Abstract
Drug discovery and development is a lengthy and expensive process. Testing new agents in humans at an early stage could reduce the time and costs involved in identifying drugs that are likely to succeed in clinical studies. New guidance has outlined the concept of exploratory clinical trials, which provide important information on a drug's distribution as well as its physiological and pharmacological effects in humans. This strategy reduces the need for preclinical testing by limiting the dose and duration of exposure to a new drug in humans to below those required by the traditional testing of investigational new drugs. Exploratory, first-in-man studies should provide insights into human physiology and pharmacology, identify therapeutic targets relevant to disease and increase our knowledge of a drug's characteristics. Implementation of a new drug also requires the development of useful biomarkers of disease and of the drug's efficacy, as well as sensitive molecular imaging techniques. In this Review, we outline the benefits of exploratory clinical trials, especially in academia, and provide an overview of the experimental tools necessary for rational drug discovery and development.
Key Points
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New drug approvals are decreasing and very few drugs are developed for the treatment of kidney disease despite the large number of patients who might benefit from these drugs
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Understanding the pathophysiology of disease and assessing a drug's effects in humans at an early stage of drug development is important to reduce the time and costs involved in research
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New guidance has defined the concept of exploratory clinical trials, which involve the administration of a small dose of compound to humans for a limited time
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Exploratory clinical trials should provide insights into human physiology and pharmacology, identify therapeutic targets relevant to disease and expand our knowledge of a drug's distribution in the kidney
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The implementation of a new drug requires the identification of biomarkers of the disease and of the drug's effectiveness, as well as development of sensitive molecular imaging techniques
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Collaboration between regulators and researchers is essential to find more efficient strategies for preclinical and clinical development of a drug
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Acknowledgements
We thank N. Hirayama for kindly providing representative pictures of docking simulation, S. Takizawa, T. Honma and T. Yano for helpful discussion, T. Mori for representative pictures of blood oxygen level-dependent MRI, and M. Ishikawa for drawing schema.
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T. Miyata researched data for the article. All the authors contributed to discussion of the content. T. Miyata and C. van Ypersele de Strihou wrote the article and reviewed and edited the manuscript before submission.
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Miyata, T., Kikuchi, K., Kiyomoto, H. et al. New era for drug discovery and development in renal disease. Nat Rev Nephrol 7, 469–477 (2011). https://doi.org/10.1038/nrneph.2011.84
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DOI: https://doi.org/10.1038/nrneph.2011.84
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