Types of studies

We will include randomized and quasi‐randomized trials (RCTs and q‐RCTs) that compare routine emergency medical services (EMS) care with EMS care plus the mobilization of community first responders in instances of OHCA.Trials with randomization by cluster will be eligible for inclusion, including cluster‐design studies with intervention cross‐over.

A trial will be eligible if, on the basis of the best available information, we judge that participants followed in the trial were assigned prospectively to either routine EMS care or routine EMS care with the addition of CFR mobilization, using a random or quasi‐random method of allocation (Higgins 2011).

The mobilization of community first responders to OHCA represents a complex community intervention that may rely on organizational structures outside the control of the healthcare system. It is likely that in some instances it would not be feasible for trial designs to use random allocation with individual participants representing the unit of allocation. For this reason randomized and quasi‐randomized trials including cluster methodologies are eligible for inclusion in this review.

We will exclude studies that primarily consider OHCA due to traumatic causes, as the core interventions provided by CFRs, namely CPR and early defibrillation, are unlikely to be of significant benefit in such circumstances.

Types of participants

We will include adults and children aged more than four weeks suffering from OHCA.

We will exclude studies primarily considering OHCA in infants at birth.

Types of interventions

We will include studies that compare routine EMS care with EMS care plus the mobilization of community first responders (as already defined) in instances of OHCA.

In some communities the statutory ambulance service is routinely provided by the local fire service. For the purposes of this review, this group represents the statutory ambulance service, as distinct from CFRs, and we will not include it as an eligible intervention in this review.

We will not include studies primarily focused on opportunistic bystanders. Individuals who are present at the scene of an OHCA event and perform CPR as a result of telephone instruction by EMS call takers are not covered by the term CFR.

We will exclude studies primarily assessing the impact of specific additional interventions such as administration of naloxone in narcotic overdose or adrenaline in anaphylaxis.

Types of outcome measures

Electronic searches

We will identify RCTs through literature searching designed to identify relevant trials as outlined in Chapter 6.4 of the Cochrane Handbook for Systematic reviews of Interventions (Higgins 2011). We will not apply restrictions by language or publication status.

We will search the following databases for relevant trials:

• Cochrane Central Register of Controlled Trials (CENTRAL) (latest Issue)

• MEDLINE (Ovid SP, 1946 onwards)

• Embase (Ovid SP, 1974 onwards)

• Web of Science (1960 to present)

We developed a draft search strategy for MEDLINE, which can be found in Appendix 1 and will be used as the basis for the search strategies in the other databases listed.

We will scan the following trials registries for ongoing and unpublished trials:

The World Health Organization International Clinical Trials Registry Platform (WHO ICTRP);
ClinicalTrials.gov

Searching other resources

We will scan the reference lists and citations of included trials and any relevant systematic reviews identified for further references to additional trials. We will scan the abstracts of conference proceedings of the American Heart Association and the European Resuscitation Council. When necessary, we will contact trial authors for additional information.

Selection of studies

Two review authors (TB and NC) will independently review all titles and abstracts received to assess potential eligibility, using the inclusion criteria outlined above. We will obtain and examine in detail full‐text copies of all papers considered potentially eligible, and will approach authors of trials for additional information where necessary. We will resolve disagreements by discussion and where we cannot reach a consensus, we will involve a third review author (GB, SM or MC).

Data extraction and management

Two review authors (TB and NC) will independently extract relevant data using our standard data extraction form (Appendix 2), which is adapted from the Cochrane Effective Practice and Organisation of Care Group (EPOC) version (EPOC 2013).

We will collect information on study design, study setting, participant characteristics, eligibility criteria, details of the intervention(s) given, the outcomes assessed, the source of study funding and any conflicts of interest. We will approach authors of included trials for additional information where necessary. We will resolve any disagreement by discussion with a third review author (GB, SM or MC). .

Assessment of risk of bias in included studies

Two review authors (TB and NC) will independently assess the validity of each included trial using the Cochrane 'Risk of bias' tool (Higgins 2011), and also provide a summary assessment of risks of bias across studies.

We will assess each included trial according to the following domains: sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting and other potential sources of bias. Where relevant, the latter will include those related to a cluster‐randomized design such as (i) recruitment bias; (ii) baseline imbalance; (iii) loss of clusters; (iv) incorrect analysis; and (v) comparability with individually randomized trials, as outlined in section 16.3.2 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

We will consider low risk of bias to represent studies with plausible bias unlikely to seriously alter the results; unclear risk of bias to represent studies with plausible bias which raises doubts about the results; and high risk of bias to represent studies with plausible bias that seriously weakens confidence in the results (Higgins 2011). We will resolve any disagreement by discussion or where necessary by the involvement of a third review author (GB, SM or MC).

We will construct a 'Risk of bias' table and generate plots of risk of bias assessments using Review Manager 5 (RevMan 2014).

