ImageA recent article in the New England Journal of Medicine by researchers from Duke University raises concerns over the increased globalization of clinical trials and the need to strengthen regulation to address this phenomenon. As pharmaceutical companies conduct more trials abroad as part of overall cost-saving measures, such a finding has implications for all stakeholders—patients, suppliers, and the drug companies themselves.

Since 2002, the number of active investigators regulated by the US Food and Drug Administration that are based outside the United States has increased 15% per year while the number of US-based investigators has declined by 5.5%, according to the article. In using the registry to examine recruitment in industry-sponsored Phase III clinical trials as of November 2007 for the 20 largest US-based pharmaceutical companies, the researchers found that approximately one-third of the trials (157 of 509) are being conducted solely outside the US and that a majority of study sites (13,521 of 24,206) are outside the US. Many of these trials are being conducted in developing countries, including Eastern Europe and the Russian Federation, says the article.

The data clearly show the globalization of clinical development, a situation that calls into question the adequacy of regulatory oversight of research, particularly in emerging markets. Regulatory bodies in established markets are typically structured to monitor studies in their own countries, not abroad, and are not sufficiently tasked to address this globalization. The researchers also raise concerns over the relevance of trials conducted on patients that may have environmental or genetic profiles specific to a population of a given country to patients outside that group as well as ethical concerns of using patients in developing nations, as these patients may participate more readily in trials for economic reasons.

These concerns over the globalization of clinical trials reflect similar problems on the pharmaceutical manufacturing side, namely the growing disconnect, either in organizational structure, resource allocation, or operation of regulatory agencies in dealing with the globalization of the pharmaceutical industry. The historic bent of pharmaceutical regulation is a framework consisting of national (i.e., FDA), regional (i.e., European Medicines Agency) or developed-nations’ (i.e., International Conference on Harmonization) interests, which simply do not fit a 21st-century reality where developing nations play a significant role in clinical development and manufacturing.

Although there have been recent efforts by FDA, EMEA, and ICH to address these shortfalls, for example, on the manufacturing side through location of national regulatory offices abroad and proposals and implemented measures to address drug import safety, the real question is whether these efforts or similar ones will be adequate to fully address the pace and extent of globalizaiton of the drug industry.

The researchers from Duke University say that long-term solutions to the problems stemming from the globalization of clinical research require input from all stakeholders—academia, industry, and regulatory agencies. They suggest beginning with a comprehensive review from representatives from developed and developing countries, perhaps commissioned by the Institute of Medicine or the World Health Organization, to build dialogue and consensus. But with these or other efforts on the clinical side, there needs to be a concomitant effort on the manufacturing side.

A cohesive and integrated system for global pharmaceutical regulation that incorporates the full continuum of functions in drug development and commercialization (clinical research, development, and manufacturing) and the myriad of players—patients, suppliers, and drug companies from both developing and developed nations need to be embodied into a solution. A tall task for sure, some might say improbable, but a truly strategic, not tactical approach, is needed.