1. Implementation of Unique Device Identification Demonstration Project – A Report from MDEpiNet Joseph P. Drozda, Jr., M.D., F.A.C.C. Director, Outcomes Research Mercy Health

2. 34 ACUTE CARE HOSPITALS 4,396 LICENSED BEDS 36,917 CO-WORKERS 185 PHYSICIAN PRACTICE LOCATIONS 4,659 MEDICAL STAFF MEMBERS 1,235 INTEGRATED PHYSICIANS $4.05 OPERATING REVENUE (Billions USD)

4. UDI Demonstration Project Aims 1.Implement a coronary artery stent UDI- based surveillance system in the EHR in a multi-hospital system (Mercy) 2.Identify obstacles to implementation of UDI in clinical information & to characterize the effectiveness of interventions to overcome them; 3.Assess the validity and utility of data obtained from the EHR and incorporated UDIs for purposes of post-market surveillance 4

5. UDI Demonstration Timeline Began work on system design: April, 2012 Identify 1 device and a multi-stakeholder group: Sep, 2012 Develop IT infrastructure : Oct, 2012 Processes & systems for surveillance: Feb, 2013 Demonstrate surveillance capabilities: May, 2013 Complete demonstration of surveillance capabilities: Oct, 2013 Final report: Dec, 2013

6. Key Components of UDI Demonstration Create Draft UDIs & associate with base attributes in the FDA’s Global UDI Database (GUDID Create clinically meaningful supplemental attributes to be stored in a reference database Create UDI data flow through ERP to cath lab to EHR to UDI data set Create UDI fields in the CathPCI Registry Perform studies to demonstrate validity and reliability of data Identify obstacles to incorporating UDIs into EHR and explore solutions 6

7. The Expert Work Group The Expert Panel: Five interventional cardiologists appointed in conjunction with ACC and SCA&I “Ex officio” members FDA representatives Coronary Stent manufacturer representatives HTG system representatives NCDR representatives 7

8. Tasks for Expert Work Group Develop a constrained list of coronary stent clinical attributes to supplement the GUDID attributes (Expert Panel) Propose a permanent home for UDI clinical attribute database (SUDID) Recommend a governance structure for the SUDID Develop a proposal for an organization and processes for ongoing maintenance of the SUDID 8

9. Table 3: SUDID Clinical Attributes and Parameters AttributeDefinitionParameterData Type LengthNominal length per manufacture specificationFractional dimension in mm 4 significant digits, w/1 precision Diameter Nominal (inner) diameter per manufacturer specification Fractional dimension in mm 4 significant digits, w/2 precision Non-conventional Property Stent having nonconventional design, variable or multiple length/diameter parameters Covered stent Bifurcation Stent Tapered Stent Alphanumeric Structural MaterialComposition of principal structural element Constrained list e.g. L605 cobalt chromium -- Constrained list to be developed Alphanumeric Coating(s) Non-Structural material covering surface of structural element Constrained list -- Constrained list to be developed --Need to handle multiples --name that would be mostly referenced --start with what is in the IFU --accommodate multiple coatings Alphanumeric Drug(s)Active agent released from stent NDC directory (default) --Use name if no applicable NDC code—do it uniformly Alphanumeric Strut Thickness Maximum nominal thickness of stent struts on a radius from the center of the stent Dimension in microns4 integer digits Surface to Artery Ratio* Percentage of the surface area of the artery covered by the stent at nominal expansion of the stent 3 significant digits, w/1 precision Expansion Method Method used to achieve nominal stent deployment Balloon Self Alphanumeric MRI CompatibilityMRI compatibility category per testing 4 categories per existing standard: --Safe --Conditional --Unsafe --Not tested 4 Categories *This attribute was originally selected by the Expert Panel but subsequently withdrawn SUDID = Supplemental Unique Device Identifier Database; IFU = Instructions for Use; NDC = National Drug Code; MRI = Magnetic Resonance Imaging

11. UDI Demonstration Project High Level Architecture

12. Single EHR UDI Tracking System Data Flow

14. The Reference Data Set of Procedures and Coronary Stents Patients and stents included in dataset if found in any one of the following datasets Cath Lab Data table in UDIR Inventory Data table in UDIR Billing Data table in UDIR Registry Data from Registry submission Completeness of each data set measured against the reference dataset

15. Unique Coronary Stent Procedure Counts (percent of procedures in reference datasets) St. LouisSpringfieldRogers(All Sites) Registry Data291 (88%)566 (87%)-857 Cath Lab Data281 (85%)546 (84%)236 (83%)1063 Inventory Data301 (91%)608 (93%)253 (89%)1162 Billing Data291 (88%)565 (87%)212 (75%)1068 Reference Dataset 3306532831266

