Pharmacogenomics, nutrigenomics, vaccinomics, and the nascent field of plant omics are examples of variability science. They are embedded within an overarching framework of personalized medicine. Across these public health specialties, the significance and biology of the placebo response have been historically neglected. A placebo is any substance such as a sugar pill administered in the guise of medication, but one that does not have pharmacological activity. Placebos do have clinical effects, however, that can be substantive in magnitude and vary markedly from person-to-person depending, for example, on the type of disease, symptoms, or clinical trial design. Research over the past several decades attests to a genuine neurobiological basis for placebo effects. All drugs have placebo components that contribute to their overall treatment effect. Placebos are used in clinical trials as control groups to ascertain the net pharmacological effect of a drug candidate. Not only less well known but also relevant to rational therapeutics and personalized medicine is the nocebo. A nocebo effect occurs when an inert substance is administered in a context that induces negative expectations, worsening patients' symptoms. With the COVID-19 pandemic, there are high public expectations for new vaccines and medicines to end the contagion, while at the same time antiscience, post-truth, and antivaccine movements are worrisomely on the rise. These social movements, changes in public health cultures, and conditioned behavioral responses can trigger both placebo and nocebo effects. Hence, in clinical trials, forecasting and explaining placebo and nocebo variability are more important than ever for robust science and personalized health care. Against this overarching context, this article provides (1) a brief history of placebo and (2) a discussion on biology, mechanisms, and variability of placebo effects, and (3) discusses three emerging new concepts: placebogenomics, nocebogenomics, and augmented placebo, that is, the notion of a “placebo dose.” We conclude with a roadmap for placebogenomics, its synergies with the nascent field of social pharmacology, and the ways in which a new taxonomy of drug and placebo variability can be anticipated in the next decade.

中文翻译：

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用安慰剂基因组学和安慰剂剂量重新思考临床试验和个性化医学

药物基因组学，营养学，疫苗学和植物组学的新兴领域是变异性科学的例子。它们被嵌入个性化医学的总体框架中。在这些公共卫生专业中，安慰剂反应的重要性和生物学历史上一直被忽略。安慰剂是任何形式的药物，例如以药物形式服用的糖丸，但不具有药理活性。但是，安慰剂确实具有临床作用，其程度可能是实质性的，并且因人而异，例如，取决于疾病的类型，症状或临床试验设计，其效果会明显不同。过去几十年的研究证明了安慰剂作用的真正的神经生物学基础。所有药物均具有安慰剂成分，有助于其总体治疗效果。安慰剂在临床试验中用作对照组，以确定候选药物的净药理作用。Nocebo不仅广为人知，而且与合理疗法和个性化医学有关。当在诱发负面期望的情况下施用惰性物质时，会出现nocebo效应，从而加剧患者的症状。随着COVID-19大流行，人们对新疫苗和新药结束传染病抱有很高的期望，与此同时，反科学，真相和反疫苗运动正在令人担忧地上升。这些社会运动，公共卫生文化的变化以及有条件的行为反应会触发安慰剂和nocebo效应。因此，在临床试验中 对于稳健的科学和个性化医疗保健而言，预测和解释安慰剂和Nocebo的变异性比以往任何时候都更为重要。在这种总体背景下，本文提供了（1）安慰剂的简要历史，（2）安慰剂效应的生物学，机制和可变性的讨论，以及（3）讨论了三个新兴的新概念：安慰剂基因组学，nocebogenomics和增强型安慰剂，即“安慰剂剂量”的概念。我们以安慰剂基因组学，与新兴的社会药理学领域的协同作用以及在未来十年中可以预期的新的药物分类法和安慰剂变异性的方法的路线图作为结束。（3）讨论了三个新出现的新概念：安慰剂基因组学，nocebogenomics和增强型安慰剂，即“安慰剂剂量”的概念。我们以安慰剂基因组学，与新兴的社会药理学领域的协同作用以及在未来十年中可以预期的新的药物分类法和安慰剂变异性的方法的路线图作为结束。（3）讨论了三个新兴的新概念：安慰剂基因组学，nocebogenomics和增强型安慰剂，即“安慰剂剂量”的概念。我们以安慰剂基因组学，与新兴的社会药理学领域的协同作用以及在未来十年中可以预期的新的药物分类法和安慰剂变异性的方法的路线图作为结束。