Neurology trial registrations on ClinicalTrials.gov between 2007 and 2018: A cross-sectional analysis of characteristics, early discontinuation, and results reporting

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Abstract

Background

Increasing neurological disease burden and advancing treatment options require clinical trials to expand the evidence base of clinical care. We aimed to characterize neurology clinical trials registered between October 2007 and April 2018 and identify features associated with early discontinuation and results reporting.

Methods

We compared 16,994 neurology (9.4%) and 163,714 non-neurology comparison trials registered to ClinicalTrials.gov. Trials therapeutic focus within neurology was assigned via combination programmatic and manual review. We performed descriptive analyses of trial characteristics, cox regression of early discontinuation, and multivariable logistic regression for results reporting within 3 years of completion.

Results

Most neurology trials were academic-funded (58.5%) followed by industry (31.9%) and US-government (9.6%). Neurology trials focused more on treatment than prevention compared to non-neurology studies. Of neurology trials, 11.3% discontinued early, and 32.2% of completed trials reported results by April 30, 2018. In multivariable analysis accounting for time-to-event, neurology trials were at lower risk of discontinuation than non-neurology trials (adjusted hazard 0.83, p < 0.0001). Both academic and government-funded trials had greater risk of discontinuation than industry (adjusted hazard 0.57 and 0.46, respectively). Among completed trials, government-funded studies (adjusted odds ratio 2.12, p < 0.0001) had highest odds of results reporting while academic trials reported less (adjusted odds ratio 0.51, p < 0.0001).

Conclusions

Funding source is associated with trial characteristics and outcomes in neurology. Improvements in trial completion and timely dissemination of results remain urgent goals for the field.

Introduction

Clinical trials present a critical mechanism for expanding evidence-based medicine, advancing therapeutics, and informing patient care. They incur a significant financial, labor, and regulatory burden on funders, investigators, and participants. The potential innovation from such studies justifies these investments, but only when researchers consistently disseminate clinical trial findings and contribute to scientific progress, even if trial results are negative.

Recent publications on neurological clinical trials paint a discouraging picture: less than half of a small sample of neurological clinical trials registered on ClinicalTrials.gov published results in peer-reviewed journals, a number that has not improved over time [1,2]. Neurology trials take on greater importance in the context of an aging global population and increasing global burden of neurological disease [3]. An analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study estimated that neurological disorders cause 10.2% of all global disability-adjusted life years, and account for 9.4 million annual deaths [4]. As health systems adapt to meet the evolving neurological needs of the population, clinical trial results will play a key part in developing efficacious medical treatments.

In this study, we examine and characterize all neurological trials registered on ClinicalTrials.gov between October 1, 2007 and April 30, 2018. Clinicaltrials.gov is one of the largest international databases of clinical trials, comprising nearly half of all global clinical trials and the majority of US-based trials [5]. We investigate trial characteristics by funding source and over time, and identify factors associated with early trial discontinuation and timely results reporting.

Section snippets

Data source

We extracted all studies registered between October 1, 2007 and April 30, 2018 from the Aggregate Analysis of ClinicalTrials.gov database [6]. We limited the analysis to interventional studies (49,446 excluded) and those registered after October 1, 2007 (44,957 excluded) coinciding with the September 27, 2007 enactment of the Food and Drug Administration Amendments Act, which required applicable trials (US-based Phase 2–4 trials of drugs, biologics, and devices) to register and report results

Trial characteristics

16,994 (9.4%) met inclusion as neurology trials, with an estimated enrollment of 4.87 million participants (Supplement Table S1), while 163,714 trials comprised the comparison group of non-neurology trials (Fig. 1). Neurology trials focused more on treatment (71.1% vs 63.7%) and less on prevention than non-neurology trials (7.2% vs 10.9%; Table 1). Neurology trials tended to have fewer estimated participants and less frequently included blinding. Overall, most trials took place in high-income

Discussion

Trials for neurological diseases represented 9% of all ClinicalTrials.gov registrations. This representation is comparable to neurological diseases' proportion of global DALYs (10%), but less than their share of global deaths (16%) [4]. This severe (and worsening [3]) morbidity coupled with the significant investment of trial resources compounds the need for ensuring trials complete and report results and remains a crucial concern in the field of neurology. To our knowledge, this is the largest

Author contributions

Brandon E. Turner MD had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. He attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. He further affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as

Ethical approval

The study used publicly available data and was therefore granted exemption from IRB approval.

Data sharing

All data was accessed through publicly available databases.

Funding

None.

Declaration of Competing Interest

Brandon E. Turner MD certifies that none of the contributing authors have any conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript. Funding/Support and role of the sponsor: No funding or other financial support was received.

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