FDA amended rule on non-IND foreign trials criticized
Some say it weakens ethical protections
The FDA's amended rule for acceptance of foreign clinical studies not conducted under an investigational new drug (IND) application has drawn fire from health advocates who say it weakens ethical protections.
The amended rule, which was published in its final version earlier this year (21 CFR Part 312) replaces the requirement that such studies be conducted in accordance with ethical principles stated in the Declaration of Helsinki with a requirement that they be conducted in accordance with good clinical practice (GCP), including approval by an independent ethics committee.
The amended rule takes effect Oct. 27.
While the stated purpose of the amendment is to "help ensure the protection of human subjects and the quality and integrity of data obtained from these studies," it has been criticized by some involved in international health research.
"I think the primary implication of this is that the United States has acted with arrogance toward the rest of the world, and told them that the standards that apply to you are not the ones that are of interest to us," says Peter Lurie, MD, MPH, deputy director of Public Citizen's Health Research Group in Washington, DC.
Lurie and Robert Reinhard, a community advisory board member for the San Francisco Department of Public Health, say the change from the Declaration of Helsinki to GCP raises several ethical issues:
- Use of placebo. There has long been debate about whether it is ethical to provide placebos to subjects in the control arm of a clinical trial in a developing country when effective treatment is available in the developed world. The Declaration of Helsinki specifically calls for placebos to be used only the in absence of existing proven therapy.
- Post-trial obligations to research subjects. The declaration states that at the conclusion of the study, all participants should be assured access to the best proven treatment identified by the study.
- Obligations to the communities where research is conducted. The declarations states that medical research is justified only when the population in which it is being carried out stands to benefit.
Reinhard and Lurie say that these issues are not addressed in the GCP.
"The GCP is a generally reasonable document," Lurie says. "But it is not, primarily, an ethics document. We don't mind if the GCP is in there in addition to some ethics standard like the Declaration of Helsinki."
He notes that the declaration itself was amended at the urging of the United States to give greater leeway for use of placebo.
Attempts to seek comment from the FDA were unsuccessful. However the published final rule does address complaints such as Lurie's and Reinhard's that were submitted while the rule was under consideration.
The rule states that the U.S. government does not fully support the most recent revision of the declaration "because it contains certain statements that may be inconsistent with U.S. law and policy [e.g., concerning use of placebos in clinical trials]." The rule also addresses the obligations in the declaration to provide post-trial treatment to participants: "[The requirement] invokes issues of health care policy that are not directly related to FDA's mission of ensuring that medical products are safe and effective."
Role for IRBs
Reinhard says he has filed objections with the FDA to the final rule and has asked for a hearing, but has not heard back from the agency.
In the absence of any change to the rule, he and Lurie say it's up to IRBs to raise these ethical issues when reviewing trials to be conducted in the developing world.
"It's not a requirement, it's not an obligation," Reinhard says. "Nonetheless, IRBs have the opportunity to use either persuasion or policy matters or other features to achieve or accomplish things the FDA is unwilling to do."
Lurie notes that various IRBs might have different positions on issues such as placebo and post-trial treatment.
"The general problem is that IRBs tend to defer to the local investigators," he says. "If somebody comes in and says this is the only way to do this, people on the IRB are in general not going to feel that they're well placed to resist that."
The FDA's amended rule for acceptance of foreign clinical studies not conducted under an investigational new drug (IND) application has drawn fire from health advocates who say it weakens ethical protections.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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