Age-treatment subgroup analyses in Cochrane intervention reviews: a meta-epidemiological study.
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ABSTRACT:
SUBMITTER: Liu P
PROVIDER: S-EPMC6805640 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
Age-treatment subgroup analyses in Cochrane intervention reviews: a meta-epidemiological study.
Liu Patrick P Ioannidis John P A JPA Ross Joseph S JS Dhruva Sanket S SS Luxkaranayagam Anita T AT Vasiliou Vasilis V Wallach Joshua D JD
BMC medicine 20191021 1
<h4>Background</h4>There is growing interest in evaluating differences in healthcare interventions across routinely collected demographic characteristics. However, individual subgroup analyses in randomized controlled trials are often not prespecified, adjusted for multiple testing, or conducted using the appropriate statistical test for interaction, and therefore frequently lack credibility. Meta-analyses can be used to examine the validity of potential subgroup differences by collating evidenc ...[more]
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Project description:BACKGROUND:Information on subgroup assessments in systematic reviews (SR) of atrial fibrillation (AF) is limited. This review aims to describe subgroup analyses in AF SRs to inform the design of SRs and randomized trials as well as clinical practice. METHODS:We conducted a cross sectional meta-epidemiological study of Cochrane AF reviews by searching AF (including variants) in the title, abstract, or keyword field without date or language restrictions (Issue 9; September 2018). Two reviewers independently extracted study characteristics to summarize frequency of subgroups pre-specified and conducted and report credibility of subgroup effects claimed. RESULTS:Of 39 Cochrane reviews identified, 17 met inclusion criteria (including 168 reports of 127 randomized trials) and the majority (16; 94.1%) conducted meta-analysis of outcomes. Most (13; 76.5%) planned pre-specified subgroup analyses; 7 of which (41.2%) conducted subgroups. In these 7 reviews, 56 subgroups were planned, 17 (30.4%) conducted and 6 (10.7%) yielded subgroup effects. Variables such as co-morbid disease, stroke risk factors, prior stroke/transient ischemic attack, age, race, and sex represented 44% (24 subgroups) of all planned subgroups (8 conducted; 14.3%); however, information on covariate selection was lacking. Overall, more subgroups were planned than conducted (mean difference (95% CI) 2.3 (1.2-3.5, p?<?0.001)). Of all subgroups conducted, anticoagulant characteristics comprised a third of all subgroup effects (n?=?5, 35.7%). The credibility of subgroups identified (n?=?14) was assessed and less than half (43%) represented one of a small number of pre-specified hypothesis and rarely were effects seen within studies (7%). Of 5 reviews that reported subgroup effects, only 3 discussed subgroup effects as part of the overall conclusions; none discussed credibility of subgroup effects. CONCLUSIONS:This meta-epidemiological review of a subset of Cochrane AF reviews suggests that planning and reporting of subgroup analyses in AF reviews can be improved to better inform clinical management. Most pre-specified subgroup analyses were not performed, important variables (such as stroke, bleeding risk, and other comorbidities) were rarely examined and credibility of subgroup effects claimed was low. Future reviews should aim to identify important subgroups in their protocols and use recommended approaches to test subgroup effects in order to better support clinical decision-making.
| S-EPMC6814034 | biostudies-literature
Project description:IntroductionThe validity of systematic reviews and meta-analysis depends on methodological quality and unbiased dissemination of trials. Our objective is to evaluate the association of estimates of treatment effects with different bias-related study characteristics in meta-analyses of interventions used for treating pain in osteoarthritis (OA). From the findings, we hope to consolidate guidance on interpreting OA trials in systematic reviews based on empirical evidence from Cochrane reviews.Methods and analysisOnly systematic reviews that compare experimental interventions with sham, placebo or no intervention control will be considered eligible. Bias will be assessed with the risk of bias tool, used according to the Cochrane Collaboration's recommendations. Furthermore, center status, trial size and funding will be assessed. The primary outcome (pain) will be abstracted from the first appearing forest plot for overall pain in the Cochrane review. Treatment effect sizes will be expressed as standardised mean differences (SMDs), where the difference in mean values available from the forest plots is divided by the pooled SD. To empirically assess the risk of bias in treatment benefits, we will perform stratified analyses of the trials from the included meta-analyses and assess the interaction between trial characteristics and treatment effect. A relevant study-level covariate is defined as one that decreases the between-study variance (τ(2), estimated as Tau-squared) as a consequence of inclusion in the mixed effects statistical model.Ethics and disseminationMeta-analyses and randomised controlled trials provide the most reliable basis for treatment of patients with OA, but the actual impact of bias is unclear. This study will systematically examine the methodological quality in OA Cochrane reviews and explore the effect estimates behind possible bias. Since our study does not collect primary data, no formal ethical assessment and informed consent are required.Trial registration numberPROSPERO (CRD42013006924).
