Comparison of Treatment Effects Between US and Non-US Study Sites in Multiregional Alzheimer Disease Clinical Trials.

Abstract

Conducting clinical trials across multiple regions of the world has become common practice. A multiregional clinical trial (MRCT) presents opportunities as well as challenges. However, regional differences of treatment effects appear in many MRCTs, which make the interpretation of clinical trial results difficult and presents challenges for clinical trial design. Alzheimer disease (AD) is a progressive neurodegenerative disorder that affects approximately 5 million people in the United States and is the sixth leading cause of death in the country. In 2014, AD cost the United States $214 billion, and the cost is expected to rise to $1.2 trillion by 2050. In this article, we utilize data from New Drug Applications (NDAs) that have been approved for the treatment of AD to study whether there are differences in treatment effect between US and non-US study sites. Using an analysis of covariance (ANCOVA) model and forest plot, we analyze the treatment difference by region (US and non-US) from 3 separate perspectives: by region for each trial, by region for each endpoint, and by region and trial for each endpoint. Overall, the analyses indicate that treatment effects in clinical trials for AD are generally in the expected direction in both US and non-US sites. There was no clear evidence of heterogeneity in treatment effects between US and non-US sites. It appears that there is no clear evidence to suggest that MRCTs should not be used to study AD.