Measures of treatment effect

We will use risk ratios (RRs) with 95% confidence intervals (CIs) to measure the following dichotomous outcomes:

• Survival at hospital discharge

• Survival at 30 days

• Survival to hospital admission

• Cardiopulmonary resuscitation performed prior to ambulance service arrival

• Defibrillation performed prior to ambulance service arrival

We will group neurological outcomes into categories of favourable (CPC score 1 or 2) or unfavourable (CPC score of 3, 4, or 5), as suggested in a previous systematic review concerning out‐of‐hospital cardiac arrest (Huang 2014). We will then use an RR with a 95% CI to present this outcome.

Health‐related quality of life can be measured by many different tools, including the Quality of Life Scale, the Personal Wellbeing Index, Short Form 36 and the Satisfaction with Life Survey (Dronavalli 2015), with potentially varying validity for this target population. We anticipate substantial heterogeneity in the measurement of this outcome, and for this reason we will assess treatment effects of health‐related quality of life by narrative description and tabulation in this review.

Unit of analysis issues

If we include studies with multiple treatment groups, we will adopt the recommendations of Higgins 2011, and will either combine the groups to create a single pair‐wise comparison or select one pair of groups and exclude the other groups.

Where we include cluster‐randomized trials, we will evaluate whether the clustering was accounted for in the determination of required sample size, whether assessment for design effect was carried out and whether the methods used in analysis are appropriate to the cluster design. If a study has been inappropriately analysed, as though the randomization was performed by individual rather than by cluster, we will adopt the advice of the Cochrane Handbook for Systematic Reviews of Interventions section 16.3.4 (Higgins 2011), and adjust for design effect where possible. This may necessitate a request to the investigators for additional individual‐level data in order to assess the intraclass correlation coefficient (ICC) in clusters.

Dealing with missing data

Where summary statistics are missing, we will contact the first author of the trial to try and retrieve relevant data in the first instance.

Where individual studies do not account appropriately for missing data or do not report how these were handled, we will consider whether it was likely to be missing at random or otherwise, and the resulting risk of bias.

Where outcome data are missing and cannot be recovered, we plan to adopt the approach suggested in the Cochrane Handbook for Systematic Reviews of Interventions Section 16.2.1 (Higgins 2011), and use available‐case analysis. We will include data only for those participants whose results are known and address the potential impact of the missing data by using the 'Risk of bias' tool. Ultimately we will consider the potential impact of including such studies in the overall assessment of intervention effect.

Assessment of heterogeneity

We will consider clinical heterogeneity, methodological heterogeneity and statistical heterogeneity as outlined by Higgins 2011.

We will address clinical heterogeneity through detailed reporting of the diagnostic and clinical definitions and characteristics of the included studies. We will conduct meta‐analysis if we consider the included studies to be sufficiently homogeneous for participants, interventions and outcomes.

We will assess methodological heterogeneity using the Cochrane 'Risk of bias' tool, already described.

We will assess statistical heterogeneity by considering the consistency of study results, and how this impacts on the meta‐analysis. Formally, we will use the Chi² test and consider a P value of less than 0.10 to represent significant heterogeneity. We will also use the I² statistic to describe the percentage of the variability in effect estimates that is due to heterogeneity rather than to sampling error (chance), and assess its potential impact on the meta‐analysis. We will interpret the I² result using the guidance provided in section 9.5.2 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Assessment of reporting biases

If at least 10 studies are included in the meta‐analysis, we will create a funnel plot to explore publication bias.

Data synthesis

If we consider it appropriate after assessment of heterogeneity, we will perform a meta‐analysis using outcomes expressed as RRs and 95% CIs.

We will use a random‐effects meta‐analysis to provide some robustness against the presence of heterogeneity, with inverse variance weighting using the DerSimonian‐Laird estimate of the between‐study variance (tau‐squared) (DerSimonian 1986).

We will perform all analysis using Review Manager 5.3 software.

If we deem individual study designs to be too diverse and that statistical combination is inappropriate, we will present the findings in a narrative fashion.

Subgroup analysis and investigation of heterogeneity

We will consider subgroup analysis for our primary outcomes, based on the following characteristics and rationale:

• Geographical setting (primarily urban or non‐urban). Urban CFR mobilization may allow shorter response time.

• Cadre of CFRs (trained laypersons, police service, fire service and off‐duty paramedics), as this may influence CFR training, the scope of intervention and the response time.

• CFRs routinely equipped with defibrillator, as defibrillation is a key time‐critical intervention following OHCA.

• Witnessed OHCA. Witnessed OHCAs are likely to have shorter intervals to the initiation of CPR and defibrillation from time of OHCA.

• Age group (children defined as individuals up to 15 years old versus adults), as the common causes of OHCA are different in children (Meyer 2012) and this may affect the efficacy of interventions.

Sensitivity analysis

We will perform sensitivity analysis by excluding trials as follows:

• Studies considered to have a high risk of bias