ADHERENCE: Focus on Hepatitis C

1. ADHERENCE: Focus on Hepatitis C

2. Background • Hepatitis C diagnosis: • 5.4% of Veterans in VA care • 1.6% of general US population • Majority infected during Vietnam era • Cirrhosis develops over 20-30 years • 1-5% die from liver cancer or cirrhosis

3. What is the reason to use medications in Hepatitis C? • Remove the virus from the blood = CURE • Prevent further damage to the liver • Reduce chance of liver cancer • Decrease the possibility of other Hep C complications

4. How is Hepatitis C treated? • Drugs are taken for a limited period of time • Two new drugs approved in 2011: Direct Acting Antivirals (DAAs) • Once chronically infected with hepatitis C the only way to get rid of it is with medication • New drugs offer cure rates of up to 40%-80% in combination • Peginterferon + Ribavirin + DAA (boceprevir or telaprevir)

5. Drug Specific Factors Affecting Adherence to DAAs

6. Consequence of Inappropriate Dosing = Resistance and Treatment Failure • Inadequate drug levels will lead to viral breakthrough Inadequate Dose Cmax Missed Dose Drug Concentration Area of Potential Replication IC 90 Cmin IC 50 Time

7. Complicated Course:Boceprevir Therapy Algorithm

9. Barriers to Adherence • Low level of health literacy/numeracy • Cognitive impairment • Psychosocial Issues (homeless, depression, low social support) • Polypharmacy • Active Substance Use/Abuse • Stigma • Difficulty taking medications (swallowing pills, schedules) • Complex regimens (pill burden, frequency, food requirements) • Adverse drug effects

10. A Problem as Old as Medicine Itself… “Keep watch also on the fault of patients which makes them lie about taking of things prescribed” • Hippocrates circa 500 B.C

11. Non-AdherenceHospitalization Risk % Adherence Hospitalization Risk (%) Sokol MC, McGuigan KA, Verbrugge RR, et al. Impact of medication adherence on hospitalization risk and health care cost. Med Care. 2005 43:521-30

12. Methods of Estimating Adherence • Directly observing therapy • Measures of drug levels/biological markers in blood • Record opening of a pill bottle electronically • Patient interviews

13. Calculations Used to Estimate Adherence Proportion (%) of days covered (PDC) Medication possession ratio (MPR) Continuous measure of medication gaps (CMG) Total days' supply Total study period days X100 Days' supply: Study period days Total days of treatment gaps Total days to end of obs. period

14. Development of a Novel Medication Possession Ratio (MPR) • Complex Running calculation • Accounts for both stockpiling and gaps in therapy • Resets when necessary

15. MPR Example Sum of Day’s Supply Received Sum of Day’s Elapsed =MPR

16. MPR Example Sum of Day’s Supply Received Sum of Day’s Elapsed =MPR Past 2 Years

17. Rx release date + days supply Rx release date + days supply MPR Example Sum of Day’s Supply Received Sum of Day’s Elapsed =MPR Past 2 Years

18. Rx release date + days supply Rx release date + days supply MPR Example Sum of Day’s Supply Received Sum of Day’s Elapsed =MPR Past 2 Years

19. Rx release date + days supply Rx release date + days supply MPR Example Sum of Day’s Supply Received Sum of Day’s Elapsed =MPR Past 2 Years Rx release date + days supply

20. MPR Validation • VISN 21 • Prescriptions for all diabetes, hypertension and hyperlipidemia medication • Laboratory results • Before starting the medication • Last result while on medication • MPR associated with lab result

21. Hypertension and Diabetes Outcomes using MPR

22. Uses for MPR • Provides an accurate way to measure adherence with respect to outcomes • This calculation can be used by providers to estimate a patients adherence • Help identify adherence rate required to maximize benefit of medication

23. Adherence important for DAAs Boceprevir Adherence and Response • Adherence strictly measured in Clinical Trials • Patients allowed a 7-9 hour dosing window • Lower SVR if outside of dosing interval • Lower SVR if dose or treatment duration <80%

