W-31: A Retrospective Analysis of Bridging Study Evaluation in Taiwan During 2011-2018: Focus on Multi-Regional Clinical Trials

Poster Presenter

Hui-Chun Hong

Pharmacokinetic Reviewer
TFDA/Center for Drug Evaluation
Taiwan

Objectives

The purpose of this study is to retrospectively analyze the outcome of bridging study evaluation (BSE) applications in terms of the existence of East Asian data from MRCTs and the reasons of a non-waiver conclusion by Taiwan FDA for BSE applications submitted from 2011 to 2018.

Method

The assessment reports of BSE applications during study period were retrieved from electronic database. The rate of waiver for bridging study was compared for BSE applications with and without MRCTs that included East Asian data, and the reasons for non-waiver granted by TFDA were also investigated.

Results

A total of 254 BSE review reports were retrieved and evaluated. We divided these BSE applications into two categories. The BSE applications with MRCTs, which included East Asian data were classified as category I. Other BSE applications, such as those with MRCTs but no East Asian data or those without MRCTs but submitted East Asia trials, were classified as category II. Overall, 55% and 45% of applications were sorted respectively into category I and II. The BSE applications in category I showed a high waiver rate of 94%. Among these waiver cases, the East Asian data in MRCTs were mostly from Japan, Korea, China, Taiwan and Thailand. About 67% of BSE applications in category II were granted a waiver of bridging study, most of which were waived based on sufficient East Asian data from the independent local trials in East Asia. Expectedly, a higher non-waiver rate in category II was mostly due to lack of East Asian data, followed by improper cross-study comparison for ethnic assessment, efficacy and safety concern in Taiwanese population, and so on.

Conclusion

The MRCTs data in bridging data package could provide more robust evidence than single regional trials for extrapolation of study results. However, the MRCTs data used for bridging strategy in the past years were evaluated through a sub-group analysis without pre-specified pooling of regions or subpopulations. The outcome of ethnic assessment based on such analysis may include the biases when pooling data. Since the planning and design of MRCTs must be pre-defined in ICH E17 guideline, the MRCTs development according to the present guideline can avoid the biases which were mentioned above and facilitate the assessment of ethnic factors on the treatment effect. Furthermore, the pharmaceutical sponsors are encouraged to include more East Asian subjects especially Taiwanese into MRCTs to expedite a bridging study waiver, which is an essential requirement of New drug application (NDA) approval in Taiwan.