Stochastic Combinatorial Optimization Approach to Biopharmaceutical Portfolio Management
Stochastic Combinatorial Optimization Approach to Biopharmaceutical Portfolio Management
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DOI：
10.1021/ie8003144
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发表时间：
2008-11-19
影响因子：
4.2
通讯作者：
Farid, Suzanne S.
中科院分区：
文献类型：
--
作者：
George, Edmund D.;Farid, Suzanne S.
生物制药组合管理中的关键战略决策包括药物选择、活动安排和第三方参与。优化战略由于不确定性、决策之间的依赖关系以及可能冲突的多个目标而变得复杂。本文提出了一个随机组合多目标优化框架的发展，旨在解决这些问题。该框架模拟投资组合管理策略，同时利用贝叶斯网络和进化计算来描述最优决策的概率结构，并将策略进化到多目标最优。这个配方被应用于一个案例研究，该案例研究需要五个治疗性抗体项目的组合。优化是由两个相互冲突的目标驱动的：最大化盈利能力和最大化盈利概率。沿着帕累托最优前沿对竞争策略的初步分析表明，在构成决策方面存在明显差异的策略可以与类似的回报-风险曲线竞争。因此，优化产生的结果不是直观的，而是表明在这样的大规模问题中可以存在策略之间的灵活性。聚类分析被用来确定沿着帕累托前沿的广泛和优越的构建块的流行率。内部药物开发通常成为更好的战略的首选组成部分，这些战略建议努力将合同费、保费、特许权使用费和对第三方的销售收入损失降至最低；在本案例研究中没有施加预算限制。看来，安排活动的战略对业绩的影响最大。与其他战略组成部分相比，投资组合结构战略似乎具有最大程度的灵活性。
Key strategic decisions in biopharmaceutical portfolio management include drug selection, activity scheduling, and third party involvement. Optimizing strategies is complicated by uncertainty, dependency relationships between decisions, and multiple objectives that may conflict. This paper presents the development of a stochastic combinatorial multiobjective optimization framework designed to address these issues. The framework simulates portfolio management strategies while harnessing Bayesian networks and evolutionary computation concertedly to characterize the probabilistic structure of superior decisions and evolve strategies to multiobjective optimality. This formulation is applied to a case study entailing a portfolio of five therapeutic antibody projects. Optimization was driven by two objectives that conflicted here: maximizing profitability and maximizing the probability of being profitable. Initial analysis of competing strategies along the Pareto optimal front indicated that strategies with clear differences in comprising decisions can compete with similar reward-risk profiles. Hence optimization yielded results that were not intuitive but instead suggested that flexibility between strategies can exist in such large-scale problems. A cluster analysis was used to identify the prevalence of broad and superior building blocks along the Pareto front. In-house development of drugs generally emerged as a preferred constituent of superior strategies which suggested a drive toward minimizing contracting fees, premiums, royalty charges, and losses in sales revenue to third parties; no budgetary constraints were imposed in this case study. It appeared that strategies for scheduling activities had the most overarching impact on performance. Strategies for portfolio structure appeared to have the greatest degree of flexibility relative to other strategic components.