year as the benefits, measured in years of quality-adjusted life (QALYs). A time horizon of five years was considered. The measure of cost-effectiveness was the ICER. Base case was estimated using the expected values of model parameters and then we performed deterministic and probabilistic sensitivity analysis using Monte Carlo simulations of 2nd order to quantify the uncertainty surrounding the parameters. These estimates were made from the systematic review previously performed in this report and from expert opinion. We presented the incremental cost-effectiveness plane, curve of acceptability and ANCOVA analysis by which we calculate the cost and effectiveness variability explained by each parameter of the model.

Project Status: Completed

Year Published: 2015

URL for published report: https://sescs.es/efectividad-de-la-colecistectomia-frente-al-tratamiento-conservador-para-la-colelitiasis-aguda/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Canary Health Service

Contact Address: Dirección del Servicio. Servicio Canario de la Salud, Camino Candelaria 44, 1ª planta, 38109 El Rosario, Santa Cruz de Tenerife

Contact Name: sescs@sescs.es

Contact Email: sescs@sescs.es