Network meta-analysis is a technique for comparing multiple treatments simultaneously in a single analysis by combining direct and indirect evidence within a network of randomized controlled trials. Network meta-analysis may assist assessing the comparative effectiveness of different treatments regularly used in clinical practice, and therefore has become attractive among clinicians. However, if proper caution is not taken in conducting and interpreting network meta-analysis, inferences might be biased. The aim of this paper is to illustrate the process of network meta-analysis with the aid of a working example on first-line medical treatment for primary open-angle glaucoma. We discuss the key assumption of network meta-analysis, as well as the unique considerations for developing appropriate research questions, conducting the literature search, abstracting data, performing qualitative and quantitative synthesis, presenting results, drawing conclusions, and reporting the findings in a network meta-analysis.

Topic Primary open angle glaucoma (POAG) is a highly prevalent condition worldwide and the most common cause of irreversible sight loss. The objective is to assess the comparative effectiveness of first line medical treatments in patients with POAG or ocular hypertension through a systematic review and network meta-analysis, and to provide relative rankings of these treatments. Clinical Relevance Treatment for POAG currently relies completely on lowering the intraocular pressure (IOP). While topical drops, lasers, and surgeries can be considered in the initial treatment of glaucoma, most patients elect to start treatment with eye drops. Methods We included randomized controlled trials that compared a single active topical medication with no treatment/placebo or another single topical medication. We searched CENTRAL, MEDLINE, EMBASE and the Food and Drug Administration's website. Two individuals independently assessed trial eligibility, abstracted data, and assessed the risk of bias. We performed Bayesian network meta-analyses. Results We included 114 randomized controlled trials with data from 20,275 participants. The overall risk of bias of the included trials is mixed. The mean reductions (95% credible intervals) in IOP in mmHg at 3 months, ordered from the most to least effective drugs were: bimatoprost 5·61 (4·94; 6·29), latanoprost 4·85 (4·24; 5·46), travoprost 4·83 (4·12; 5·54), levobunolol 4·51 (3·85; 5·24), tafluprost 4·37 (2·94; 5·83), timolol 3·7 (3·16; 4·24), brimonidine 3·59 (2·89; 4·29), carteolol 3·44 (2·42; 4·46), levobetaxolol 2·56 (1·52; 3·62), apraclonidine 2·52 (0·94; 4·11), dorzolamide 2·49 (1·85; 3·13), brinzolamide 2·42 (1·62; 3·23), betaxolol 2·24 (1·59; 2·88), and unoprostone 1·91 (1·15; 2·67). Conclusions All active first-line drugs are effective compared to placebo in reducing IOP at 3 months. Bimatoprost, latanoprost, and travoprost are among the most efficacious drugs, although the within class differences were small and may not be clinically meaningful. All factors, including adverse effects, patient preferences, and cost should be considered in selecting a drug for a given patient.

BackgroundCryptococcal meningitis is a severe fungal infection that occurs primarily in the setting of advanced immunodeficiency and remains a major cause of HIV‐related deaths worldwide. The best induction therapy to reduce mortality from HIV‐associated cryptococcal meningitis is unclear, particularly in resource‐limited settings where management of drug‐related toxicities associated with more potent antifungal drugs is a challenge.ObjectivesTo evaluate the best induction therapy to reduce mortality from HIV‐associated cryptococcal meningitis; to compare side effect profiles of different therapies.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE (PubMed), Embase (Ovid), LILACS (BIREME), African Index Medicus, and Index Medicus for the South‐East Asia Region (IMSEAR) from 1 January 1980 to 9 July 2018. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and the ISRCTN registry; and abstracts of select conferences published between 1 July 2014 and 9 July 2018.Selection criteriaWe included randomized controlled trials that compared antifungal induction therapies used for the first episode of HIV‐associated cryptococcal meningitis. Comparisons could include different individual or combination therapies, or the same antifungal therapies with differing durations of induction (less than two weeks or two or more weeks, the latter being the current standard of care). We included data regardless of age, geographical region, or drug dosage. We specified no language restriction.Data collection and analysisTwo review authors independently screened titles and abstracts identified by the search strategy. We obtained the full texts of potentially eligible studies to assess eligibility and extracted data using standardized forms. The main outcomes included mortality at 2 weeks, 10 weeks, and 6 months; mean rate of cerebrospinal fluid fungal clearance in the first two weeks of treatment; and Division of AIDS (DAIDS) grade three or four laboratory events. Using random‐effects models we determined pooled risk ratio (RR) and 95% confidence interval (CI) for dichotomous outcomes and mean differences (MD) and 95% CI for continuous outcomes. For the direct comparison of 10‐week mortality, we assessed the certainty of the evidence using the GRADE approach. We performed a network meta‐analysis using multivariate meta‐regression. We modelled treatment differences (RR and 95% CI) and determined treatment rankings for two‐week and 10‐week mortality outcomes using surface under the cumulative ranking curve (SUCRA). We assessed transitivity by comparing distribution of effect modifiers between studies, local inconsistency through a node‐splitting approach, and global inconsistency using design‐by‐treatment interaction modelling. For the network meta‐analysis, we applied a modified GRADE approach for assessing the certainty of the evidence for 10‐week mortality.Main resultsWe included 13 eligible studies that enroll...

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IMPORTANCETrustworthy clinical practice guidelines require reliable systematic reviews of the evidence to support recommendations. Since 2016, the American Academy of Ophthalmology (AAO) has partnered with Cochrane Eyes and Vision US Satellite to update their guidelines, the Preferred Practice Patterns (PPP).OBJECTIVE To describe experiences and findings related to identifying reliable systematic reviews that support topics likely to be addressed in the 2016 update of the 2011 AAO PPP guidelines on cataract in the adult eye.DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study. Systematic reviews on the management of cataract were searched for in an established database. Each relevant systematic review was mapped to 1 or more of the 24 management categories listed under the Management section of the table of contents of the 2011 AAO PPP guidelines. Data were extracted to determine the reliability of each systematic review using prespecified criteria, and the reliable systematic reviews were examined to find whether they were referenced in the 2016 AAO PPP guidelines. For comparison, we assessed whether the reliable systematic reviews published before February 2010 the last search date of the 2011 AAO PPP guidelines were referenced in the 2011 AAO PPP guidelines. Cochrane Eyes and Vision US Satellite did not provide systematic reviews to the AAO during the development of the 2011 AAO PPP guidelines.MAIN OUTCOMES AND MEASURES Systematic review reliability was defined by reporting eligibility criteria, performing a comprehensive literature search, assessing methodologic quality of included studies, using appropriate methods for meta-analysis, and basing conclusions on review findings. RESULTSFrom 99 systematic reviews on management of cataract, 46 (46%) were classified as reliable. No evidence that a comprehensive search had been conducted was the most common reason a review was classified as unreliable. All 46 reliable systematic reviews were cited in the 2016 AAO PPP guidelines, and 8 of 15 available reliable reviews (53%) were cited in the 2011 PPP guidelines. CONCLUSIONS AND RELEVANCEThe partnership between Cochrane Eyes and Vision US Satellite and the AAO provides the AAO access to an evidence base of relevant and reliable systematic reviews, thereby supporting robust and efficient clinical practice guidelines development to improve the quality of eye care.