24. MPR Report from VA HCV Clinical Case Registry (CCR)

26. Hepatitis C DAA Dashboard Report Hepatitis C Interactive Report

27. VISN 21 Dashboard

28. Interactive Report

29. Step 1: Select a site

30. Step 2: Select a drug

31. Step 3: Select therapy status

32. Main Report Scroll to the right for more information

33. Main Report- Continued

34. Drill down for more data Click “+” to the left of the patient’s name

35. Monitoring safety & efficacy Scroll to the right for more information

36. Monitoring safety & efficacy

37. Monitoring medication adherence • Adherence • Calculated Medication Possession Ratio (MPR) • MPR < 90% is shown as red

38. Monitoring medication adherence Days Overdue Calculated using last fill date and days supplied

39. Monitoring medication adherence Patient Instructions included- show dose reductions

40. Hepatitis C Clinical Case Registry (CCR) Hepatitis C Interactive Report

41. VA HCV Clinical Case Registry (CCR)

42. Clinical Reports BMI by Range Clinic Follow-up Combined Meds and Labs Current Inpatient List Diagnoses Liver Score by Range MELD, MELD-Na, APRI, FIB-4 Patient Medication History Procedures Registry Lab Tests By Range Registry Medications Renal Function by Range Administrative Reports General Utilization and Demographics Inpatient Utilization Lab Utilization List of Registry Patients Outpatient Utilization Pharmacy Prescription Utilization Radiology Utilization Hepatitis C CCR Reports

43. Description of Clinical Reports Useful for Managing Treatment • Clinic Follow-up • Identify pts seen/not seen in specified date range; provides date last seen • Diagnoses • Identify Pts with particular diagnoses • List of Registry Patients • all patients confirmed in the registry • Patient Medication History • fill dates, type (original/refill), method of pick-up, days supply for selected pts • Procedures • MRI, US, biopsy… • Registry Lab Tests By Range • Find pts who fall within a specified lab result range (HCV RNA >100) • Registry Medications • Pts receiving registry medications (summary =count by medication; complete= lists pts by medication combination)

44. Configuration Meds date range Medication selection Lab date range Lab selection Utilization date range Combined Medication and Lab report (CM&L)

45. Answer Simple  Complex Questions Of patients in the registry, which ones • Did / Did not have… (med, lab, procedure) • During date range…(ever, defined by you) …are potentially eligible for treatment …ever had PegIFN in the past, when? (trx-experienced) …have never received PegIFN? (trx-naïve) …on treatment never had an HCV RNA PCR? …had Liver Bx in last 6 months? …who had RBV in last 3 months had Hgb <10 in last 3 months? …who had RBV and ESA in last 6 mos had Hgb >11 on most recent test? …treatment-experienced, with advanced liver disease

46. Clinic Follow-upIdentify pts seen/not seen in a particular clinic during a specified date range; provides date last seen; can select any clinic or group of clinics. Option to include only patients with specific diagnoses

47. Pharmacy Medication History

48. Registry Lab Tests By Range

49. Measuring and Managing Medication: Uses of the Local Clinical Case Registry for HCV • Identify patients on treatment • Medication review • Medication Monitoring • Patient management • Toxicity, response • Adherence to guidelines • Continuity of care • Screening • Treatment outcomes

50. Reminder Dialog for Hepatitis C [ ] HCV Treatment Nonpharmacologic intervention [ ]Adherence Assessed     [ ] Knowledge of regimen(dose,frequency,food requirements)assessed [text box] [ ] Refill records reviewed [text box]     [ ] Adherence discrepancies exist based on refill records   [ ] Patient verbally confirms remaining supplies which correlate with current wk of tx      [ ] Adherence discrepancies exist based on pt supplies        [ ] Report of missed doses [text box]             [ ] Other adherence issues identified:[textbox] [ ] Medication Education Provided: [text box] [ ] Medication reconciliation performed         [ ] Copy provided for patient             [ ] Non-VA medication updated in CPRS             [ ] OTC medications documented [text box]