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Project description:BackgroundTreatment by covariate interactions can be explored in reviews using interaction analyses (e.g., subgroup analysis). Such analyses can provide information on how the covariate modifies the treatment effect and is an important methodological approach for personalising medicine. Guidance exists regarding how to apply such analyses but little is known about whether authors follow the guidance.MethodsUsing published recommendations, we developed criteria to assess how well interaction analyses were designed, applied, interpreted, and reported. The Cochrane Database of Systematic Reviews was searched (8th August 2013). We applied the criteria to the most recently published review, with an accessible protocol, for each Cochrane Review Group. We excluded review updates, diagnostic test accuracy reviews, withdrawn reviews, and overviews of reviews. Data were summarised regarding reviews, covariates, and analyses.ResultsEach of the 52 included reviews planned or did interaction analyses; 51 reviews (98%) planned analyses and 33 reviews (63%) applied analyses. The type of analysis planned and the type subsequently applied (e.g., sensitivity or subgroup analysis) was discrepant in 24 reviews (46%). No review reported how or why each covariate had been chosen; 22 reviews (42%) did state each covariate a priori in the protocol but no review identified each post-hoc covariate as such. Eleven reviews (21%) mentioned five covariates or less. One review reported planning to use a method to detect interactions (i.e., interaction test) for each covariate; another review reported applying the method for each covariate. Regarding interpretation, only one review reported whether an interaction was detected for each covariate and no review discussed the importance, or plausibility, of the results, or the possibility of confounding for each covariate.ConclusionsInteraction analyses in Cochrane Reviews can be substantially improved. The proposed criteria can be used to help guide the reporting and conduct of analyses.
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Project description:BackgroundMost meta-analyses include data from one or more small studies that, individually, do not have power to detect an intervention effect. The relative influence of adequately powered and underpowered studies in published meta-analyses has not previously been explored. We examine the distribution of power available in studies within meta-analyses published in Cochrane reviews, and investigate the impact of underpowered studies on meta-analysis results.Methods and findingsFor 14,886 meta-analyses of binary outcomes from 1,991 Cochrane reviews, we calculated power per study within each meta-analysis. We defined adequate power as ?50% power to detect a 30% relative risk reduction. In a subset of 1,107 meta-analyses including 5 or more studies with at least two adequately powered and at least one underpowered, results were compared with and without underpowered studies. In 10,492 (70%) of 14,886 meta-analyses, all included studies were underpowered; only 2,588 (17%) included at least two adequately powered studies. 34% of the meta-analyses themselves were adequately powered. The median of summary relative risks was 0.75 across all meta-analyses (inter-quartile range 0.55 to 0.89). In the subset examined, odds ratios in underpowered studies were 15% lower (95% CI 11% to 18%, P<0.0001) than in adequately powered studies, in meta-analyses of controlled pharmacological trials; and 12% lower (95% CI 7% to 17%, P<0.0001) in meta-analyses of controlled non-pharmacological trials. The standard error of the intervention effect increased by a median of 11% (inter-quartile range -1% to 35%) when underpowered studies were omitted; and between-study heterogeneity tended to decrease.ConclusionsWhen at least two adequately powered studies are available in meta-analyses reported by Cochrane reviews, underpowered studies often contribute little information, and could be left out if a rapid review of the evidence is required. However, underpowered studies made up the entirety of the evidence in most Cochrane reviews.
