Responding to Globalization

A framework for protecting participants worldwide

International markets are now home to more than half the world’s clinical trials, including 40 to 65 percent of studies investigating U.S. Food and Drug Administration (FDA)-regulated products. Bioethicists and others have expressed concerns that monitoring has not kept pace with global growth. At the same time, they recognize that the trend toward global research will only continue. The goal, then, is not to reduce the number of global trials but to find ways to ensure adequate safeguards for research participants and, ultimately, for patients who use the resulting products.

• Why sponsors turn to global markets
• Oversight and other challenges
• AAHRPP’s role

Why sponsors turn to global markets
Many attribute the increase in conducting clinical trials in global markets to reduced costs. However, according to Albert J. Allen, M.D., Ph.D., Senior Medical Fellow for Bioethics and Pediatric Capabilities at Eli Lilly and Company, “when you factor in the work required to get multiple international sites up to speed and increasing costs in some regions such as Asia, there’s not as big a difference in costs as many think.”

Instead, two other factors draw sponsors to international markets:

• Access to larger numbers of participants for phase 3 trials. U.S. investigative sites simply do not enroll enough patient-participants to receive FDA approval in a timely, cost-effective manner. To meet FDA requirements for study enrollment and minimize delays in bringing medicines to market, research sponsors increasingly look to countries where more people are available and willing to volunteer.
• Changing requirements for international approval. Many countries now have their own regulatory agencies and require that medicines be approved by those agencies—even if the medicines have already been approved in the U.S. or in European countries. Therefore, to make medicines available to patients worldwide, pharmaceutical companies often must conduct trials in specific global markets.

Oversight and other challenges
One of the greatest concerns of those involved in protecting research participants is the challenge of monitoring multiple global sites. In its June 2010 report, “Challenges to FDA’s Ability to Monitor and Inspect Foreign Clinical Trials,” the Department of Health and Human Services Office of Inspector General (OIG) noted that the “FDA inspected clinical investigators at less than 1 percent of foreign sites.” The same report found that “80 percent of approved marketing applications for drugs and biologics contained data from foreign clinical trials.”

Other challenges of globalization include bridging language and cultural differences; meeting regulatory requirements of all nations involved; assessing skills and qualifications of the research team; evaluating the strength of the institutional review board or ethics committee; monitoring the quality of the data; and, above all, ensuring the strongest possible protections for research participants.

The OIG report acknowledged that the FDA has taken steps to improve its oversight of foreign clinical data. Even so, the report called on the FDA to make additional changes, including expanding its oversight of foreign clinical trials in three ways:

• Continuing to develop inspection agreements with foreign regulatory bodies.
• Inspecting clinical trials in more countries.
• Looking to new models of oversight.

AAHRPP’s role
AAHRPP is a natural partner in this effort. Applying AAHRPP’s rigorous standards around the globe can duplicate the positive results achieved in the U.S. in the decade since AAHRPP was founded.

In fact, AAHRPP has set an ambitious goal of establishing one standard for research protections worldwide. In keeping with that goal, AAHRPP has developed standards that acknowledge and account for the variations in research regulations from country to country. In general:

• AAHRPP accreditation standards are based on the International Conference on Harmonisation-Good Clinical Practice (E6) guideline and on FDA and DHHS regulations.
• All organizations are evaluated according to the same set of AAHRPP accreditation standards. In addition, organizations based outside the U.S. must comply either with their own nation’s regulations or those of the U.S.—whichever are more stringent.

Already, organizations in Canada, China, India, Korea, and Singapore have earned AAHRPP accreditation, delivering the message—to sponsors, participants, and the general public—that they offer an assurance of quality that others cannot claim. AAHRPP’s influence will grow overseas, just as in the U.S. Increasingly, international organizations that earn AAHRPP accreditation will become the research partners of choice for sponsors and research organizations in the U.S. and around the globe.