Discontinuation and nonpublication of interventional clinical trials conducted in patients with mild cognitive impairment and Alzheimer's disease

Taygan Yilmaz; Roos J Jutten; Cláudia Y Santos; Kimberly A Hernandez; Peter J Snyder

doi:10.1016/j.trci.2018.03.005

Discontinuation and nonpublication of interventional clinical trials conducted in patients with mild cognitive impairment and Alzheimer's disease

Alzheimers Dement (N Y). 2018 Apr 25:4:161-164. doi: 10.1016/j.trci.2018.03.005. eCollection 2018.

Authors

Taygan Yilmaz¹, Roos J Jutten², Cláudia Y Santos^{3

4}, Kimberly A Hernandez³, Peter J Snyder^{4

5

6}

Affiliations

¹ Lifespan-Rhode Island Hospital, Providence, RI, USA.
² Alzheimer Center, Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
³ Lifespan-Rhode Island Hospital, Clinical Research Center, Providence, RI, USA.
⁴ Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA.
⁵ Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI, USA.
⁶ Department of Neurology, Alpert Medical School of Brown University, Providence, RI, USA.

Abstract

Introduction: Discontinuation and nonpublication of interventional clinical trials represents a waste of already scarce resources. We sought to identify the prevalence of discontinuation and nonpublication of interventional clinical trials conducted in patients afflicted by mild cognitive impairment and Alzheimer's disease.

Methods: We conducted a retrospective, cross-sectional study on mild cognitive impairment and Alzheimer's disease-based interventional clinical trials in ClinicalTrials.gov dating back to 1995. The analyzed data included trial phase, intervention type, enrollment, and funding sources. Fisher's exact and χ² tests were used to determine any potential associations between trial characteristics and completion.

Results: A total of 744 studies were identified, of which 502 (67%) were industry-sponsored ones. A total of 127 (17%) were discontinued prematurely. Of the 617 completed trials, 450 (73%) were not published, representing approximately 66,655 participants who incurred the risks of trial participation without subsequently contributing to the medical literature. Similarly, there were 18,246 patients from unpublished, discontinued trials. Of the 744 trials examined, 247 publications from 167 trials could be identified via PubMed/MEDLINE and EMBASE searches. Most notably, the odds of nonpublication among industry-sponsored trials were more than 75% higher than those in studies funded by academia (odds ratio = 1.78; 95% confidence interval, 1.14-2.78; P = .01). Furthermore, industry-sponsored trials had a 50% greater odds of study discontinuation compared with trials funded by academia (odds ratio = 1.50; 95% confidence interval, 1.04-2.16; P = .03).

Discussion: The nonpublication of many trials and preliminary results of trials that are discontinued early dilutes the quality and decreases the comprehensive nature of the medical literature. This occurs in both industry and academia. Publication of inconclusive or negative results ensures that all research activities, regardless of outcome, contribute to global medical knowledge.

Keywords: Alzheimer's disease; Clinical trials; Discontinuation; Mild cognitive impairment; Nonpublication.