Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders Proceedings of a Workshop (2017) / Chapter Skim
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7 Regulatory Perspectives
7 Regulatory Perspectives
Pages 55-60
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From page 55... ...
Regulatory agencies grapple with many of the questions discussed at the workshop regarding what levels of evidence are needed to conduct efficient clinical trials in humans, what constitutes an acceptable outcome measure, and what is the role of surrogate outcomes, said Linda Brady, director of the division of neuroscience and basic behavioral science at the National Institute of Mental Health. The workshop specifically focused on how to address these issues when predictive animal models of disease are not available for preclinical studies.
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From page 56... ...
. For example, in considering approval of interferon-based drugs for multiple sclerosis, strong magnetic resonance imaging data supported a single study showing reduced exacerbation rates as the basis for accelerated approval, despite a lack of clinical data demonstrating efficacy.
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NEW APPROACHES IN ESTABLISHING SAFETY AND CONDUCTING TOXICOLOGY STUDIES Thomas Hartung, professor and chair of evidence-based toxicology at the Johns Hopkins Bloomberg School of Public Health, offered a perspective based on his experience as head of the European Commission's Center for the Validation of Alternative Medicine, his experience at Hopkins, and his work at Organome, a technology company that is developing "mini-brains" similar to the organoids described by Lee Rubin in Chapter 4. Hartung said that about 20 percent of drug failures in clinical trials are attributable to unanticipated side effects, and that side effects account for 8 percent of drugs withdrawn from the market.
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From page 58... ...
For example, the Human Toxome Project,1 funded by the National Institutes of Health Transformative Research Grant program, brought together multiple institutions to formulate multi-omics approaches for developing technologies to better understand molecular pathways of toxicity. Another project in Europe brought together legacy data to build the largest toxicology database in the world (Luechtefeld et al., 2016)
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From page 59... ...
At the same time, increased investment for natural history studies with deep phenotyping will be needed to enable segmentation of heterogeneous populations and testing of specific biological questions. Hyman added that an increasing understanding of genetics and genetic risk factors might also allow stratification in natural history studies, further increasing the power of those studies.
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From page 60... ...
Several workshop participants said the absence of a clear regulatory path is a barrier to developing treatments for chronic diseases, where combinations of surrogate markers may be used as the basis of approval, even if it is provisional approval with postmarketing monitoring in Phase IV. A few participants also expressed concern about having an adequately trained workforce, particularly in basic science, to ensure continued progress in developing therapeutics for nervous system disorders.
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