1. Measuring Adherence Jonathan Shuter, M.D. Treatment Adherence Network Meeting 2/27/01

2. Measuring Adherence--One Extreme • “I firmly believe that if the whole materia medica as now used could be sunk to the bottom of the sea, it would be all the better for mankind--and all the worse for the fishes.” 1860: Oliver Wendell Holmes to the Massachusetts Medical Society

3. Measuring Adherence--The Other Extreme D.O.T.

4. Measuring Adherence--The Middle Ground • Methods that quantify missed and taken doses • Methods that measure physiologic effects • Methods that assess systemic blood levels of drug

5. Cheap Correlated with virologic outcomes (report of non-adherence is more reliable than report of adherence) Overestimates adherence Self-Report Pro’s Con’s

6. Clinician-Estimated Adherence Pro’s Con’s • Cheap • Most poorly correlated of all measures with actual adherence PROVIDERS ARE TERRIBLE JUDGES OF ACTUAL ADHERENCE AND OF THEIR PATIENTS’ ABILITY TO ADHERE!

7. Pill Counts Pro’s Con’s • Cheap • Useful adjunct to self-report • Overestimates adherence • “Pill dumping” • Time consuming • Casts provider in role of medication monitor, not ally/advocate

8. Pharmacy Records Pro’s Con’s • Cheap • Useful adjunct to self-report • Cannot stand alone as adherence measurement method • One patient may use many pharmacies • Picking up prescriptions does not equate with taking medications • Patients may have other sources of medications

9. Electronic Monitoring Pro’s Con’s • Best correlation with virologic outcomes • Data is available in a computer accessible format • Allows more detailed view of non-adherence patterns (weekends, nighttime, etc.) • Expensive • Poor patient acceptance • Not infallible (patients can open bottle and not take pill) • Not compatible with pillbox • Usually only measures one medication

10. Measuring Adherence--The Middle Ground • Methods that quantify missed and taken doses • Methods that measure physiologic effects • Methods that assess systemic blood levels of drug

11. Indirect Laboratory Markers • AZT=========> Increased MCV • ddI==========> Increased uric acid • Indinavir======> Increased bilirubin

12. Laboratory Markers • Viral load • CD4 • Genotypic/phenotypic resistance

13. Measuring Adherence--The Middle Ground • Methods that quantify missed and taken doses • Methods that measure physiologic effects • Methods that assess systemic blood levels of drug

14. Plasma Levels Pro’s Con’s • Correlates with virologic outcomes • Only method that ensures that the patient actually ingested the drug • May allow insight into absorption or drug interaction problems • Very expensive • Levels are extremely variable • Only provides information about the last dose

15. Montefiore Data

16. Montefiore Data • 30/106 (28.3%) patients prescribed ART responded “Never” [miss medications], every time they were interviewed. • These patients are not distinguished by any specific characteristic measured in the study. There are trends toward underrepresentation of females and IDUs in this group. • Analyzed variables include age, gender, ethnicity, HIV risk behavior, AIDS, adverse effects, and depression score.

17. Conclusions • There is no perfect method or combination of methods available to measure adherence • Nevertheless, numerous methods of measurement correlate with virologic outcomes, and thus provide useful information • Some method of adherence measurement should be used for all patients, but decisions regarding which method/s should be individualized