Types of studies

Randomised controlled trials (RCTs) comparing any type of OTC cough medication with a placebo (or control group) with cough as an outcome and where cough is secondary to acute pneumonia. We excluded quasi‐randomised trials.

Types of participants

We considered studies of both children and adults with cough of less than four weeks in duration that was related to pneumonia. We specifically excluded studies of cough of more than four weeks in duration and cough related to another underlying cardio‐respiratory condition (for example, suppurative lung disease, chronic obstructive airway disease, asthma). However, we considered studies which included cough of mixed aetiologies if data were available for the subgroup of patients with pneumonia.

Types of interventions

RCT comparisons of any type of OTC cough medication as an adjunct therapy to antibiotics. We did not include trials comparing only two or more medications without a placebo comparison group. We included trials that included the use of other medications or interventions if all participants had equal access to such medications (including antibiotics) or interventions.

Types of outcome measures

We attempted to obtain data on at least one of the following outcome measures.

Electronic searches

For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 12, part of The Cochrane Library,www.thecochranelibrary.com (accessed 22 January 2014), which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1966 to January week 2, 2014), OLDMEDLINE (1950 to 1965), EMBASE (1980 to January 2014), CINAHL (2009 to January 2014), LILACS (2009 to January 2014) and Web of Science (2009 to January 2014).

We used the following search strategy to search MEDLINE and CENTRAL. We adapted the search strategy for EMBASE (see Appendix 2), CINAHL (see Appendix 3), LILACS (see Appendix 4) and Web of Science (see Appendix 5).

MEDLINE (OVID)
1 Cough/
2 cough*.tw.
3 1 or 2
4 exp Pneumonia/
5 (pneumon* or bronchopneumon*).tw.
6 4 or 5
7 3 and 6
8 exp Antitussive Agents/
9 antitussiv*.tw,nm.
10 exp Expectorants/
11 expectorant*.tw,nm.
12 exp Cholinergic Antagonists/
13 (cholinergic adj2 (blocking or antagonist*)).tw,nm.
14 (anticholinergic* or anti‐cholinergic*).tw,nm.
15 exp Histamine H1 Antagonists/
16 histamine h1 antagonist*.tw,nm.
17 (antihistamin* or anti‐histamin*).tw,nm.
18 mucolytic*.tw,nm.
19 exp Drug Combinations/
20 drug combination*.tw.
21 exp Nonprescription Drugs/
22 ((non prescribed or non‐prescribed or nonprescribed or non prescription* or non‐prescription* or nonprescription*) adj3 (drug* or medicin* or pharmaceut* or medicat*)).tw.
23 (over‐the‐counter* or over the counter or otc).tw.
24 (cough* adj3 (mixture* or suppress* or medicin* or remed* or relief* or formula* or syrup*)).tw.
25 or/8‐24
26 7 and 25

There were no language or publication restrictions.

Searching other resources

We searched the trials registries ClinicalTrials.gov and WHO ICTRP (searched 20 January 2014). We also searched lists of references in relevant publications.

Selection of studies

Two review authors (CCC, ABC) independently reviewed the literature searches to identify potentially relevant trials for full review from the title, abstract or descriptors. We conducted searches of bibliographies and texts to identify additional studies. The same two review authors independently selected trials for inclusion from the full text, using specific criteria. There was no disagreement. A third review author (ACC) was the nominated adjudicator in case of any disagreements.

Data extraction and management

We reviewed trials that satisfied the inclusion criteria and extracted the following information: study setting; year of study; source of funding; patient recruitment details (including number of eligible patients); inclusion and exclusion criteria; other symptoms; randomisation and allocation concealment method; numbers of participants randomised; blinding (masking) of participants, care providers and outcome assessors; dose and type of intervention; duration of therapy; co‐interventions; numbers of patients not followed up; reasons for withdrawals from study protocol (clinical, side effects, refusal and other); details on side effects of therapy and whether intention‐to‐treat (ITT) analyses were possible. We extracted data on the outcomes described previously. It was planned that further information would be requested from the trial authors, where required.

Assessment of risk of bias in included studies

Two review authors (CCC, ABC) independently performed a potential bias assessment on studies included in the previous review. We described seven components of potential biases under Assessment of reporting biases in our updated review

Measures of treatment effect

We undertook an initial qualitative comparison of all the individually analyzed studies to determine if pooling of results (meta‐analysis) was reasonable. This took into account differences in study populations, inclusion and exclusion criteria, interventions, outcome assessment and estimated effect size. We included the results from studies that met the inclusion criteria and reported any of the outcomes of interest in the subsequent meta‐analyses.

We calculated individual and pooled statistics for continuous outcomes measured on the same metrics as mean differences (MD) and standard mean differences, as indicated, with 95% confidence intervals (CIs). We combined data for continuous outcomes measured on different metrics, with a standardised mean difference (SMD). We calculated individual and pooled statistics as odds ratio (OR) with 95% CIs for dichotomous variables.

Unit of analysis issues

Had there been any cross‐over studies, we would have calculated mean treatment differences from raw data, extracted or imputed and entered as fixed‐effect generic inverse variance (GIV) outcomes, to provide summary weighted differences and 95% CIs. Only data from the first arm would have been included in a meta‐analysis where data were combined with parallel studies (Elbourne 2002).

Dealing with missing data

We planned to contact trial authors for missing data when the studies were less than 15 years old.

Assessment of heterogeneity

We described any heterogeneity between the study results and tested to see if it reached statistical significance using the I² statistic (Higgins 2003). Heterogeneity is considered significant when the P value of the Chi² test is < 0.10 (Higgins 2011). We would have included the 95% CI estimate using a random‐effects model had there been concerns about statistical heterogeneity.

Assessment of reporting biases

In this updated review, in line with the new Cochrane process, we assessed the risk of bias of each study including sequence generation, allocation concealment, blinding and reporting of outcome data.

While there are other possible biases (such as publication bias detected by funnel plot) as outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011), these were not included.

Data synthesis

We calculated odds ratios (ORs) using a modified ITT analysis for dichotomous outcome variables of each individual study. This analysis assumed that participants not available for outcome assessment had not improved (and probably represented a conservative estimate of effect). We calculated the summary weighted ORs and 95% CI (fixed‐effect model) using the computer program RevMan 2012. We calculated the number needed to treat to benefit (NNTB) from the pooled OR and its 95% CI, applied to a specified baseline risk using an online calculator (Cates 2003).

We assumed the cough indices to be normally distributed continuous variables so that the mean difference in outcomes could be estimated (mean difference). We would have estimated the standardised mean difference if studies had reported outcomes using different measurement scales.

Subgroup analysis and investigation of heterogeneity

We planned an a priori subgroup analysis for:

1. children (14 years and younger) versus adolescents and adults (older than 14 years);

2. hospitalised versus ambulatory settings;

3. classes of OTC cough medications:

   1. antitussives (codeine and derivatives);

   2. expectorants;

   3. mucolytics;

   4. antihistamine‐decongestant combinations;

   5. antihistamines alone;

   6. other drug combinations;

   7. males versus females in adults.

Sensitivity analysis

It was planned that sensitivity analyses be carried out to assess the impact of potentially important factors on the overall outcomes:

1. study quality;

2. study size;

3. variation in the inclusion criteria;

4. differences in the medications used in the intervention and comparison groups;

5. differences in outcome measures;

6. analysis using a random‐effects model;

7. analysis by 'treatment received';

8. analysis by 'ITT';

9. analysis by study design, parallel and cross‐over studies.