Types of studies

We will include studies with the following design characteristics:

• randomised controlled trials, including cluster‐randomised trials and quasi‐randomised trials, and cross‐over trials if the data from the first phase are available;

• patients were followed up for at least two weeks.

We will exclude studies with the following design characteristics:

• randomised patients by side of nose (within‐patient controlled) because it is difficult to ensure that the effects of any of the interventions considered can be localised; or

• perioperative studies, where the sole purpose of the study was to investigate the effect of nasal saline irrigation on surgical outcomes.

Types of participants

Patients (adults and children) with clinical symptoms characteristic of allergic rhinitis with a positive radioallergosorbent test (RAST) or skin prick test (SPT).

We will exclude studies that included a majority (more than 50%) of participants with:

• non‐allergic rhinitis;

• chronic rhinosinusitis;

• acute sinusitis;

• cystic fibrosis;

• immunotherapy started within the prior year;

• any alteration of allergic rhinitis‐specific pharmacotherapy (antihistamines, intranasal corticosteroids, anti‐leukotrienes) during the trial;

• aspirin‐exacerbated respiratory disease;

• surgery for turbinate reduction within three months prior to study.

Where a study includes a mixed group of participants, we will exclude it if more than 50% of the participants met the 'excluded' population criteria above, unless the study reports the results for the different populations separately. Similarly, where more than 50% of the people in the study have allergic rhinitis we will include the study but, where possible, we will only use the results for the population with allergic rhinitis.

Types of interventions

The use of saline, as an active treatment, delivered to the nose by any means (douche, irrigation, pulsed, spray or nebuliser).

Tonicity: we will include all concentrations of saline. 'Hypotonic' will be defined as a concentration of less than 0.9% NaCl, 'physiologic' as 0.9% NaCl and 'hypertonic' as greater than 0.9% NaCl.

Volume: we will include all volumes of saline treatments. 'Very low‐volume' will relate to misting sprays or other delivery methods where the volume of application is likely to be less than 5 mL per nostril per application. 'Low‐volume' will be defined as between 5 mL and 59 mL per nostril per application. 'High‐volume' will be defined as a volume of 60 mL or greater per nostril per application.

We will include studies investigating 'buffered' saline solutions where the aim is to adjust the pH of the solution. We will exclude studies that used formulations of saline solution that contain other additives, such as xylitol, antibacterials and surfactants. We will also exclude studies using other formulations, such as lactated Ringer's solution.

There will be no minimum duration of treatment.

Types of outcome measures

We will analyse the following outcomes in the review, but we will not use them as a basis for including or excluding studies.

Electronic searches

Published, unpublished and ongoing studies will be identified by searching the following databases from their inception:

• the Cochrane Register of Studies ENT Trials Register (search to date);

• Cochrane Register of Studies Online (search to date);

• Ovid MEDLINE (1946 to date);

  • Ovid MEDLINE (In‐Process & Other Non‐Indexed Citations);

  • PubMed (as a top up to searches in Ovid MEDLINE);

• Ovid EMBASE (1974 to date);

• Ovid CAB abstracts (1910 to date);

• Ovid AMED (1985 to date);

• LILACS (search to date);

• KoreaMed (search to date);

• IndMed (search to date);

• PakMediNet (search to date);

• Web of Knowledge, Web of Science (1945 to date);

• ClinicalTrials.gov, www.clinicaltrials.gov (search via the Cochrane Register of Studies to date);

• World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (search to date);

• ISRCTN, www.isrctn.com (search to date);

• Google Scholar (search to date);

• Google (search to date).

The subject strategies for databases will be modelled on the search strategy designed for CENTRAL (Appendix 1). Where appropriate, these will be combined with subject strategy adaptations of the highly sensitive search strategy designed by Cochrane for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, Box 6.4.b. (Handbook 2011)).

Searching other resources

We will scan the reference lists of identified publications for additional trials and contact trial authors if necessary. In addition, the Information Specialist will search Ovid MEDLINE, theCochrane Library and Google to retrieve existing systematic reviews relevant to this systematic review, so that we can scan their reference lists for additional trials.

Selection of studies

At least two review authors (KH and SG) will independently screen all titles and abstracts of the studies obtained from the database searches to identify potentially relevant studies. At least two review authors (KH and CP) will evaluate the full text of each potentially relevant study to determine whether it meets the inclusion and exclusion criteria for this review.

