FDA hints it will show 'additional flexibility' when it comes to approving device clinical trials

The FDA released an overview of its considerations and process for reviewing so-called investigational device exemptions (IDEs), which give researchers permission to test developmental devices on humans.

The purpose of the IDE process is "to encourage, to the extent consistent with the protection of the public health and safety and with ethical standards, the discovery and development of useful devices intended for human use and to that end to maintain optimum freedom for scientific investigators in their pursuit of that purpose," the FDA says.

The key to IDE approval is to convince the agency that risks to the subjects are "outweighed by the anticipated benefits to the subjects and the importance of the knowledge to be gained," according to the draft guidance.

The FDA stresses that it will accept greater uncertainty about the risks and benefits of devices in premarket settings.

"Where appropriate, FDA may allow additional flexibility in how outstanding issues can be addressed (i.e., future concerns, study design considerations, contingent approval, staged approval), to allow clinical investigations to commence without unnecessary delay, while ensuring that human subjects are adequately protected," the document says.

After all, an IDE approval signals permission to commence human clinical trials. But the tolerance for risk and uncertainty vary depending on the device's stage of development.

"Specifically, a greater degree of uncertainty is expected for novel technologies, and at earlier stages of device development, such as first in human or early feasibility trials, while relatively more certainty is expected in traditional feasibility and pivotal trials. At earlier stages, the focus is on appropriate risk mitigation measures for anticipated possible risks and unanticipated risks, whereas in later stages focus shifts increasingly to mitigating the most probable risks," the FDA writes.

"Later stage studies, particularly those intended to support future regulatory applications, are typically designed to assess safety and effectiveness outcomes in an intended patient population, with sufficient information to quantify uncertainty in each."

The most interesting and surprising part of the guidance is its request for a section on patient preference information. The topic received its own guidance recently, and the FDA's interest in the subject extends to IDE studies.

Such data can be used to approve an IDE with a subset of the population that is willing to accept the risk/benefit profile of the device, FDA says, writing, "when available, information characterizing subject tolerance for risk and perspective on benefit may provide useful context for assessing the benefits and risk of a proposed clinical investigation." The document suggests using patient preference information to find subjects with a greater appetite for risk.

Another important statement that companies should consider when trying to get these devices to market faster: "In some cases, nonclinical testing (e.g., in vitro tests, animal studies, and computer modeling and simulation) can obviate or reduce the need for additional clinical testing to evaluate certain aspects of device design or performance."

A good portion of the guidance describes qualities the FDA uses to assess risks and benefits, including their severity, likelihood and duration. Risks and benefits to others, like clinicians and caretakers, are also considered, as is the availability of alternative forms of treatment for the condition being treated.

The guidance seems to fit with the FDA's new goal of speedy approvals and particularly the focus on bringing early-stage trials to the U.S. in a bid to strengthen the domestic industry. (The trend has been toward conducting trials in Europe, where the regulatory burden is lower.)

The document says FDA "intends to permit appropriate latitude for the conduct of IDE studies within the boundaries of applicable laws and regulations."

The FDA is accepting comments on the draft guidance for 90 days. 

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