| S-EPMC3609745 | biostudies-literature
Project description:ObjectiveTo compare the methodological quality and conclusions in Cochrane reviews with those in industry supported meta-analyses and other meta-analyses of the same drugs.DesignSystematic review comparing pairs of meta-analyses that studied the same two drugs in the same disease and were published within two years of each other.Data sourcesCochrane Database of Systematic Reviews (2003, issue 1), PubMed, and Embase.Data extractionTwo observers independently extracted data and used a validated scale to judge the methodological quality of the reviews.Results175 of 1596 Cochrane reviews had a meta-analysis that compared two drugs. Twenty four meta-analyses that matched the Cochrane reviews were found: eight were industry supported, nine had undeclared support, and seven had no support or were supported by non-industry sources. On a 0-7 scale, the median quality score was 7 for Cochrane reviews and 3 for other reviews (P < 0.01). Compared with industry supported reviews and reviews with undeclared support, Cochrane reviews had more often considered the potential for bias in the review--for example, by describing the method of concealment of allocation and describing excluded patients or studies. The seven industry supported reviews that had conclusions recommended the experimental drug without reservations, compared with none of the Cochrane reviews (P = 0.02), although the estimated treatment effect was similar on average (z = 0.46, P = 0.64). Reviews with undeclared support and reviews with not for profit support or no support had conclusions that were similar in cautiousness to the Cochrane reviews.ConclusionsIndustry supported reviews of drugs should be read with caution as they were less transparent, had few reservations about methodological limitations of the included trials, and had more favourable conclusions than the corresponding Cochrane reviews.
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Project description:BACKGROUND:Multivariate meta-analysis (MVMA) jointly synthesizes effects for multiple correlated outcomes. The MVMA model is potentially more difficult and time-consuming to apply than univariate models, so if its use makes little difference to parameter estimates, it could be argued that it is redundant. METHODS:We assessed the applicability and impact of MVMA in Cochrane Pregnancy and Childbirth (CPCB) systematic reviews. We applied MVMA to CPCB reviews published between 2011 and 2013 with two or more binary outcomes with at least three studies and compared findings with results of univariate meta-analyses. Univariate random effects meta-analysis models were fitted using restricted maximum likelihood estimation (REML). RESULTS:Eighty CPCB reviews were published. MVMA could not be applied in 70 of these reviews. MVMA was not feasible in three of the remaining 10 reviews because the appropriate models failed to converge. Estimates from MVMA agreed with those of univariate analyses in most of the other seven reviews. Statistical significance changed in two reviews: In one, this was due to a very small change in P value; in the other, the MVMA result for one outcome suggested that previous univariate results may be vulnerable to small-study effects and that the certainty of clinical conclusions needs consideration. CONCLUSIONS:MVMA methods can be applied only in a minority of reviews of interventions in pregnancy and childbirth and can be difficult to apply because of missing correlations or lack of convergence. Nevertheless, clinical and/or statistical conclusions from MVMA may occasionally differ from those from univariate analyses.
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Project description:OBJECTIVE:To simulate possible changes in systematic review results if rapid review methods were used. STUDY DESIGN AND SETTING:We recalculated meta-analyses for binary primary outcomes in Cochrane systematic reviews, simulating rapid review methods. We simulated searching only PubMed, excluding older articles (5, 7, 10, 15, and 20 years before the search date), excluding smaller trials (<50, <100, and <200 participants), and using the largest trial only. We examined percentage changes in pooled odds ratios (ORs) (classed as no important change [<5%], small [<20%], moderate [<30%], or large [?30%]), statistical significance, and biases observed using rapid methods. RESULTS:Two thousand five hundred and twelve systematic reviews (16,088 studies) were included. Rapid methods resulted in the loss of all data in 3.7-44.7% of meta-analyses. Searching only PubMed had the smallest risk of changed ORs (19% [477/2,512] were small changes or greater; 10% [260/2,512] were moderate or greater). Changes in ORs varied substantially with each rapid review method; 8.4-21.3% were small, 1.9-8.8% were moderate, and 4.7-34.1% were large. Changes in statistical significance occurred in 6.5-38.6% of meta-analyses. Changes from significant to nonsignificant were most common (2.1-13.7% meta-analyses). We found no evidence of bias with any rapid review method. CONCLUSION:Searching PubMed only might be considered where a ?10% risk of the primary outcome OR changing by >20% could be tolerated. This could be the case in scoping reviews, resource limitation, or where syntheses are needed urgently. Other situations, such as clinical guidelines and regulatory decisions, favor more comprehensive systematic review methods.
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