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A comparison of the statistical performance of different meta-analysis models for the synthesis of subgroup effects from randomized clinical trials.

ABSTRACT: BACKGROUND:When investigating subgroup effects in meta-analysis, it is unclear whether accounting in meta-regression for between-trial variation in treatment effects, but not between-trial variation in treatment interaction effects when such effects are present, leads to biased estimates, coverage problems, or wrong standard errors, and whether the use of aggregate data (AD) or individual-patient-data (IPD) influences this assessment. METHODS:Seven different models were compared in a simulation study. Models differed regarding the use of AD or IPD, whether they accounted for between-trial variation in interaction effects, and whether they minimized the risk of ecological fallacy. RESULTS:Models that used IPD and that allowed for between-trial variation of the interaction effect had less bias, better coverage, and more accurate standard errors than models that used AD or ignored this variation. The main factor influencing the performance of models was whether they used IPD or AD. The model that used AD had a considerably worse performance than all models that used IPD, especially when a low number of trials was included in the analysis. CONCLUSIONS:The results indicate that IPD models that allow for the between-trial variation in interaction effects should be given preference whenever investigating subgroup effects within a meta-analysis.

SUBMITTER: da Costa BR

PROVIDER: S-EPMC6815379 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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A comparison of the statistical performance of different meta-analysis models for the synthesis of subgroup effects from randomized clinical trials.

da Costa Bruno R BR Sutton Alex J AJ

BMC medical research methodology 20191026 1

<h4>Background</h4>When investigating subgroup effects in meta-analysis, it is unclear whether accounting in meta-regression for between-trial variation in treatment effects, but not between-trial variation in treatment interaction effects when such effects are present, leads to biased estimates, coverage problems, or wrong standard errors, and whether the use of aggregate data (AD) or individual-patient-data (IPD) influences this assessment.<h4>Methods</h4>Seven different models were compared i ...[more]

PMID: 31655550

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Project description:ImportanceMany published randomized clinical trials (RCTs) make claims for subgroup differences.ObjectiveTo evaluate how often subgroup claims reported in the abstracts of RCTs are actually supported by statistical evidence (P < .05 from an interaction test) and corroborated by subsequent RCTs and meta-analyses.Data sourcesThis meta-epidemiological survey examines data sets of trials with at least 1 subgroup claim, including Subgroup Analysis of Trials Is Rarely Easy (SATIRE) articles and Discontinuation of Randomized Trials (DISCO) articles. We used Scopus (updated July 2016) to search for English-language articles citing each of the eligible index articles with at least 1 subgroup finding in the abstract.Study selectionArticles with a subgroup claim in the abstract with or without evidence of statistical heterogeneity (P < .05 from an interaction test) in the text and articles attempting to corroborate the subgroup findings.Data extraction and synthesisStudy characteristics of trials with at least 1 subgroup claim in the abstract were recorded. Two reviewers extracted the data necessary to calculate subgroup-level effect sizes, standard errors, and the P values for interaction. For individual RCTs and meta-analyses that attempted to corroborate the subgroup findings from the index articles, trial characteristics were extracted. Cochran Q test was used to reevaluate heterogeneity with the data from all available trials.Main outcomes and measuresThe number of subgroup claims in the abstracts of RCTs, the number of subgroup claims in the abstracts of RCTs with statistical support (subgroup findings), and the number of subgroup findings corroborated by subsequent RCTs and meta-analyses.ResultsSixty-four eligible RCTs made a total of 117 subgroup claims in their abstracts. Of these 117 claims, only 46 (39.3%) in 33 articles had evidence of statistically significant heterogeneity from a test for interaction. In addition, out of these 46 subgroup findings, only 16 (34.8%) ensured balance between randomization groups within the subgroups (eg, through stratified randomization), 13 (28.3%) entailed a prespecified subgroup analysis, and 1 (2.2%) was adjusted for multiple testing. Only 5 (10.9%) of the 46 subgroup findings had at least 1 subsequent pure corroboration attempt by a meta-analysis or an RCT. In all 5 cases, the corroboration attempts found no evidence of a statistically significant subgroup effect. In addition, all effect sizes from meta-analyses were attenuated toward the null.Conclusions and relevanceA minority of subgroup claims made in the abstracts of RCTs are supported by their own data (ie, a significant interaction effect). For those that have statistical support (P < .05 from an interaction test), most fail to meet other best practices for subgroup tests, including prespecification, stratified randomization, and adjustment for multiple testing. Attempts to corroborate statistically significant subgroup differences are rare; when done, the initially observed subgroup differences are not reproduced.

