Fighting Back Against “The Constant Gardener” Perception

May 8, 2008

The Constant Gardener,” a 2001 novel and 2005 movie, revolves in part around an ethically questionable drug trial a foreign drug company conducts in Africa.  Real life events have also occurred where a company was accused of ethical violations during the conduct of foreign clinical studies.  In 2001, “The Washington Post” ran a series of articles titled “The Body Hunters” describing the news organization’s investigation into corporate drug tests around the world. 

Since 1975, FDA has required any clinical study used to support the approval of a drug application to meet certain ethical and data management criteria, including meeting the standards of the 1989 version of the Declaration of Helsinki or the local laws of the country, whichever provided greater protection for the research subjects.  Although the Declaration of Helsinki has been amended several times since 1989 (most recently in 2004) FDA did not adopt the later versions due to various factors, including, recent changes that FDA portrayed as an attack on the use of placebos in clinical studies and that could make it more difficult to assess the safety and efficacy of proposed drug products.

On April 28, 2008, FDA promulgated final regulations revising the standards foreign clinical trials that are not conducted under an Investigational New Drug application (“IND”) must meet to support an IND or New Drug Application submission.  The regulation (at 21 C.F.R. § 312.120) only applies to a minority of studies, as FDA estimates that only about 15% of all foreign trials for drugs intended to eventually be submitted to the Agency are not conducted under an IND.  The new regulation lays out specific requirements these studies must meet.  Studies failing to meet these requirements must still be identified in regulatory submissions, but FDA will only consider them for safety issues and they will not contribute to the Agency’s efficacy evaluation unless a waiver is sought.

The specific requirements identified by FDA in § 312.120 include following Good Clinical Practices (“CGPs”), and allowing the Agency the option to validate foreign clinical data through an onsite inspection.  Major GCP components include the prior approval and continued oversight of an Independent Ethics Committee (“IEC”), and obtaining documented informed consent from every clinical study subject.  The new regulation defines an IEC to mean “a review panel that is responsible for ensuring the protection of the rights, safety, and well-being of human subjects involved in a clinical investigation and is adequately constituted to provide assurance of that protection.”  An Institutional Review Board is a type of IEC.  The new regulation also details what must be submitted to show compliance with GCPs. 

By Gwendolyn M. McKee

Categories: Drug Development