16. Patient Counts by Month and System for St. Louis and Springfield

17. Percent Agreement by System Combinations for St. Louis and Springfield System % Registry DataCath Lab DataInventory Data Billing Data YYYY 73% YNYY 9% NYNN 4% NNYN 3% YYYN NYYN 2% NNNY YYNY 1% NYYY NNYY 0.4% YNYN 0.3% YNNY 0.1% YNNN NYNY YYNN

18. Stent Counts by Site and System (percent of stents in reference datasets) St. LouisSpringfieldRogersAll Sites Cath PCI514 (76.3%)877 (81.1%)--1391 Merge603 (89.5%)902 (83.4%)412 (80.6%)1917 OptiFlex539 (80.0%)929 (85.9%)432 (84.5%)1900 Billing496 (73.6%)768 (71.0%)344 (67.3%)1608 Reference Dataset 6741082511

19. Coronary Stent Count Comparison at Mercy Hospital St. Louis and Springfield

20. Overall Scan Compliance Inventory DataCath Lab DataInventory/Cath Lab Rogers74485686.9% (744/856) Springfield1996227987.6% (1996/2279) St Louis897109781.8% (897/1097) Total3637423285.9% (3637/4232)

21. Inventory /Cath Lab (%) Scan Compliance – by Month

24. Scan Compliance – Non Regular Hour vs Regular Hour Inventory/Cath Lab (%)

25. Scan Compliance – Emergent (AMI) vs Non-emergent Inventory/Cath Lab (%)

26. Options for Device Comparisons in the UDIR Baseline patient characteristics Demographic Clinical (lab, diagnoses, etc.) Devices Product identifier +/- production identifier Attributes Outcomes (MACE) Individual Combined

27. Statistical Analyses Step 1 Detect safety signal (a) with different drug attributes, (b) combined drug attributes Step 2 Investigate MACE events in different follow-up periods Step 3 Identify selection bias Step 4 Reduce selection bias Step 5 Examine match-pair samples

28. Case Selection Flow Diagram 2484 procedures performed between 1-Nov-12 and 26-Oct-13 (total 2250 patients) 1808 procedures with 1963 stents (total 1657 patients) 1640 procedures with 1772 stents (total 1545 patients) Stents:  1166/1545: Everolimus drug  176/1545: Zotarolimus drug  19/1545: Paclitaxel drug  184/1545: Bare metal 676 procedures excluded:  482 no stent attributes  189 blank drug attribute in SUDID  5 invalid medical records 112 patients excluded:  73 had >= 2 stents with different drug attributes at initial procedure  39 had stents with different drug attribute at subsequent procedure

29. Step 1a: Device attribute: Drug Patient characteristics: All Outcome: Mortality Mortality Paclitaxel: 19 patients with 0 deaths Zotarolimus: 176 patients with 7 deaths Everolimus: 1166 patients with 28 deaths Bare metal: 184 patients with 18 deaths

30. Mortality Drug eluting stent: 1361 patients with 35 deaths Bare metal: 184 patients with 18 deaths Step 1b: Device attribute: DES Combined Patient characteristics: All Outcome: Mortality

31. Step 2: Investigate Mortality in Different Follow-up Periods Mortality (Total 53)DESBMSP-value 30 days (N=1405, 35 deaths)1.6% (20/1230)8.6% (15/175)<0.0001 60 days (N=1246, 40 deaths)2.2% (24/1096)10.7% (16/150)<0.0001 90 days (N=1111, 43 deaths)2.8% (27/982)12.4% (16/129)<0.0001 120 days (N=947, 45 deaths)3.4% (28/832)14.8% (17/115)<0.0001 150 days (N=798, 49 deaths)4.6% (32/702)17.7% (17/96)<0.0001 180 days (N=665, 50 deaths)5.6% (33/586)21.5% (17/79)<0.0001 210 days (N=539, 51 deaths)7.2% (34/472)25.4% (17/67)<0.0001 240 days (N=374, 52 deaths)10.6% (34/322)34.6% (18/52)<0.0001 270 days (N=281, 52 deaths)14.2% (34/240)43.9z% (18/41)<0.0001 300 days (N=202, 52 deaths)20.4% (34/167)51.4% (18/35)0.0004 330 days (N=129, 52 deaths)33.3% (34/102)66.7% (18/27)0.0035 360 days (N=61, 53 deaths)85.4% (35/41)90.0% (18/20)NA

