Types of studies

We will include all published and unpublished randomised controlled trials (RCTs), including cluster‐randomised trials. We will exclude cross‐over studies. There will be no time or language limitations on included studies.

Types of participants

Participants will include susceptible adults and children (the age limit to define children will be 18 years and under), of any gender and ethnicity, who have no vestibular, visual or neurological co‐morbidities.

We will include:

• susceptible participants in whom motion sickness is induced under natural conditions such as air, sea and land transportation.

Susceptibility will be defined as:

• previous experience of motion sickness; and/or

• motion sickness susceptibility based on the result of any validated scale.

We will include studies in which motion sickness is induced under experimental conditions but we will analyse data from these studies separately.

Types of interventions

The main intervention will be all antihistamines regardless of:

• class (first or second‐generation);

• route of administration; or

• dosage.

Comparison interventions will include:

• no treatment;

• placebo;

• any other pharmacological interventions (for example: scopolamine, phenytoin, ondansetron, metoclopramide); and

• any non‐pharmacological interventions (for example: acupuncture, transcutaneous electrical nerve stimulation, habituation techniques).

The main comparison will be:

• antihistamine versus no treatment or placebo.

Other possible comparison pairs include:

• antihistamine versus scopolamine;

• antihistamine versus antiemetics;

• antihistamine versus neuroleptics;

• antihistamine versus µ‐opiate receptor agonists;

• antihistamine versus sympathomimetics;

• antihistamine versus acupuncture;

• antihistamine versus acupressure;

• antihistamine versus autogenic feedback training exercises;

• antihistamine versus transcutaneous electrical nerve stimulation.

Concurrent use of other medication will be acceptable if used equally in each group.

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Published, unpublished and ongoing studies will be identified by searching the following databases from their inception: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

• EBSCO CINAHL (1982 to date);

• Ovid CAB abstracts (1910 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 theCochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, Box 6.4.b. (Higgins 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

Two review authors (NK and YS) will independently sift through the initial search results and identify studies that appear to meet our inclusion criteria. We will then obtain full‐text articles for the studies on this preliminary list. We will independently examine these studies and select those that meet our inclusion criteria. If there are any discrepancies, we will resolve this by reviewing the original study. We will consult the third review author (NM) where necessary.

Data extraction and management

Two review authors (NK and YS) will independently extract data using standardised forms. If there are any missing or incomplete data, we will contact the study author. If there are any discrepancies, we will consult the third review author (NM).

We will extract the following:

• Study design features (double‐/single‐/non‐blinded; cluster/parallel‐group)

• Setting

• Sample size

• Participant (baseline) characteristics (age, gender, susceptibility to motion sickness and how this was assessed, co‐morbidities)

• Inclusion criteria

• Exclusion criteria

• Method of induction of motion sickness

• Duration of motion

• Type of antihistamine used (name, class, route, dosage)

• Comparison intervention

• Outcomes

• Funding sources

• Study author declarations of interest

See Appendix 2.

Assessment of risk of bias in included studies

NK and YS will independently assess the risk of bias of the included studies. This will be determined using Cochrane's tool for assessing the risk of bias as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

We will consider the following domains and assign a judgement based on the following criteria:

Measures of treatment effect

For dichotomous data, we will calculate individual and pooled statistics as risk ratios (RR) with 95% confidence intervals (95% CI). We will assess continuous data (for example, heart rate) using the mean difference (MD) for outcomes measured on the same scale and/or the standardised mean difference (SMD) for outcomes measured on different scales. We will use a change from baseline for this analysis. We will complete an intention‐to‐treat analysis, assuming that the relevant data are available in the included studies.

Unit of analysis issues

For multi‐arm studies, we will establish which comparisons are relevant to this review and include data from the respective arms. We will not include cross‐over studies.

Dealing with missing data

If we identify missing data, we will attempt to contact the trial author by email. If we are unable to contact the author and/or if the author is unable to provide the relevant information, we will assume the missing data to be 'missing at random' and we will conduct the data analysis using only the available data.

Assessment of heterogeneity

We will assess clinical, methodological and statistical heterogeneity. We will measure statistical heterogeneity using the Chi² test and the I² statistic. For the latter, according to the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), a value of > 50% suggests substantial heterogeneity.

Assessment of reporting biases

We will address publication bias (between‐study reporting bias) by searching for published, unpublished and ongoing trials in the specified trial databases. We will ensure data from all the available outcomes across all papers are recorded, taking care not to duplicate results. Where potentially eligible but unpublished trials are identified, we will contact the authors to acquire the full study results and/or to find out the reasons why these results have not been published. For ongoing trials, we will include results available until the date of publication of this review. We will address language bias by including studies in any language and we will obtain an English translation where possible. We will address outcome (within‐study) reporting bias by ensuring results are presented as indicated in the protocol, which will have been published beforehand. We will assess between‐study reporting bias as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Data synthesis

If data are comparable, we will combine data to give a summary measure of effect using the methods set out in Measures of treatment effect. If data are missing, we will use the available data to perform a meta‐analysis using Review Manger 5.3 (RevMan 2014), in the absence of significant clinical or statistical heterogeneity. We will test for heterogeneity using the I² statistic and we will assume significant heterogeneity if the I² is greater than 50% (i.e. more than 50% of the variability in outcome between trials could not be explained by sampling variation) (Higgins 2011). We will use a fixed‐effect model in the absence of statistical heterogeneity and a random‐effects model if heterogeneity is present. For key outcomes presented in the 'Summary of findings' table, we will also convey the pooled results as absolute numbers (as number needed to treat).

Subgroup analysis and investigation of heterogeneity

If there are sufficient studies available we will conduct the following subgroup analyses in RevMan, using the formal test for subgroup differences (RevMan 2014):

• age (adults versus children); and

• motion sickness that has been induced under experimental conditions versus natural conditions (such as air, sea and land transportation).

Adults and children may report symptoms differently and antihistamines may have differing effects on each group (for example, children may be more susceptible to the side effects of antihistamines). The subjective experience of motion sickness symptoms may differ when motion sickness is induced under experimental conditions compared to naturally occurring conditions.

Therefore these subgroups have been selected as variability in these conditions may affect the outcome.

Sensitivity analysis

Two review authors (NK and YS) will independently conduct a sensitivity analysis by identifying studies with a high risk of bias using the Cochrane 'Risk of bias' tool and excluding these studies from the analysis.