The conduct of clinical trials for U.S. Food and Drug Administration (FDA) drug approvals—whether they take place in an academic medical centers or private practices—is no longer the exclusive realm of the United States. A large percentage of trials today take place outside North America, with increasing numbers in developing countries.
The FDA says that at least 80% of approved marketing applications for drugs and biologics contain data from foreign clinical trials. A June 2010 Department of Health and Human Services (HHS) Office of the Inspector General report noted that, although Western Europe accounts for most foreign clinical trial participants and sites, Central and South America had the highest average number of participants per site.1 Additionally, developing nations are aggressively seeking clinical trials.
Belimumab Approval Highlights Challenges of Global Trials
A recent example is the drug belimumab (Benlysta), approved by the FDA on March 10, 2011, for the treatment of systemic lupus erythematosus (SLE). According to research on the drug, at least half of which was conducted outside North America and Western Europe, benefits were lower for U.S. residents and Canadians.
The first therapy in more than 50 years to be FDA approved for SLE, belimumab is the first in a new class of drugs called B-lymphocyte stimulator-specific inhibitors. According to a briefing for the FDA Arthritis Advisory Committee, its efficacy was questioned in certain populations, including Africans and African-Americans.2 Additionally, the briefing noted “an inconsistent efficacy trend across different geographical regions of the world with numerically smaller separation of efficacy measures between placebo and belimumab for patients from [the] U.S. and Canada compared to some other regions.”
The belimumab story illustrates a concern with foreign clinical trial participants: Results from populations outside of the United States, especially in developing countries, may not be generalizable to the U.S. population.
Concerns about International Studies
“In rheumatology, where we’re talking about immune-modifying types of drugs, we don’t know a lot about variation in pharmacogenomics across populations,” says Kevin Schulman, MD, MBA, director of the Center for Clinical and Genetic Economics at Duke Clinical Research Institute in Durham, N.C. “We don’t know a lot about disease severity or practice patterns. So, how do we interpret information that we get in these other environments where many of these issues are left unexplored in a clinical trial?”
Dr. Schulman was the senior author of a 2009 New England Journal of Medicine article entitled “Ethical and Scientific Implications of the Globalization of Clinical Research.”3 The article notes that “geographically distinct populations can have different genetic profiles, and these differences have been shown to be related to the safety and effectiveness of drugs and even medical devices.”