Criteria for considering studies for this review

Search methods for identification of studies

We will search The Cochrane Hepato‐Biliary Group Controlled Trials Register (Gluud 2006), theCochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded (Royle 2003). We have given the preliminary search strategies in Table 1 with the time span for the searches. As the review progresses, we will improve the search strategies if necessary. We will also search the reference list of included trials to identify further trials.

Data collection and analysis

Trial selection and extraction of data
The first two authors, independently of each other, will identify the trials for inclusion. We will also list the excluded studies with the reasons for the exclusion.

The first two authors will independently extract the following data:
(1) Year and language of publication.
(2) Country.
(3) Year of conduct of trial.
(4) Inclusion and exclusion criteria.
(5) Diagnostic tests performed.
(6) Sample size.
(7) Population characteristics, such as age and sex ratio.
(8) Period of infusion of CCK.
(9) Cut‐off value for diagnosis of gallbladder dyskinesia.
(10) Mean gallbladder ejection fraction.
(11) Outcomes (mentioned above).
(12) Methodological quality (described below).
(13) Sample size calculation.
(14) Intention‐to‐treat analysis.

We will seek any unclear or missing information by contacting the authors of the individual trials. If there is any doubt whether the trials share the same patients, completely or partially (by identifying common authors and centres), we will contact the authors of the trials to clarify whether the trial report has been duplicated.

We will resolve any differences in opinion through discussion.

Assessment of methodological quality
We will assess the methodological quality of the trials independently, without masking of the trial names. We will follow the instructions given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2006) and the Cochrane Hepato‐Biliary Group Module (Gluud 2006). Due to the risk of biased overestimation of intervention effects in randomised trials with inadequate methodological quality (Schulz 1995; Moher 1998; Kjaergard 2001), we will look at the influence of methodological quality of the trials on the results by evaluating the reported randomisation and follow‐up procedures in each trial. If information is not available in the published trial, we will contact the authors in order to assess the trials correctly. We will assess generation of allocation sequence, allocation concealment, blinding, and follow‐up.

Generation of the allocation sequence

• Adequate, if the allocation sequence was generated by a computer or random number table. Drawing of lots, tossing of a coin, shuffling of cards, or throwing dice will be considered as adequate if a person who was not otherwise involved in the recruitment of participants performed the procedure.

• Unclear, if the trial was described as randomised, but the method used for the allocation sequence generation was not described.

• Inadequate, if a system involving dates, names, or admittance numbers were used for the allocation of patients. These studies are known as quasi‐randomised and will be excluded from the review regarding their benefits.

Allocation concealment

• Adequate, if the allocation of patients involved a central independent unit, on‐site locked computer, or sealed envelopes.

• Unclear, if the trial was described as randomised, but the method used to conceal the allocation was not described.

• Inadequate, if the allocation sequence was known to the investigators who assigned participants. Such studies will be excluded from the review regarding their benefits.

Blinding
Double blinding will not be assessed since we expect that there will be no 'double‐blind' trials. However, we will record whether any of the outcomes were assessed by a blinded observer or blinded assessor.

Follow‐up

• Adequate, if the numbers and reasons for dropouts and withdrawals in all intervention groups were described or if it was specified that there were no dropouts or withdrawals.

• Unclear, if the report gave the impression that there had been no dropouts or withdrawals, but this was not specifically stated.

• Inadequate, if the number or reasons for dropouts and withdrawals were not described.

Statistical methods
We will perform the meta‐analyses according to the recommendations of The Cochrane Collaboration (Higgins 2006) and the Cochrane Hepato‐Biliary Group Module (Gluud 2006). We will use the software package RevMan 4.2 (RevMan 2003). For dichotomous variables, we will calculate the relative risk (RR) with 95% confidence interval. For continuous variables, we will calculate the weighted mean difference (WMD) for outcomes like hospital stay and the standardised mean difference (SMD) for outcomes like quality of life (where different scales might be used) with 95% confidence interval. We will use a random‐effects model (DerSimonian 1986) and a fixed‐effect model (DeMets 1987). In case of discrepancy between the two models, we will report both results; otherwise we will report only the results from one of the models based on the heterogeneity. Heterogeneity will be explored by chi‐squared test with significance set at P value 0.10, and the quantity of heterogeneity will be measured by I² (Higgins 2002). An I² of 25% or more will be considered to represent heterogeneity and we will report the random‐effects model. Otherwise, we will report the fixed‐effect model.

We will adopt the 'available‐case analysis' (Higgins 2006). The analysis will be performed on an intention‐to‐treat basis (Newell 1992). In case we find 'zero‐event' trials in statistically significant outcomes, we will perform a sensitivity analysis with and without empirical continuity correction factors as suggested by Sweeting et al (Sweeting 2004). We will also report the risk difference.

Subgroup analysis
We will perform the following subgroup analyses:
‐ Trials with low bias risk (adequate methodology) compared to trials with high bias risk (unclear or inadequate methodologies).
‐ Different gallbladder ejection fractions.
‐ Adults and paediatric patients.
‐ Open and laparoscopic cholecystectomy.

Bias exploration
We will use a funnel plot to explore bias (Egger 1997; Macaskill 2001). Asymmetry in funnel plot of trial size against treatment effect will be used to assess this bias. We will perform linear regression approach described by Egger et al to determine the funnel plot asymmetry (Egger 1997).