1. REGISTRY ASSESSMENT OF PERIPHERAL INTERVENTIONAL DEVICES (RAPID): Superficial femoral and Popliteal EvidencE Development (SPEED) A NEST Coordinating Center Demonstration Project Overview of the Process and Statistical Analysis Plan
Yu-Ching Cheng, PhD
FDA/CDRH/OSB/DEPI
On behalf of the RAPID/SPEED Project
September 10, 2018
VISION Think Tank Meeting

2. Agenda RAPID/SPEED Overview
Statistical Analysis Plan for Developing the Dynamic Objective Performance Criteria (OPC) in SPEED

3. RAPID- Registry Assessment of Peripheral Interventional Devices
Launched on June 5, 2015 & managed by the Duke Clinical Research Institute (DCRI).
Collaborators from:
Professional societies and their registries
Academia
Medical device manufacturers
United States federal agencies
International partners
Health information technology vendor and clinical research organizations
Reference: Morales JP, Cronenwett J and Thatcher R. Endovascular Today 2016;15:85-94; Jones WS et al. J Vasc Surg 2018;67:637-45

4. RAPID Leadership Principal Investigators Pablo Morales, MD FDA
Robert Thatcher
4C Medical Technologies
Jack Cronenwett, MD
Society for Vascular Surgery (SVS), Vascular Quality Initiative (VQI)
MDEpiNet Key Advisors
Mitchell Krucoff, MD
Duke Clinical Research Institute (DCRI)
Danica Marinac-Dabic, MD, PhD, MMSc
Project Management and Informatics Support
Mina Baqai, Katy Knowlin, Sarah Palmer, Rebecca Wilgus
DCRI

5. RAPID Objective
Designed to advance the foundational elements of a total product life cycle (TPLC) assessment of medical devices used to treat and manage peripheral artery disease.

6. RAPID Phases Phase I (completed) Phase II/III PROJECT (ongoing)
To identify the minimal set of core data elements for registry assessment of peripheral arterial interventional devices.
Phase II/III PROJECT (ongoing)
Use the RAPID core data elements to facilitate peripheral device development while addressing regulatory needs.
SPEED- Superficial Femoral and Popliteal Evidence Development:
To use the VQI database to develop contemporary, dynamic objective performance criteria (OPC) for superficial femoral (SFA) and popliteal artery (POP) endovascular interventions.
Working Groups:
Protocol & Statistics
Governance
Informatics
Outreach/Visibility
GUDID

7. RAPID/SPEED Overview
PPP w/ reps from Industry, Regulatory, Payers, Prof. Societies, and Patients
Develop clinical, statistical and informatics teams to address detailed issues
Identify a minimum core data set
Identify potential sources of information with acceptable quality
Prospectively develop a protocol and statistical analysis plan
Identify incl/excl, key covariates, analysis populations, and outcomes
execute the analysis and report results
sub-teams provide feedback
Partnership agrees to OPC and website with calculator created
Review OPC and update every x years
SNIS 24JUL2018

8. Agenda RAPID/SPEED Overview
Statistical Analysis Plan for Developing the Dynamic Objective Performance Criteria (OPC) in SPEED

9. VQI participating center and physicians
Data Source
Vascular Quality Initiative (VQI) Peripheral Vascular Intervention Registry (PVI)
VQI participating center and physicians
Collecting:
Patient demographics
Comorbidities
procedure detail including device class
in-hospital and one-year outcomes
Data validation through CMS claims data

10. Patient Selection
Including patients with lesions in the superficial femoral arteries (SFA) or popliteal arteries (POP) that were treated with angioplasty, stent, and/or atherectomy between 2010 and 2015.
Excluding:
Aneurysmal disease of the SFA or POP and non-atherosclerotic etiology
Treatment for acute limb ischemia
Treatment of common femoral artery or profunda femoral artery occlusive disease
Emergency procedures
Patients treated with PVI and concomitant femoral endarterectomy at any time prior to the index procedure
Surgery
SPEED: Overview of SAP
5/2/2018

11. Data Completeness
Assess the completeness for each outcome, covariate and their combinations. The data completeness are reported at the patient, limb, artery, and lesion level depending on the variable.
The above information, in consultation with the protocol & statistics team, will be used to determine if any of the covariates needs to be imputed.
SPEED: Overview of SAP
5/2/2018

