Causality assessment of adverse events in phase Ⅰ clinical trials
10.3760/cma.j.issn.1008-5734.2019.01.006
- VernacularTitle:Ⅰ期临床试验中不良事件的因果关系评价
- Author:
Chunhua WANG
1
;
Xiao HU
;
Cuicui YANG
;
Chaoying HU
;
Lan ZHANG
Author Information
1. 遵义医学院基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563000;首都医科大学宣武医院药学部,北京100053
- Publication Type:Journal Article
- Keywords:
Clinical trial;
phase Ⅰ;
Drug evaluation;
Causality
- From:
Adverse Drug Reactions Journal
2019;21(1):30-35
- CountryChina
- Language:Chinese
-
Abstract:
Phase Ⅰ clinical trial is a preliminary clinical pharmacology and human safety evaluation test of investigational products and used to observe the tolerance of human body to investigational products and obtain pharmacokinetic data in human body. The lack of clinical safety data of investigational products makes it difficult to judge the causality of adverse events (AE)in trials. There is no uniform criteria for causality assessment. Hill criterion is more widely used at present. There are 3 methods to assess the causality between investigational products and AE: expert judgment, algorithms, and probabilistic approaches. The major method for causality assessment of AE used in China,which is similar to the expert judgment method,is basically consistent with that in the World Health Organization′s Uppsala Monitoring Center (UMC). However,these evaluation methods are more suitable for post-marketing drug evaluation than for phase Ⅰ clinical trials. With the join of our country in the International Conference on Harmonisation (ICH),Phase Ⅰ clinical trials have gradually increased. Related evaluation guidelines should be published and an AE database should be established in China,basing on the metabolic and pharmacodynamic characteristics of the investigational products (including data from the preclinical studies)and the clinical manifestations of the subjects,and referring to the Hill criteria commonly used in the world,to conduct phase Ⅰ clinical trials well on the premise of guaranteeing the safety of the subjects and provide more valuable and accurate information for the following studies of investigational products at home and abroad.
