Dataset Information

Hiding negative trials by pooling them: a secondary analysis of pooled-trials publication bias in FDA-registered antidepressant trials.

ABSTRACT:

Background

Previous studies on reporting bias generally examined whether trials were published in stand-alone publications. In this study, we investigated whether pooled-trials publications constitute a specific form of reporting bias. We assessed whether negative trials were more likely to be exclusively published in pooled-trials publications than positive trials and examined the research questions, individual trial results, and conclusions presented in these articles.

Methods

Data from a cohort of 105 randomized controlled trials of 16 antidepressants were extracted from earlier publications and the corresponding Food and Drug Administration (FDA) reviews. A systematic literature search was conducted to identify pooled-trials publications.

Results

We found 107 pooled-trials publications that reported results of 23 (72%) of 32 trials not published in stand-alone publications. Only two (3.8%) of 54 positive trials were published exclusively in pooled-trials publications, compared with 21 (41.1%) of 51 negative trials (p < 0.001). Thirteen (12%) of 107 publications had as primary aim to present data on the trial's primary research question (drug efficacy compared with placebo). Only four of these publications, reporting on five (22%) trials, presented individual efficacy data for the primary research question. Additionally, only five (5%) of 107 pooled-trials publications had a negative conclusion.

Conclusions

Compared with positive trials, negative trials of antidepressants for depression were much more likely to be reported exclusively in pooled-trials publications. Pooled-trials publications flood the evidence base with often-redundant articles that, instead of addressing the original primary research question, present (positive) results on secondary questions. Therefore, pooled-trials publications distort the apparent risk-benefit profile of antidepressants.

SUBMITTER: de Vries YA

PROVIDER: S-EPMC6712952 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Hiding negative trials by pooling them: a secondary analysis of pooled-trials publication bias in FDA-registered antidepressant trials.

de Vries Ymkje Anna YA Roest Annelieke M AM Turner Erick H EH de Jonge Peter P

Psychological medicine 20180928 12

<h4>Background</h4>Previous studies on reporting bias generally examined whether trials were published in stand-alone publications. In this study, we investigated whether pooled-trials publications constitute a specific form of reporting bias. We assessed whether negative trials were more likely to be exclusively published in pooled-trials publications than positive trials and examined the research questions, individual trial results, and conclusions presented in these articles.<h4>Methods</h4>D ...[more]

PMID: 30261934

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Project description:ImportancePublishing study protocols might reduce research waste because of unclear methods or incomplete reporting; on the other hand, there might be few additional benefits of publishing protocols for registered trials that are never completed or published. No study has investigated the proportion of published protocols associated with published results.ObjectiveTo estimate the proportion of published trial protocols for which there are not associated published results.Design, setting, and participantsThis cross-sectional study used stratified random sampling to identify registered clinical trials with protocols published between January 2011 and August 2022 and indexed in PubMed Central. Ongoing studies and those within 1 year of the primary completion date on ClinicalTrials.gov were excluded. Published results were sought from August 2022 to March 2023 by searching ClinicalTrials.gov, emailing authors, and using an automated tool, as well as through incidental discovery.Main outcomes and measuresThe primary outcome was a weighted estimate of the proportion of registered trials with published protocols that also had published main results. The proportion of trials with unpublished results was estimated using a weighted mean.ResultsFrom 1500 citations that were screened, 308 clinical trial protocols were included, and it was found that 87 trials had not published their main results. Most included trials were investigator-initiated evaluations of nonregulated products. When published, results appeared a mean (SD) of 3.4 (2.0) years after protocol publications. With the use of a weighted mean, an estimated 4754 (95% CI, 4296-5226) eligible clinical trial protocols were published and indexed in PubMed Central between 2011 and 2022. In the weighted analysis, 1708 of those protocols (36%; 95% CI, 31%-41%) were not associated with publication of main results. In a sensitivity analysis excluding protocols published after 2019, an estimated 25% (95% CI, 20%-30%) of 3670 (95% CI, 3310-4032) protocol publications were not associated with publication of main results.Conclusions and relevanceThis cross-sectional study of clinical trial protocols published on PubMed Central between 2011 and 2022 suggests that many protocols were not associated with subsequent publication of results. The overall benefits of publishing study protocols might outweigh the research waste caused by unnecessary protocol publications.

