Lost in Translation: Neuropsychiatric Drug Development

Abstract

Recent studies have identified troubling method and practice lapses in neuropsychiatric drug developments. These problems have resulted in errors that are of sufficient magnitude to invalidate clinical trial data and interpretations. We identify two potential sources for these difficulties: investigators selectively choosing scientific practices for demonstrations of efficacy in human-testing phases of drug development and investigators failing to anticipate the needs of practitioners who must optimize treatment for the individual patient. When clinical investigators neglect to use clinical trials as opportunities to test hypotheses of disease mechanisms in humans, the neuropsychiatric knowledge base loses both credibility and scope. When clinical investigators do not anticipate the need to translate discoveries into applications, the practitioner cannot provide optimal care for the patient. We conclude from this evidence that clinical trials, and other aspects of neuropsychiatric drug development, must adopt more practices from basic science and show greater responsiveness to conditions of clinical practice. We feel that these changes are necessary to overcome current threats to the validity and utility of studies of neurological and psychiatric drugs.

Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat

“…This article is a PNAS Direct Submission. 1 To whom correspondence should be addressed. Email: astong@musc.edu.…”

“…This requires a biomarker of addiction suitable for rapid testing in animals, and applicable in humans. However, animal models of neuropsychiatric diseases generally lack predictive validity (1,2), and prevalent approaches that use drug self-administration in animals have not yet led to a successful clinical treatment for psychostimulant dependence (3,4).…”

Treatment of Dementia: Pharmacological Approaches

“…A peculiar human trait, cognitive impairment, for instance becomes practically immeasurable in mice, the in-vitro models most often used in trials [ 4 ]. One other obstacle we face is that a plethora of negative research data have gone unpublished and are therefore practically useless [ 4 ]. There are currently many compounds that evolve around a number of fairly newly discovered hypotheses explaining AD.…”

“…It is not for the lack of trying with existing and new molecules, but because there have been obstacles in neuropsychiatric research to produce data that are clinically actionable and sustainable [ 4 ]. A peculiar human trait, cognitive impairment, for instance becomes practically immeasurable in mice, the in-vitro models most often used in trials [ 4 ].…”

Disclosure of Clinical Trial Results When Product Development Is Abandoned

“…However, this assumption could be erroneous because we do not know if there are drugs that were e ective in the models but did not exhibit e cacy or that had unacceptable side e ects in clinical trials and were therefore terminated by their sponsors. Similar concerns have been identi ed in psychiatric drug research, leading to the conclusion that "translational medicine cannot approach its full potential if negative drug developments are unpublished" (23).…”