Center for Personalized Health, Northwell Health, New York, New York.
Donald and Barbara Zucker School of Medicine at Hofstra University/Northwell Health, Hempstead, New York.
JAMA Pediatr. 2021 Apr 1;175(4):404-409. doi: 10.1001/jamapediatrics.2020.5801.
Conventional randomized clinical trials (RCTs) compare treatment effectiveness to provide support for evidence-based treatments that can be generalized to the average patient. However, the information obtained from RCTs may not always be useful for selecting the best treatment for individual patients. This article presents a complementary approach to identifying optimized treatments using experimental designs that focus on individuals. Personalized, or N-of-1, designs provide both a comparative analysis of treatments and a functional analysis demonstrating that changes in patient symptoms are likely because of the treatment implemented. This approach contributes to the zeitgeist of personalized medicine and provides clinicians with a paradigm for investigating optimal treatments for rare diseases for which RCTs are not always feasible, identifying personally effective treatments for patients with comorbidities who have historically been excluded from most RCTs, handling clinical situations in which patients respond idiosyncratically (either positively or negatively) to treatment, and shortening the time lag between identification and implementation of an evidence-based treatment. These designs merge experimental analysis of behavior methods used for decades in psychology with new methodological and statistical advances to assess significance levels of changes in individual patients, and they can be generalized to larger populations for meta-analytic purposes. This article presents a case for why these models are needed, an overview of how to apply personalized designs for different types of clinical scenarios, and a brief discussion of challenges associated with interpretation and implementation of personalized designs. The goal is to empower pediatricians to take personalized trial designs into clinical practice to identify optimal treatments for their patients.
传统的随机临床试验 (RCT) 将治疗效果进行比较，为可以推广到一般患者的基于证据的治疗方法提供支持。然而，从 RCT 中获得的信息并不总是对为个别患者选择最佳治疗方法有用。本文提出了一种使用关注个体的实验设计来确定优化治疗方法的补充方法。个性化或 N-of-1 设计既提供了治疗方法的对比分析，也提供了功能分析，证明患者症状的变化很可能是由于实施的治疗方法引起的。这种方法符合个性化医学的时代精神，为临床医生提供了一种研究罕见疾病最佳治疗方法的范例，这些疾病的 RCT 并不总是可行的，为历来被大多数 RCT 排除在外的合并症患者确定个人有效的治疗方法，处理患者对治疗反应奇特（无论是积极还是消极）的临床情况，并缩短从确定到实施基于证据的治疗的时间滞后。这些设计将心理学中几十年来使用的行为方法的实验分析与新的方法学和统计进展相结合，以评估个体患者变化的显著性水平，并且可以推广到更大的人群进行荟萃分析。本文提出了为什么需要这些模型的理由，概述了如何为不同类型的临床情况应用个性化设计，并简要讨论了与个性化设计的解释和实施相关的挑战。目标是使儿科医生能够将个性化试验设计应用于临床实践，为患者确定最佳治疗方法。
