Funding source and primary outcome changes in clinical trials registered on ClinicalTrials.gov are associated with the reporting of a statistically significant primary outcome: a cross-sectional study

Ramagopalan, Sreeram V; Skingsley, Andrew; Handunnetthi, Lahiru; Magnus, Dan; Klingel, Michelle; Pakpoor, Julia; Goldacre, Ben

doi:10.12688/f1000research.6312.1

Cited by 17 publications

(14 citation statements)

References 5 publications

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“…Reporting of significant results for the first primary outcome posted were more frequent for trials sponsored by industry than academic sources, which is consistent with previous studies finding that industry trials are more likely than public trials to report significant results in published articles [32, 33] and at ClinicalTrials.gov [31]. In addition, reporting of significant results was also more common for phase 3 trials and for trials with an inactive control.…”

Section: Discussionsupporting

confidence: 88%

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Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials

Dechartres

Bond

Scheer

et al. 2016

BMC Med

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BackgroundPublication bias and other reporting bias have been well documented for journal articles, but no study has evaluated the nature of results posted at ClinicalTrials.gov. We aimed to assess how many randomized controlled trials (RCTs) with results posted at ClinicalTrials.gov report statistically significant results and whether the proportion of trials with significant results differs when no treatment effect estimate or p-value is posted.MethodsWe searched ClinicalTrials.gov in June 2015 for all studies with results posted. We included completed RCTs with a superiority hypothesis and considered results for the first primary outcome with results posted. For each trial, we assessed whether a treatment effect estimate and/or p-value was reported at ClinicalTrials.gov and if yes, whether results were statistically significant. If no treatment effect estimate or p-value was reported, we calculated the treatment effect and corresponding p-value using results per arm posted at ClinicalTrials.gov when sufficient data were reported.ResultsFrom the 17,536 studies with results posted at ClinicalTrials.gov, we identified 2823 completed phase 3 or 4 randomized trials with a superiority hypothesis. Of these, 1400 (50%) reported a treatment effect estimate and/or p-value. Results were statistically significant for 844 trials (60%), with a median p-value of 0.01 (Q1-Q3: 0.001–0.26). For the 1423 trials with no treatment effect estimate or p-value posted, we could calculate the treatment effect and corresponding p-value using results reported per arm for 929 (65%). For 494 trials (35%), p-values could not be calculated mainly because of insufficient reporting, censored data, or repeated measurements over time. For the 929 trials we could calculate p-values, we found statistically significant results for 342 (37%), with a median p-value of 0.19 (Q1-Q3: 0.005–0.59).ConclusionsHalf of the trials with results posted at ClinicalTrials.gov reported a treatment effect estimate and/or p-value, with significant results for 60% of these. p-values could be calculated from results reported per arm at ClinicalTrials.gov for only 65% of the other trials. The proportion of significant results was much lower for these trials, which suggests a selective posting of treatment effect estimates and/or p-values when results are statistically significant.

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Section: Discussionsupporting

confidence: 88%

“…Only one research note evaluated an association between changes in primary outcomes and reporting a significant result [31]. …”

Section: Discussionmentioning

confidence: 99%

Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials

Dechartres

Bond

Scheer

et al. 2016

BMC Med

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“…As other authors 5,6,12,13,14 have reported, completion status and errors in registry information is common in healthcare research; it is encouraging that we found moderately good agreement in outcome measures with registered protocols. Investigators need to continue to upload results to clinical trial registries and…”

Section: Discussionsupporting

confidence: 80%

Agreement of Primary Outcomes in Chiropractic-Related Clinical Trials Registered in clinicaltrials.gov with Corresponding Publication.

