Appendix 1. Methods to be used in subsequent updates of this review
Data extraction and management
We will design a form onto which data can be extracted. For eligible studies, review authors will extract data using the agreed upon form. We will resolve discrepancies through discussion; if required, we will consult a review arbiter. We will enter data into Review Manager software (RevMan 2011) and will check them for accuracy.
When information regarding any of the above is unclear, we will attempt to contact authors of the original reports to obtain further details.
Assessment of risk of bias in included studies
Review authors will independently assess risk of bias for each study, using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will resolve disagreements by discussion or with involvement of a review arbiter. We will assess the following criteria.
We will describe for each included study the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups. We will assess the risk of bias methods as:
low risk (any truly random process, e.g. random number table; computer random number generator);
high risk (any non-random process, e.g. odd or even date of birth; hospital or clinic record number); or
We will describe in sufficient detail for each included study the method used to conceal the allocation sequence and will determine whether intervention allocation could have been foreseen in advance of, or during, recruitment, or changed after assignment. We will assess the risk of bias methods as:
We will describe for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We will judge studies to be at low risk of bias if they were blinded, or if we judge that lack of blinding could not have affected the results. We will assess blinding separately for different outcomes or classes of outcomes. We will assess the risk of bias methods as:
adequate, inadequate or unclear for participants;
adequate, inadequate or unclear for personnel; or
adequate, inadequate or unclear for outcome assessors.
We will describe for each included study, and for each outcome or class of outcomes, the completeness of data, including attrition and exclusions from the analysis. We will state whether attrition and exclusions were reported, the numbers included in the analysis at each stage (compared with the total number of randomly assigned participants), reasons for attrition or exclusion when reported and whether missing data were balanced across groups or were related to outcomes. When sufficient information is reported, or can be supplied by the trial authors, we will re-include missing data in the analyses that we undertake. We will assess the risk of bias methods as:
We will describe for each included study how we investigated the possibility of selective outcome reporting bias and what we found. We will assess the risk of bias methods as:
low risk (when it is clear that all of the study’s prespecified outcomes and all expected outcomes of interest to the review have been reported);
high risk (when not all of the study’s prespecified outcomes have been reported; one or more reported primary outcomes were not prespecified; outcomes of interest were reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported); or
We will describe for each included study any important concerns we have about other possible sources of bias (e.g. early termination of trial due to data-dependent process, extreme baseline imbalance). We will assess whether each study was free of other problems that could put it at risk of bias. We will assess other sources of bias as:
high risk; or
We will make explicit judgements about whether studies are at high risk of bias, according to the criteria given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). With reference to the above, we will assess the likely magnitude and direction of the bias and whether we consider it likely to impact the findings. We will explore the impact of the level of bias by undertaking sensitivity analyses (see Sensitivity analysis).