Kenneth A. Getz
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Over the past five years, there has been a largely unnoticed, yet dramatic, shift in the use of ex-U.S.–based investigative
sites. Major pharmaceutical and biotechnology companies have been placing an increasing proportion of their clinical trials
at offshore locations throughout eastern Europe, Latin America, and parts of Asia. Indeed, some sponsors report that they
now routinely place a majority of their clinical trials among ex-U.S.–based investigative sites. This shift has major implications
not only for U.S.-based investigative sites but also for sponsors and CROs looking to optimize their relationships with an
increasingly global network of investigators.
Shifting tides
It is widely accepted that conducting trials overseas is far less expensive, and there is a healthy supply of well-trained
physicians there eager to serve as investigators and study coordinators. Drug shipment issues have largely been overcome,
and the adoption of eClinical technology solutions has helped to address operating support issues that used to bottleneck
overseas projects.
Most importantly, the abundance of treatment-naïve patients abroad has translated into speedier clinical trial recruitment
and improved retention rates. In the developing world, vast numbers of patients suffer from diseases ranging from the familiar
to the exotic. These patients are often eager to enroll in clinical trials at the request of their physicians and eager to
gain access to free medical care, tests, and complimentary therapies that they otherwise could not afford. Overseas influx
In an analysis of 1572 filings with the Food and Drug Administration (FDA), the Tufts Center for the Study of Drug Development
has found that the majority of investigative sites still hail from the United States, but the geographic mix is in rapid flux.
A decade ago, for FDA-regulated studies, less than one in ten investigative sites was ex-U.S.; in 2004, one out of three sites
was ex-U.S. The Tufts Center also found that, whereas the overall number of principal investigators within the United States
has been growing by 8% annually since the late 1990s, the number of ex-U.S. principal investigators has been growing by more
than 20% annually during that same time period. Since 2001, the number of new domestic investigators has been declining by
11% each year.
Major pharmaceutical companies have already tipped the balance in favor of ex-U.S. investigative sites, or they are planning
to do so within the next couple of years. Wyeth, for example, reports that it now does more than half of its clinical trials
among ex-U.S.–based investigative sites. This year, nearly 60% of all investigative sites recruited by Novartis were ex-U.S.
sites. Midsized P&G Pharmaceuticals, now conducting more than one-third of its trials among ex-U.S. sites, says that it is
routinely looking to place trials overseas, often as replacements for traditionally U.S.-based investigators.
GlaxoSmithKline said that it conducted 29% of its clinical trials abroad last year and hopes to increase that figure to 50%
by the end of 2006. "We have a robust Phase II pipeline," said Rick Koenig of GlaxoSmithKline. "The challenge is to move those
compounds to Phase III and on to market in an expeditious way. We find that conducting trials in developing nations is less
expensive and faster than in either the United States or western Europe. In some instances, the difference is as much as tenfold.
We need sites that do strong quality work, and we can find them in places outside of traditional markets," said Koenig.
Merck is conducting significantly more studies internationally than in the past. More than 40% of its investigative sites
are based outside the United States, according to Jorge Guerra, MD, executive director of clinical research operations. Merck's
ex-U.S. clinical research is now being conducted predominantly in central and eastern Europe, Latin America, Australia, New
Zealand, and, increasingly, the Asia-Pacific region. Korea, which until recently allowed only postmarketing studies, is the
latest addition. "In the aggregate, studies conducted in 60 countries outside the United States are only slightly less expensive
to do than inside the United States," said Guerra. "Personnel costs in Latin America are definitely lower," he added, "but
the savings are offset by higher shipping and courier expenses."
