Survey finds United States still leading clinical trials by number and density.
By Deborah Borfitz
April 1, 2008 | Outsourcing of biopharmaceutical clinical trials to China and India is growing at a substantial rate, but in real terms the much-ballyhooed nations are still "very minor players," says Ernst Berndt, professor of applied economics at the MIT Sloan School of Management. So is every other country except the United States, which commands a 48.7 percent share of total trial activity and has eight times the number of trial sites of second-place Germany.
These were among the findings of a study by Berndt and his colleagues, based on an analysis of data on ClinicalTrials.gov and published in the January 2008 issue of Nature Reviews Drug Discovery. Eastern Europe, Latin America, and even Peru posted healthy growth, "not just Asia," notes Berndt. "I think a lot of people lump the outsourcing of technology with the outsourcing of trials."
India, a growing global hub for trial-related technology, is well positioned to become a major clinical trials player, says Berndt. It has more biotech manufacturing activity than fast-growing Russia by virtue of its well-established generic drug and "fermentation" industries. "In a lot of places [including Germany] where beer is made, biotech springs up. They use similar principles in their manufacturing processes."
Trial density, the proportion of recruiting sites relative to overall population, is greatest in the United States, Canada, and several Western European countries, says Berndt. But it's becoming substantial in some Eastern European countries such as the Czech Republic, Hungary, and Estonia. Presumably, this makes the region increasingly able to offer a competitive number of sites suitable for global trials.
Interestingly, Western Europe does the largest proportion of Phase IV work, says Berndt, "perhaps reflecting reimbursement requirements." Early trials are disproportionately high in North America, while confirmatory trials are most common in Eastern Europe, Latin America, and Asia.
In relative terms, traditional clinical trials regions are growing more slowly or not at all while emerging regions are ramping up, says Berndt. Academic centers in Europe and North America "should think through the long-term budgetary implications of no longer being sites of big Phase III trials."
In absolute terms, it is "not clear yet what is happening," says Berndt. He plans to compare 2006 and 2007 data to see if the number of U.S. sites increased despite the country's 6.5 percent declining share of overall growth. France, Canada, the United Kingdom, Belgium, and Sweden also saw a decline in growth share.
The implications of these trends are many, says Berndt. Protocol design is currently the focus of oversight by the FDA. Less than 1 percent of investigative sites in any given year are audited to see if they're actually conducting a trial as specified by the protocol. But just last month the FDA said it "hopes" to establish five satellite offices in India, China, Central and South America, and the Middle East to help monitor trials.
Pooling data from ethnically and culturally diverse populations may become problematic with the march toward personalized medicine and pharmacogenomics, says Berndt, and at some point may even reverse the current globalization trend.
Drug-naïve patients on vegetarian diets may also be differentially affected by classes of drugs commonly used in the Western world. Further, the integrity of the informed consent process may be jeopardized in nations where the physician-patient relationship is more "hierarchical."
On Berndt's agenda is to "study the notion that it's easier to outsource trials that are algorithmic and mechanical, such as blood pressure and cholesterol counts, versus subjective endpoints such as pain, mood, and emotion. I wouldn't be surprised if the therapeutic areas that get outsourced are straightforward, with quantifiable endpoints."
This article appeared in Bio-IT World Magazine.
Subscriptions are free for qualifying individuals. Apply Today.