Thursday, February 19, 2009

DCRI researchers discuss the implications of conducting clinical trials overseas
By Maggie De Pano, DCRI Communications

The number of countries serving as clinical trial sites for U.S.-based pharmaceutical and device companies has more than doubled from 1995 to 2005, as illustrated by a review of 300 journal articles reporting on clinical trial results. This trend has led to substantial costs savings for industry, especially in developing countries offering cheap labor and large pools of potential study participants that shorten timelines for clinical testing.

There are also benefits that transcend the concerns of for-profit companies. DCRI researchers led by Kevin A. Schulman, MD wrote that conducting clinical trials in developing countries can foster positive relationships among investigators all over the world, as well as address questions regarding the safety and efficacy of drugs and devices that are relevant to the international community.

The globalization of clinical trials, however, raises a number of ethical and scientific concerns. DCRI researchers discussed these concerns in the February 19 issue of The New England Journal of Medicine. They also proposed solutions, many of which call on the contributions of stakeholders in academia, industry, and regulatory agencies worldwide.

First, none of the U.S. company-sponsored multicenter trials the authors examined focused on diseases that disproportionally affect developing countries. Instead, they tested products that will most likely be sold in wealthy nations, so study participants may not even benefit from what is being tested on them. The authors encouraged trial sponsors to address this issue by describing how study populations will match their intended markets. They also supported target enrollment efforts in geographic regions on the basis of a product’s intended use, citing FDA and NIH policies mandating the target enrollment of women and minorities in clinical trials as examples of such a strategy.

Second, regulatory agencies in countries where a drug or device is being marketed may know very little about the conduct and quality of research in places where those products were tested, due to limitations in jurisdiction. As such, the authors recommended the development of a central statistical monitoring system designed to find unusual data patterns in trial results. They also encouraged the creation of a formal mechanism for sharing regulatory oversight between government agencies on a global basis, a public registry of Institutional Review Boards, and an inventory of country-specific provisions for the ethical oversight of clinical research.

Third, the authors stated that investigators in developing countries are generally less experienced and familiar with guidelines regarding their rights to access data and control the publication of trial results. Yet these rights preserve the transparency and integrity of research. Given this situation, they recommended using the FDA Amendments Act of 2007 to reinforce publication regardless of where the research is being conducted. They also encouraged the creation of mechanisms for clinical trials leadership that incorporate representatives from key countries involved in the study, as well as the use of legal agreements designed to preserve the rights of study investigators.

Other problems outlined in the article include increased costs and delays associated with compensating study participants; confidentiality agreements in commercial contracts that reduce the transparency and efficiency of research; and the lack of pharmacogenomic information on trial subjects who are geographically distinct and thus might possess genetic profiles that respond differently to the same drug or device. You can find a more detailed discussion of problems and solutions in the full article.

Other DCRI researchers who contributed to the article include John G. McHutchison, MD; Eric D. Peterson, MD, MPH; Robert Harrington, MD; and Robert Califf, MD.