The recent New England Journal of Medicine (NEJM) article that criticized contract research organizations (CROs) was a roundhouse kick to the gut of that industry.

The Oct. 4, 2007 article, written by New York psychiatrist and professor Miriam Shuchman, asserted that as CROs have expanded from $7 billion in revenues in 2001 to $17.8 billion today, science has suffered. Ignoring thousands of trials that unfold without a hitch, Shuchman cites several headline-grabbing studies-gone-awry that involved CROs. (Think TeGenero.) Shuchman believes that the industry has no clear regulatory oversight, leaving the door open for unethical behavior on the part of CROs and the sponsors who hire them.

The commercialization of clinical trials, writes Shuchman, is a matter of ever-growing societal importance as CROs take over more of Phase I, II and III research—64 percent of it in 2003, compared to just 28 percent 10 years earlier.

ACRO Stunned

The CRO industry’s top trade organization, Association of Clinical Research Organizations (ACRO), is still reeling from the article. While it hasn’t assembled facts from members to refute the NEJM on a point-by-point, trial-by-trial basis, ACRO is trying to respond to the journal’s jabs and set the record straight.

“If the overall impression is that, rather than this being a very highly regulated environment with significant oversight for all stakeholders, that this is in fact a slipshod enterprise, then that is a problematic message to deliver to the public,” says Doug Peddicord, the association’s executive director.

Bad Trickle Down

Peddicord says he worries about the negativity of the NEJM piece trickling down from physicians to patients—patients who might have someday participated in a trial but perhaps now won’t. Still, the trade group has no plans to try to debunk the NEJM article, other than post a letter on its own website, a letter the NEJM declined to publish.

Peddicord continued, “I’m concerned that a leading journal—one I presume has a commitment to clinical research as a part of not only increasing new medical knowledge but of increasing the number of new treatments and drugs available to patients who need them—would take an editorial position that would suggest that clinical trials entail higher risk than they actually do.”

Responsible to Whom?

In particular, Peddicord takes umbrage at the journal’s assertion that one can’t be exactly sure who, ultimately, CROs answer to: the sponsor or the FDA? The article quotes Rachel Behrman—deputy director of the FDA‘s Office of Medical Policy, Center for Drug Evaluation and Research (CDER)—saying that it’s unclear whether CROs are directly responsible to sponsors or the FDA. Author Shuchman goes on to say that the FDA is working to clarify the matter with new guidance.

But Peddicord argues that that matter is already clear and has been for some time. He quotes FDA regulation: 21 CFR 213.52, which reads, in part:

“A sponsor may transfer responsibility for any or all of the obligations ... to a contract research organization. Any such transfer shall be described in writing .... A contract research organization that assumes any obligation of a sponsor shall comply with the specific regulations ... applicable to this obligation and shall be subject to the same regulatory action as a sponsor for failure to comply with any obligation assumed under these regulations. Thus, all references to ‘sponsor’ ... apply to a contract research organization to the extent that it assumes one or more obligations of the sponsor.”

CROs as Sweatshops

Also appalling to the industry, says Peddicord, was the notion that, compared to sponsors’ in-house research teams, CROs are, in effect, sweatshops with lowly-paid employees and high turnover. Peddicord says the NEJM, in making that claim, cited an unpublished paper that includes “interviews with a half dozen pharmas,” which makes such a claim nothing more than “anecdotal.”

“Whether it’s accurate, we can’t say,” Peddicord says.

Same Talent Pool

He did say that a 2004 ACRO member survey showed that, of a workforce of about 30,000, 2,500 CRO employees were in-house physicians or PhD scientists, who, presumably, wouldn’t work for sweatshop wages. (There are no public data on whether CRO usage of employees with advanced degrees is comparable to that of the pharmaceutical and biotech companies).  “Job-to-job, pharma, biotech and CRO employees are essentially drawn from the same professional pool,” says Peddicord. “We see lots of cross-sector movement.”

That too is anecdotal, he acknowledged.

No Scapegoats

And as for the allegation that CROs can be convenient scapegoats for sponsors that choose not to do the right thing with data or patients? Peddicord doubts that happens.

“[Our members] are leading global CROs,” he says. “They have enormous expertise and sophistication in terms of regulatory responsibility. We are obviously interested in maintaining partnerships [with sponsors], but we are also interested in fulfilling our real core responsibility, which involves protecting the integrity of the data and research participants.”

ACRO is almost six years old. Its members are Covance, Kendle International, PRA International, United BioSource, MDS, Medifacts International, Parexel International, PPD, PharmaNet Development Group, and Quintiles Transnational.

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. Here’s an earlier ClinPage article on the NEJM article on CROs.

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