32. Step 3: Identify Selection Bias Baseline Characteristics (N=1405) DES (n=1230)BMS (n=175)P-valueStandardized Diff (DES-BMS) % Female32.4% (398/1230)32.6% (57/175)0.9549-0.43 Age > 6553.1% (653/1230)53.1% (93/175)0.98940 Caucasian95.9% (1177/1227)92.5% (161/174)0.050514.58 Married69.6% (854/1227)59.2% (103/174)0.006921.95 Alcohol used (Y)37.4% (440/1178)32.9% (53/161)0.29649.44 Illicit drug used (Y)6.0% (66/1106)10.9% (16/147)0.0319-17.69 Acute MI (Y)35.0% (431/1230)53.1% (93/175)<0.0001-37.08 Cardiac arrest (Y)0.3% (4/1230)1.1% (2/175)0.1652-9.61 Shock (Y)1.9% (23/1230)9.7% (17/175)<0.0001-33.84 COPD (Y)12.9% (158/1230)18.9% (33/175)0.0339-16.46 Diabetes mellitus (Y)37.0% (455/1230)27.4% (48/175)0.014420.66 Dialysis (Y)1.9% (23/1230)0.6% (1/175)0.348211.72 EF < 30% (Y)2.0% (25/1230)5.7% (10/175)0.0078-19.32

33. Step 4: Reduce Selection Bias Baseline Characteristics (N=290) DES (n=145)BMS (n=145)P-valueStandardized Diff (DES-BMS) % Female33.1% (48/145)34.5% (50/145)0.9012-2.96 Age > 6546.9% (68/145)42.8% (62/145)0.55508.25 Caucasian95.9% (139/145)94.5% (137/145)0.78536.55 Married57.2% (83/145)56.6% (82/145)0.90561.21 Alcohol used (Y)28.3% (41/145)31.0% (45/145)0.6998-5.91 Illicit drug used (Y)10.3% (15/145) NA0 Acute MI (Y)53.1% (77/145)52.4% (76/145)0.90641.4 Shock (Y)9.0% (13/145)8.3% (12/145)0.83432.49 COPD (Y)20.7% (30/145) NA0 Diabetes mellitus (Y)28.3% (41/145)29.7% (43/145)0.8971-3.09 EF < 30% (Y)4.8% (7/145)6.2% (9/145)0.7980-6.14

34. Step 5: Examine Matched-pair Samples McNemar’s Test Statistic (1 degree of freedom)1.1429 (p=0.2850) Simple Kappa Coefficient Kappa (ASE)0.1735 (0.1348) Test for Kappa = 0 Statistic (two-side p-value)2.1494 (p=0.0316)

35. MI Paclitaxel: 19 patients with 0 MACE MI Everolimus: 1166 patients with 34 MACE MIs Zotarolimus: 176 patients with 6 MACE MIs Bare metal: 184 patients with 5 MACE MIs Step 1a: Device attribute: Drug Patient characteristics: All Outcome: Myocardial Infarction (MI)

36. ST Paclitaxel: 19 patients with 1 MACE ST Everolimus: 1166 patients with 27 MACE STs Zotarolimus: 176 patients with 6 MACE STs Bare metal: 184 patients with 4 MACE STs Step 1a: Device attribute: Drug Patient characteristics: All Outcome: Stent Thrombosis (ST)

37. TR Paclitaxel: 19 patients with 1 MACE TR Everolimus: 1147 patients with 113 MACE TRs Zotarolimus: 172 patients with 17 MACE TRs Bare metal: 182 patients with 18 MACE TRs After excluding 25 patients who had unmatched procedure dates: Step 1a: Device attribute: Drug Patient characteristics: All Outcome: Total Revascularization (TR)

38. Obstacles Technical: Biggest problem so far is Merge Agreeing on: Industry-wide standards Device attributes Organizational infrastructure and support for designing and maintaining a UDI system The business case for all stakeholders 38

39. UDI Phase 2 Purpose: Build a national network of UDI enabled EHR data sets around national registries for device surveillance and research. The UDI Alliance: HTG Health Systems (Mercy, Mayo, Geisinger, Intermountain, and Kaiser) National medical societies and registries (ACC/NCDR) Industry (Medtronic, Abbott, Boston Scientific Consumer groups/patient representatives

40. Coronary Stent Distributed Data Sharing Network

41. Thanks! Joseph P. Drozda, Jr., M.D., F.A.C.C. Director, Outcomes Research Mercy 14528 South Outer Forty Chesterfield, MO 63017 314-628-3864 Mobile: 314-308-1732 Joseph.Drozda@Mercy.net 41