Prevalence of primary outcome changes in clinical trials registered on ClinicalTrials.gov: a cross-sectional study

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

doi:10.12688/f1000research.3784.1

Cited by 45 publications

(44 citation statements)

References 7 publications

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“…To date, we found one previous study 12 that has evaluated chiropractic's publication rate and no chiropractic studies assessing outcome agreement in a clinical trial registry. To further build upon the knowledge base for this manual healthcare, more of chiropractic-related clinical research needs to be completed.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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 Likewise, there is a disappointing rate of unpublished trials.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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Section: Discussionmentioning

confidence: 99%

“…A study by Wells and Lawrence 12 found bias in chiropractic-related publications and spoke to a need for more investigators to add results to clinical trial registries. Our study found more "chiropractic" studies than Wells and Lawrence when searching the same database (160 vs. 65).…”

Section: Methodsmentioning

confidence: 99%

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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“…Several studies in the medical literature assess the quality of the data reported to the registry and the results database along different dimension, e.g., information about scientific leadership [54], consistency of reported primary outcomes [55,56], comparisons to results published in academic journals [53,57], and the provision of Individual Participant Data (IPD) [58]. All these studies, as well as overall assessments by the curators of the database [19,20], find ambiguous results and see scope for improvement [59].…”

Section: Background On Clinicaltrialsgovmentioning

confidence: 99%

Why So Many Significant Phase 3 Results in Clinical Trials?

2019

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Planning and execution of clinical research and publication of results should conform to the highest ethical standards, given that human lives are at stake. However, economic incentives can generate conflicts of interest for investigators, who may be inclined to withhold unfavorable results or even tamper with the data. Analyzing p-values reported to the Clini-calTrials.gov registry with two different methodologies, we find suspicious patterns only for results from trials conducted by smaller industry sponsors, with presumably less reputation at stake. First, a density discontinuity test reveals an upward jump at the classical threshold for statistical significance for Phase 3 results by small industry sponsors, suggesting some selective reporting. Second, we find an excess mass of significant results in Phase 3 compared to Phase 2. However, we can explain almost completely this excess mass for large industry sponsors, once we account for the incentives to selectively continue research through a novel technique linking trials across phases. In contrast, for trials sponsored by small pharmaceutical companies, selective continuation of trials economizing on research costs only explains one third of the increase in the number of significant results from Phase 2 to Phase 3. The different pattern depending on the type of sponsor suggests that reputational concerns can mitigate the short-run economic incentives that undermine integrity in reporting results of clinical research.

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“…None of the RCTs discussed above were flagged in our ClinicalTrials.gov search, so issues such as primary outcome changes and/or unmotivated subgroup analysis, issues which mar many RCTs have not been examined. However, it is reasonable to assume that reductions in VAS scores are a primary outcome.…”

Section: Efficacy Of Peamentioning

confidence: 99%

“…→~2.2 cm (celecoxib reduced from~7.8 →~1.4 cm). Unclear whether the significant finding was part of the original study design or a post-hoc subgroup analysis None of the RCTs discussed above were flagged in our ClinicalTrials.gov search, so issues such as primary outcome changes and/or unmotivated subgroup analysis, issues which mar many RCTs[65,66] have not been examined. However, it is reasonable to assume that reductions in VAS scores are a primary outcome.…”

mentioning

confidence: 99%

Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy

Gabrielsson

Mattsson

Fowler

2016

Brit J Clinical Pharma

121

117

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Palmitoylethanolamide (PEA) has been suggested to have useful analgesic properties and to be devoid of unwanted effects. Here, we have examined critically this contention, and discussed available data concerning the pharmacokinetics of PEA and its formulation. Sixteen clinical trials, six case reports/pilot studies and a meta‐analysis of PEA as an analgesic have been published in the literature. For treatment times up to 49 days, the current clinical data argue against serious adverse drug reactions (ADRs) at an incidence of 1/200 or greater. For treatment lasting more than 60 days, the number of patients is insufficient to rule out a frequency of ADRs of less than 1/100. The six published randomized clinical trials are of variable quality. Presentation of data without information on data spread and nonreporting of data at times other than the final measurement were among issues that were identified. Further, there are no head‐to‐head clinical comparisons of unmicronized vs. micronized formulations of PEA, and so evidence for superiority of one formulation over the other is currently lacking. Nevertheless, the available clinical data support the contention that PEA has analgesic actions and motivate further study of this compound, particularly with respect to head‐to‐head comparisons of unmicronized vs. micronized formulations of PEA and comparisons with currently recommended treatments.

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Prevalence of primary outcome changes in clinical trials registered on ClinicalTrials.gov: a cross-sectional study

Cited by 45 publications

References 7 publications

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

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

Why So Many Significant Phase 3 Results in Clinical Trials?

Palmitoylethanolamide for the treatment of pain: pharmacokinetics, safety and efficacy

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