 the world. “These genetic polymorphisms can affect drug metabolism and how effectively a drug might work,” Glickman told ARF. “It's entirely conceivable that the same drug being tested in the U.S. versus in a developing country could produce markedly different results.”
Others agree that cultural, healthcare, and genetic differences can shift trial outcomes. “I think that many of the concerns raised in this article are reasonable and appropriate,” said Paul Aisen, University of California, San Diego, who heads the NIA-funded Alzheimer’s Disease Cooperative Study.
Regional differences in life expectancy, for instance, become important in clinical trials of AD, a disorder whose primary risk factor is age. In the recent Phase 2 trial of Dimebon conducted in Russia (see ARF related news story), where men typically die in their sixties (compared to U.S. men who on average live to almost 80), the research participants had a mean age significantly lower than in U.S. and Western Europe trial sites. “That’s a difference that has to be examined and considered,” Aisen said.
However, he believes other issues highlighted in the new study “go too far.” One of these concerns the mismatch, in some cases, between the populations testing a compound and the intended market for that drug. Drugs for common diseases are increasingly being tested on people in developing countries but are primarily sold in wealthy nations. Conversely, “we didn't find many trials being conducted for diseases like tuberculosis or malaria, which disproportionately affect the developing world,” Glickman said.
Aisen does not see these discrepancies as deal breakers. “I don't believe it is unethical to use international trial sites that do not accurately reflect the ultimate market for the drugs being tested,” he told ARF. Aisen pointed out that though the U.S. Food and Drug Administration generally requires that some research subjects be in the U.S., there are no strict guidelines regarding what proportion. Beyond that, he contends that clinical research carries many benefits that do not depend on trial outcome. The participants receive extra care and attention, as well as new information, simply by taking part in a trial. Local physicians learn state-of-the-art management. In addition, global trials promote exchange of knowledge and experience between investigators in different countries. “International conduct of clinical trials benefits everyone,” Aisen said. “It benefits the local communities, and it benefits global health by supporting the development of new treatments.” He and the study authors agree that centralized oversight and improved international collaborations between investigators could help ensure that clinical trials adhere to global standards of scientific rigor and ethical behavior.—Esther Landhuis
- Decullier E, Chan AW, Chapuis F. Inadequate dissemination of phase I trials: a retrospective cohort study. PLoS Med. 2009 Feb 17;6(2):e1000034. PubMed.
- Glickman SW, McHutchison JG, Peterson ED, Cairns CB, Harrington RA, Califf RM, Schulman KA. Ethical and scientific implications of the globalization of clinical research. N Engl J Med. 2009 Feb 19;360(8):816-23. PubMed.