Develop clinical care pathways for treatment of symptomatic gallstones in a UK NHS context.

Summarise evidence of the clinical effectiveness and safety of each observation /conservative treatment alternative to surgery.

Determine which management options are most likely to be efficient for implementation into the UK NHS.

Identify and prioritise future research.

Comprehensive literature searches will be conducted to identify reports of published, ongoing, and unpublished studies on the clinical and/or cost-effectiveness of cholecystectomy versus non-surgical interventions for the management of patients with symptomatic gallstones and cholecystitis. Highly sensitive search strategies will be designed, including appropriate subject headings and text word terms, interventions under consideration and relevant study designs. Searches will be run from 1980 to date, to mirror the use of surgical techniques currently available in clinical practice as well as the introduction of novel interventions for the management of symptomatic gallstones. Databases to be searched will include MEDLINE, MEDLINE in process, EMBASE, Science Citation Index, Biosis and the Cochrane Central Register of Controlled Trials (CENTRAL). Reports of relevant evidence syntheses will also be sought from the Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Review of Effects (DARE).

Ongoing studies will be identified through searching the WHO International Clinical Trials Registry, Current Controlled Trials, Clinical Trials and the NIHR Portfolio. Recent conference proceedings of key organisations such as the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland, the Association of Laparoscopic Surgeons of Great Britain and Ireland and the British Society of Gastroenterology will be screened for further relevant reports. The websites of regulatory bodies and HTA agencies will also be checked to identify relevant unpublished reports.

Reference lists of all included studies will be perused to identify additional potentially relevant reports. Clinical experts in the field will be contacted to provide details of any further potentially relevant reports that they are aware of.

Evidence from randomised controlled trials (RCTs) which compare cholecystectomy (open or laparoscopic) with non-surgical interventions (i.e. observation/conservative treatments) will be deemed suitable for inclusion irrespective of language, blinding, and publication status. Where insufficient evidence from RCTs is available to answer the review question, data from non-randomised comparative studies will be considered. The following types of report will be excluded:

• Reviews, editorials and opinions;

• Case series and case reports;

• Reports published in non-English languages for which a translation cannot be organised.

Gallstones disease is one of the most common and costly gastrointestinal disorders in Western countries. Approximately 15% of the adult western population suffer from gallstones. Gallstones may be "silent", even for years, and do not require medical treatment. However, between 1% and 4% of gallstones become symptomatic within a year and do require treatment. Surgery is the treatment of choice for symptomatic gallstones with 63,915 surgical removals of the gallbladder performed in England and Wales during 2010-2011 and 53,700 patients waiting for surgery. Laparoscopic cholecystectomy has become the therapy of choice for patients with symptomatic gallstones with or without cholecystitis and the rate of surgical procedures has increased over time. Whilst many studies have concentrated on the best timing of performing surgery and on operative outcomes and complications the question whether cholecystectomy is always required in patients with mild, uncomplicated symptomatic gallstones has not been rigorously evaluated in a UK setting. A recent randomised controlled trial comparing cholecystectomy with ‘observation’ (including pain management and dietary advice) has concluded that expectant management is a safe alternative to surgery in mild uncomplicated patients, as the risk of developing complications is low and quality of life and pain measurements are not significantly affected.

The population considered will be adults (18 years and older or as defined by the trialists) with first episode of symptomatic gallstones (biliary colic or cholecystitis) being considered for cholecystectomy in a secondary care setting. Patients with acute severe cholecystitis (e.g. obstruction of the cystic duct or neck of the gallbladder by gallstones) and/or cholangitis (inflammation of a bile duct) or pancreatitis will not be considered suitable for inclusion as they normally require urgent or emergency intervention. Similarly, patients with symptomatic gallstones complicated by severe concomitant diseases, critically ill patients, and/or patients who are judged to be unfit or unsuitable for surgery will not be considered within the scope of this review.

The intervention considered will be surgical removal of the gallbladder (open or laparoscopic).

The comparator intervention will be observation (watchful waiting) and/or conservative treatment. ‘Conservative treatment’ refers here to the course of analgesics/ anti-inflammatory drugs accompanied by lifestyle advice. Patients with cholecystitis and signs of inflammation may also be prescribed antibiotics.

‘Delayed surgery’ will not be considered a suitable comparator.

For the purpose of this review, ‘first episode of symptomatic gallstones’ is defined as the first instance in which the patient presents for secondary care attention (with the possibility of receiving surgical treatment) even though the clinical history may document previous clinical symptoms or pain attacks. The gallstones disease will be confirmed by ultrasonography.

