# Presentation: 501760

## Medco-Mayo Warfarin Study Briefing for Personalized Health Care Workgroup

- J. Russell Teagarden, Medco
- Thomas Moyer, PhD, Mayo Clinic- Rochester
- April 7, 2008

## Warfarin-associated hospitalizations

- Testing for warfarin metabolism rate may reduce risk for hospitalization associated with hemorrhage or thrombosis.
- Testing may reduce the number of dose adjustments required.
- Greater dose adjustments = greater risk for hospitalization

| Dose adjustment | N | IP event rate |
| --- | --- | --- |
| ≤ 1 | 1,214 | 19.60% |
| 2 or more | 319 | 30.72% |
| Total | 1,533 | 21.92% |

**CYP2C9 + VKORC1**

- Sources: 1.Medco data. 2.FDA Advisory Committee; fda.gov/cder/genomics. April 26, 2006.

**Risk associated with dose adjustment and any hemorrhage/ thrombosis hospitalization event****1**

## Major Issue

- Clinicians have _not adopted_ pharmacogenetic studies into patient care because, while research data are available to suggest a relationship between pharmacogenetics and drug response, no outcomes data in large populations have been reported, and no professional societies have recommended adoption of pharmacogenetic testing.

## Medco-Mayo Study

**Examine whether pharmacogenetic testing for new users to warfarin managed in a primary care, non-academic setting results in significant reduction in hospitalizations for hemorrhage or thromboembolism within a 6 month time frame.**
**Matched cohort design**
**1500 genotyped new users will be compared to 2 control groups**
**One historical group drawn from the same sampling population one year earlier (~5500 patients)**
**Another concurrent control group (~5500 patients)**
**Outcomes measured in all three populations**

## Medco-Mayo Study

**Additional objectives focus on the impact of pharmacogenetic testing on:**
**Time to stable warfarin dose**
**Costs**
**Total health care resource utilization.**

## High Level Process Flow

- Evaluate patient profiles to determine eligibility

**Identification**

**Contacts**

**Intervention**

**Follow-up**

- Lab sample is drawn and sent to the Mayo Lab
- Mayo processes the lab test and returns the results and dosing implications to the physician

- Contact patient to discuss eligibility and obtain consent
- Contact physician and provide information on testing

- Mayo responds to physician inquiries
- Medco responds to general patient inquiries, refers to physician for questions
- Medco monitors for Rx changes and medical resource utilization

## Interpretation

- This most common haplotype is likely to experience normal response to warfarin.
- This haplotype has less than normal sensitivity to warfarin.  Warfarin dose increase may be required to maintain optimal INR.
- This haplotype has mild sensitivity to warfarin.  Frequent INR monitoring should be considered.
- This haplotype has moderate sensitivity to warfarin.  Warfarin dose decrease and frequent INR monitoring should be considered.
- This haplotype has high sensitivity to warfarin.  Warfarin dose decrease and frequent INR monitoring should be considered.
- This haplotype is rare and has very high sensitivity to warfarin.  Warfarin dose decrease and frequent INR monitoring should be considered.
- This haplotype is very rare and has very high sensitivity to warfarin.  Warfarin dose decrease and frequent INR monitoring should be considered.

## Measurement Plan

- Primary Endpoints:
- Number of hospitalizations for hemorrhage or thromboembolism
- Time to steady state warfarin dose
- Number of dose alterations during the six month study period
- Secondary Endpoints:
- Total health care resource utilization: hospitalization, ER visits, MD/clinic visits, labs, and prescription drugs related to the use of warfarin
- Proportion of patients and physicians willing to participate overall and based on whether physicians or patients are contacted first about the study
- Proportion of physicians willing to alter dose based on pharmacogenomic test results

## Analysis Methods

- Benchmark Database

- t0

- t6

- t0

- t6

- New to Warfarin Study Participants

- New to Warfarin Hx Controls

- New to Warfarin Concurrent controls

- t-6

- Comparisons:
- Within client - controls for plan design characteristics
- Benchmark – Adjust for secular trend and practice patterns

- Confounders:
- Age, sex, comorbidity, previous
- Hospitalization...
- Outcomes:
- Warfarin related ICD-9 defined
- events

- Clients Enrolled in Warfarin Pilot

## Some Findings After 454 Tests

- Patients:
- Ave age: 66 yrs
- Sex: Male 64%, Female 36%
**Test results****	****	****Count ****	****	****   % **
- < Normal                    124 		27.31%
- Normal                   	 135 		29.74%
- Mild                     	  52 		11.45%
- Moderate                    107  		23.57%
- High                     	  28 		  6.17%
- Very High                      8 		  1.76%
**Total             ****	****	****454 ****	****	****100%**

## Dose changes by phenotype in 178 patients within 21 days of lab results

| Phenotype | Count |  %  | Pre Weekly dose (mg) | Post daily dose (mg) | Change |
| --- | --- | --- | --- | --- | --- |
| < Normal | 55 | 30.90% | 38.18  | 43.27  | 5.09  |
| Normal | 44 | 24.72% | 37.13  | 38.27  | 1.15 |
| Mild | 24 | 13.48% | 40.14  | 41.40  | 1.26  |
| Moderate | 43 | 24.16% | 33.07  | 30.40  | -2.67 |
| High | 9 | 5.06% | 34.61  | 29.46  | -5.15 |
| Very High | 3 | 1.69% | 46.67  | 25.67  | -21.00 |
| Overall |               178  | 100.00% | 36.91  | 37.68  | 0.77  |

## Medco-Mayo Relationship: What Makes It Work? 

- Both organizations are interested in what is best for the patient
- Both organizations are interested in implementing pharmacogenomics into clinical practice
- Both organizations understand the importance of outcomes data to facilitate professional acceptance
- Medco is willing to explore its massive patient outcomes database to achieve above
- Mayo interested in providing academic credibility to outcomes studies above
- Both organizations believe that individualized medicine will shape the future practice of medicine