FDA is proposing a new voluntary, interactive review process to help companies maximize their chances of gaining investigational device exemption approval for a study that also has a good chance of supporting marketing clearance or approval.

The “pre-decisional IDE review process” would allow device makers to submit full protocols and data to FDA and receive detailed feedback on possible insufficiencies before formally filing for an IDE. The process would pinpoint not only issues that will lead to IDE rejection but also problems that are likely to limit a firm’s chances of gaining marketing approval after a study is complete.

The process is detailed in a revised draft guidance issued June 14. The document is an update to a 2011 draft guidance on possible FDA decisions that could result from an IDE submission.

The initial draft guidance tweaked the definition of an IDE “approval with conditions” and introduced the concept of staged IDE approvals. (See Also see "Jumpstarting U.S. Device Trials? FDA Makes Effort In New Draft Guidelines" - Medtech Insight, 14 November, 2011..) Those concepts are generally supported by industry and remain consistent in the new draft. But the FDA Safety and Innovation Act of 2012 required FDA to rework other parts of the 2011 draft guidance. (See Also see "FDA To Re-Issue Draft Guidance On Investigational Device Exemption Standards" - Medtech Insight, 4 March, 2013..)

“This type of voluntary program will not likely be suitable for all IDE sponsors and [FDA] does not intend that this program become a routine step prior to submission of an IDE,” FDA clarifies.

The act prohibits FDA from disapproving an IDE solely because the study may not support approval or clearance of the device. That rationale is not listed in FDA regulations as a reason to disapprove an IDE. The regulations cite issues including untrue statements, risks outweighing anticipated benefits of a study, unsound science or reason to believe a device is ineffective, as valid reasons for rejecting an IDE.

But the 2011 draft guidance included a line that some manufacturers saw as a claim by FDA that it could reject an IDE solely because reviewers didn’t think the data would be sufficient to support a marketing submission. The guidance came amid growing industry complaints that FDA was rejecting an increasing proportion of IDEs. (See [A#01120326010].)

The FDASIA provision was an attempt by lawmakers to respond to industry concerns that FDA was overreaching in its IDE authority. In response, the new draft guidance incorporates the FDASIA statutory language, explicitly stating that FDA cannot disapprove an IDE purely because the collected data may not successfully support a 510(k) or PMA.

But the revised draft also turns the issue around: “The agency recognizes that some IDE sponsors may wish to determine whether the pivotal study design may support a marketing application if it is successfully executed and meets its stated endpoints without raising unforeseen safety concerns.”

The most substantive changes in the revised draft guidance address this wish.

Could Lead To Faster Study Starts

Among the most significant additions to the revised draft guidance is the introduction of the pre-decisional IDE review process.

“FDA believes this process could result in faster approval of IDE submissions that may support market approval or clearance, and help to address several commonly reported challenges in the initiation of clinical trials, such as delays in IRB approvals and reimbursement from third party payers,” the agency writes.

On the other hand, the process involves multiple extra steps that could take 65 days or more before an IDE application is submitted.

“This type of voluntary program will not likely be suitable for all IDE sponsors and [FDA] does not intend that this program become a routine step prior to submission of an IDE,” FDA states.

Under the pre-decisional program, a device sponsor can submit planned IDE protocols and supporting data and reports. FDA will have five days to determine if the submission is sufficiently complete and, if it is, the agency will accept the submission and initiate a 30-day review clock.

After the 30 days, FDA must email the sponsor with a list of issues that would result in IDE disapproval; would need to be addressed as a condition of IDE approval; or would be identified as a study design consideration that will be a factor in marketing approval even if the IDE is approved. Within 15 days after that, FDA must meet with the sponsor (or hold a teleconference) to discuss the feedback in more detail.

The sponsor can elect to move to the formal IDE review process at that point or wait until after it receives a more comprehensive written appraisal of its pre-decisional IDE. Alternatively, it could seek additional information from FDA in a further back-and-forth process.

An IDE that incorporates the feedback from FDA is likely to be approved more quickly, the agency suggests.

“Ultimately, this process is intended to lead to faster enrollment and completion of trials for selected devices,” the draft guidance states.

But the pre-decisional process is also intended to promote “more efficient allocation of FDA and sponsor resources, with submission of higher quality IDE applications and higher quality data generated from studies.”

In that direction, if FDA determines in the initial five-day review that a sponsor does not have a submission of sufficient quality to warrant review, the company will be either turned away to resubmit with more information or diverted to the current pre-submissions program.

The pre-submissions program shares a theme with the proposed pre-decisional IDE program, but FDA makes a clear distinction between the two. The former is not necessarily as much of a fast-track to near-term IDE submission as the latter, the agency suggests. In particular, FDA will not review a company’s data during a pre-submissions meeting and can only respond to specific questions posed by a company about clinical trial plans. (See Also see "FDA Addresses Pre-Submission Meetings In Draft Guidance" - Medtech Insight, 16 July, 2012..)

FDA Will Stand By Its Finding Of Data Adequacy

Distinct from the pre-decisional IDE process, FDA’s new draft also describes a refined approach to explaining to companies, as part of the actual IDE decision letter, how their study design may be helping or hurting their marketing approval chances.

While the agency makes clear that such factors will not be weighed in the IDE approval decision, it also makes clear that FDA’s review of the study during the IDE stage has important implications for how the agency approaches the eventual marketing submission.

If FDA states in the IDE letter that the study design will be adequate, the agency plans to hold itself to that determination in most cases.

FDA says it will state in the IDE letter whether it believes the study design is adequate to support a future approval or clearance. And if the agency states in the letter that the design will be adequate, FDA plans to hold itself to that determination.

“If FDA determines that a pivotal study design is adequate and may support a future marketing application, FDA intends to consider changes to its assessment of the study design only if the sponsor materially changes the device or the study design, or if important issues relevant to a determination of safety and effectiveness have emerged since the time of the IDE approval,” the draft guidance states.

The draft guidance also describes a “study design considerations” section of the standard IDE letter that will detail issues that could weaken a marketing application even if they do not hinder approval of the IDE. IDE letters have included this new section since last fall, according to FDA officials.

Issues that might be addressed include the selection of primary and secondary endpoints, plans for randomization and control groups and a company’s statistical plan, among other matters.

The revised draft guidance also includes some additional explanatory detail on factors that could support an IDE disapproval. Further, the new document includes a flow chart of the pre-decisional IDE process; a separate chart detailing the elements of a “device evaluation strategy” that should be included as part of the submission for that program; and a checklist for what needs to be included in a complete pre-decisional IDE application.

The Pre-Decisional IDE: FDA’s New Proposal To Help Studies Get Started Right

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