The medical device product development cycle can take several years and cost millions of dollars, especially when a clinical study is required. With an investment that large, it’s smart strategy to ensure your study design is locked-in well before you submit an investigational device exemption (IDE) application to FDA. We believe the voluntary FDA Q-Submission Program, specifically the pre-sub meeting process, can serve as a powerful tool to optimize your clinical strategies and save you time and money. In this first of a two-part article on this topic, we share five proven tips to prepare for a successful FDA pre-sub meeting for your clinical study. 

Benefits of a Clinical Study Pre-Sub

Many clinical study sponsors bypass opportunities to connect early and often with FDA due to fears of getting “locked into” a plan of action they are not prepared to execute or concerns that an additional interaction might prolong the overall process. Don’t make that mistake. Go! Meet the FDA personnel you will be working with, in person if possible.

When you put a high-quality study design synopsis (something we’d love to help you create) in front of FDA during the pre-sub process, you can obtain valuable FDA feedback and guidance that will prevent delays and surprises during your IDE submission. This is an opportunity to ensure you speak the same language as FDA regarding your study endpoint definitions, an important detail that is often overlooked and leads to snags during IDE review. Early FDA feedback on your safety and efficacy endpoints and statistical methods will help ensure your proposed study design produces the necessary data to support your future market authorization applications. In addition, we recommend the pre-sub includes other key study design elements, such as the indications for use statement, patient population, sample size, test methods, and follow-up requirements.

To optimize your pre-sub interactions with FDA decision-makers, it’s critical to start with a thoughtful plan for the pre-sub meeting request and the type of feedback you would like to receive. Below are five proven tips that will help you prepare for a successful FDA pre-sub meeting.

Tip #1: Plan time in your product development schedule for pre-subs

The pre-sub process takes about 120 days, from request to acceptance of the meeting minutes, and the result is non-binding feedback. This means you do not have to implement all recommendations; however, FDA is your ultimate audience for IDE submission and product authorization, and they put substantial thought and resources into reviewing and providing guidance for pre-subs, so don’t brush off their input either.

If there is any doubt about whether FDA will accept your product development and clinical strategies, we encourage you to plan ample time for the pre-sub process. Clinical study discussions with FDA should happen well in advance of IDE submission, so you can receive and incorporate FDA feedback before you begin executing your plan, before you get too deep into time-consuming and expensive strategies that never stood a chance resulting in time and money lost. In other words, plan for a pre-sub clinical study meeting in parallel with your early product development activities.

Tip #2: Prepare a pre-sub request that defines clear strategy and clear questions for FDA

To request a pre-sub, you will submit a documentation package that describes your product, the intended use, your proposed regulatory pathway with rationale, and a detailed clinical study design synopsis that includes the following:

  • Patient population
  • Eligibility criteria
  • Study design (e.g., single arm, randomized)
  • Endpoints with relevant definitions cited
  • Statistical methods
  • Evaluation and follow-up assessments and visit schedule

To ensure appropriate support for your clinical strategy, you may also choose to include pre-clinical test plans.  Most importantly, the pre-sub documentation package should include specific questions for which you would like FDA feedback. Never generically ask, “Should we randomize?” or “What’s our endpoint?” Instead, boldly define your desired approach and support the strategies with sound rationale. Ask FDA specific questions about their agreement with the proposals or their suggestions to improve or streamline.  

While FDA cannot tell you if a proposed study design will guarantee market authorization, they can advise you about their preferred study endpoints and follow-up requirements, often informed by their experience with other sponsors and products, knowledge not yet published in formal guidance documents. The FDA Q-Submission guidance document linked above has additional details on meeting request format and logistics, as well as a helpful appendix with sample questions.

Tip #3: Immediately begin meeting preparations

FDA will review your pre-sub meeting request and provide written feedback about five days before your scheduled meeting date. We have seen times as short as one weekend between receiving FDA written feedback and the scheduled meeting date, so begin meeting preparations even before you receive the feedback. We suggest the following preparations at minimum:

  • Confirm the meeting time and logistics with the FDA lead reviewer
  • Identify your meeting attendees (e.g., company personnel, regulatory consultants, clinical research organization (CRO) team members, and physician medical advisors)
  • Develop a meeting presentation slide deck based on your pre-sub content, leaving placeholders to address the written feedback from FDA
  • Designate your lead presenter, slide manager, and dedicated note-taker

Tip #4: Triage FDA feedback to ensure an efficient meeting

When you receive FDA written feedback, carefully review it with your team. If it fully addresses all the questions posed, you may consider cancelling the meeting, which FDA invites you to do. If you wish to proceed with the meeting, determine which FDA feedback can be accepted outright without further conversation and which needs clarification during the one-hour meeting. Focus on topics that require interactive discussion and manage your time accordingly.

To facilitate this internal triage process, you may find it helpful to create a table summarizing FDA feedback and your planned responses. Carefully consider how far you are willing to go in negotiating agreements with FDA. For example, are you willing to add a control arm and randomize your study? Are you willing to extend your follow-up timepoints or add specific assessment measures? Do you have flexibility regarding the wording in your indications statement? These questions will help you analyze and establish your limits ahead of time, which will better inform your discussion during the meeting.

Tip #5: Send a meeting presentation to FDA that clearly identifies outstanding questions

Using the meeting presentation slide deck discussed in tip #3 above, incorporate a summary of FDA written feedback, and ensure that your outstanding questions are clearly noted. FDA may not be prepared to address new data, proposals, or questions live during the meeting, so stick to the information in your initial request. While minor clarifications or short-term project updates may be communicated through email with your lead reviewer, large-scale changes to your original strategy should be handled through a pre-sub supplement. After you review the slide deck with your team, send it to your FDA lead reviewer at least three days before the meeting.

Next Steps

As is probably evident by now, BRIGHT is a big believer in the power of the pre-sub meeting for your clinical study. Our experience reflects the potential benefits advertised by FDA, including the improved quality and shortened review times for subsequent IDE submissions and market authorization applications. We hope these tips will help you achieve similar benefits. Stay tuned for our next blog post, where we will share proven tips for conducting a successful pre-sub meeting and handling post-meeting activities.

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