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Kenneth A. Getz

According to several independent studies: Less than one-third of investigative sites in any multicenter program are outstanding performers; 20% will meet expectations; and approximately half will underperform or fail to enroll a single patient. At the same time, sponsors concede that for any given study they do not know which sites will deliver and which will not due to numerous factors, including the motivation of the investigators and study staff; complexity and demands of the protocol; and competition for study volunteers.

My colleagues and I at the Tufts Center for the Study of Drug Development (Tufts CSDD) have been monitoring several trends in the investigative site landscape that threaten to make improvements in sponsor–site collaborative effectiveness even more elusive. What follows is a brief discussion of these trends based on data maintained and provided by the FDA. It's important to note that although this data captures a majority percentage of the global investigative site landscape, it does not include all of it. Comparable and comprehensive data on investigative sites regulated by other agencies around the world is not available.

Globalization

The number of investigators conducting FDA-regulated studies is increasing. At the same time, a large and growing percentage of investigators are no longer based in North America and Western Europe. This trend highlights the rising, and costly, logistical complexity of finding, building, managing, and monitoring relationships with investigative sites dispersed around the world.

Worldwide, more than 26,000 unique investigators conducted FDA-regulated clinical trials in 2007. Globally, the number of investigators grew at an annual rate of 8.7% from 1990 to 2000. Since 2001, however, growth in the absolute number of investigators has been slower, at 2.1% annually.

The proportion of investigators based in North America has steadily declined from 96% of the total global pool of FDA-regulated investigators in 1990 to 54% in 2007. Western Europe has held a share of approximately 12% to 14% of all FDA-regulated investigators for the past five years.

Latin America, Eastern Europe, and Asia have seen rapid growth in the number of FDA-regulated investigators, mostly for confirmatory, later stage clinical studies. Steady growth in the proportion of investigators in emerging regions is due to many factors, including lower relative study conduct costs, harmonization of good clinical practice guidelines, well-positioned CROs, and the availability of large numbers of well-trained professionals and treatment-naïve patients.

At the end of 2008, 8.5% of active FDA-regulated investigators were based in Central and Eastern Europe. Asia and Latin America each hosted 5.5% of all investigators.

Interestingly, we've observed a decline in the number of active FDA-regulated investigators conducting Phase II and III trials in North America, while the opposite has occurred in Phase I studies. Growth in North America-based FDA-regulated investigators in early, first-in-man clinical studies has been substantially faster than that observed in Western Europe and in emerging regions. This is due to a number of factors, including sponsors' belief that Phase I studies are more economical and can be initiated faster in North America.

Privatization

Since the early 1990s in the United States, drug development sponsors have facilitated the privatization of clinical trial conduct in their search for lower cost, higher performing investigative sites. Today, the U.S. investigative site market is comprised of three primary segments.

The Part-time segment is made up of physicians in private, community settings that derive the majority (85% or more) of their annual revenue from clinical practice. In 2007, this highly fragmented and transient group has surpassed Academic Medical Centers (AMCs) as the largest market segment, with a 38% share of total clinical trial grants.