# Presentation: 618123

## Genomic Medicine:  A Revolution in Medical Practice in the 21st Century

**Francis S. Collins, M.D., Ph.D.**
**National Human Genome Research Institute**
**World Health Care Congress**
**April 17, 2006**

## Slide 2

## Slide 3

## All of the original goals of the Human Genome Project have been accomplished

**What’s next?**

## Slide 5

## Finding the genes that contribute to common conditions like cancer, diabetes, congestive heart failure, Parkinson’s disease, schizophrenia, autism, stroke, and osteoporosis is critically important.

**But until now, terribly difficult.**

**Variant A**

**Variant B**

## Slide 8

## www.hapmap.org

**www.hapmap.org**

## Slide 10

## The First HapMap Success Story:Age-Related Macular Degeneration

- <date/time>

**The First HapMap Success Story:****Age-Related Macular Degeneration**

**Two other risk variants have**
**been identified in the last two months.**
**Together these account for 74%**
**of risk, and point to powerful**
**new approaches to prevention**
**and treatment.**

**Notes:**
Several independent research groups representing NEI intramural scientists and extramural grantees have identified a common variant in complement factor H gene as a risk factor for developing AMD. 
The CFH gene is responsible for a protein that helps regulate inflammation in part of the immune system that attacks diseased and damaged cells. In certain patients with AMD, inflammation in the eyes may trigger a biological process leading to the disease. 
People whose genetic make-up includes a variant of the CFH gene are 7.4 times more likely to develop AMD. The study was based on whole genome analysis of participants from the NEI-sponsored Age-Related Eye Diseases Study, a major clinical study that closely followed nearly 5,000 patients with varying stages of AMD. 

These reports result from long term NIH investments in generating state-of-the-art research tools and reagents through the Human Genome Project and genetic initiatives supported by the NEI.

## Disease with Genetic Component

- <date/time>

**Disease with Genetic Component**

**Accelerated by**
**Human Genome**
**Project and**
**HapMap**

## PKU Screening	

- All published studies show that PKU screening and treatment represent a net direct cost savings to society

**Phenylketonuria: Screening and Management **
**NIH Consensus Statement Online 2000**

**Notes:**
All the PK cost assessments for the US are so old (1970’s and 80’s) that the full articles aren’t available on PubMed – the only recent analyses are European.
This NIH Consensus statement is the most comprehensive thing I could find

## Hereditary NonPolyposis Colon Cancer (HNPCC)

**Hereditary NonPolyposis Colon Cancer (HNPCC)**

**Uterine**
**Cancer**
**48**

**Colon**
**Cancer**
**56**

**Colon**
**Cancer**
**51**

## Identifying Those At Risk

**Identifying Those At Risk**

**Uterine**
**Cancer**
**48**

**Colon**
**Cancer**
**51**

**Colon**
**Cancer**
**56**

## HNPCC Screening – is it cost-effective?  Need to know...

**Sensitivity, specificity, and timing of genetic test**
**Genotype-phenotype association**
**Prevalence of genetic mutations**
**Clinical outcome and severity**
**Interventions available for mutation carriers**
**Effectiveness of interventions**

## Cost Results Depend on Family Relationships  

- Patients only = $42,210 per life-year gained
- Patients + siblings + children = $7,556 per life-year gained

- Ramsey et al., Ann Intern Med 135:577-88, 2001

## Disease with Genetic Component

- <date/time>

**Disease with Genetic Component**

**Accelerated by**
**Human Genome**
**Project and**
**HapMap**

## Overview of Procedures for Microarray Analysis of Tumor Samples

***Source: N Engl J Med, Vol 344 (8), 2001.***

**Overview of Procedures for Microarray Analysis of Tumor Samples**

## Multigene Assay Predicts Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer

**Source: Paik, et al., N Engl J Med, December 2004**

**Multigene Assay Predicts Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer**

**Gene expression analysis was combined with an algorithm for calculating risk for distant recurrence of breast cancer.**

## Gene Expression Profiling for Breast Cancer Recurrence:Economic Benefits?	

- Hypothetical Analyses:
- Oncotype DX  (Genomic Health)
- Hornberger et al., Am J Manag Care. 2005; 11: 313-324
- MammaPrint – Netherlands/Agendia U.S.
- Oestreicher et al., Genet Med 2005; 7:380-389

**Notes:**
Studies of two different assays designed to identify low-risk breast cancer patients with localized disease who can avoid adjuvant chemotherapy – Oncotype DX and MammaPrint.

The hypothetical analyses reached different results re: use of GEP – one showed extended survival, one did not.

Oncotype DX test cost - $3460
Genomic Health estimates that 30,000 – 50,000 women per year in the US fit their testing population – ER+, negative node breast cancer 

FYI Scott Ramsey is the 2nd author on the Oestreicher paper, which concludes: 

“Although gene expression profiling in breast cancer holds great promise [the analyses] suggest that additional refinement and validation are needed before use in clinical practice.”  Oestreicher et al., Genet Med 2005:7(6)

## Disease with Genetic Component

- <date/time>

**Disease with Genetic Component**

**Accelerated by**
**Human Genome**
**Project and**
**HapMap**

## Using Genetic Information to Predict Drug Metabolism: The AmpliChip CYP450 

***Source: Caraco, Y., N Engl J Med, 2004***

**A range of drug metabolism phenotypes is observed for individuals based upon the particular cytochrome P-450 genes they possess.**

**Notes:**
Many drugs metabolized through cytochrome P-450 pathway
Individual variability in CYP450 isoforms contributes to observed range of metabolic phenotypes.
Analyzes genetic variation in CYP450-CYP2D6 and CYP450-CYP2D19 genes
Approved for use in U.S. and Europe

## Predicted economic benefit of CYP2C9 testing for warfarin dosing

- Predict 1 major bleed prevented for every 44 patients screened ($135/assay)
- $6,000 testing costs ~ cost of 1 major bleed
- Neutral economic result, but significant improvement in patient outcome
- Prospective trial needed

- Higashi and Veenstra, Am J Manag Care 2003; 9: 493-500

## Slide 25

## Disease with Genetic Component

- <date/time>

**Disease with Genetic Component**

**Accelerated by**
**Human Genome**
**Project and**
**HapMap**

## GleevecTM – Specifically Targets

**An Abnormal Protein, Blocking **
**Its Ability To Cause Chronic Myeloid Leukemia**

## Cost-Effective?

- Gleevec as 1st line therapy for CML
- 6 years increased survival over interferon-alpha therapy
- $43,100/per life-year saved

**Reed et al, Cancer 101:2574-83, 2004**

## Slide 30

## Slide 31

## S.306

**S.306**

**109th**

**HR.1227**

- Type your question here and then click Search.

**Notes:**
Discrimination doesn’t really fit this presentation, but LLR and I thought you might want to plug the bill at the end here when you talk about ethical considerations. 

## Genomic Medicine:Predictive, personalized, and pre-emptive