Dataset Information

Reporting and interpretation of subgroup analyses in heart failure randomized controlled trials.

ABSTRACT:

Aims

This study aimed to investigate the reporting of subgroup analyses in heart failure (HF) randomized controlled trials (RCTs) and to determine the strength and credibility of subgroup claims.

Methods and results

All primary HF RCTs published in nine high-impact journals from 1 January 2008 to 31 December 2017 were included. Multivariable regression analysis was used to identify factors that may favour the reporting of results in specific subgroups. Strength of the subgroup effect claimed was classified into (i) strong, (ii) likely, or (iii) suggestive. Credibility of subgroup claim was scored using a pre-specified 10 pointer criteria. Of the 261 HF RCTs studied, 107 (41%) reported subgroup analyses. Twenty-five (23%) RCTs claimed a subgroup effect for the primary outcome of which six (24%) made a strong claim, eight (32%) claimed a likely effect, and 11 (44%) suggested a possible subgroup effect. Seven of the 25 RCTs did not employ interaction testing for subgroup claims of the primary outcome. Three out of 10 pre-specified credibility criteria were satisfied by half of the trials. Fourteen trials justified the choice of subgroups, and 10 explicitly stated they were underpowered to detect differences within subgroups. Source of funding did not influence the frequency of reporting subgroup analyses (OR 0.53, 95% CI 0.78-3.62, P = 0.52).

Conclusions

Appropriate credibility criteria were rarely met even by HF RCTs that held strong subgroup claims. Subgroup analyses should be pre-specified, be adequately powered, present interaction terms, and be replicated in independent data before being integrated into clinical decision making.

SUBMITTER: Khan MS

PROVIDER: S-EPMC7835611 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Reporting and interpretation of subgroup analyses in heart failure randomized controlled trials.

Khan Muhammad Shahzeb MS Khan Muhammad Arbaz Arshad MAA Irfan Simra S Siddiqi Tariq Jamal TJ Greene Stephen J SJ Anker Stefan D SD Sreenivasan Jayakumar J Friede Tim T Tahhan Ayman Samman AS Vaduganathan Muthiah M Fonarow Gregg C GC Butler Javed J

ESC heart failure 20201130 1

<h4>Aims</h4>This study aimed to investigate the reporting of subgroup analyses in heart failure (HF) randomized controlled trials (RCTs) and to determine the strength and credibility of subgroup claims.<h4>Methods and results</h4>All primary HF RCTs published in nine high-impact journals from 1 January 2008 to 31 December 2017 were included. Multivariable regression analysis was used to identify factors that may favour the reporting of results in specific subgroups. Strength of the subgroup eff ...[more]

PMID: 33254286

Similar Datasets

Project description:ObjectiveTo investigate the impact of industry funding on reporting of subgroup analyses in randomised controlled trials.DesignSystematic review.Data sourcesMedline.Study selectionRandomised controlled trials published in 118 core clinical journals (defined by the National Library of Medicine) in 2007. 1140 study reports in a 1:1 ratio by high (five general medicine journals with largest number of total citations in 2007) versus lower impact journals, were randomly sampled. Two reviewers, independently and in duplicate, used standardised, piloted forms to screen study reports for eligibility and to extract data. They also used explicit criteria to determine whether a randomised controlled trial reported subgroup analyses. Logistic regression was used to examine the association of prespecified study characteristics with reporting versus not reporting of subgroup analyses.Results469 randomised controlled trials were included, of which 207 (44%) reported subgroup analyses. High impact journals (adjusted odds ratio 2.64, 95% confidence interval 1.62 to 4.33), non-surgical (versus surgical) trials (2.10, 1.26 to 3.50), and larger sample size (3.38, 1.64 to 6.99) were associated with more frequent reporting of subgroup analyses. The strength of association between trial funding and reporting of subgroups differed in trials with and without statistically significant primary outcomes (interaction P=0.02). In trials without statistically significant results for the primary outcome, industry funded trials were more likely to report subgroup analyses (2.29, 1.30 to 4.72) than non-industry funded trials. This was not true for trials with a statistically significant primary outcome (0.79, 0.46 to 1.36). Industry funded trials were associated with less frequent prespecification of subgroup hypotheses (31.3% v 38.0%, adjusted odds ratio 0.49, 0.26 to 0.94), and less use of the interaction test for analyses of subgroup effects (41.4% v 49.1%, 0.52, 0.28 to 0.97) than non-industry funded trials.ConclusionIndustry funded randomised controlled trials, in the absence of statistically significant primary outcomes, are more likely to report subgroup analyses than non-industry funded trials. Industry funded trials less frequently prespecify subgroup hypotheses and less frequently test for interaction than non-industry funded trials. Subgroup analyses from industry funded trials with negative results for the primary outcome should be viewed with caution.

