方法对比

	多中心I期临床试验	自适应I期临床试验
领域	流行病学	流行病学
方法族	Process / pipeline	Process / pipeline
起源年份	1970s–1980s (formalized in FDA Phase I guidance 1977; ICH E6 GCP 1996)	1990 (model-based adaptive era); rule-based designs from the 1970s–1980s
提出者	Established through FDA regulatory guidance and ICH harmonization frameworks	O'Quigley, Pepe, and Fisher (CRM); earlier rule-based 3+3 designs pre-date it
类型	Interventional clinical study design	Adaptive clinical trial design
开创性文献	International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). (2016). ICH Harmonised Guideline: Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2). ICH.	O'Quigley, J., Pepe, M., & Fisher, L. (1990). Continual reassessment method: a practical design for phase 1 clinical trials in cancer. Biometrics, 46(1), 33–48.
别名	multisite Phase I trial, multi-institutional Phase I study, Phase I dose-escalation multicenter study, first-in-human multicenter trial	adaptive dose-escalation trial, adaptive dose-finding study, model-based adaptive Phase I design
相关	6	1
摘要	A multicenter Phase I clinical trial is the first systematic administration of an investigational agent to humans, conducted simultaneously across two or more clinical sites. Its primary objectives are to characterize the safety and tolerability profile of the intervention, determine the maximum tolerated dose (MTD), and describe pharmacokinetic and pharmacodynamic behavior. Distributing enrollment across sites increases participant accrual speed and enhances the generalizability of early-phase safety data.	An adaptive Phase I clinical trial is a first-in-human or early-phase dose-finding study that continuously updates the recommended dose after each patient cohort using a prespecified statistical model, rather than following a fixed rule. The goal is to identify the maximum tolerated dose (MTD) or the recommended Phase II dose (RP2D) efficiently while minimising exposure of participants to sub-therapeutic or toxic doses. Adaptive designs — most notably the Continual Reassessment Method (CRM) — replace or augment traditional rule-based designs such as the 3+3 schema.