To the Editor: In their article, Glickman et al. (Feb. 19 issue)1examine the growing phenomenon of clinical trials being conductedoutside the regulatory framework of the developed world. Theyrightfully point out some of the ethical and scientific pitfallsof these investigations. However, they do not mention that theoffshoring of clinical studies can also deprive critically illpatients in the developed world access to some of the latestdrugs and devices, the underlying basic research for which waspaid for through taxes by these same persons. Perhaps this issue,as opposed to paternalistic concerns about inadequate regulationwithin the Third World, represents the biggest ethical dilemmawe confront in this era of research globalization.
John R. Adler, Jr., M.D. Stanford University Stanford, CA 94305 jra{at}stanford.edu
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 outsourcingof clinical trials may compromise ethical and scientific integrity,but they fail to acknowledge an important safety net that doesexist. The Food and Drug Administration (FDA) reviews resultsof studies regardless of their country of origin, and regulationsrequire that the supporting clinical investigations performedunder investigational-new-drug applications1 be held to thesame standards regardless of whether the clinical sites arelocated in the United States. The FDA Guidance for Industry:Acceptance of Foreign Clinical Studies2 permits acceptance ofdata from a foreign clinical study "only if the study conformsto the ethical principles contained in the Declaration of Helsinki"or with laws and regulations of the country, whichever providethe greatest ethical protections. Aside from the ethical imperative,what is the economic advantage to the company of collectingpoor-quality data that could compromise the final regulatoryreview? There is always room to improve regulatory capacityand training here and abroad, but this article dwells on potentialinsufficiencies rather than on the advantages of engaging internationalresearchers 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 illpatients in high-income countries access to cutting-edge therapies.Research for these therapies, in particular, requires studydesigns that incorporate the complex environment of highly developedintensive and emergency care settings.1,2 More broadly, thecurrent emphasis on translational research is based on the conceptof bench-to-bedside research.3 This type of research may warrantspecial consideration in the globalization of clinical trials.
We agree with Andrews on the important safety net that the FDAprovides in clinical studies outside the United States. Yet,the FDA has been challenged by "ever-expanding responsibilitiesin the face of a mostly flat annual budget."4 Thus, we cannotcount on the FDA alone to ensure the ethical underpinnings ofthe global clinical research process.
Since the publication of our article, we have been made awareof independent investigations into the clinical research processin low- and middle-income countries that have validated manyof the concerns we expressed.5 At the same time, some of ourcolleagues in those countries have expressed concerns that ourarticle calls into question the integrity of their work andour collaborations. This dichotomy underlies our basic concernsabout the issues of ethical and research integrity in the globalizationof clinical research. Currently, there is neither a global mechanismto identify investigators and institutions who strive to meetthe highest ethical and scientific standards for clinical researchnor a systematic means of tracking those who have violated thesestandards. We believe that implementing the recommendationsin our article will help to remedy this situation.
Greater international cooperation among industry sponsors, contractresearch organizations, and interested governments could beused to further ensure the application of internationally establishedprinciples 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 kevin.schulman{at}duke.edu
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][Web of Science][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]
312.23(a)(6)(b).
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