Project description:ImportanceThe published evidence in support of probiotic use is conflicting, which may be a result of selective publication of probiotic trials.ObjectivesTo compare the proportion of registered trials that evaluate pediatric probiotics vs those that evaluate antibiotics that are published and to identify study-related factors associated with publication status.Design, setting, and participantsThis cross-sectional study evaluated eligible trials registered in ClinicalTrials.gov, an online clinical trials registry, from July 1, 2005, to June 30, 2016. Eligible studies included participants younger than 18 years, evaluated a probiotic or 1 of the 5 most commonly prescribed antibiotics in children and adolescents, and randomized study participants. All searches were updated and finalized as of September 9, 2020.ExposuresProbiotic or antibiotic.Main outcomes and measuresThe primary outcome was study publication status. In addition, exposure status (probiotic vs antibiotic), trial result, and funding source were assessed for independent association with publication status. Whether study design elements, publication journal impact factor, and the interval from study completion to publication differed by exposure status were also evaluated.ResultsA total of 401 unique trials (265 probiotic and 136 antibiotic) met eligibility criteria. A greater proportion of antibiotic compared with probiotic studies were published (83 [61.0%] vs 119 [44.9%]; difference, 16.1% [95% CI, 5.8%-25.9%]). After adjustment for funding source, blinding, and purpose, studies evaluating an antibiotic were more likely to be published (odds ratio, 2.1 [95% CI, 1.3-3.4]). No other covariates included in the model were independently associated with publication status. Antibiotic trials, compared with probiotic trials, were more likely to have a therapeutic purpose (114 [83.8%] vs 117 [44.2%]; difference, 39.6% [95% CI, 31.1%-48.3%]) and to be multicenter (46 [33.8%] vs 46 [17.4%]; difference, 16.5% [95% CI, 7.5%-25.7%]). The median impact factor of the journals in which the studies were published was higher for the antibiotic trials (7.2 [IQR, 2.8-20.5] vs 3.0 [IQR, 2.3-4.2]; P < .001). The median number of days to publication did not differ between the probiotic and antibiotic trials (683 [IQR, 441-1036] vs 801 [IQR, 550-1183]; P = .24).Conclusions and relevanceThe findings of this cross-sectional study suggest that probiotic studies are less likely to be published than antibiotic trials. No other study characteristics were associated with publication status. This finding raises concerns regarding the results of meta-analyses of probiotic trials.

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Project description:BackgroundRandomized controlled trials (RCTs) are the gold standard for evidence-based practice, but their development and implementation is resource intensive. We aimed to describe modern RCTs in gastrointestinal (GI) cancer and identify predictors of successful accrual and publication.Materials and methodsClinicalTrials.gov was queried for phase III GI cancer RCTs opened between 2010 and 2019 and divided into two cohorts: past and recruiting. Past trials were analyzed for predictors of successful accrual and the subset with ≥3 years follow-up were analyzed for predictors of publication. Univariate and multivariable (MVA) logistic regression were used to identify covariates associated with complete accrual and publication status.ResultsA total of 533 GI RCTs were opened from 2010 to 2019, 244 of which are still recruiting. In the "past" trials cohort (235/533) MVA, Asian continent of enrollment was a predictor for successful accrual, whereas trials with prolonged enrollment (duration longer than median of 960 days) trended to failed accrual. Predictors for publication on MVA included international enrollment and accrual completion. Sponsorship was not associated with accrual or publication. Notably, 33% of past trials remain unpublished, and 60% of trials that were closed early remain unpublished.ConclusionAccrual rate and the primary continent of enrollment drive both trial completion and publication in GI oncology. Accrual must be streamlined to enhance the impact of RCTs on clinical management. A large portion of trials remain unpublished, underscoring the need to encourage dissemination of all trials to, at a minimum, inform future trial design.Implications for practiceTwo-thirds of gastrointestinal (GI) oncology phase III randomized controlled trials successfully accrue; however, one third of these trials are unpublished and more than half of trials that close early are unpublished. The strongest predictors for publication are successful accrual and international collaborations. Initiatives to optimize the trial enrollment process need to be explored to maximize the potential for trials to engender progress in clinical practice. Moreover, this study identified a significant publication bias in the realm of GI oncology, and the field should promote reporting of all trials in order to better inform future trial questions and design.

Dataset Information

Hiding negative trials by pooling them: a secondary analysis of pooled-trials publication bias in FDA-registered antidepressant trials.

Background

Methods

Results

Conclusions

Publications

Hiding negative trials by pooling them: a secondary analysis of pooled-trials publication bias in FDA-registered antidepressant trials.

Similar Datasets

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