We will resolve any differences by discussion and consensus, with the involvement of a third author for clinical and/methodological input where necessary.

Data extraction and management

At least two review authors (KH and SG) will independently extract data from each study using a standardised data collection form (see Appendix 2). Whenever a study has more than one publication, we will retrieve all publications to ensure complete extraction of data. Where there are discrepancies in the data extracted by different review authors, we will check these against the original reports and we will resolve differences by discussion and consensus, with the involvement of a third author or a methodologist where appropriate. We will contact the original study authors for clarification or for missing data whenever required. If differences are found between publications of a study, we will contact the original authors for clarification. We will use data from the main paper(s) if no further information is found.

We will include key characteristics of the studies, such as study design, setting, sample size, population and how outcomes were defined or collected in the studies. In addition, we will also collect baseline information on prognostic factors or effect modifiers. For this review, this will include:

• age of participants;

• intermittent or persistent allergic rhinitis;

• type of allergic trigger (e.g. mites, pollens, animals, etc.);

• severity of allergic rhinitis ('mild' or 'moderate/severe' as defined in ARIA 2008).

For the outcomes of interest to the review, we will extract the findings of the studies on an available case analysis basis; i.e. we will include data from all patients available at the time points based on the treatment randomised whenever possible, irrespective of compliance or whether patients had received the treatment as planned.

In addition to extracting prespecified information about study characteristics and aspects of methodology relevant to risk of bias, we will extract the following summary statistics for each trial and each outcome:

• For continuous data: the mean values, standard deviations and number of patients for each treatment group. Where endpoint data are not available, we will extract the values for change from baseline. We will analyse data from measurement scales such as RQLQ and EQ‐5D as continuous data.

• For binary data: the numbers of participants experiencing an event and the number of patients assessed at the time point.

• For ordinal scale data: if the data appear to be approximately normally distributed or if the analysis that the investigators performed suggested parametric tests were appropriate, then we will treat the outcome measures as continuous data. Alternatively, if data are available, we plan to convert into binary data.

We have prespecified the time points of interest for the outcomes in this review (Types of outcome measures). While studies may have reported data at multiple time points, we will only extract the longest available data within the time points of interest. For example, if a study reports data at one, two and four weeks, we will only extract and analyse the data for the four‐week follow‐up.

Assessment of risk of bias in included studies

KH and SG will undertake assessment of the risk of bias of the included trials independently, with the following taken into consideration, as guided by theCochrane Handbook for Systematic Reviews of Interventions (Handbook 2011):

• sequence generation;

• allocation concealment;

• blinding;

• incomplete outcome data;

• selective outcome reporting; and

• other sources of bias.

We will use the Cochrane 'Risk of bias' tool in RevMan 5.3 (RevMan 2014), which involves describing each of these domains as reported in the trial and then assigning a judgement about the adequacy of each entry: 'low', 'high' or 'unclear' risk of bias.

Measures of treatment effect

We will summarise the effects of dichotomous outcomes (e.g. proportion of patients with symptom resolution) as risk ratios (RR) with 95% confidence intervals (CIs). For the key outcomes that we will present in the 'Summary of findings' table, we will also express the results as absolute numbers based on the pooled results and compared to the assumed risk. We also plan to calculate the number needed to treat to benefit (NNTB) using the pooled results. The assumed baseline risk will typically be either (a) the median of the risks of the control groups in the included studies, this being used to represent a 'medium risk population' or, alternatively, (b) the average risk of the control groups in the included studies used to represent the 'study population' (Handbook 2011). If a large number of studies are available, and where appropriate, we also plan to present additional data based on the assumed baseline risk in (c) a low‐risk population and (d) a high‐risk population.

For continuous outcomes, we will express treatment effects as a mean difference (MD) with standard deviation (SD). If different scales are used to measure the same outcome we will use the standardised mean difference (SMD), and we will provide a clinical interpretation of the SMD values.

Unit of analysis issues

This review will not use data from phase II of cross‐over studies or from studies where the patient is not the unit of randomisation, i.e. studies where the side of the nose (right versus left) was randomised.

If we find cluster‐randomised trials, we will analyse these according to the methods in section 16.3.3 of the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2011).

