CDRH Details Relaxed Data Standard for IDEs for Early Feasibility Studies

By Jay W. Cormier –

Notwithstanding the government shutdown, on Tuesday, October 1st, FDA’s Center for Devices and Radiological Health (“CDRH”) issued a final guidance regarding filing for an investigational device exemption (“IDE”) for medical device early feasibility studies.  At the heart of the guidance is that an IDE application for an early feasibility study may be based on less nonclinical data than would be expected for a traditional feasibility or pivotal study.

For purposes of the guidance document, FDA defines an “early feasibility study” as:

a limited clinical investigation of a device early in development, typically before the device design has been finalized, for a specific indication (e.g., innovative device for a new or established intended use, marketed device for a novel clinical application).  It may be used to evaluate the device design concept with respect to initial clinical safety and device functionality in a small number of subjects (generally fewer than 10 initial subjects) when this information cannot practically be provided through additional nonclinical assessments or appropriate nonclinical tests are unavailable.  Information obtained from an early feasibility study may guide device modifications.  An early feasibility study does not necessarily involve the first clinical use of a device.

It is important for our readers to note that the guidance only applies to early feasibility studies for significant risk devices, as defined in 21 C.F.R. § 812.3(m). 

The guidance document discusses how to report prior investigations, establishing the investigational plan for the device, study changes, and design controls for these devices that are defined to be subject to significant changes before final designs have been established.  The guidance document details, with at times extreme specificity, the particular content and format the CDRH expects for these IDE applications.  For example, when discussing prior investigations using the device, FDA asks that sponsors submit such information in a device evaluation table consisting of nine specific columns that each contains pre-specified types of information. 

The upside for sponsors is that CDRH acknowledges that although the basic principles of an IDE apply to all device clinical studies, in these very early studies a smaller amount of supporting data is expected, and data gaps are not necessarily deal breakers for the IDE application.  Additionally, CDRH will be more flexible with how it approaches device and protocol changes during the studies.  Because of the nature of an early feasibility study, CDRH will also allow 5-day notification of five categories of changes that would otherwise not be permitted in a pivotal study.

CDRH notes that, when submitting an IDE for an early feasibility study, sponsors should be able to answer the following six questions with supporting information:

1. What is the clinical condition to be treated or assessed by the device?
2. What is the standard of care for the clinical condition and expected clinical outcomes associated with the standard of care?
3. What are the anticipated benefits associated with use of the study device?
4. Is the information included in the Report of Prior Investigations (Section 6 of the guidance) adequate to support initiation of the study?
5. Does the Investigational Plan include a thorough risk analysis, sufficient risk mitigation strategies, adequate human subject protection measures, and an appropriate clinical study protocol (see Section 7 of the guidance)?
6. Are the potential risks associated with the device use likely to be outweighed by the anticipated benefits of the early feasibility study, that is, is initiation of the clinical study justified based on the clinical need for the device, Report of Prior Investigations and Investigational Plan?

Because there will be less supportive data regarding the benefit-risk calculus, CDRH will, not unexpectedly, take a closer look at the various mechanisms available to mitigate potential risks associated with the device.  These additional risk mitigation strategies may include: more stringent criteria for study site and investigator selection, limiting the size of the study, more timely reporting of serious adverse events, and increased patient follow-up assessments.

Due to the flexibility given to sponsors of IDEs for early feasibility studies in significant risk devices, and because the specific expectations from CDRH will differ depending on the particulars of the study device, CDRH strongly recommends that sponsors consult with them prior to submitting the IDE application via the pre-submission process.  Although the guidance document provides a lot of detail and direction to sponsors, we agree that such pre-submission meetings should be helpful in avoiding unnecessary delays in obtaining IDE approval for these important device studies.