Ethnic factors in the acceptability of foreign clinical data:The role of ICH E5 guidance in international drug development

【摘要】：正The discovery and development of new drugs is an expensive and lengthy process that can cost several hundr- ed million dollars and over a decade of development.The need to repeat large-scale clinical trials in new regions for a drug already deemed safe and efficient for human use in a specific ICH region adds to the cost and delays avail- ability of potentially useful medications in the new region. A case can also be made that this represents unnecessary human experimentation in some instances.The adoption of the ICH E5 guidance by Japan,US,EU has led to more streamlined development and made important new drugs available more quickly in new regions.Central to this is the concept of a bridging study.A bridging study,while it can have multiple objectives and can take one of several designs,allows one to extrapolate to a new region,safety and efficacy data obtained in a foreign region.Clinical pharmacology principles play a key role in the E5 process and help determine the nature and extent of the bridging study.Thus,a medicinal agent is characterized as less or more sensitive to ethnic factors based on PK/PD character- istics.These include pharmacokinetic linearity or lack thereof,fiat or steep dose/effect response curve,single or multiple pathways of metabolism,low potential for drug- drug and drug food interactions,and high or low bioavail- ability.In addition to PK/PD principles,several other as- pects need to be considered.These include medical prac- tice and conduct of clinical trials in different regions.If a medicinal agent is ethnically insensitive based on PK/PD characteristics,and medical practice and clinical conduct are similar between two regions,a bridging study may not be needed.On the other hand,a drug which is character- ized as more sensitive to ethnic factors is likely to need more extensive bridging studies,or if necessary,confirma- tory clinical trims.Thus,the ICH E5 guidance provides a rational scientific framework by which decisions on extrap- olation of data obtained in foreign regions can be made. The rapid adoption of this framework is especially notice- able in Japan,where the successful registration of new drugs using principles of the ICH E5 guidance has been increasing since the guidance went into effect.Using sev- eral examples of drugs that have been successfully regis- tered using the ICH E5 guidance,the central role of PK/ PD principles and approaches will be highlighted.The im- portance of this guidance for emerging large pharmaceutical markets such as China will also be discussed.