The medical device industry is none too pleased with a proposed regulation released in February 2013 that would require all companies to make sure their clinical trials, no matter where in the world those trials are conducted, to adhere to US clinical trials regulations.
The US Food and Drug Administration's (FDA) draft regulation, Human Subject Protection: Acceptance of Data From Clinical Studies for Medical Devices, would notably require sponsors to obtain approval from an independent ethics committee (also known as an Institutional Review Board or an Ethical Review Board), and obtain and document informed consent of study participants.
"The proposed rule is intended to update the standards for FDA acceptance of data from clinical studies conducted outside the US and to help ensure the protection of human subjects and the quality and integrity of data obtained from these studies," FDA wrote in the regulation.
The goal, regulators explained, was to promote consistency in the trials while assuring that human subjects participating in the trials were given adequate protections. FDA now accepts data from foreign-conducted clinical studies so long as they meet 21 CFR 812-14, which states that the obtained data must be scientifically valid and must have been collected per the ethical guidelines of the Declaration of Helsinki or local laws (whichever offers stronger protection to research subjects).
This data is most commonly used in support of an application that includes data from the US, but FDA encourages sponsors to meet with it if the application will be "based solely on foreign clinical data." Those requirements are less stringent than required for clinical trials conducted within the US, which are held to various US-specific regulations such as 21 CFR 56 (IRBs) and 21 CFR 50 (informed consent).
However, these requirements are just for Premarket Approval (PMA) applications, as FDA's 510(k) and Investigational Device Exemption (IDE) regulations do not address FDA requirements for the acceptance of data from either inside or outside the US.
These inconsistencies were-and are-troubling to FDA, which argues in the proposed regulation that it "believes that the requirements for FDA's acceptance of data from clinical studies should be consistent regardless of the type of submission or application in which the data are submitted to FDA."
Why the need for consistency? Several reasons, regulators say. First, standards continue to evolve far beyond those first elucidated by the Helsinki Declaration, including the development of good clinical practice (GCP) guidelines issued by the World Health Organization, the International Standards Organization, the Pan American Health Organization and the International Conference on Harmonisation (ICH), among others.
Many of these standards are adopted either in whole or in part by FDA, and it said it now wants to amend 21 CFR 814.15, 807 and 812 to require all clinical trials conducted for medical devices to meet GCP standards set by FDA.
"We believe that the proposed standard helps to ensure adequate human subject protection and the quality and integrity of data obtained from such studies, while also being sufficiently flexible to accommodate differences in how countries regulate the conduct of clinical research and obtain informed consent."
The change should also make sure data is of the same quality and integrity, regardless of its geographic source, FDA argued. Some of the most crucial parts of GCP highlighted by FDA include provisions of assurance that results are credible, accurate and monitored throughout the trial.
Protections for human subjects, too, will get an upgrade under the proposed rule, with FDA pushing a harmonized, "unifying approach, which may simplify such trials and decrease the regulatory burden on sponsors."
FDA also said that under the rule, it would require that 510(k) and IDE applications adhere to the same standards as PMAs. This will "help ensure the protection of human subjects and the quality and integrity of data obtained from these studies," it wrote.
At the time of the document's release, Regulatory Focus stipulated that industry could come out against the regulation en masse, arguing that the changes would dramatically increase the costs of regulatory compliance in foreign markets where many have turned in recent years to cut down on the high costs of trials. In addition, it could prove difficult to meet both FDA's standards for clinical trials and those of the host country of the trial.
FDA seemed to try to pre-empt these arguments, writing that a single set of standards would make compliance easier. "Under the current regulations, in a study involving multinational investigational sites, several different standards may be followed leading to increased complexity in the conduct of the study." By adopting a single standard, then, sponsors might stand to save money by only needing to worry about a single standard instead of potentially dozens.
Industry Slams Proposal
But if FDA hoped that its comments would allay industry incredulity, comments submitted to FDA's federal docket indicate that this attempt was unsuccessful.
Medical device industry group AdvaMed said it was "very concerned" about the proposed rule, arguing that without international support, trials could run into significant problems. FDA's approach, it said, seems based on the International Conference on Harmonization's (ICH) model for pharmaceutical products. "Unfortunately, no such harmonized international medical device good clinical practice guideline exists for medical device and in vitro diagnostic clinical investigations," it said.
"Absent a similar common foundation for medical devices, FDA and industry alike may run into resistance from the OUS regulatory and clinical community to implementation of the proposed rule," it continued. Such a rule should be put on hold until an internationally-harmonized system is put into place, AdvaMed concluded.
Johnson & Johnson, too, railed against the rule, saying it strongly supported AdvaMed's comments and had several other concerns unique to its own operations. In particular, J&J said it was concerned that definitions of several clinical terms may not be applicable in other countries, such as "significant risk" and "non-significant risk," and would therefore be unable to "perform the appropriate assessment" of the trial.
Other companies threw their support behind AdvaMed's comments as well, including St. Jude Medical and Roche, while other companies-Cook Medical, Boston Scientific, and the Association of Clinical Research Professionals-broadly mirrored the concerns raised by AdvaMed in their own comments.
The full docket of comments may be found here.