Pharmacogenomics and Pharmacoepidemiology
Slide 1 of 9: Applications of Cancer Pharmacogenomics in a Naturalistic Setting
Robert S. Epstein, M.D., M.S.
Chief Medical Officer
Medco
July 21, 2009
Slide 2 of 9:
Naturalistic setting of Medco
- Supports PPWG preliminary recommendations
Retrospective database research possibilities
- Extend prior research
- Expand size, outcomes
- Supply information about ‘usual care’ patients
Prospective research/programs
- Adoption statistics – clinician, patients
- Population-based prevalence numbers
Slide 3 of 9: Relation to Comparative Effectiveness Research (CER)
“Compare the effectiveness of genetic and biomarker testing and usual care in preventing and treating breast cancer..…”
Key Elements¹
- Direct comparison of effective interventions
- Study of patients in typical day-to-day clinical care
- Aim to tailor decisions to the needs of individual patients
¹Source: Institute of Medicine Report Brief June 2009: Initial national priorities for comparative effectiveness research
Slide 4 of 9: Naturalistic Setting of Medco
Pharmacy and a database system
- 2200 pharmacists serve ~8 million US lives
- Wired pharmacies (all 60,000) serve an additional ~ 55+ million US lives
- On ~20 million lives – longitudinal data on hospitalizations, labs, visits, procedures and coding for diagnoses linked with prescription data
Slide 5 of 9: Retrospective Study and Pharmacogenomics: Example of Phenocopying a Genetic Mutation
Increased risk of breast cancer recurrence in women initiating tamoxifen with CYP2D6 inhibitors by R. E. Aubert¹, E. J. Stanek¹, J. Yao,¹ J. R. Teagarden¹, M. Subar¹, R. S. Epstein¹, T. C. Skaar², Z. Desta², D. A. Flockhart²;
¹Medco Health Solutions, Franklin Lakes, NJ; ²Indiana University School of Medicine, Indianapolis, IN. Presented at ASCO June 2009.
Slide 6 of 9: Background
Hepatic cytochrome P450 2D6 (CYP2D6) is key in metabolic activation of tamoxifen to its active metabolite, endoxifen.
Previous studies have shown that women receiving tamoxifen who have reduced-function CYP2D6 polymorphisms and are poor metabolizers have lower levels of endoxifen and higher recurrence rates.
Previous small studies with CYP2D6 inhibitors and tamoxifen show reductions in endoxifen (45-58%), but have not delineated their impact on breast cancer recurrence.
Slide 7 of 9: Study Design
Retrospective cohort analysis of medical and pharmacy claims from a 10 million-member Integrated Database (Medco Health Solutions, Inc)
- ICD-9 and CPT-4 codes
Study Population:
- Women who initiated tamoxifen therapy 07/01/2003 - 12/31/2005
Inclusion criteria:
- Continuously eligible 6-months prior to initiating tamoxifen
- Tamoxifen-naïve (6-month negative history)
- Tamoxifen persisting at least 24 months post-initiation and reasonable level of adherence (MPR ≥ 0.70)
- Diagnosis of breast cancer
Slide 8 of 9: CYP2D6 Inhibitor Exposure Cohorts
Cohort stratification based on therapy received at any time over initial 24 months of follow-up after initiating tamoxifen therapy determined to be a CYP2D6-inhibitor by any of 4 reference documents
No CYP2D6-inhibitor Exposure
- Patients with no prescription claim for a drug considered CYP2D6 inhibitor at anytime during the follow-up period
CYP2D6-inhibitor Exposure
- CYP2D6 inhibitor with overlapping days of therapy with tamoxifen
Slide 9 of 9: Primary End Point
Follow-up measurement starts 6-months post-initiation of therapy and continued through 12/31/2007
Hospitalization for breast cancer during the follow-up period (determined by ICD-9 and CPT-4 codes)
- Breast cancer diagnosis or one or more of the following procedures:
- Lumpectomy
- Partial mastectomy
- Lymph node dissection
- Mastectomy
- Radiation therapy