1. Pharmacy Benefits Management Services www.pbm.va.gov1 Pharmacy Benefits Management Services Ophthalmology FAC September 25, 2009

2. Pharmacy Benefits Management Services www.pbm.va.gov 2 Mission of the VA PBM To improve the health status of veterans by encouraging the appropriate use of medications in a comprehensive medical care setting.

3. Pharmacy Benefits Management Services www.pbm.va.gov 3 Key Functions of the National PBM Services Drug benefit design Evidence-based formulary management Utilization management Staff education (CE / CME) Patient safety (VAMedSafe, adverse drug event (ADE) reporting, post marketing surveillance)

4. Pharmacy Benefits Management Services www.pbm.va.gov 4 VA MedSafe Improve the safety of prescribing practices and medication administration for veterans  Identify and track ADEs  Address preventable ADEs  Evaluate interventions  Educate and communicate  Promote medication safety research in VA

5. Pharmacy Benefits Management Services www.pbm.va.gov 5 Key Objectives of the Formulary Process Promote formulary decisions that are evidenced-based, not preference-based Promote appropriate drug therapy and discourage inappropriate drug therapy Reduce the geographic variability in utilization of pharmaceuticals across the VA Promote portability and uniformity of the drug benefit Initiate patient safety of the drug benefit Design and implement relevant outcomes assessment projects

6. Review: RX volume RX expenditures New Drugs Identify areas of opportunity Review: Medical Literature VA Prescribing Clinical Need Assess feasibility Present issue to stakeholders Medical Advisory Panel (MAP) VISN Formulary Leaders (VFLs) Get input from front line clinical staff Chief Clinical Consultants DoD Pharmacoeconomic Center P & T Committee Determine action(s) Nothing One or more of : Guideline Criteria for Use National Contract Incentive Agreement Implement action(s) One or more of: Issue Drug Use Criteria Conduct Solicitation Negotiate BPA Monitor Performance Contract Participation Utilization Management Use of Criteria PBM-MAP Drug Use Management Process START

7. Pharmacy Benefits Management Services www.pbm.va.gov 7 How the National PBM Supports the VANF, Providers, and Patients Clinical Document Development 1. New Molecular Entity Drug Monographs (NMEs) 2. Criteria for Use (CFU) 3. Drug Class Reviews 4. Guidance and White Papers 5. Clinical Practice Guidelines

8. Pharmacy Benefits Management Services www.pbm.va.gov 8 New Molecular Entity Drug Monographs Review efficacy, safety, cost, and other data of NMEs  “A medication containing an active substance that has never before been approved for marketing in any form in the United States”  Includes drug and biologic products Involve an extensive literature review and evidence-based medicine approach Assess the evidence and clinical significance Recommend place in therapy Support criteria for use decisions

9. Pharmacy Benefits Management Services www.pbm.va.gov 9 Criteria for Use Outline appropriate place in therapy Use clinical trial results (drug monograph) and expert / field opinions to determine appropriateness Consist of  Inclusion and exclusion criteria checklists  Renewal or discontinuation criteria checklist  Dosing, monitoring, and special considerations Discourage inappropriate use Encourage safe and cost-effective use Aim to provide uniform pharmacy benefit

10. Pharmacy Benefits Management Services www.pbm.va.gov 10 Drug Class Reviews Are similar to NME monographs Use evidence-based evaluation to determine  Therapeutic interchangeability  Eligibility for competitive solicitation Compare data for efficacy, safety, tolerability, monitoring, drug interactions, drug administration, cost, and other pharmaceutical issues

11. Pharmacy Benefits Management Services www.pbm.va.gov 11 Peer Review Process

12. Pharmacy Benefits Management Services www.pbm.va.gov 12 Peer Review Process for Documents NME Monographs, Drug Class Reviews, and CFU sent to VFLs for dissemination  VISN and local P&T Committees  Pharmacy Chiefs  Chief Medical Officers  Local subject matter experts Field Advisory Committees (FACs) or Technical Advisory Groups (TAGs) VHA Chief Consultants

13. Pharmacy Benefits Management Services www.pbm.va.gov 13 Peer Review Process for Documents Conflict of Interest (COI)  Required with comments on Drug Class Reviews for national contracting  Requested of field reviewers on CFU documents

14. Pharmacy Benefits Management Services www.pbm.va.gov 14 National PBM Supports Implementation of Formulary Change Announcement of National Formulary changes in PBM-MAP E z Minutes Letters to prescribers and patients Addition of drug-drug interactions to the NDF ADE reporting and monitoring

15. Pharmacy Benefits Management Services www.pbm.va.gov 15 Keeping up with changes PBM INTRAnet site vaww.pbm.va.gov PBM INTERnet site www.pbm.va.gov www.pbm.va.gov PBM-MAP Broadcast Programs PBM-MAP E z Minutes

16. Pharmacy Benefits Management Services www.pbm.va.gov 16 VHAPBH Ask PBM Clinical AskPBMClinical@va.gov

17. Ophthalmology issues  Ophthalmic NSAID  Bevacizumab safety  Cyclosporine drops  Triamcinolone drops Pharmacy Benefits Management Services www.pbm.va.gov 17

