Nonpublication of trial results for new neurological drugs: A systematic review

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Neurological diseases exact immense and growing burdens on society.1 Unfortunately, neurological drug development requires larger financial and time commitments compared to many other fields4 and remains highly failure prone, with only 9% of agents put into trials advancing to regulatory licensure.5 As a consequence, many pharmaceutical companies are reducing investments in neurological drug development.6
One reason why attrition is so common is that pathophysiological processes driving central nervous system (CNS) disease are not well understood,7 thus confounding programs of rational drug development.9 Related to this, many neurological diseases—like Alzheimer's (AD) or Parkinson's disease (PD)—lack animal models that fully recapitulate human disease phenomena.10 Against this backdrop, unsuccessful translation trajectories provide vital feedback on the biological premises, animal models, and pharmacodynamic markers that drive neurological drug development.
Information from unsuccessful translation trajectories often has implications for clinical care as well. It can provide safety information should the drug be repositioned for other indications. Moreover, treatment decisions are often informed by pathophysiological models of disease, especially in the setting of off‐label prescription. For instance, the use of recombinant factor VIIa for hemorrhagic stroke was largely informed by knowledge of its mechanism of action.13 Trials are often the most reliable way of validating these mechanistic theories.
Previous studies have indicated that many prelicensure trials are never published,14 thus limiting opportunities to exploit findings from unsuccessful translation trajectories. Such nonpublication also violates human protection policies18 and potentially erodes participant trust in the research enterprise.20 That subjects participating in trials of stalled neurological drugs may be suffering advanced disease, lacking decisional capacity, or may have been exposed to unsafe or ineffective products makes nonpublication still more ethically problematic.
In this study, we evaluated publication rates for trials testing neurological drugs that reached pivotal testing before 2013. We also examined reporting of trial results through mechanisms like company repositories or trial registries.
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