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Figure.
Time to Publication of Clinical Trials for Each Subcategory
Time to Publication of Clinical Trials for Each Subcategory

Error bars indicate SD.

Table.  
Baseline Characteristics of the Neurology Clinical Trials
Baseline Characteristics of the Neurology Clinical Trials
1.
Chen  R, Desai  NR, Ross  JS,  et al.  Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers.  BMJ. 2016;352:i637.PubMedGoogle Scholar
2.
Ross  JS, Mocanu  M, Lampropulos  JF, Tse  T, Krumholz  HM.  Time to publication among completed clinical trials.  JAMA Intern Med. 2013;173(9):825-828.PubMedGoogle Scholar
3.
Zarin  DA, Tse  T, Williams  RJ, Carr  S.  Trial reporting in clinicaltrials.gov—the final rule.  N Engl J Med. 2016;375(20):1998-2004.PubMedGoogle Scholar
4.
Ross  JS, Mulvey  GK, Hines  EM, Nissen  SE, Krumholz  HM.  Trial publication after registration in clinicaltrials.gov: a cross-sectional analysis.  PLoS Med. 2009;6(9):e1000144.PubMedGoogle Scholar
5.
Ross  JS, Tse  T, Zarin  DA, Xu  H, Zhou  L, Krumholz  HM.  Publication of NIH funded trials registered in clinicaltrials.gov: cross sectional analysis.  BMJ. 2012;344:d7292.PubMedGoogle Scholar
Research Letter
July 2018

Publication and Dissemination of Results in Clinical Trials of Neurology

Author Affiliations
  • 1Department of Neurology, Yale University School of Medicine, New Haven, Connecticut
  • 2Medical student, Yale University School of Medicine, New Haven, Connecticut
  • 3Department of Medicine, Yale University School of Medicine, New Haven, Connecticut
JAMA Neurol. 2018;75(7):890-891. doi:10.1001/jamaneurol.2018.0674

Result dissemination is important for scientific progress; however, 25% to 50% of clinical trials are not published.1,2 To increase dissemination, the National Library of Medicine established an online registry, ClinicalTrials.gov. This database contains over 224 000 trials3; approximately 60% will supply results through the website4 and 46% will be published in a peer-reviewed journal.4 This study sought to comprehensively classify neurology trials within ClinicalTrials.gov to compare publication rates as well as time to publication.

Methods

An aggregate search was performed on July 19, 2016, through ClinicalTrials.gov, for closed interventional trials conducted within the United States between October 1, 2007, and July 1, 2014. The study was approved by the Yale School of Medicine Institutional Review Board.

Using the search term nervous system disease, the search was refined to ensure that trials were conducted within the specified time to allow at least 2 years for potential dissemination.1,5 Subcategories were subsequently assigned and potential publications were identified. A systematic 3-step process similar to previous studies1 was used to verify publication status, including (1) identification of relevant publications via the associated ClinicalTrials.gov webpage; (2) search of SCOPUS (Elsevier) with the specified terms for the [intervention] and [condition treated] and [primary investigator]; and (3) comparison of trial characteristics against potential publications. All statistical tests were conducted using SPSS, version 19 software (SPSS Inc), including a 2-tailed (P < .05) repeated measures analysis of variance to compare time to publication across subcategories.

Results

A total of 2072 trials were identified on ClinicalTrials.gov using the specified criteria (Table). There was a concentration of phase 2 trials (22.7% [470 of 2072]), with funding mainly from industry (50.7% [1051 of 2072]) or other nongovernmental sources (54.1% [1121 of 2072]). National Institutes of Health (NIH) funding resulted in a significantly higher publication rate (χ21 = 5.23; P = .02), with 54.3% (145 of 267) published compared with only 46.8% (845 of 1805) of non–NIH-funded studies. Regarding dissemination, 40.6% of the studies (841 of 2072) provided results through ClinicalTrials.gov and 47.8% (990 of 2072) published results in a scientific journal. Among the identified studies, 57.1% (1183 of 2072) achieved their primary end point. The mean (SD) time to publication was 26.4 (15.2) months for all trials, with a significant difference among subcategories (Figure) (F9 = 2.793; P = .003). Studies of vascular neurology had the fastest time to publication, with a median of 18 (13.8) months, which was more rapid than those of behavioral‎/neuropsychiatry (P = .002; SD, 16.5 months), pain medicine (P = .03; SD, 15.6 months), and epilepsy (P = .01; SD, 17.0 months) on follow-up testing.

