Amanda K Hakala1, Dean Fergusson2, Jonathan Kimmelman1. 1. Studies of Translation, Ethics, and Medicine (STREAM), Biomedical Ethics Unit, McGill University, Montreal, Quebec, Canada. 2. Centre for Practice Changing Research, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Abstract
OBJECTIVE: To evaluate nonpublication rates among trials of new successful and unsuccessful neurological drugs. METHODS: "Licensed" drugs consisted of all novel agents receiving US Food and Drug Administration (FDA) licensure 2005-2012 inclusive in seven neurological disorders. "Stalled" drugs included all experimental agents tested in the same domains that had at least one completed phase III trial in the same time frame, but failed to receive FDA approval. Trials of these drugs were included in our sample if their primary outcome collection occurred before October 1, 2010. We determined the publication status of eligible trials using searches of clinicaltrials.gov, Google Scholar, PubMed, Embase, sponsor websites, and direct electronic query of trial contacts and sponsors. The primary outcome was time to journal publication (or results reporting in other media) after study completion. RESULTS: The adjusted hazard ratio for publication was 1.79 (95% confidence interval, 1.20-2.67) in favor of licensed drugs. Based on the criteria for nonpublication in this report, 14,092 and 33,882 volunteers participated in unpublished trials of licensed and stalled neurological drugs, respectively. Result data were not publicly available in any form for 10% (16 of 163) and 46% (94 of 203) of trials of licensed and stalled drugs, respectively. INTERPRETATION: Results of trials for stalled drugs are heavily under-reported. This deprives research and care communities of evidence about pathophysiology, drug class effects, and the value of surrogate endpoints in trials. Ann Neurol 2017;81:782-789.
OBJECTIVE: To evaluate nonpublication rates among trials of new successful and unsuccessful neurological drugs. METHODS: "Licensed" drugs consisted of all novel agents receiving US Food and Drug Administration (FDA) licensure 2005-2012 inclusive in seven neurological disorders. "Stalled" drugs included all experimental agents tested in the same domains that had at least one completed phase III trial in the same time frame, but failed to receive FDA approval. Trials of these drugs were included in our sample if their primary outcome collection occurred before October 1, 2010. We determined the publication status of eligible trials using searches of clinicaltrials.gov, Google Scholar, PubMed, Embase, sponsor websites, and direct electronic query of trial contacts and sponsors. The primary outcome was time to journal publication (or results reporting in other media) after study completion. RESULTS: The adjusted hazard ratio for publication was 1.79 (95% confidence interval, 1.20-2.67) in favor of licensed drugs. Based on the criteria for nonpublication in this report, 14,092 and 33,882 volunteers participated in unpublished trials of licensed and stalled neurological drugs, respectively. Result data were not publicly available in any form for 10% (16 of 163) and 46% (94 of 203) of trials of licensed and stalled drugs, respectively. INTERPRETATION: Results of trials for stalled drugs are heavily under-reported. This deprives research and care communities of evidence about pathophysiology, drug class effects, and the value of surrogate endpoints in trials. Ann Neurol 2017;81:782-789.
Authors: Jeremy Brown; Paul G Wakim; Carlos Faraco; Cristina Saugar-Lanchas; Codrin Lungu; Carolina Mendoza-Puccini; Ellen Rosenberg; Clinton Wright Journal: Ann Neurol Date: 2021-12 Impact factor: 11.274
Authors: Aden C Feustel; Amanda MacPherson; Dean A Fergusson; Karl Kieburtz; Jonathan Kimmelman Journal: Neurology Date: 2019-12-02 Impact factor: 9.910