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      Indirect Comparisons: A Review of Reporting and Methodological Quality

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      PLoS ONE
      Public Library of Science

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          Abstract

          Background

          The indirect comparison of two interventions can be valuable in many situations. However, the quality of an indirect comparison will depend on several factors including the chosen methodology and validity of underlying assumptions. Published indirect comparisons are increasingly more common in the medical literature, but as yet, there are no published recommendations of how they should be reported. Our aim is to systematically review the quality of published indirect comparisons to add to existing empirical data suggesting that improvements can be made when reporting and applying indirect comparisons.

          Methodology/Findings

          Reviews applying statistical methods to indirectly compare the clinical effectiveness of two interventions using randomised controlled trials were eligible. We searched (1966–2008) Database of Abstracts and Reviews of Effects, The Cochrane library, and Medline. Full review publications were assessed for eligibility. Specific criteria to assess quality were developed and applied. Forty-three reviews were included. Adequate methodology was used to calculate the indirect comparison in 41 reviews. Nineteen reviews assessed the similarity assumption using sensitivity analysis, subgroup analysis, or meta-regression. Eleven reviews compared trial-level characteristics. Twenty-four reviews assessed statistical homogeneity. Twelve reviews investigated causes of heterogeneity. Seventeen reviews included direct and indirect evidence for the same comparison; six reviews assessed consistency. One review combined both evidence types. Twenty-five reviews urged caution in interpretation of results, and 24 reviews indicated when results were from indirect evidence by stating this term with the result.

          Conclusions

          This review shows that the underlying assumptions are not routinely explored or reported when undertaking indirect comparisons. We recommend, therefore, that the quality of indirect comparisons should be improved, in particular, by assessing assumptions and reporting the assessment methods applied. We propose that the quality criteria applied in this article may provide a basis to help review authors carry out indirect comparisons and to aid appropriate interpretation.

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          Most cited references44

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          The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials.

          When little or no data directly comparing two treatments are available, investigators often rely on indirect comparisons from studies testing the treatments against a control or placebo. One approach to indirect comparison is to pool findings from the active treatment arms of the original controlled trials. This approach offers no advantage over a comparison of observational study data and is prone to bias. We present an alternative model that evaluates the differences between treatment and placebo in two sets of clinical trials, and preserves the randomization of the originally assigned patient groups. We apply the method to data on sulphamethoxazole-trimethoprim or dapsone/pyrimethamine as prophylaxis against Pneumocystis carinii in HIV infected patients. The indirect comparison showed substantial increased benefit from the former (odds ratio 0.37, 95% CI 0.21 to 0.65), while direct comparisons from randomized trials suggests a much smaller difference (risk ratio 0.64, 95% CI 0.45 to 0.90; p-value for difference of effect = 0.11). Direct comparisons of treatments should be sought. When direct comparisons are unavailable, indirect comparison meta-analysis should evaluate the magnitude of treatment effects across studies, recognizing the limited strength of inference.
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            Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses.

            To determine the validity of adjusted indirect comparisons by using data from published meta-analyses of randomised trials. Direct comparison of different interventions in randomised trials and adjusted indirect comparison in which two interventions were compared through their relative effect versus a common comparator. The discrepancy between the direct and adjusted indirect comparison was measured by the difference between the two estimates. Database of abstracts of reviews of effectiveness (1994-8), the Cochrane database of systematic reviews, Medline, and references of retrieved articles. 44 published meta-analyses (from 28 systematic reviews) provided sufficient data. In most cases, results of adjusted indirect comparisons were not significantly different from those of direct comparisons. A significant discrepancy (P<0.05) was observed in three of the 44 comparisons between the direct and the adjusted indirect estimates. There was a moderate agreement between the statistical conclusions from the direct and adjusted indirect comparisons (kappa 0.51). The direction of discrepancy between the two estimates was inconsistent. Adjusted indirect comparisons usually but not always agree with the results of head to head randomised trials. When there is no or insufficient direct evidence from randomised trials, the adjusted indirect comparison may provide useful or supplementary information on the relative efficacy of competing interventions. The validity of the adjusted indirect comparisons depends on the internal validity and similarity of the included trials.
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              Multidisciplinary strategies for the management of heart failure patients at high risk for admission: a systematic review of randomized trials.

              The aim of this study was to determine whether multidisciplinary strategies improve outcomes for heart failure (HF) patients. Because the prognosis of HF remains poor despite pharmacotherapy, there is increasing interest in alternative models of care delivery for these patients. Randomized trials of multidisciplinary management programs in HF were identified by searching electronic databases and bibliographies and via contact with experts. Twenty-nine trials (5,039 patients) were identified but were not pooled, because of considerable heterogeneity. A priori, we divided the interventions into homogeneous groups that were suitable for pooling. Strategies that incorporated follow-up by a specialized multidisciplinary team (either in a clinic or a non-clinic setting) reduced mortality (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.59 to 0.96), HF hospitalizations (RR 0.74, 95% CI 0.63 to 0.87), and all-cause hospitalizations (RR 0.81, 95% CI 0.71 to 0.92). Programs that focused on enhancing patient self-care activities reduced HF hospitalizations (RR 0.66, 95% CI 0.52 to 0.83) and all-cause hospitalizations (RR 0.73, 95% CI 0.57 to 0.93) but had no effect on mortality (RR 1.14, 95% CI 0.67 to 1.94). Strategies that employed telephone contact and advised patients to attend their primary care physician in the event of deterioration reduced HF hospitalizations (RR 0.75, 95% CI 0.57 to 0.99) but not mortality (RR 0.91, 95% CI 0.67 to 1.29) or all-cause hospitalizations (RR 0.98, 95% CI 0.80 to 1.20). In 15 of 18 trials that evaluated cost, multidisciplinary strategies were cost-saving. Multidisciplinary strategies for the management of patients with HF reduce HF hospitalizations. Those programs that involve specialized follow-up by a multidisciplinary team also reduce mortality and all-cause hospitalizations.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2010
                10 November 2010
                : 5
                : 11
                : e11054
                Affiliations
                [1]Centre for Medical Statistics and Health Evaluation, University of Liverpool, Liverpool, United Kingdom
                Canadian Agency for Drugs and Technologies in Health, Canada
                Author notes

                Wrote the paper: SD CTS. Planned a search strategy, developed quality assessment criteria, and designed eligibility, data extraction, and quality assessment forms: SD. Pre-piloted the forms, searched for reviews, assessed eligibility, extracted data, and assessed the quality of indirect comparisons: SD. Summarised the data extracted and the quality assessment and prepared the first version of the review: SD. Proposed the review and provided comments on the manuscript: PW. Discussed ideas: CG. Undertook eligibility assessments, data extraction and quality assessment: CTS.

                Article
                10-PONE-RA-17720R1
                10.1371/journal.pone.0011054
                2978085
                21085712
                cd4017f8-ede9-4238-ac91-d62c1aefe605
                Donegan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 7 April 2010
                : 15 October 2010
                Page count
                Pages: 11
                Categories
                Research Article
                Mathematics/Statistics
                Evidence-Based Healthcare/Clinical Decision-Making
                Evidence-Based Healthcare/Statistical Methodologies and Health Informatics

                Uncategorized
                Uncategorized

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