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:Acute heart failure (AHF) is a major public health concern, affecting 26 million worldwide. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering drugs, comprising canagliflozin, dapagliflozin, and empagliflozin that are being explored for AHF. We aim to meta-analyze the effectiveness of SGLT2 inhibitors compared to placebo for primary outcomes including all-cause and cardiovascular mortality, heart failure events, symptomatic improvement, and readmissions. Our secondary outcome is the risk of serious adverse events. This meta-analysis has been designed in accordance with the PRISMA Statement 2020. A systematic search across PubMed, Scopus, and Cochrane Library was conducted through August 13, 2022. The following keywords were utilized: sglt2, sodium-glucose transporter 2 inhibitors, sglt2 inhibitors, decompensated heart failure, de-novo heart failure, and/or acute heart failure. Only randomized controlled trials (RCTs) with adult patients (>18 years), hospitalized with de-novo AHF, acutely decompensated chronic heart failure with reduced, borderline, or preserved ejection, and receiving SGLT2 inhibitors were included. A quantitative analytical methodology was applied where the standardized mean difference (SMD) applying 95% confidence intervals (CI) for continuous outcomes and risk ratio (RR) with 95% CI was yielded. All tests were carried out on Review Manager 5.4 (Cochrane). In total, three RCTs were included pooling in a total of 1831 patients where 49.9% received SGLT2 inhibitors. The mean age was 72.9 years in the interventional group compared to 70.6 years in the placebo. Only 33.7% of the sample was female. The follow-up spanned 2−9 months. Heart failure events were reduced by 62% in the interventional group (RR = 0.66, p < 0.0001). readmissions had a reduced risk of 24% with SGLT2 inhibitors (RR = 0.76, p = 0.03). We assessed the efficacy and safety of SGLT2 inhibitors in preventing complications post-AHF. The odds of all-cause mortality, cardiovascular mortality, heart failure events, and re-admissions rates were substantially reduced within the first 1−9 months of hospitalization.

Project description:Spin in the reporting of randomized controlled trials, where authors report research in a way that potentially misrepresents results and mislead readers, has been demonstrated in the broader medical literature. We investigated spin in wound care trials with (a) no statistically significant result for the primary outcome and (b) no clearly specified primary outcome.We searched the Cochrane Wounds Group Specialised Register of Trials for randomized controlled trials (RCTs). Eligible studies were: Parallel-group RCTs of interventions for foot, leg or pressure ulcers published in 2004 to 2009 (inclusive) with either a clearly identified primary outcome for which there was a statistically non-significant result (Cohort A) or studies that had no clear primary outcome (Cohort B).We extracted general study details. For both Cohorts A and B we then assessed for the presence of spin. For Cohort A we used a pre-defined process to assess reports for spin. For Cohort B we aimed to assess spin by recording the number of positive treatment effect claims made. We also compared the number of statistically significant and non-significant results reported in the main text and the abstract looking specifically for spin in the form of selective outcome reporting.Of the 71 eligible studies, 28 were eligible for Cohort A; of these, 71% (20/28) contained spin. Cohort B contained 43 studies; of these, 86% (37/43) had abstracts that claimed a favorable treatment claim. Whilst 74% (32/43) of main text results in Cohort B included at least one statistically non-significant result, this was not reflected in the abstract where only 28% contained (12/43) at least one statistically non-significant result.Spin is a frequent phenomenon in reports of RCTs of wound treatments. Studies without statistically significant results for the primary outcome used spin in 71% of cases. Furthermore, 33% (43/132) of reports of wound RCTs did not specify a primary outcome and there was evidence of spin and selective outcome reporting in the abstracts of these. Readers should be wary of only reading the abstracts of reports of RCTs of wound treatments since they are frequently misleading regarding treatment effects.

Dataset Information

Reporting and interpretation of subgroup analyses in heart failure randomized controlled trials.

Aims

Methods and results

Conclusions

Publications

Reporting and interpretation of subgroup analyses in heart failure randomized controlled trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets