Clinical Trials Go Global

One example of how medications affect ethic groups differently is noted by John Cush, MD, director of clinical rheumatology at Baylor Research Institute in Dallas. “When you look at the use of many current drugs on the market, whether methotrexate, Arava [leflunomide], or [tumor necrosis factor] inhibitors, they are used at lower doses in Japanese and Chinese populations, as pharmacokinetics and tolerability is different in these populations.”

Another concern about outsourcing is whether the foreign site has proper regulatory oversight, even though all clinical studies are supposed to be conducted under guidelines established by the International Conference on Harmonization, which has met frequently since 1991 to develop technical requirements for safe, effective, and high-quality drug development.⁴

Interestingly, a number of foreign studies have shown higher response rates to both active and placebo treatment, notes Arthur F. Kavanaugh, MD, professor of medicine in the rheumatology, allergy, and immunology division at the University of California, San Diego. “It’s hard to know why,” he says. “There are multiple factors. When you’re analyzing data region by region, you’ll see dramatic variation in the active treatment and placebo responses in different parts of the world.” He says results could be skewed when patients suddenly have access to treatments not previously available. “There may be a huge incentive for patients to get access to a medication, for physicians to get medication for their patients, and even for physicians to get the remuneration and recognition that can come from being an investigator in clinical trials,” Dr. Kavanaugh notes.

A large percentage of trials today take place outside North America, with increasing numbers in developing countries.

The Who and Why Behind Clinical Trials

Today it is Contract Research Organizations (CROs) that have increasingly taken a larger role in preclinical through phase III studies. From about 4,900 in 2000, CRO-conducted trials numbered 8,600 in 2010, according to the Tufts Center for the Study of Drug Development in Boston. The Association of Contract Research Organizations (ACRO) notes that CRO revenue was about $20 billion in 2010, representing one-third of total pharmaceutical and biotechnology development spending.

John J. Lewis, ACRO vice president, says his organization represents the larger global companies, including nine of the top 10 and 60% of the CRO industry revenue. However, many small companies also call themselves CROs and, according to Lewis, they could easily number in the thousands globally.

“Countries have different levels of regulatory maturity, and we try to adjust for that,” Lewis says. “Our members are going with the sponsor to the FDA to present data. We’re working closer with sponsors and regulators to clearly define the lines of responsibility.”