Regulatory Editor

The comment period is now closed for the draft guidance for FDA's acceptance of data for device trials conducted outside the U.S., and much of the commentary reflects concerns about the interaction of the draft and an effort to harmonize good clinical practices (GCPs) across nations. One trade association states that device makers may have a tough time making use of the provisions of the draft in the current GCP state of affairs, and that FDA might consider re-opening the comment period for the draft after the GCP issue is resolved.

FDA published the draft guidance earlier this year with the observation that the document presents no new policy on the subject, but was intended to clarify existing policy (Medical Device Daily, April 22, 2015). The agency also acknowledged the existence of the February 2013 draft GCP rule, which has yet to emerge in final form. The Food and Drug Administration Safety and Innovation Act of 2012 directs FDA to work with regulators in other nations to harmonize GCPs, but that effort has to date yielded little tangible results in the context of medical devices.

The Advanced Medical Technology Association (AdvaMed; Washington) made note of the predicament in its July 1 comment to the docket, hinting at a belief that the utility of the draft relies on the completion of two prior steps. AdvaMed's Tara Federici, VP for technology and regulatory affairs, remarked that the International Medical Device Regulators Forum had declined to adopt a preliminary framework for harmonized device GCPs, but she said the association is of the view that "absent a harmonized international guideline, we anticipate that FDA and industry will encounter challenges" in implementing the February 2013 draft GCP rule.

Federici added that other nations may be less than amenable to allowing FDA access to local clinical sites for audit purposes, and that device makers may find it difficult to obtain the identities of ethics committee members in other nations, information FDA would require for applications containing OUS study data. Federici advised the agency to allow sponsors to spell out the conditions leading to GCP non-compliance in these OUS studies before rejecting an application, and recommended the agency revisit the OUS study data acceptance draft upon publication of the GCP final rule.

The Medical Imaging & Technology Alliance (MITA; Arlington, Va.) took a different tack in its July 2 critique of the draft, first pointing to the draft's mention of the Helsinki Declaration for human subject protections. MITA's Thad Flood, the association's industry director, questioned why compliance with the Helsinki provisions might "fail to meet the standards set by FDA in a manner uniquely attributable to being OUS in origin."

Flood argued that studies conducted in the U.S. are subject to a set of concerns similar to those pertaining to OUS studies, adding that the issue of whether a study population is representative of a device's intended patient population "is not strictly a function of OUS data." However, he acknowledged that sponsors are liable for offering "additional justification" for demonstrating that the OUS study population bears a sufficient resemblance to the intended U.S. patient population to make the study data useful for FDA.

Flood seemed to argue that FDA's demand that nation-specific GCPs be demonstrably superior to the patient protections found in the Helsinki Declaration is superfluous, making the case that demonstrating that the GCPs in question are "similar [to the Helsinki provisions] or sufficient" to ensure patient protection "should be accepted" by FDA. He also stated that FDA has adopted the provisions of ISO 14155 in reference to the draft's mention of the draft GCP rule, although Flood stops short of suggesting that the adoption of the GCP final rule is thus unnecessary to ensure compliance with appropriate standards of clinical practice.

AHA cites NOACs in comments for Watchman NCA

The Medicare national coverage analysis for the Boston Scientific (Marlborough, Mass.) Watchman device is well underway, and dozens of entities have sounded off on the matter. Among the comments posted is one from the American Heart Association (AHA; Dallas), which expressed reservations about the device's use, given the lack of comparative data with novel oral anti-coagulants (NOACs).

The Centers for Medicare & Medicaid Services (CMS) opened the coverage analysis May 21 with a projected date of Nov. 21 for the proposed coverage memo (MDD, May 27, 2015), and many of the comments offered to the docket indicate support for coverage. However, AHA President Elliott Antman said the data supporting the device in lieu of warfarin "is only modest," pointing to an updated FDA analysis of data from the Prevail trial that observed 13 ischemic strokes in the device arm compared to one among controls. Antman noted further that 10 of these events took place more than a year after implant.

The AHA document described the meta-analysis of the Prevail and Protect trials and their respective continued access protocols as demonstrating significantly fewer instances of hemorrhagic strokes, although Antman stated that ischemic stroke ran in the opposite direction. He remarked further that the lack of comparative data matching the device against NOACs suggested "it cannot be assumed that the comparative results for the device might not be worse."

Antman noted that the coverage request came with the proviso that a physician take into consideration a patient's previous experience with oral anticoagulation along with consideration of "unavailability of an approved alternative anticoagulation agent." AHA's position is essentially that patients may be considered for the device assuming "a clearly defined contraindication to both warfarin and all of the NOACs currently available in the U.S."

GAO: flag addresses to suppress fraud

The Government Accountability Office (GAO) issued a July 21 report examining Medicare's methods for screening out potentially fraudulent operations, suggesting that two sore spots remain. One of these is the procedure to establish a physician's licensure status, and the other is a verification practice for provider location.

GAO said its review of 2013 data suggested that more than one in five Medicare providers had listed addresses that were potentially ineligible for participation, and the report included a picture of a private sector mail service store front and another of a mailbox said to have been listed as the address of a provider. GAO urged CMS to add flags to applications to detect potentially problematic addresses, a recommendation with which CMS is said to have agreed.

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