Dealing with missing data

We will contact study authors via email whenever the outcome of interest is not reported if the methods of the study suggest that the outcome had been measured. We will do the same if not all data required for meta‐analysis are reported, unless the missing data are standard deviations. If standard deviation data are not available we will approximate these using the standard estimation methods from P values, standard errors or 95% CIs if these are reported, as detailed in the Cochrane Handbook for Systematic Reviews of Interventions (Handbook 2011). Where it is impossible to estimate these, we will contact the study authors.

Apart from imputations for missing standard deviations, we will not conduct any other imputations. We will extract and analyse data for all outcomes using the available case analysis method.

Assessment of heterogeneity

We will assess clinical heterogeneity (which may be present even in the absence of statistical heterogeneity) by examining the included trials for potential differences between studies in the types of participants recruited (including age of participants), interventions or controls used and the outcomes measured.

We will assess statistical heterogeneity by visually inspecting the forest plots and by considering the Chi² test (with a significance level set at P < 0.10) and the I² statistic, which calculates the percentage of variability that is due to heterogeneity rather than chance, with I² values over 50% suggesting substantial heterogeneity (Handbook 2011).

Assessment of reporting biases

We will assess reporting bias as between‐study publication bias and within‐study outcome reporting bias.

Data synthesis

We will conduct all meta‐analyses using Review Manager 5.3 (RevMan 2014). For dichotomous data, we plan to analyse treatment differences as a risk ratio (RR) calculated using the Mantel‐Haenszel methods. We plan to analyse time‐to‐event data using the generic inverse variance method.

For continuous outcomes, if all the data are from the same scale, we will pool mean values obtained at follow‐up with the change in outcomes (i.e. difference between pre‐ versus post‐treatment values) and report this as a MD. However, if the SMD has to be used as an effect measure, we will not pool change and endpoint data.

When statistical heterogeneity is low, random‐effects versus fixed‐effect methods yield trivial differences in treatment effects. However, when statistical heterogeneity is high, the random‐effects method provides a more conservative estimate of the difference.

Subgroup analysis and investigation of heterogeneity

Where data are available, we plan to conduct some subgroup analyses regardless of whether statistical heterogeneity is observed, as these are widely suspected to be potential effect modifiers. For this review, this includes the following.

• Volume of saline delivery (e.g. 'very low', 'low' and 'high' volume). There is evidence of a difference in effectiveness between high‐ and low‐volume saline irrigation in patients with chronic sinonasal symptoms (Pynnonen 2007).

• Tonicity of saline solution (hypertonic, isotonic and hypotonic solutions). There is some evidence in other conditions that tonicity may have an effect on the efficacy of nasal saline (Berjis 2011; Rabago 2005).

• Alkalinity of saline solution. There is evidence that increased alkalinity of the saline solution improves some nasal symptoms (Chusakul 2013).

• Patient age (children, adults or mixed population). There may be differences in physiology that are unknown and compliance and volumes may well be quite different in the paediatric population compared to adults.

We plan to present the main analyses of this review according to the volume of saline delivery. We intend to present all other subgroup analysis results in tables.

In addition to the subgroups above, we plan to conduct the following subgroup analyses in the presence of statistical heterogeneity:

• method of delivery (e.g. nebuliser, sprays, irrigations);

• duration of treatment;

• frequency of allergic rhinitis symptoms (e.g. intermittent or persistent as defined by ARIA 2008), where an older study using the 'seasonal' and 'perennial' classification is used, we will interpret seasonal as 'intermittent' allergic rhinitis and 'perennial' as 'persistent' unless there is specific information in the paper that would make this inappropriate.

• severity of symptoms (mild, moderate/severe as defined by ARIA 2008).

When studies have a mixed group of patients, we plan to analyse the study as one of the subgroups (rather than as a mixed group) if more than 80% of the participants belong to one category. For example, if 81% of patients are over 18, we will analyse the study as though the participants were adults.

Sensitivity analysis

We plan to carry out sensitivity analyses to determine whether the findings are robust to the decisions made in the course of identifying, screening and analysing the trials. We plan to conduct sensitivity analysis for the following factors, whenever possible:

• impact of model chosen: fixed‐effect versus random‐effects model;

• risk of bias of included studies: evaluating the impact of missing data on the results of the studies due to participant attrition, to determine whether the missing outcome data for the participants in the trial could have influenced the results of the review;

• how outcomes were measured: we plan to investigate the impact of including data where the validity of the measurement instrument used was unclear.

If any of these investigations find a difference in the size of the effect or heterogeneity, we will mention this in the 'Effects of interventions' section.