Types of studies

We will include randomised or quasi‐randomised trials (randomisation based on alternation, date of birth, or case record number) regardless of their publication status or language of publication. We will consider the first phase of cross‐over studies if data of the first phase are reported separately. If these data are not available the study will be excluded to avoid biased results. Cluster‐randomised trials will be excluded.

Types of participants

Inclusion: Men and women 18 years of age or older receiving percutaneous nephrolithotomy (PNL) for nephrolithiasis. Only studies on unilateral PNL using a single‐tract access (or separate analysis for single‐tract access cases) will be included.

Exclusion: Patients with kidney transplantation, horseshoe kidney and other malformations or congenital abnormalities of the kidney.

Should we identify studies in which only a subset of participants are relevant to this review, we will include such studies if data are available separately for the relevant subset.

Types of interventions

We plan to investigate the following comparisons. Auxiliary procedures will have to be the same in the experimental and comparator groups to establish fair comparisons. Studies with combined percutaneous and retrograde intrarenal surgery (RIRS) will be excluded. We will include studies with interventions in all operating positions (prone and supine, semi‐supine, lateral).

Types of outcome measures

We will not use the measurement of the outcomes assessed in this review as an eligibility criterion.

Electronic searches

We will search the following databases.

• Cochrane Library

  • Cochrane Database of Systematic Reviews (CDSR) (www.cochranelibrary.com/cochrane‐database‐of‐systematic‐reviews/index.html)

  • Cochrane Central Register of Controlled Trials (CENTRAL) (www.cochranelibrary.com/about/central‐landing‐page.html)

  • Database of Abstracts of Reviews of Effects (DARE) (community.cochrane.org/editorial‐and‐publishing‐policy‐resource/overview‐cochrane‐library‐and‐related‐content/databases‐included‐cochrane‐library/database‐abstracts‐reviews‐effects‐dare)

  • Health Technology Assessment Database (HTA) (www.inahta.org/hta‐tools‐resources/database/)

• MEDLINE (via Ovid)

• Embase (via Ovid)

• Web of Science (www.apps.webofknowledge.com)

We will also search the following.

• ClinicalTrials.gov (www.clinicaltrials.gov/)

• World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (www.who.int/ictrp/)

If we detect additional relevant key words during any of the electronic or other searches, we will modify the electronic search strategies to incorporate these terms and document the changes.

Searching other resources

We will search reference lists of potentially eligible trials or ancillary publications to identify unpublished studies. We will search the reference lists of retrieved included trials, reviews, meta‐analyses and health technology assessment reports. We will also contact study authors of included trials, and companies, to identify any further unpublished studies that we may have missed. We will search for grey literature by screening abstract proceedings of relevant meetings from 2013 to 2016:

• American Urological Association: www.auanet.org/;

• European Association of Urology: eaumunich2016.uroweb.org/;

• World Congress of Endourology: www.endourology.org/;

• Experts in stone disease: esdconference.com/; and

• EULIS Meeting: www.sciencedirect.com/science/journal/15699056.

Selection of studies

We will use Covidence software (Covidence 2016) for reference management. Two review authors (KW, SH) will independently screen the abstract, title, or both, of retrieved records, to determine which studies should be assessed further. Two review authors (KW, SH) will investigate all potentially‐relevant records as full texts, map records to studies, review against the inclusion and exclusion criteria and classify studies as included studies, excluded studies, studies awaiting classification, or ongoing studies in accordance with the criteria for each provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). We will resolve any discrepancies through consensus or recourse to a third review author (SS). If resolution of a disagreement is not possible, we will designate the study as 'awaiting classification' and we will contact study authors for clarification. We will document reasons for exclusion of studies that may have reasonably been expected to be included in the review in a 'Characteristics of excluded studies' table. We will present an adapted PRISMA flow diagram showing the process of study selection (Liberati 2009).

Data extraction and management

We will develop a dedicated data abstraction form that we will pilot test ahead of time.

For studies that fulfil inclusion criteria, two review authors (KW, SH) will independently abstract the following information, which we will provide in the 'Characteristics of included studies' table

• Study design

• Study dates (if dates are not available then this will be reported as such)

• Study settings and country

• Participant inclusion and exclusion criteria

• Participant demographic and clinical baseline characteristics: gender, age, stone laterality, size, history of prior PNL, American Society of Anesthesiologists (ASA 2014) score if provided

• The number of participants by study and by study arm

• Details of relevant experimental and comparator interventions, such as size of the outer tract diameter and the diameter of the nephrostomy or double‐J stent used

• Definitions of relevant outcomes, and method and timing of outcome measurement as well as any relevant subgroups

• Study funding sources

• Declarations of interest by study authors

We will extract outcomes data relevant to this Cochrane review as needed for calculation of summary statistics and measures of variance. For dichotomous outcomes, we will attempt to obtain numbers of events and totals for population of a 2 x 2 table, as well as summary statistics with corresponding measures of variance. For continuous outcomes, we will attempt to obtain means and standard deviations or data necessary to calculate this information.

