Criteria for considering studies for this review
Types of studies
Any randomised controlled or prospective controlled trials. If no randomised controlled trials are found, prospective controlled studies will be examined.
Types of participants
Participants with cancer-related pain, aged 18 years and above.
Types of interventions
Any corticosteroid used to treat cancer-related pain.
All routes of drug administration will be considered.
Types of outcome measures
Patient-reported pain intensity and pain relief using validated scales (Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), Numerical Rating Scale (NRS)).
Search methods for identification of studies
We will not apply language, date or publication status (published in full, published as abstract, unpublished) restrictions to the search.
We will search the following databases:
The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library)
MEDLINE (OVID) (1966 to present)
EMBASE (OVID) (1970 to present)
CINAHL (1982 to present)
Science Citation Index (Web of Science) (1899 to present)
Conference Proceedings Citation Index - Science (Web of Science) (1990 to present).
The search strategy for MEDLINE (OVID) can be seen in Appendix 1.
Searching other resources
We will check the bibliographic references of relevant identified studies in order to find additional trials not identified by the electronic searches. We will also search www.Clinicaltrials.gov, the metaRegister of Controlled Trials (mRCT www.controlled-trials.com/mrct/), and the WHO International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/) for ongoing trials. We will contact authors of the included studies to ask if they know of any other relevant studies. We will contact investigators/researchers, pharmaceutical companies, and international funding agencies interested in this field to identify any further studies. We will search the Internet using the Google scholar search engine (www.googlescholar.com) with selected terms from the above strategy, for any further unpublished or grey literature.
Data collection and analysis
Selection of studies
One of the authors (KR) will run the searches and collate the search results. Two of the review authors will independently assess the titles and abstracts of all the studies identified by the search for potential inclusion. We will independently consider the full records of all potentially-relevant studies for inclusion by applying the selection criteria outlined in the ‘Criteria for considering studies for this review’ section. We will resolve potential disagreements by discussion. If we cannot reach agreement, we will seek the opinion of a third review author for a final judgment.
We plan to include a PRISMA study flow diagram in the full review (Liberati 2009) to document the screening process, as recommended in Part 2, Section 11.2.1 of the Cochrane Handbook (Higgins 2011).
Data extraction and management
Two review authors will independently extract data from the studies, using a piloted data extraction form. Data extracted will include information about the year of study, study design, number of participants treated, participant demographic details, type of cancer, drug and dosing regimen, study design (placebo or active control) and methods, study duration and follow-up, outcome measures (measurement of pain, pain scale), withdrawals and adverse events. We will resolve potential disagreements by discussion. If there are studies for which only a subgroup of the participants meet the inclusion criteria for the current review, we will only extract data on this subgroup provided randomisation will not be broken. If there are any missing data, we will attempt to contact the authors of the original studies for clarification.
Assessment of risk of bias in included studies
Two of the authors will independently assess the risk of bias of each of the included studies by using the ’Risk of bias’ assessment method outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). For each study we will assess the risk of bias for the following domains:
Selection bias (random sequence generation, allocation concealment)
Performance bias (blinding of patients, blinding of treating personnel)
Detection bias (blinding of outcome assessment)
Attrition bias (incomplete outcome data)
Selective reporting (reporting bias due to selective outcome reporting)
Other sources of bias (bias due to problems not covered elsewhere).
Measures of treatment effect
For dichotomous outcomes between groups, we will estimate and compare the risk ratio (RR) using a 95% confidence interval (CI). For continuous outcomes between groups, we will measure arithmetic means and standard deviation (SD) and report the mean difference (MD) with 95% CI. When an outcome was derived with different instruments measuring the same construct, we will use standardized mean difference (SMD) with 95% CIs.
For unwanted effects, we will calculate the numbers needed to treat to harm (NNH) using dichotomous data to calculate risk ratio (RR) with 95% confidence intervals (CI). We will use the following terms to describe adverse outcomes in terms of harm or prevention of harm:
When significantly fewer adverse outcomes occur with corticosteroids than with control (placebo or active) we will use the term 'number needed to treat to prevent one event' (NNTp).
When significantly more adverse outcomes occur with corticosteroids compared with control (placebo or active) we will use the term 'number needed to harm or cause one event' (NNH).
Unit of analysis issues
We will only include studies in which randomisation is by the individual patient; this may include cross-over or n = 1 studies.
Dealing with missing data
In cases where data are missing, we will contact the authors to request the missing data. Intention-to-treat (ITT) analysis will be used. If there are missing participants or information, they will be assigned to a zero improvement category where possible. The method of assessing data processed from withdrawals will be ascertained where possible. Where there are substantial numbers (> 10%) of participants missing from analyses, we will comment, and plan to perform sensitivity analyses.
Assessment of heterogeneity
There may be an effect of differences between patients, environment (inpatient vs. outpatient) and outcome measures. We will assess heterogeneity by using the I2 statistic. We will consider I2 values above 50% to represent substantial heterogeneity in line with Higgins 2011 and we will assess potential sources of heterogeneity through subgroup analyses.
Assessment of reporting biases
We will interpret the results of tests in the light of visual inspection of the funnel plot. If there is evidence of small study effects, we will consider publication bias as only one of a number of possible explanations (Higgins 2011).
We will enter the data extracted from the included studies into Review Manager (RevMan 2012) which will be used for data synthesis. Where appropriate, we will pool data for each dichotomous outcome and calculate risk ratios with 95% confidence intervals (CI) using the fixed-effect model, together with numbers needed to treat to benefit (NNTs) with 95% CIs and, for adverse events, numbers needed to treat to harm (NNHs) with 95% CIs .
Subgroup analysis and investigation of heterogeneity
Different aspects of the trials are likely to contribute heterogeneity to the proposed main analyses. If there are sufficient data, we will therefore perform subgroup analyses based on: type of corticosteroid, doses, route of administration, types of cancer, type of pain (nociceptive, neuropathic, cancer-related, treatment-related), and length of the trials.
If sufficient data are available, we will examine the robustness of the meta-analyses by conducting sensitivity analyses using different components of the 'Risk of bias' assessment, particularly those relating to whether allocation concealment and patient/assessor blinding were adequate. We will conduct further sensitivity analyses to examine the impact of missing data on the results if a large proportion of the studies are at an ’unknown’ or ’high risk’ of attrition bias, and finally, sensitivity analyses will examine whether publication status and trial size influence the results.
Summary of findings table
A Summary of findings table will be included as outlined in Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) (including a grade of the quality of evidence).