The October 4, 2007, edition of the New England Journal of Medicine (NEJM) is not online for free; we can’t link to it. But it contains a discussion of the booming contract research organization (CRO) industry. The CRO industry’s growth is a forehead-smacking surprise to the journal, which says the industry has $18 billion in revenues and plays a role in 64 percent of Phase I-III trials.

Major media outlets will eventually follow up with their own looks at the CRO industry. All of the NEJM allegations will resonate in the academic world. What remains to be seen is how they will play on Main Street.

About The Author

The article was written by Miriam Shuchman, who is both a journalist and a Dartmouth- and Mass-General trained psychiatrist. Shuchman works at SUNY-Buffalo and as a national correspondent for the NEJM. She is the author of The Drug Trial, a book about the Nancy Olivieri controversy at Apotex.

In a highly unscientific sample of the CRO industry’s activity, Shuchman paints a pretty unflattering portrait. Rather than describe thousands of CRO-supported trials that unfold smoothly, she focuses on half a dozen high-profile, controversial studies that made news. The key anti-CRO perspectives in the NEJM article are based on those studies, not the bulk of what CROs do. The key points:

• The CRO industry functions in an ambiguous regulatory environment at the FDA. A high-level FDA manager, Rachel Behrman, is quoted as saying “it’s not clear” whether CROs are directly accountable to the FDA or their clients. New guidelines are in the works, the NEJM says.

• The CRO industry ethically calls attention to problems, but sponsors choose to conceal the information. As an example, Shuchman recounts the controversy in a trial of the antibiotic Ketek, in which PPD disclosed warnings about a site to Aventis that were ignored. Shuchman also mentions the Bayer episode, in which a post-marketing trial was hidden from the FDA until Ingenix forced Bayer to disclose it.

• The CRO industry puts low costs and productivity above the careful quest for knowledge. The NEJM quotes an academic researcher saying that there is 100 percent employee turnover on some trials, simply due to low salaries at CROs.

Capitalism 101

The article notes that academic research organizations (AROs) have lost market share in assisting with research at the expense of the CRO. That’s an understatement. Part of the NEJM’s motivation for its article may be sour grapes in academia about the loss of billions of dollars in projects to CROs.

Sadly, a larger economic context is absent from the NEJM article. Globalization is a reality. Outsourcing affects everything. Most Americans know this. Also, there is something called ... capitalism. Capitalism is not pretty. It is not gentle. But it accomplishes difficult tasks like building jetliners and finding cures for blindness. Capitalism, for better or worse, has allowed the CRO industry to flourish. CROs exist because sponsors need them.

New Target

Modern clinical trials have outgrown many academic institutions. The speed, complexity, and international aspects of trials have made industry-sponsored research a huge operational challenge. Many university physicians can’t meet those challenges as easily as they did a decade ago. Such doctors remain genuinely precious as intellectual thought leaders. But they haven’t been able to get the job done for industry. Journal articles won’t change that. Aside from operational inefficiencies (which Shuchman concedes) the world of academic trials has its own problems, especially with statistically underpowered studies.

The scientific integrity of the CRO industry is, we think, a nonissue. Sponsors call the shots. Sponsors shoulder final responsibility for the trials they design. Even in the examples cited by Shuchman, sponsors absorbed the publicity and regulatory damage.

The heart of the matter is simple. The CRO industry is now in the gunsight of the NEJM. The first shot has been fired. The publicity-averse nature of the CRO industry will cause it to absorb more shots from peer-reviewed journals. Maybe many shots. It will not be possible for most CROs to step into the spotlight and defend themselves; they prefer a low profile. As a result, the CRO-sponsor relationship carries new reputational risks for both sides. Those risks need to be assessed while trials are being planned, not after they pop up in the news.

One last thing. If you work for a CRO and know of any scientists or regulatory folks who can refute the NEJM claims, we’re all ears.