From call centers to... clinical trials

Fascinating post at CenterWatch on the rapid growth of global outsourcing of clinical trials. I highly recommend this post in its entirety.

The study, published in Wednesday’s New England Journal of Medicine (NEJM), reports that the number of countries conducting drug testing has doubled in the past 10 years, and, in November 2007, a total of 13,521 of 24,206 investigative sites being used for studies sponsored by U.S. big pharma were international.

Kevin A. Schulman, the lead author of the NEJM article and a professor of medicine at Duke, was interviewed by NYT. It is surprising just how nascent this field is:

The Duke study has ignited furor from the halls of big pharma. They point to the success of international trials for Gardasil (the quadrivalent HPV vaccine from Merck), and the clinical importance of this vaccine for developing countries. Why, they argue, should we prevent the rest of the world from sharing the cutting-edge therapies that we enjoy here at home? The U.S. enjoys the largest and most innovative pharmaceutical industry in the world, so why not expand our global market share by exporting business worldwide?

Indeed, global outsourcing may provide ancillary benefits ("collateral rescue") to entire resource-poor communities: an executive at Millenium Pharmaceuticals recently told me that his company has invested millions of dollars directly into hospital infrastructure improvements throughout the EMEA region, simply to bring up local quality standards to meet the FDA's trial compliance guidelines.

While there's nothing inherently bad about conducting trials internationally, most criticism stems from concern that good clinical trial practices (things like informed consent, blinded controls, patient compliance and followup) are much harder to enforce abroad. It's also questionable whether data collected in one patient population (e.g., Western Saharans) can be used to justify a claim for efficacy in another (e.g., Southern Californians).

Furthermore, Phase I trials, which primarily involve healthy volunteers, will often use monetary incentives to recruit patients. The ethics of doing this in the developing world is murky at best, particularly when individual incentive structures are sharply skewed by widespread poverty, famine, or conflict. I haven't yet heard any good consensus frameworks for thinking about the ethics of risk v. benefit within the context of international trial design.

CenterWatch offers its own multi-point rebuttal of the Duke study:

• The sample size is almost half of the trials listed at the time, compared to a more comprehensive analysis of clinical trials listed in August of 2007 done by Goldman Sachs.
• The study’s analysis of the 20 largest drugmakers in the U.S. excludes more than 1,900 other companies developing drugs around the world.
• Of the 20 countries outside the U.S. doing the most trials in August of 2007 (from the Goldman study), only four—Poland (13th), Russia (17th), Brazil (19th), and the Czech Republic (20th) could be considered emerging markets.
• The percentage of clinical trials initiated overseas increased from about 13% in 1997 to about 30% in 2005. At the end of 2007, the number was just under 34%. The number of trials being conducted worldwide has gone from around 22,000 in 1997 to about 37,000 in 2007.
• While the number of clinical trials initiated overseas has increased dramatically, the study overstates the share of trials overseas by more than 20 percentage points.

John Lewis of the Association of Clinical Research Organizations (ACRO) posted a lengthy (if boilerplate) comment after the post that's at least worth checking out for its predicability.