12. Analytical Populations
Subgroups based on treated vessel:
Patients where the index procedure has treated lesions that are located in the SFA alone
Patients where the index procedure has treated lesions that are located in the POP alone
Patients where the index procedure has treated lesions in either the SFA, POP or both
For each vessel-based subgroup, an OPC will be developed for the following sets of treatment procedures:
All patients with any of the following: PTA, Stent, or Atherectomy
Percutaneous Transluminal Angioplasty (PTA) only
Stent with or without PTA
Atherectomy with or without PTA
Stent + Atherectomy
5/2/2018

13. Outcomes of Interests Mortality: any cause
Major amputation: below or above knee amputation of index limb
Amputation free survival (AFS): composite of freedom from mortality and major amputation
Target lesion revascularization (TLR): repeat intervention (open surgical or percutaneous) on the index artery(ies):
Open surgery: any endarterectomy or infrainguinal bypass of target lesion previously treated with PVI
Interventional: any angioplasty, atherectomy, stent or stent graft or thrombolysis performed on target lesion previously treated with PVI
Target lesion occlusion: binary loss of patency or occluded at follow-up
Target vessel revascularization: Any new qualifying procedure within the target vessel
Technical failure: inability to cross lesion or occlusion, SFA-POP artery dissection or perforation requiring treatment, distal embolization requiring treatment, or residual stenosis >=30%. 

14. Covariates of interest
History (Left and Right):
Indication
Pathology
Prior inflow bypass
Prior inflow PTA/Stent
Prior leg bypass
Prior leg PTA/Stent
Prior major amputation
Prior minor amputation
Pre-rx TBI
Pre-rx ABI
Baseline
Age
Gender
Date of death
Race/Ethnicity
Weight, Height, BMI
Smoking
Hypertension
Diabetes
Coronary Artery Disease (CAD) Symptoms
Prior CHF
COPD
Dialysis
Creatinine
Living Status
Discharge Status
Ambulatory Status
ASA Class
Pre-operation medications
Prior bypass
Prior PVI
Prior major amputation
Procedures:
Urgency
Largest sheath size
Side (lesion level)
TASC-Trans-Atlantic Society Consensus (lesion level)
Total occlusion length (lesion level)
Total treated length (lesion level)
Adjunct (lesion level)
Balloon/stent max diameter (lesion level)
Arterial dissection
Arterial perforation
Distal embolization
Proximal run off score (SFA, POP, Profunda) (L and R)
Distal run off score (AT, PT, Peroneal) (L and R)
Post-op:
Access site stenosis/occlusion
Discharge medication: ASA, anticoagulation, betablocker, platelet inhibitor, statin
5/2/2018

15. Data Analyses Descriptive statistics for baseline characteristics
Univariable analyses of covariate and outcomes of interests, by vessel*treatment type.
Multivariable analyses for outcomes of interests, by vessel*treatment type.
OPCs for outcomes of interests, by vessel*treatment type:
Estimates adjusted for various covariates
5/2/2018

16. SPEED Analytical Team FDA Team: VISION Programming Team
Analysts: Yu-Ching Cheng, PhD & Li Wang, PhD (Division of Epidemiology; Director: Danica Marinac-Dabic, MD, Ph.D.)
Advisors:
Office of Surveillance and Biostatistics (Director: Thomas Gross, MD, MPH)
Nelson Lu, Ph.D. (Division of Biostatistics; Director: Ram Twari, Ph.D.)
Office of Device Evaluation, Division of Cardiovascular Devices
Misti Malone, PhD
VISION Programming Team
SPEED Analytical Team works interactively with the RAPID Statistical Work Group (Lead: Roseann White, PhD) throughout the analyses

17. Dataset for SPEED Analysis
30,899 patients transferred from VQI:
25,077 patients with 1 procedure
5,822 patients with more than 1 procedure
38,344 procedures:
26,389 procedures with follow-up information
# of lesions treated:
SFA: 32,385 (22,362 with follow-up information)
POP: 15,886 (11,001 with follow-up information)

18. Summary
SPEED project: use the VQI database to develop contemporary, dynamic OPCs for superficial femoral (SFA) and popliteal artery endovascular interventions
These OPCs could potentially be used in designing a device approval clinical trial.
Demonstrate the feasibility of data extraction from a registry and lay the groundwork for a coordinated registry network (CRN).
Extensive analyses are conducted:
Analyses for completeness: ~60 covariates x 9 outcomes
OPC Analyses: 3 sub groups (SFA, POP, SFA and/or POP)  5 sets of treatments  9 outcomes x ~60covariates (univariable + 1 multivariable)
Status
Evaluating OPC for TLR

19. Questions?
RAPID website: