Clinical Evaluations – Methods

Francis D. Pagani, MD

An early feasibility study (EFS) is a limited clinical investigation of a device early in development. It typically:

— enrolls a small number of subjects;

— is used to evaluate the device design concept with respect to initial clinical safety and device functionality; and

— may guide device modifications for a future pilot or pivotal trial.

The Center for Devices and Radiological Health (CDRH)’s EFS Program facilitates the conduct of early feasibility studies in the United States to increase access for patients to potentially beneficial technologies and to support device innovation (1). The EFS Program provides a mechanism for innovators to work directly and early with sponsors, Food and Drug Administration (FDA) review teams, and clinicians so they can increase the efficiency of their device development. Early clinical experience obtained from an EFS can provide insights for sponsors and FDA review teams into device proof of concept, patient characteristics that may impact performance, operator technique refinements, device safety, necessary device modifications, and human factors.

Components of the EFS Program include:

— Opportunities for interactive review

— Assistance in submission preparation from an EFS Program representative

— Potential for less nonclinical data to support study initiation relative to the data needed for larger clinical studies based on use of clinical mitigation strategies

— New mechanisms for timely device review and interactive clinical protocol modifications

The EFS Program is open to devices subject to premarket approval (PMA) (2) or premarket notification, including 510(k) (3), De Novo classification (4), or humanitarian device exemption (5). EFS may be applicable when clinical experience is necessary because nonclinical testing is unavailable or inadequate to provide the information needed to advance device development. Therefore, EFS may be conducted on new devices without prior clinical experience and in some cases, may also be conducted on devices with limited prior clinical experience. For example devices previously used under a compassionate use approval (6), devices used outside of the United States, or marketed devices being proposed for a new indication are suitable for investigation in an EFS.

While an EFS can answer the question of preliminary safety and performance of a device, the safety and effectiveness of a device are evaluated in a pivotal study in patients in whom the device will be used. The approvability of a device depends on the safety and effectiveness shown in the target population. Therefore, it is critical to design a pivotal clinical study that can demonstrate that in a significant portion of the target population clinically significant results outweigh the probable risks. The specific trial design depends on the characteristics of the device (e.g., invasiveness and duration of support) and more importantly, the indications. A randomized controlled trial (RCT) is often the most convincing method for such a trial design, and it is classically considered to provide the best level of evidence. However, an RCT is not always possible (e.g., due to the lack of a standard of care as a comparator), nor is it always necessary, depending on existing knowledge about an indication and a type of device.