18. Pharmacy Benefits Management www.pbm.va.gov 18 Ophthalmic NSAIDs Overall, no substantive differences in efficacy or safety between products. (Review Posted) Current Formulary Agents  diclofenac, flurbiprofen, ketorolac Most frequently used in VA: Ketorolac Dosing differences (generally 14 days post-op)  Diclofenac, ketorolac, flurbiprofen-QID Acuvail (ketorolac 0.45% PF), BID dosing, FDA approved post- cataract (expected availability 9-09) Ketorolac 0.4 and 0.5% patent expiration 11-09  Nepafenac-TID  Bromfenac-BID Xibrom QD-once daily product expecting FDA approval late 2009 Bromfenac’s patent expired 1-09

19. Ophthalmic NSAIDs Recommendations (MAP and VPE) VPE  No changes to the VANF at this time  Ask Ophthalmology FAC if they have a preference between ketorolac, bromfenac or nepafenac  PBM to seek TPR or BPA from manufacturers  Once the pricing and preferences between the 3 agents are known, the VPE/MAP can determine which “third ophthalmic NSAID” would be preferred NF or added to the VANF. MAP  Keep the current formulary ophthalmic NSAIDs and add bromfenac to the VANF due to the less frequent dosing and cost advantage (cost was ~$23)  The MAP also agreed with the VPEs for the PBM to solicit reduced pricing for all branded products (ketorolac, bromfenac and nepafenac). Pharmacy Benefits Management www.pbm.va.gov 19

20. Ophthalmic NSAIDs Ophthalmology FAC  Less frequent dosing is a significant advantage since patients are using other drops as well. Pricing (see attachment for new pricing)  Inadequate time for PBM to seek TPR or BPA from all branded manufacturers  Price of bromfenac increased >100%  Lost VA price for nepafenac Pharmacy Benefits Management www.pbm.va.gov 20

21. Ophthalmic NSAIDs-Considerations Generic availability of ketorolac and bromfenac? Significant price increase for bromfenac  Less data than ketorolac, diclofenac overall  Short-term use  Other drops may be QID as well Nepafenac  TID, lost VA pricing New Products:  Acuvail (ketorolac 0.45% PF): BID dosing, expected availability 9-09  Xibrom QD: QD dosing, expected approval late 2009 Refer to attachment for updated pricing, use and purchases from FY2Q09 and FY3Q09 Pharmacy Benefits Management www.pbm.va.gov 21

22. Bevacizumab and Ranibizumab Rapid cycle analysis using integrated databases to assess potential endophthalmitis for patients administered an intravitreal injections of bevacizumab and ranibizumab was conducted Pharmacy Benefits Management Services www.pbm.va.gov 22

23. Objective and Methods Objective: To determine the prevalence and crude incidence rate of endophthalmitis following bevacizumab or ranibizumab intravitreal injections Datasets:  Rx data: from April 2006 to 1Qtr 09 was used. All patients with Rx for bevacizumab and ranibizumab were extracted  Dx Data: patients with an ICD-9 code for endophthalmitis (4/06-9/08) were identified from the AAC Pharmacy Benefits Management Services www.pbm.va.gov 23

24. Methods Prevalence rate was determined for endohpthalmitis for bevacizumab and ranibizumab. A retrospective new-user, follow-up design was used to determine the crude incidence rate for endopthalmitis for both agents with calculated 95% CI. Events were validated and the verified numbers were used to calculate the crude incidence rate Pharmacy Benefits Management Services www.pbm.va.gov 24

25. Results (prevalence) Pharmacy Benefits Management Services www.pbm.va.gov 25 DrugPatients with VED Endophth almitis Rate/100095% CI Bev3249206.164.0-9.5 Ran2466166.494.0-10.6

26. Results- incidence DrugPatients with VED Endophthalm itis Rate/100095% CI Bev212672.241.1-4.7 ran236241.690.6-4.5 Pharmacy Benefits Management Services www.pbm.va.gov 26

27. Summary Early bevacizumab and ranibizumab signal showed slight increased rates of endophthalmitis. Further validation and detailed confirmation decreased rate to less than 1 per 1000 patients ( Bev =0.96, Ran=0.43 Spike in site cases secondary to other issues potentially associated with drug administration. Pharmacy Benefits Management Services www.pbm.va.gov 27

28. Pending monographs Cyclosporine ophthalmic Preservative free triamcinolone ophthalmic Artificial tears- nomenclature CFU for DRVO (retinal vein occlusion) DME (macular edema) Difluprednate Lidocaine ointment Update pegaptanib monograph Update ranibizumab monograph Pharmacy Benefits Management Services www.pbm.va.gov 28

29. Recently completed Betaxolol 0.5% solution added to VANF Bevacizumab in AMD CFU update Labeling standard for ophthalmic bottles currently on national contract Pharmacy Benefits Management Services www.pbm.va.gov 29