Regulatory Editor

The live case has become a staple for medical society meetings that deal with cutting-edge medical technology, and the FDA had proposed in a 2014 draft guidance that the sponsor of the investigational device explain in a regulatory filing why that live case broadcast is not in violation of the general ban on promotion of unapproved devices. That language does not appear in the live case final guidance, however, removing a potentially show-stopping hurdle from one of the most popular means of disseminating information to physicians regarding these novel technologies.

The draft guidance emerged with the notation that live case presentations may constitute protocol deviations for investigational device exemptions (IDEs), in part because the subject of the live case is by definition unblinded to adjudicators. The draft also highlighted the hazards associated with additional personnel and video equipment in the operating room or cath lab, but the agency also made the argument that the guidance would cut down on the need for supplements to investigational device exemptions that are filed strictly for the purpose of obtaining FDA approval for the live case. (See BioWorld MedTech, April 21, 2014.)

The Advanced Medical Technology Association (Advamed) indicated opposition to the requirement that the sponsor explain why a live case does not qualify as a promotional activity, stating that such a requirement is "overly burdensome and unnecessary." Tara Federici, then the association's VP for technology and regulatory affairs, said the agency might reasonably expect the sponsor to explain the need for a live case, but that the FDA should be able to determine whether a request for a live case constitutes a violative promotion based on the sponsor's request.

Cook's Ferguson: Prescience in short supply

The docket for the draft also drew comment from Stephen Ferguson, board chairman of the Cook Group Inc., of Bloomington, Ind., who said the net effect of the draft might be to discourage live case presentations. Ferguson said the draft's claim that the intent was to reduce the need for IDE supplements solely for live case presentations would seem to suggest that sponsors can accurately predict the number of live cases that would ultimately be requested. He requested that the FDA drop the live case presentation requirement from the draft prior to finalizing the guidance.

The final guidance omits the discussion of reduced requests for live cases, seemingly in response to Ferguson's comments. However, Advamed's Federici likewise took aim at the notion that a sponsor will be plausibly able to anticipate any and all need for live cases. Federici urged the agency to revise the passage by making clear that information about a specific live case presentation – or even whether such a presentation will be conducted – will not be known as of the date of the IDE filing. However, the final guidance requires that sponsors report on all live cases in the related regulatory filing, including live cases that were attempted and abandoned as well as those that were approved but not performed.

The FDA said in the draft that any live cases being webcast into the U.S. from other nations should comport with the provisions of the draft, although the draft also said, "foreign manufacturers and study sponsors should follow the laws and regulations" of the controlling national jurisdiction as well. Ferguson suggested that the FDA make clear in the final that the laws of the nation where the live case takes place will supersede the FDA's guidance and regulation, whereas Federici suggested that the agency tighten the scope of this provision to live case presentations performed "by investigational sites" outside the U.S. (OUS). Her reasoning in this instance was that the device in question might be approved in that OUS jurisdiction and thus the manufacturer has "limited ability to control the broadcast" of that live case. The FDA apparently concluded that this consideration could not be tenably addressed as it is omitted entirely from the final.

Despite urging sponsors to spell out their expectations regarding live case presentations, the draft repeatedly cites those instances as protocol deviations, which Federici said called for some clarification. She said not all live cases constitute protocol deviations, and suggested that each proposed live case ought to be individually evaluated for its potential impact on the study. Ferguson said the draft had implied that all live cases constituted protocol deviations even though the broadcast of the procedure might constitute the only difference in that patient's treatment. The term "protocol deviation" appears only once in the final guidance, however, in a section that lists the general conditions for requests for live cases, whereas the draft stated that an investigational plan must account for live cases, even in single-arm studies in which bias due to lack of randomization is not a concern.

The final guidance offers a few more suggestions regarding the impact of live cases on the study protocol, however, including a suggestion that the sponsor describe how bias in selection of patients for live cases would be minimized. The sponsor will also have to determine prospectively how the live case or cases will affect the endpoint analyses, including whether the live case subjects would be reported as a separate cohort. The effect on sample size should also be calculated and reported in the IDE application, the final guidance said.

No Comments