A new draft guidance document published by the US Food and Drug Administration (FDA) is aimed at clarifying which information should be included in an investigational device exemption (IDE) application if the sponsor intends or anticipates including a "live case presentation" during the course of the clinical trial.
Many high-risk (Class III) "significant risk" medical devices are subject to the premarket application (PMA) process, which requires sponsors to submit clinical data in support of their applications. Those clinical data are obtained only after a sponsor is able to obtain approval to begin the trial, which it obtains through the submission (and approval) of an investigational device exemption (IDE) to FDA.
As with its pharmaceutical counterpart, the investigational new drug (IND) application, the IDE is actually an exemption from federal law, which ordinarily prohibits most unapproved products from entering into interstate commerce, even for clinical testing purposes.
FDA's overall purpose is to ensure that the rights of subjects participating in the proposed trial will be protected, and that they aren't subject to any unreasonable safety risks based on earlier data, such as from healthy human subjects or testing on animals.
But not all clinical trials are created equal. Some are small, others large. Some involve just a few researchers at a single site, others hundreds across dozens of sites around the world.
And then there are trials which involve what are known as "live case presentations," defined by FDA as:
"The treatment of a human subject under the auspices of an approved or conditionally approved IDE, conducted and broadcast in real time, or recorded for broadcast at a later time."
These presentations are typically intended to teach others how to perform a procedure so that it can be replicated or improved upon. However, FDA notes that they are used quite uncommonly in IDE settings.
That being said, the presentations may "increase awareness of the study for potential investigators and facilitate the recruitment of subjects," leading to "new therapies being made available sooner," FDA said.
FDA's new draft guidance is intended to address several problems present in the status quo, the agency wrote.
First, it is intended to improve the quality of IDE submissions in the hopes of ensuring greater consistency and safety. The guidance explains at length the requirements sponsors need to meet with respect to risks analysis, informed consent, pediatric requirements, and data collection and analysis.
At the core of these concerns is that the procedure, which is sometimes longer or more complicated than non-televised procedures owing to the time it takes to verbally explain what is being done or get adequate camera angles on a technique, may unnecessarily harm patients. Companies need to conduct a thorough risks analysis to determine if the presentation would, among other things, increase the risks of infection, blood loss or operator error. Subjects must also explicitly consent to involvement in the live case presentation, FDA said. In all but "rare instances," it will not be appropriate to use children in live case presentations.
The guidance also includes extensive information about what information about planned/anticipated live presentations will need to be included in the IDE, such as how many live case presentations the sponsor intends to conduct, the details of how the presentations will be distributed (e.g. live at a medical meeting), the qualifications of the operator or investigator, risk mitigation methods, and the presentation's effect on data collection (e.g. effects on randomization, selection bias).
FDA also explains in the guidance that since unplanned live case presentations "represent protocol deviations to the approved research [plan]," sponsors need to submit live case presentation requests at least 30 days prior to the planned presentation. However, this will not be appropriate in all cases. "A live case presentation request is not appropriate for a study nearing completion since the purpose of a live case presentation is to increase awareness of the study for potential investigators and facilitate recruitment of subjects," FDA noted.
The guidance also addresses other assorted topics. For example, does the broadcast of a "live case presentation" constitute a promotional activity? 21 CFR 812.7(a) and (d) prohibit a company from promoting or marketing a product that has not been approved, and FDA said they also apply to live case presentations. "Broadcasts of live case presentations may be considered promotional in nature," FDA said.
Sponsors can get around this stumbling block by providing FDA with a "rationale" in its IDE application or IDE supplement "for why the live case presentation would not be in violation of the prohibited practices, including promotion, test marketing and representing the investigational device as safe and effective for the purposes for which it is being investigated."
The presentations must also clearly identify at the beginning of the presentation that it is using an unapproved device, FDA added.
Comments on the draft guidance are due by 16 July 2014.
Draft Guidance: Live Case Presentations During Investigational Device Exemption (IDE) Clinical Trials (FR)