New England Journal of Medicine
Volume 360 — June 25, 2009 — Number 26
http://content.nejm.org/current.shtml

:
Ethical and Scientific Implications of the Globalization of Clinical Research

To the Editor: In their article, Glickman et al. (Feb. 19 issue)1 examine the growing phenomenon of clinical trials being conducted outside the regulatory framework of the developed world. They rightfully point out some of the ethical and scientific pitfalls of these investigations. However, they do not mention that the offshoring of clinical studies can also deprive critically ill patients in the developed world access to some of the latest drugs and devices, the underlying basic research for which was paid for through taxes by these same persons. Perhaps this issue, as opposed to paternalistic concerns about inadequate regulation within the Third World, represents the biggest ethical dilemma we confront in this era of research globalization.
John R. Adler, Jr., M.D.
Stanford University
Stanford, CA 94305
References
Glickman SW, McHutchison JG, Peterson ED, et al. Ethical and scientific implications of the globalization of clinical research. N Engl J Med 2009;360:816-823. [Free Full Text]

To the Editor: Glickman et al. imply that international outsourcing of clinical trials may compromise ethical and scientific integrity, but they fail to acknowledge an important safety net that does exist. The Food and Drug Administration (FDA) reviews results of studies regardless of their country of origin, and regulations require that the supporting clinical investigations performed under investigational-new-drug applications1 be held to the same standards regardless of whether the clinical sites are located in the United States. The FDA Guidance for Industry: Acceptance of Foreign Clinical Studies2 permits acceptance of data from a foreign clinical study “only if the study conforms to the ethical principles contained in the Declaration of Helsinki” or with laws and regulations of the country, whichever provide the greatest ethical protections. Aside from the ethical imperative, what is the economic advantage to the company of collecting poor-quality data that could compromise the final regulatory review? There is always room to improve regulatory capacity and training here and abroad, but this article dwells on potential insufficiencies rather than on the advantages of engaging international researchers to develop global products.
Charla A. Andrews, M.S.
Dale and Betty Bumpers Vaccine Research Center
Bethesda, MD 20892-3011
References
21 C.F.R. 312.23(a)(6)(b).
Guidance for industry: acceptance of foreign clinical studies. Rockville, MD: Food and Drug Administration, March 2001.

The authors reply: Adler points out the important implication that offshoring of clinical studies can deprive critically ill patients in high-income countries access to cutting-edge therapies. Research for these therapies, in particular, requires study designs that incorporate the complex environment of highly developed intensive and emergency care settings.1,2 More broadly, the current emphasis on translational research is based on the concept of bench-to-bedside research.3 This type of research may warrant special consideration in the globalization of clinical trials.

We agree with Andrews on the important safety net that the FDA provides in clinical studies outside the United States. Yet, the FDA has been challenged by “ever-expanding responsibilities in the face of a mostly flat annual budget.”4 Thus, we cannot count on the FDA alone to ensure the ethical underpinnings of the global clinical research process.

Since the publication of our article, we have been made aware of independent investigations into the clinical research process in low- and middle-income countries that have validated many of the concerns we expressed.5 At the same time, some of our colleagues in those countries have expressed concerns that our article calls into question the integrity of their work and our collaborations. This dichotomy underlies our basic concerns about the issues of ethical and research integrity in the globalization of clinical research. Currently, there is neither a global mechanism to identify investigators and institutions who strive to meet the highest ethical and scientific standards for clinical research nor a systematic means of tracking those who have violated these standards.     We believe that implementing the recommendations in our article will help to remedy this situation.

Greater international cooperation among industry sponsors, contract research organizations, and interested governments could be used to further ensure the application of internationally established principles and policies in clinical research.

Seth W. Glickman, M.D., M.B.A.
Charles B. Cairns, M.D.
University of North Carolina
Chapel Hill, NC 27599

Kevin A. Schulman, M.D.
Duke University
Durham, NC 27710

References
Glickman SW, Anstrom K, Li L, et al. Challenges in enrollment of minority, pediatric, and geriatric patients in emergency and acute care clinical research. Ann Emerg Med 2008;51:775-780. [CrossRef][ISI][Medline]

Cobb JP, Cairns CB, Bulger E, et al. The United States Critical Illness and Injury Trials Group: an introduction. J Trauma (in press).

Zerhouni EA. Translational and clinical science — time for a new vision. N Engl J Med 2005;353:1621-1623. [Free Full Text]

Okie S. A to-do list for the new FDA commissioner. N Engl J Med 2009;360:1373-1378. [Free Full Text]

Hundley K. Testing grounds: our medicine at what cost? St. Petersburg Times. December 2008. (Accessed June 4, 2009, at http://www.tampabay.com/specials/2008/reports/india/.)