Project description:Objective To evaluate the frequency, validity, and relevance of statistically significant (P<0.05) sex-treatment interactions in randomized controlled trials in Cochrane meta-analyses.Design Meta-epidemiological study.Data sources Cochrane Database of Systematic Reviews (CDSR) and PubMed.Eligibility criteria for study selection Reviews published in the CDSR with sex-treatment subgroup analyses in the forest plots, using data from randomized controlled trials.Data extraction Information on the study design and sex subgroup data were extracted from reviews and forest plots that met inclusion criteria. For each statistically significant sex-treatment interaction, the potential for biological plausibility and clinical significance was considered.Results Among the 41 reviews with relevant data, there were 109 separate treatment-outcome analyses ("topics"). Among the 109 topics, eight (7%) had a statistically significant sex-treatment interaction. The 109 topics included 311 randomized controlled trials (162 with both sexes, 46 with males only, 103 with females only). Of the 162 individual randomized controlled trials that included both sexes, 15 (9%) had a statistically significant sex-treatment interaction. Of four topics where the first published randomized controlled trial had a statistically significant sex-treatment interaction, no meta-analyses that included other randomized controlled trials retained the statistical significance and no meta-analyses showed statistical significance when data from the first published randomized controlled trial were excluded. Of the eight statistically significant sex-treatment interactions from the overall analyses, only three were discussed by the CDSR reviewers for a potential impact on different clinical management for males compared with females. None of these topics had a sex-treatment interaction that influenced treatment recommendations in recent guidelines. UpToDate, an online physician-authored clinical decision support resource, suggested differential management of men and women for one of these sex-treatment interactions.Conclusion Statistically significant sex-treatment interactions are only slightly more frequent than what would be expected by chance and there is little evidence of subsequent corroboration or clinical relevance of sex-treatment interactions.

Project description:BackgroundRadiation dermatitis (RD) is a prevalent and difficult-to-manage consequence of radiation therapy (RT). A variety of interventions have been proven effective in preventing and treating RD. However, the optimal approach remains unclear. This network meta-analysis (NMA) conducted a comparison and ranking of the effectiveness and patient-reported outcomes (PROs) of the interventions currently utilized in RD.MethodsPubMed, Web of Science, Embase, and Cochrane Library were searched to identify pertinent randomized controlled trials (RCTs) focused on the prevention and treatment of RD. The primary outcome measures included the incidence of grade≥2 RD (i.e., percentage of moist desquamation) and RD score. The secondary outcome measures encompassed patients' subjective assessment scores of pains, itching and burning sensations.ResultsOur meta-analysis encompassed 42 studies and 4884 participants. Regarding the primary outcomes, photobiomodulation treatment (PBMT) ranked first in surface under curve cumulative ranking area (SUCRA:0.92) for reducing the incidence of grade≥2 RD. It demonstrated a significant difference when compared to Trolamine (OR 0.18,95%CrI 0.09-0.33) and Xonrid® (OR 0.28,95%CrI 0.12-0.66). Mepitelfilm (SUCRA: 0.98) achieved the highest rank in reducing the RD score, demonstrating superiority over StrataXRT® (MD -0.89, 95% CrI -1.49, -0.29). Henna (SUCRA: 0.89) demonstrated the highest effectiveness in providing pain relief, with a significant difference compared to Hydrofilm (MD -0.44, 95% CrI -0.84, -0.04) and Mepitelfilm (MD -0.55, 95% CrI -0.91, -0.19). Hydrofilm (SUCRA: 0.84) exhibited the fewest itching sensations, demonstrating superiority over Mepitelfilm (MD -0.50, 95% CrI -0.84, -0.17). No statistically significant difference was observed among various interventions in the assessment of burning sensations.ConclusionPBMT and Mepitelfilm demonstrated better efficacy in reducing the incidence of grade≥2 RD and RD score, respectively. In terms of PROs, Henna and Hydrofilm had fewer complaints in pain and itching sensations, respectively. However, studies with larger sample size on different interventions are warranted in the future.Trial registrationPROSPERO registration number CRD42023428598.

Project description:ObjectiveTotal knee replacement (TKA) is an effective way to treat teratogenic and disabling knee diseases such as advanced osteoarthritis. Tourniquets are often used in TKA to reduce bleeding and to get a better visualization of the surgical field, while it is related to safety concerns. We did this network meta-analysis to comprehensively compare the efficacy and safety of various tourniquet application strategies.MethodPubMed, Embase, Cochrane Library, CNKI, and WanFang Database were systematically searched from January 1990 to May 2020. A network meta-analysis with a frequentist framework was done to assess the relative efficacy and safety by comparing seven clinical important endpoints.Results38 eligible studies that assessed 3007 participants who underwent TKA were included in this network meta-analysis. Tourniquet inflation before osteotomy then deflation after wound closure effectively reduce perioperative bleeding (WMD compared with control group -234.66, 95% CI [-409.19 to -60.13]), while shortening the operation time (WMD -8.98, 95%CI [-14.07 to -3.88]) and reducing postoperative complications, including DVT (OR -0.58, 95%CI [-1.19 to 0.03]) and minor wound complications (OR -1.38, 95%CI [-3.00 to 0.25]). No difference was found in the late postoperative knee pain and function outcomes.ConclusionsUsing tourniquets during the entire operation can effectively reduce blood loss, but it also can cause many safety problems, including DVTs, wound oozing, delayed healing, and serious wound complications. Tourniquet inflation before osteotomy then deflation after wound closure effectively can reduce perioperative bleeding while shortening the operation time and reducing postoperative complications, so it could be the ideal tourniquet application strategy in TKA.Key messagesThis is the first study that comprehensively compared different tourniquet application strategies to evaluate their impact on postoperative recovery following TKA, and five clinically important endpoints were assessed in this study: perioperative blood loss, operation time, postoperative pain and function, and complications.We conclude that tourniquet inflation before osteotomy then deflation after wound closure could be the ideal tourniquet application strategy in TKA.

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A comparison of the statistical performance of different meta-analysis models for the synthesis of subgroup effects from randomized clinical trials.

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A comparison of the statistical performance of different meta-analysis models for the synthesis of subgroup effects from randomized clinical trials.

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