We will resolve any disagreements by discussion, or, if required, by consultation with a third review author (SS).

We will provide information, including trial identifier, about potentially relevant ongoing studies in the table 'Characteristics of ongoing studies'.

We will attempt to contact authors of included studies to obtain key missing data as needed.

Assessment of risk of bias in included studies

Two review authors (KW, SH) will assess the risk of bias of each included study independently. We will resolve disagreements by consensus, or by consultation with a third review author (SS).

We will assess risk of bias using Cochrane's 'Risk of bias' assessment tool (Higgins 2011b). We will assess the following domains.

• Random sequence generation (selection bias)

• Allocation concealment (selection bias)

• Blinding of participants and personnel (performance bias)

• Blinding of outcome assessment (detection bias)

• Incomplete outcome data (attrition bias)

• Selective reporting (reporting bias)

• Other sources of bias

We will judge risk of bias domains as 'low risk', 'high risk' or 'unclear risk' and will evaluate individual bias items as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b). We will present a 'Risk of bias' summary figure to illustrate these findings.

For performance bias (blinding of participants and personnel) and detection bias (blinding of outcome assessment), we will evaluate the risk of bias separately for each outcome, and we will group outcomes according to whether measured subjectively or objectively when reporting our findings in the 'Risk of bias' tables.

We define the following endpoints as subjective outcomes.

• Postoperative pain

• Stone‐free rate

• Adverse events other than Clavien 5

• Blood transfusions

• Fever

• Urinary leak

We define the following endpoints as objective outcomes.

• Surgery‐related mortality

• Severe adverse events Clavien 5

• Operating time

• Length of hospital stay

• Readmission during the first 30 days after the intervention

We will also assess the attrition bias (incomplete outcome data) on an outcome‐specific basis, and will present the judgement for each outcome separately when reporting our findings in the 'Risk of bias' tables.

We will further summarise the risk of bias across domains for each outcome in each included study, as well as across studies and domains for each outcome, in accordance with the approach for summary assessments of the risk of bias presented in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b).

Measures of treatment effect

RevMan will be used to analyse results and treatment effects. We will express dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs). We will express continuous data as mean differences (MDs) with 95% CIs unless different studies use different measures to assess the same outcome, in which case we will express data as standardised mean differences with 95% CIs.

Unit of analysis issues

The unit of analysis will be the individual participant. Cross‐over trials and cluster‐randomised trials will be treated as explained in Types of studies. Trials with more than two intervention groups for inclusion in the review will be managed in accordance with guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011c).

Dealing with missing data

We will obtain missing data from study authors, if feasible, and will perform intention‐to‐treat (ITT) analyses if data are available.

We will investigate attrition rates, e.g. drop‐outs, losses to follow‐up and withdrawals, and will critically appraise issues of missing data. We will not impute missing data.

Assessment of heterogeneity

In the event of excessive heterogeneity, we will not report outcome results as the pooled effect estimate in a meta‐analysis but will provide a narrative description of the results of each study.

We will identify heterogeneity (inconsistency) through visual inspection of the forest plots to assess the amount of overlap of CIs, and the I² statistic, which quantifies inconsistency across studies to assess the impact of heterogeneity on the meta‐analysis (Higgins 2002; Higgins 2003); we will interpret the I² statistic as follows (Deeks 2011):

• 0% to 40%: may not be important;

• 30% to 60%: may indicate moderate heterogeneity;

• 50% to 90%: may indicate substantial heterogeneity; and

• 75% to 100%: considerable heterogeneity.

When we find heterogeneity, we will attempt to determine possible reasons for it by examining individual study and subgroup characteristics.

Assessment of reporting biases

We will attempt to obtain study protocols to assess for selective outcome reporting.

If we include 10 studies or more investigating a particular outcome, we will use funnel plots to assess small study effects. Several explanations can be offered for the asymmetry of a funnel plot, including true heterogeneity of effect with respect to trial size, poor methodological design (and hence bias of small trials) and publication bias. We will therefore interpret results carefully.

Data synthesis

Unless there is good evidence for homogeneous effects across studies, we will summarise data using a random‐effects model. We will interpret random‐effects meta‐analyses with due consideration of the whole distribution of effects. In addition, we will perform statistical analyses according to the statistical guidelines contained in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a). For dichotomous outcomes, we will use the Mantel‐Haenszel method; for continuous outcomes, we will use the inverse variance method. We will use RevMan software to perform analyses.

Subgroup analysis and investigation of heterogeneity

• Stones size (diameter > 2 cm versus < 2 cm)

• Stone location (lower calyx versus other localisation

Sensitivity analysis

We plan to perform sensitivity analyses in order to explore the influence of the following factors (when applicable) on effect sizes:

• restricting the analysis by taking into account risk of bias, by excluding studies at 'high risk' or 'unclear risk'.