Discussion

We found that 48% of neurology trials (990 of 2072) were published in a scientific journal at a median (SD) of 25 (15.2) months, which is comparable to previous work.4,5 However, our review suggested lower rates of dissemination through ClinicalTrials.gov. Among subcategories, pain medicine composed the largest percentage, likely due to overlap between multiple specialties interested in pain alleviation. Neuro-oncology had unique characteristics, including a higher proportion of NIH funding, higher rates of overall publication, and shorter median time to publication. The central driving factor may be NIH funding, which was associated with a significantly higher publication rate. Vascular neurology trials had the fastest time to publication, which could stem from the prevalence of vascular niche journals, allowing for easier dissemination. An important limitation of this analysis is the finite search criteria and databases used to identify publications; however, given that our rates mirror previous work, these errors were likely minimized.

This analysis suggests that neurology trials face similar dissemination problems as other clinical trials. Areas of improvement include reporting raw results through ClinicalTrials.gov, achieving other means of data sharing between institutions, and avoiding the propensity to publish only studies achieving their primary outcome. Signs of encouragement include more journals requiring trial registration numbers, which promotes research tracking. In addition, institutes like our own are creating data-sharing platforms (eg, Yale University Open Data Access). While we found differences among subcategories, these may stem from underlying funding sources. Overall, these results re-emphasize the necessary steps required for the timely dissemination of research results.

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Article Information

Accepted for Publication: January 18, 2018.

Corresponding Author: Kevin N. Sheth, MD, Department of Neurology, Yale University School of Medicine, 15 York St, LCI 1003, New Haven, CT 06510 (kevin.sheth@yale.edu).

Published Online: April 30, 2018. doi:10.1001/jamaneurol.2018.0674

Author Contributions: Dr Sreekrishnan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Sreekrishnan, Ross, Seth.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Sreekrishnan, Mampre.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Sreekrishnan, Miyares.

Administrative, technical, or material support: Mampre, Ormseth, Miyares, Leasure, Seth.

Study supervision: Seth.

Conflict of Interest Disclosures: In the past 36 months, Dr Ross has received research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from Medtronic, Inc, and the US Food and Drug Administration (FDA) to develop methods for postmarketing surveillance of medical devices, from the FDA to establish Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation program, from the Blue Cross Blue Shield Association to better understand medical technology evaluation, from the Centers for Medicare & Medicaid Services to develop and maintain performance measures that are used for public reporting, and from the Agency for Healthcare Research and Quality, the National Heart, Lung and Blood Institute of the National Institutes of Health, and the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International and to establish the Collaboration for Research Integrity and Transparency at Yale University.

References
1.
Chen  R, Desai  NR, Ross  JS,  et al.  Publication and reporting of clinical trial results: cross sectional analysis across academic medical centers.  BMJ. 2016;352:i637.PubMedGoogle Scholar
2.
Ross  JS, Mocanu  M, Lampropulos  JF, Tse  T, Krumholz  HM.  Time to publication among completed clinical trials.  JAMA Intern Med. 2013;173(9):825-828.PubMedGoogle Scholar
3.
Zarin  DA, Tse  T, Williams  RJ, Carr  S.  Trial reporting in clinicaltrials.gov—the final rule.  N Engl J Med. 2016;375(20):1998-2004.PubMedGoogle Scholar
4.
Ross  JS, Mulvey  GK, Hines  EM, Nissen  SE, Krumholz  HM.  Trial publication after registration in clinicaltrials.gov: a cross-sectional analysis.  PLoS Med. 2009;6(9):e1000144.PubMedGoogle Scholar
5.
Ross  JS, Tse  T, Zarin  DA, Xu  H, Zhou  L, Krumholz  HM.  Publication of NIH funded trials registered in clinicaltrials.gov: cross sectional analysis.  BMJ. 2012;344:d7292.PubMedGoogle Scholar
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