Results of clinical trials for “stalled” neurological drugs — those which had at least one completed Phase III trial but failed to receive FDA approval — are heavily underreported, found a new study. “There are several ethical concerns,” says Jonathan Kimmelman, PhD, one of the study’s authors and an associate professor in the Biomedical Ethics Unit at Montreal-based McGill University.

“Nonpublication fails to redeem the sacrifice that patients make when they enroll in clinical trials to advance medical science,” says Kimmelman. The study found that 14,092 and 33,882 volunteers participated in unpublished trials of licensed and stalled neurological drugs, respectively.

Many patients in neurological trials have advanced disease, and may have diminished mental capacity. “This makes it all the more important to show proper regard for their contributions to science by disseminating the results of such trials,” says Kimmelman.

Nonpublication of trials for drugs that never get licensed is “doubly troubling,” adds Kimmelman. This is because patients in such trials have been exposed to a drug that is later deemed either unsafe or ineffective.

Nonpublication deprives patients and healthcare systems of safety and efficacy evidence. “It also forgoes an opportunity to update our theories of disease processes, since every time we run a trial we learn indirectly about how those processes work,” says Kimmelman.

Results 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.

“All this is especially concerning in neurology for several reasons,” says Kimmelman. The failure to report this information slows the process of medical research in neurology — an area characterized by very pressing needs with few effective treatments, notes Kimmelman.

Since the failure rate in neurology drug development is among the highest in any disease area, says Kimmelman, “we ought to be capturing and utilizing every bit of evidence we can.”

Some evidence suggests that high failure rates are causing companies to diminish their investments in neurological drug development. “This portends an evidence-spare future for neurological drug development,” says Kimmelman. “It further highlights the importance of circulating what evidence we do gather.”

REFERENCE

  1. Hakala AK, Fergusson D, Kimmelman J. Nonpublication of trial results for new neurological drugs: A systematic review. Ann Neurol 2017 May 9. doi: 10.1002/ana.24952. [Epub ahead of print]

SOURCE

  • Jonathan Kimmelman, Associate Professor, Biomedical Ethics Unit, McGill University, Montreal, Quebec, Canada. Phone: (514) 398-3306. Fax: (514) 398-8349. Email: jonathan.kimmelman@mcgill.ca.