Analyses in 2011

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  • Co-developing a drug with a diagnostic to create a stratified medicine — a therapy that is targeted to a specific patient population on the basis of a clinical biomarker — presents challenges for product developers, regulators, payers and physicians. With the aim of developing a shared framework and tools for addressing these challenges, this article presents an analysis using data from case studies in oncology and Alzheimer's disease, coupled with integrated computational modelling of clinical outcomes and economic value, to quantify the effects of decisions on key issues such as the design of clinical trials.

    • Mark R. Trusheim
    • Breon Burgess
    • Michael C. Palmer
    Analysis
  • In the past 15 years, it has become clear that physicochemical properties of drug candidates, such as lipophilicity and molecular mass, have an important influence on the likelihood of compound-related attrition during development. By analysing the properties of compounds described in patents from leading pharmaceutical companies between 2000 and 2010, this article indicates that a substantial part of the industry has not modified its drug design practices accordingly and is still producing compounds with suboptimal physicochemical profiles.

    • Paul D. Leeson
    • Stephen A. St-Gallay
    Analysis
  • Schiöth and colleagues examine the drugs approved by the US Food and Drug Administration over the past 30 years and analyse the interactions of these drugs with therapeutic targets encoded by the human genome, identifying 435 effect-mediating drug targets. They also analyse trends in the introduction of drugs that modulate previously unexploited targets, and discuss the network pharmacology of the drugs in the data set.

    • Mathias Rask-Andersen
    • Markus Sällman Almén
    • Helgi B. Schiöth
    Analysis
  • To investigate whether some strategies have been more successful than others in the discovery of new drugs, this article analyses the discovery strategies and the molecular mechanism of action for 259 new drugs that were approved by the US Food and Drug Administration between 1999 and 2008. Observations from this analysis — such as the fact that the contribution of phenotypic screening to the discovery of first-in-class small-molecule drugs exceeded that of target-based approaches in an era in which the major focus was on target-based approaches — could have important implications for efforts to increase the productivity of drug research and development.

    • David C. Swinney
    • Jason Anthony
    Analysis
  • Although investment in pharmaceutical research and development (R&D) has increased substantially in recent decades, the lack of a corresponding increase in the output in terms of new drugs being approved indicates that therapeutic innovation has become more challenging. Here, using a large database that contains information on R&D projects for more than 28,000 compounds investigated since 1990, Riccaboni and colleagues examine the factors underlying the decline in R&D productivity, which include an increasing concentration of R&D investments in areas in which the risk of failure is high.

    • Fabio Pammolli
    • Laura Magazzini
    • Massimo Riccaboni
    Analysis
  • A common assumption in current drug discovery strategies is that compounds with highin vitro potency at their target(s) have a greater potential to translate into successful, low-dose therapeutics, which is reflected in screening cascades with in vitro potency embedded as an early filter. This analysis of the publicly available ChEMBL database, which includes more than 500,000 drug discovery and marketed oral drug compounds, suggests that the perceived benefit of high in vitropotency may be negated by poorer absorption, distribution, metabolism, elimination and toxicity (ADMET) properties.

    • M. Paul Gleeson
    • Anne Hersey
    • John Overington
    Analysis