终止新药研发项目为何如此困难?

ipsvirus

【新闻事件】：今天《Nat. Rev. Drug Discov.》发表一篇罗氏科学家写的一篇评论文章，讨论终止新药研发项目为何如此困难。他们认为人的本性和企业文化是无法及时终止劣质项目的主要障碍。 比如科学家过度乐观、不愿放弃已经投入很多的项目，而企业对成功项目的奖励超过失败项目，虽然有些成功项目代价过高， 尤其是考虑到机会成本。另外无法判断项目成功可能（测试特异性）以及缺少优质项目也是原因。最后文章给出了针对这些问题的7点解决方案。

【药源解析】: 项目取舍对新药企业至关重要，因为新药项目投资巨大，选错方向一是浪费了人力物力，更重要的是失去了做更优质项目的机会。前一阵诺华颁发“勇气奖”鼓励及时终止僵尸项目也是出于这个考虑。虽然回头看很多项目应该早就终止，今天这篇文章提到的企业和个人的诸多毛病也都是事实，但解决这个问题却并不容易。

自由竞争是个法力无边的纠错机制。人的弱点很多，但自由竞争这个看不见的老师会教你如何改造。每个人都希望睡到自然醒，但多数人都有一个闹钟。为什么？因为如果你爸不是李刚太阳升起的时候你最好开始忙碌，否则就会被淘汰。企业的运作缺陷一个道理。所以现在终止新药项目困难的核心问题是大家不知道什么时候、怎么终止项目才有竞争优势。

事实上并不是所有人都支持kill the losers这个策略。传奇CEO Vagelos说新药的诀窍是在很少的项目上投很多的钱。如果整个制药工业按今天文章最后提出的那7点建议运行，历史上最成功的药物很多都不会诞生。他汀的第一个动物模型无效，Prozac第一个二期临床失败，第一个进入临床的质子泵抑制剂毒性太大，统统拉出去枪毙？

如果现在请制药界的顶尖专家挑出10个最应该终止的项目，10年以后回头看可能会令人非常尴尬。大家经常说kill the losers，好像losers都脑门上印着字儿一样。事实上优质项目和劣质项目的区别非常微妙，好比根据高中运动会成绩判断谁以后在奥运会的成绩会更好。象我百米15秒这样的losers当然很容易去除，但制药工业面临的任务是比较博尔特和刘易斯。如果把新药算成猜谜，你如果只猜中5%你基本要被淘汰，你要是能猜对10%你就会成为行业巨头。这里面的差距非常小。

90%的项目没上临床就被终止，进入临床的又有90%最终被终止，所以并非每个项目都长生不老。是否有僵尸项目？毫无疑问。但我认为企业和个人的行为并非主要原因，文章提出的7点建议也和现在运行模式一样会被滥用。我相信自由竞争会纠正一切错误模式，只要你知道什么是正确模式。

来源：美中药源

ipsvirus

Plan for implementing quick-kill strategies
We offer a seven-step plan for the successful implementation of quick-kill strategies:

• Abandon denialism. Progression-seeking behaviour incurs massive opportunity costs. Focusing on cycle-time reduction in the past meant the industry became really slick at delivering projects that were terminated in later-stage development.
  

• Banish 'success' and 'failure' from the organizational lexicon. Good decisions — either to progress a marketable product or to terminate an unmarketable product — are all successes. Learn from both kinds.
  

• Rebuild reward systems to reward good decisions rather than good outcomes.
  

• Place project progression targets in a quality framework, or abandon them altogether. Targets encourage progression-seeking behaviour and invite gaming of the system, and they do not work in isolation.
  

• Quantify and communicate opportunity costs in the organization. Reframe progression-seeking behaviour in terms of opportunity costs and consider termination decisions as prospective gains rather than losses.
  

• Overhaul feedback systems, in order to allow staff to learn the outcome of early development decisions and avoid repeating the same mistakes.
  

• Develop a communication plan for staff and shareholders that presents the new model and the probable timescales. Communication with the financial markets is particularly important.
  

ipsvirus

Why is it hard to terminate failing projects in pharmaceutical R&D?

Richard W. Peck,        Dennis W. Lendrem,        Iain Grant,        B. Clare Lendrem        & John D. Isaacs

'Quick-kill' strategies in pharmaceutical research and development aim to reduce late-stage attrition by bringing project termination decisions forward, to an earlier point in the process. How can the barriers to implementing such strategies be overcome?

Currently, pharmaceutical research and development (R&D) productivity is low, late-stage attrition rates are high and drug development is costly1. Much of this cost is due to spending on molecules that do not complete development. A possible solution has been known for some time: 'quick-kill' strategies that seek to reduce late-stage attrition by bringing forward decisions to terminate projects to an earlier point in the process2. There are technical challenges in implementing such strategies to support experimental medicine approaches in early-stage clinical trials, including developing more-sensitive bioassays for adverse effects and more-specific biomarkers based on clinical pharmacology. However, we consider that the real obstacles to implementation are behavioural, cultural and organizational. Here, we highlight these obstacles and discuss strategies to overcome them.

http://www.nature.com/nrd/journa ... 725.html#affil-auth