Model-Based Drug Development: A Rational Approach to Efficiently Accelerate Drug Development
Model-Based Drug Development: A Rational Approach to Efficiently Accelerate Drug Development
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DOI：
10.1038/clpt.2013.54
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发表时间：
2013-06-01
影响因子：
6.7
通讯作者：
Lalonde, R. L.
中科院分区：
文献类型：
--
作者：
Milligan, P. A.;Brown, M. J.;Lalonde, R. L.
制药业继续面临重大挑战。进入开发阶段的化合物很少能进入市场，而每项成功所需的投资可能超过18亿美元。尽管努力提高效率和生产力，但总投资继续增加，而新药产量却在下降。随着每个开发阶段的成本呈指数级增长，第二阶段和第三阶段的失败是最浪费的。在今天的发展范式中，后期失败主要是由于功效不足。这表现为无法与安慰剂充分区分（无论是新的还是已有的机制），或者无法与现有化合物充分区分。在此背景下，本文将通过一系列示例讨论基于模型的药物开发（MBDD）方法在加速和优化化合物开发策略方面的作用。
The pharmaceutical industry continues to face significant challenges. Very few compounds that enter development reach the marketplace, and the investment required for each success can surpass $1.8 billion. Despite attempts to improve efficiency and increase productivity, total investment continues to rise whereas the output of new medicines declines. With costs increasing exponentially through each development phase, it is failure in phase II and phase III that is most wasteful. In today's development paradigm, late-stage failure is principally a result of insufficient efficacy. This is manifested as either a failure to differentiate sufficiently from placebo (shown for both novel and precedented mechanisms) or a failure to demonstrate sufficient differentiation from existing compounds. Set in this context, this article will discuss the role model-based drug development (MBDD) approaches can and do play in accelerating and optimizing compound development strategies through a series of illustrative examples.