Primary outcomes

1. Disease-related morbidity

a. Recurrence of symptoms

b. Complications (e.g. pancreatitis)

c. Number of visits to primary care settings or hospital emergency department

d. Analgesic requirements

2. Need for surgical, endoscopic or radiological intervention

3. Need for further medical intervention

4. Surgery-related morbidity (e.g. bile duct injury, infection, bleeding, reoperation rate, recurrent pain, diarrhoea)

5. Quality of life (as defined by the studies’ authors)

6. Cost of initial and any subsequent treatments

7. Mortality

Secondary outcomes

None

One reviewer will screen the titles and, when available, abstracts of all reports identified by the search strategies. All potentially relevant reports will be retrieved in full and assessed independently by two reviewers. Any disagreement that cannot be resolved by consensus will be referred to a third party.

A data extraction form will be specifically designed to collect data from included studies. Two independent reviewers will extract the following information from each individual study (without concealing the study authorship or other publication details): journal name, year of publication, study design and method of patients recruitment, setting, number and characteristics of participants (e.g. gender, age, clinical history, risk factors, previous ‘gallstones attacks’, concomitant disease), characteristics of interventions (e.g. type, duration, cost) and outcome measures. Any disagreements will be resolved by consensus or arbitration by a third party.

The methodological quality of included RCTs will be assessed by means of The Cochrane Collaboration’s tool for assessing risk of bias. Two reviewers will independently assess the risk of bias within each included trial based on the following domains: sequence generation, allocation concealment, blinding, incomplete outcome data, and selective outcome reporting.

A modified version of the Cochrane risk of bias tool, which the Cochrane Non-Randomised Methods Group, adapted to include potential topic-specific confounders, will be used for assessing risk of bias in non-randomised comparative studies. The project group will identify a priori the main confounders (by outcome) for non-randomised comparative studies and imbalance in any of the confounders (e.g. age and gender differences between comparative groups) will affect study quality. Individual outcomes will be scored as High risk of bias, Low risk of bias or Unclear. Any disagreements between reviewers will be resolved by consensus or arbitration by a third party.

Where the same outcome is assessed by more than one included study, a quantitative synthesis of results will be carried out. Results of each study will be tabulated and summarised according to type of study design for each outcome and plotted as point estimates with corresponding 95% confidence intervals. Mean differences will be reported for continuous outcomes (e.g. number of visits to GP or hospital, quality of life measures), and risk ratios for dichotomous outcomes (e.g. morbidity event rates, need for further treatment, mortality). Heterogeneity between studies will be assessed by visual inspection of forest plots and from Mantel-Haenszel chi-square and I-square tests. If there is no evidence of heterogeneity, then pooled summary estimates will be derived from fixed-effects meta-analyses. Where significant heterogeneity exists, random effects meta-analyses will be used and potential sources of heterogeneity will be assessed e.g. by checking the appropriateness of the choice of effect measures or by exploratory analyses of subgroups. If multiple interventions are identified, then network meta-analysis methods (in which the research team is experienced) may be considered to derive summary estimates that would not be possible to obtain from traditional pairwise meta-analyses. If a quantitative synthesis is considered to be inappropriate or not feasible for any outcome, then a narrative synthesis of the findings will be provided for the included studies.

None planned.

Review findings will be disseminated through relevant conference presentations, research seminars and clinical meetings

Miriam Brazzelli

Health Services Research Unit

University of Aberdeen

1st Floor

Health Sciences Building

Foresterhill

Aberdeen AB25 2ZD

m.brazzelli@abdn.ac.uk

Aberdeen Health Technology Assessment Group

www.abdn.ac.uk/hsru

Dr Miriam Brazzelli, Aberdeen Health Technology Assessment Group
Dr Moira Cruickshank, Aberdeen Health Technology Assessment Group
Ms Mary Kilonzo, Health Economics Research Unit, University of Aberdeen
Dr Paul McNamee, Health Economics Research Unit, University of Aberdeen
Dr Graham Scotland, Health Services Research Unit, University of Aberdeen
Ms Fiona Stewart, Health Services Research Unit, University of Aberdeen
Mr Andrew Elders, Health Services Research Unit, University of Aberdeen
Professor Craig Ramsay, Health Services Research Unit, University of Aberdeen

Dr Irfan Ahmed, NHS Grampian & University of Aberdeen
Dr John Leeds, NHS Grampian
Professor Alison Avenell, Health Services Research Unit, University of Aberdeen
Dr Heather Peace, Nutrition Science and Policy Branch, Food Standards Agency, St Magnus House, Aberdeen

None

01 September 2012

14 March 2013

NICE TAR contract.

None known

English

Scotland

Subject indexing assigned by CRD

Adult; Cholecystectomy, Laparoscopic; Cholelithiasis; Gallstones; Humans

22 August 2012

22 August 2012