By Bruce W. McNulty, MD
This article is part of our MedRIB project and was published July 09, 2008.
Two articles on Contract Research Organizations (CROs) have appeared in the New England Journal of Medicine in the last 8 months that deserve a few comments.
In the Oct 4th, 2007 issue, Miriam Shuchman, MD wrote an article entitled, Ã¢â‚¬Å“Commercializing Clinical Trials Ã¢â‚¬â€œ Risks and Benefits of the CRO Boom.Ã¢â‚¬Â The article describes something that many are likely unaware of, which is that a lot of research, primarily from pharmaceutical companies, has moved out of the companies themselves, as well as universities, into what has become known as Contract Research Organizations or CROs. The article provides great detail on the structure and functions of these organizations. It can be found at http://content.nejm.org/cgi/content/short/357/14/1365, although a subscription is required to read the entire text.
The article describes how in about five years CROs have grown from a $7 billion to an almost $18 billion industry and are known for the speed at which they can deliver results. It notes that in 2004, the 10 largest CROÃ¢â‚¬â„¢s enrolled more than 640,000 patients in clinical trials looking at the effects of medications and therapies.
According to Shuchman, the problem arises in part because Ã¢â‚¬Å“drug regulations were written in the 1970s, about a decade before the contract research industry emerged, and thus donÃ¢â‚¬â„¢t really address the problem of CRO accountability.Ã¢â‚¬Â Dr. Shuchman does not explain in what ways industry regulations do not apply equally to big pharma and CROs, however, what the article clearly indicates is that in outsourcing research generally and clinical trials in particular, the CROs are able to skirt regulatory controls such as those intended to ensure subject safety, methodological rigor, and the sharing of experimental outcomes. This idea was echoed by Michelle Mello from the Harvard School of Public Health, who stated that CROs Ã¢â‚¬Å“fly under the radar.Ã¢â‚¬Â
According to Shuchman, because of the lack of clarity as to how these regulations apply to CROs, there have already been problems associated with FDA approval of certain medications, including Ketec, which we will discuss in the next post. ShuchmanÃ¢â‚¬â„¢s paper also discusses other concerns as well, such as the inexperience of the research staff, lower pay scale, and pressure on the CROÃ¢â‚¬â„¢s to deliver positive research to continue to get contracts. An alternative model called Academic Research Organizations in a university setting uses faculty members to oversee research. These tend to be less efficient that CROÃ¢â‚¬â„¢s however, and also face considerable pressure to show results that support the sponsoring companyÃ¢â‚¬â„¢s study designs and protocols or risk losing the contract to a CRO.
Unrelated to the actual quality of the research itself, but important to be aware of as part of the discussion, is the treatment of study subjects themselves. If you look at the May 29th, 2008 NEJM at http://content.nejm.org/cgi/content/full/358/22/2316?query=TOC
you will find a fairly frightening description of where test subjects may be found to participate in clinical research. It raises the issue, Ã¢â‚¬Å“Is it ethically problematic to pay poor people to test the safety of new drugs?Ã¢â‚¬Â The practice of paying people to participate in trials is not new, but by moving this research out of the labs of the drug companies or universities, into the less regulated world of CROs, is raising concerns about the ethical dimensions of this work. According to the article, only 16% of academic health centers provide injured subjects with free care, as for the CROs, the number is not reported. Amazing! There is an implied warning here: be careful before you sign that waiver.
The article goes on to point out that many of these issues are rising from the transformation of clinical research Ã¢â‚¬Å“into a businessÃ¢â‚¬Â rather than something pursued as academic research. Unfortunately, the FDA seems ill-equipped to provide the oversight needed in this area of research. Neither article implies that CROÃ¢â‚¬â„¢s donÃ¢â‚¬â„¢t and havenÃ¢â‚¬â„¢t done strong work. However, the concern that remains is the lack of oversight when dealing with human test subjects and medical research needs to be addressed.