Our search will be refined for individual databases by a highly e

Our search will be refined for individual databases by a highly experienced medical librarian (RC; see online supplementary appendix 1, which is a proposed search strategy for MEDLINE). Reviewers will scan the bibliographies of all retrieved trials and other relevant publications, including reviews Lapatinib clinical and meta-analyses, for additional relevant articles. Eligibility criteria and their application to potentially eligible articles Using standardised

forms, reviewers trained in health research methodology will work in pairs to screen, independently and in duplicate, titles and abstracts of identified citations, and acquire the full-text publication of articles that both reviewers judge as potentially eligible. Using a standardised form, the same reviewer teams will independently apply eligibility criteria to the full text of potentially eligible trials. We will measure agreement between reviewers to assess the reliability of full-text review using the guidelines proposed by Landis and Koch.61 Specifically, we will calculate Îș values, and interpret them using the following thresholds: <0.20 as slight agreement, 0.21–0.40 as fair agreement, 0.41–0.60 as moderate agreement, 0.61–0.80 as substantial agreement and >0.80 as almost perfect agreement. Eligible trials will be: (1) enrol patients presenting

with chronic neuropathic pain (see online supplementary appendix 2 for lists of all syndromes we are studying) and (2) randomise patients to alternative interventions (pharmacological or non-pharmacological)

or to an intervention and control arm. Data abstraction and analysis Before starting data abstraction, we will conduct calibration exercises to ensure consistency between reviewers. Teams of reviewers will extract data independently and in duplicate from each eligible study using standardised forms and a detailed instruction manual to inform tailoring of an online data abstraction programme, DistillerSR (http://systematic-review.net/). We will extract data regarding patient demographics, trial methodology, intervention details and outcome data guided by the Initiative on Methods, Measurement and Pain Assessment in Clinical Trials (IMMPACT).62 63 Specifically, we will collect outcome data across AV-951 the following nine IMMPACT-recommended core outcome domains: (1) pain; (2) physical functioning; (3) emotional functioning; (4) participant ratings of improvement and satisfaction with treatment; (5) symptoms and adverse events; (6) participation disposition; (7) role functioning; (8) interpersonal functioning; and (9) sleep and fatigue. We will collect data for all adverse outcomes as guided by Ioannidis and Lau.64 We will resolve disagreements by discussion to achieve consensus.

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