Côté

Perle²,

Martin³

2020

Preprint

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Introduction:Previous analysis of registered clinical trials has found a disappointing number of study protocols result in publications which change what the registered a priori primary outcome measure is. Likewise, there is a disappointing rate of unpublished trials. Similar research has not been published on chiropractic-related studies. Primarily this investigation determined if reported primary outcomes in chiropractic-related clinical trials registered in clinicaltrials.gov match their published results. Secondarily, other outcome measures and publication status are assessed.Methodology:Clinicaltrials.gov was searched for chiropractic-related trials, using the search terms “chiropractic”, “chiropractor”, and having a completed status. Publication status was determined by searching PubMed (pubmed.gov), Index to Chiropractic Literature (chiroindex.org), and Google Scholar (scholar.google.com) through 29 May 2020. If the study was published, outcome measures were compared between the clinicaltrials.gov entry and the published paper to assess for consistency by two independent investigators. If there was disagreement between investigators, a third evaluated the data and decided if the published paper agreed with the clinicaltrials.gov entry.Results:Within clinicaltrials.gov 171 chiropractic-related protocols were identified. Twenty-five (25) had results posted and 102 were published. Twenty-nine of those entries produced multiple papers consisting of protocols, plot/feasibility studies, clinical trials, and poster presentations. Of the 102 studies published, 92 (90.2%) had agreement between their primary outcome and the listed entry on clinicaltrials.gov and 82 (80.4%) agreed with the secondary outcomes in the registered protocol. Entries on clinicaltrials.gov had a 59.6% (102/171) publication rate and a 14.6% (25/171) rate of displaying their results. Conclusion:A modest rate of agreement (90.2%) between clinicaltrails.gov entries and the 102 published papers (59.6% publication rate) were found. While chiropractic-related clinical trials are fewer in number compared to medical trials, chiropractic-related research has a substantially better rate of primary and secondary outcome concordance with registered protocols and a better publication rate. Investigators need to continue to upload results onto clinicaltrials.gov and seek publication regardless of the study findings. It is important to publish negative results so as not to introduce publication bias into systematic reviews and meta-analyses. Both positive and negative findings are important when evaluating treatments and determining the best care for patients.

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“…However, we believe a strong case can be made for all clinical trials to be conducted and reported exclusively as RRs. Even though trial registration is now the norm, registration does not guarantee that trials are preregistered rather than "post-registered" 105 , that trial results will be reported free from bias 106,107 , or that the results will be published at all 108,109 . With trials being vulnerable to all the same publication and reporting biases that afflict basic research, and with the first RR model for clinical trials now available at BMC Medicine 110 , the next decade will likely see mounting pressure on clinical trial funders and major medical journals to embrace the format, ideally via RR funding models to maximise efficiency.…”

Section: Improving Quality Accountability and Rewardsmentioning

confidence: 99%

The past, present, and future of Registered Reports

Chambers¹,

Tzavella²

2020

Preprint

103

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Registered Reports are a form of empirical journal article in which study proposals are peer reviewed and pre-accepted before research is undertaken. By deciding which articles are published based on the question, theory, and proposed methods, Registered Reports offer a powerful remedy for a range of reporting and publication biases. Here we reflect on the history, progress and future prospects of the Registered Reports initiative, and also offer practical guidance for authors, reviewers, and editors encountering the format for the first time. While the key ingredients of pre-study review and results-blind acceptance are far from novel – and are already adopted independently in a variety of contexts – Registered Reports are the first mechanism to combine them into a mainstream policy that has won appeal with multiple stakeholders in the research process. We review early evidence that Registered Reports are working as intended, while at the same acknowledging that they are not a universal solution for irreproducibility. We also consider how the policies and practices surrounding Registered Reports are changing, or must change in future, to address limitations and adapt to new challenges. In spite of these caveats, we conclude that Registered Reports are promoting reproducibility, transparency and self-correction across a wide range of disciplines, and may help reshape how society evaluates research and researchers.

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Funding source and primary outcome changes in clinical trials registered on ClinicalTrials.gov are associated with the reporting of a statistically significant primary outcome: a cross-sectional study

Cited by 17 publications

References 5 publications

Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials

Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials

Agreement of Primary Outcomes in Chiropractic-Related Clinical Trials Registered in clinicaltrials.gov with Corresponding Publication.

The past, present, and future of Registered Reports

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