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Benefits to Industry ParticipationMay 2, 2018

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Gain New Perspective

Industry questions can be addressed through participation:

1. Is the FDA committed to using Real World Data for Regulatory Decision Making?

2. What submission path is required to expand indications?3. What type of data is collected in registries?4. How much will it cost?5. How is GUDID data used?

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Is the FDA committed to using Real World Data for Regulatory Decision Making?

FDA has shown commitment to use of RWE in many ways:

1. FDA active participation in the RAPID project2. Released Real World Guidance Document

“Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices”; August 31, 2017

3. Endovascular Today article written by Eleni Whatley and Misti Malone “Current Considerations on Real-World Evidence Use in FDA Regulatory Submissions”

4. FDA funding significant portion of SPEED data transfer and analysis5. FDA statisticians analyzed SPEED data

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Submission Path

180 Day PMA Supplement = User Fee $46,615 (FY 2018)• No change to indication wording• Add sizes (longer, different diameter)• Add wording to labeling related to compatibility between devices• Add clinical data to labeling

Panel Track PMA Supplement = User Fee $233,073 (FY 2018)• Indication wording changes• Lesion Length• In Stent Restenosis• Expanded Lesion Location (Prox Popliteal to Full Popliteal)

RTR = User Fee $21,753 (FY 2018)• Add MR safety wording to labeling• Minor design change reviewed by one discipline (e.g., intermediate balloon

size for DCB)

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What type of data is collected in registries?

Phase 1 – Clinical Core Data Elements were published• Standardizing data elements will allow ability to combine data sources• In next phase, helpful to standardize definitions (e.g., definition of Severely

Calcified Lesions)

Phase 2 – Explored VQI Database• VQI database fields • How registries get information (industry, publications)• Routinely collect clinical information and have ability to query sites for

additional information• Limitations (device type, endpoints, imaging)

Phase 3 – Add Data Sources• Newer VQI data (post Oct 2016)• Other registries• MDIC NEST

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Indication Expansion with RWE

Current Indication

Indicated to improve luminal diameter in the treatment of symptomatic de-novo or restenotic lesions in the native superficial femoral artery (SFA) and/or proximal popliteal artery (PPA).

Proposed Indication

Indicated to improve luminal diameter in the treatment of symptomatic de-novo or restenotic lesions in the native superficial femoral artery (SFA) and/or full popliteal artery (P1-P3).

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Study Design

DesignRetrospective, non-randomized, propensity score 1:1 match to PTAPre-specified analysis of existing VQI registry data.

Primary ObjectiveTo expand the labeled indications of the SFA/PPA device to include distal popliteal based on Real World Evidence (RWE) from the VQI PCI registry.

Safety Endpoint (non-inferior to PTA) composite MAE:• All cause death through 30 Days• Target limb major amputation through 12 months• TLR through 12 months

Effectiveness Endpoint (superior to PTA):Original thought: Vessel Primary Patency at 12 months via DUSUsing VQI Registry: Freedom from TLR

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How much will it cost? Timeline?

CostFDA Pre-submission discussions

Obtain VQI DataStep 1- Propensity MatchStep 2 – Outcome DataStatistical Analysis (sponsor)150 patients: $200K-$500K

Panel Track PMA/S$233,073

US Labeling Updates$20K (much more expensive if global DFU)______________________________Total = $450K-$750K

Timeline3 months

3 months

6 months

2 months

______________________________Time: 14+ months

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How is GUDID used?

• Fields clinicians find most useful (clinical relevant size, VQI collects diameter and length)

• FDA database release in March allowed industry to unlock and update records

• Share complexities of industry updates (different for company with 100 records vs. 10,000 records)

• Industry needs to prioritize compliance requirements and dates (US GUDID, EU MDR – EUDAMED)