Personalization of Therapeutic Efficacy and Risk

非甾体类抗炎药（NSAIDs）在全球有数千万人使用。虽然它们能缓解疼痛和炎症，但我们对它们的作用机制知之甚少。它们还会造成严重的胃肠道和心血管不良反应，据信已造成数千人死亡。尽管在随机试验中纳入了超过10万名患者，我们仍然不知道关节炎和心脏病患者的非甾体抗炎药的选择，也不知道非甾体抗炎药的临床疗效是否不同。在这里，我们提出了一种范式转换的战略方法，通过使用非甾体抗炎药的个性化治疗来获得收益并管理风险。

DESCRIPTION: Nonsteroidal anti-inflammatory drugs (NSAIDs) are consumed by tens of millions worldwide. Although they relieve pain and inflammation, we understand poorly their mechanism of action. They also cause serious gastrointestinal and cardiovascular adverse effects and are thought to have caused thousands of deaths. Despite enrolling more than 100,000 patients in randomized trials, we still do not know the NSAID of choice for patients with arthritis and heart disease or if NSAIDs differ in clinical efficacy. Here we propose a paradigm shifting, strategic approach to harvest benefit and manage risk by personalizing therapy with NSAIDs. Data from studies from yeast, mammalian cells, zebrafish, mice and humans will be integrated to develop signaling networks that reflect perturbation by model NSAIDs and that generate hypotheses ultimately addressed by prospective, randomized trials in humans. Our hope is that these iteratively refined models, progressively informed by human data, will lead to algorithms of incremental value to clinicians in the prediction of efficacy and adverse effects. This interdisciplinary strategy will deliver innovative tools and technologies, quantitative models and biomarkers of drug response and if successful will allow more rational prescription of NSAIDs to minimize risk and maximize benefit to individuals, creating a novel paradigm for the development and approval of drugs, the design of randomized trials and the treatment of chronic disease.