User:Mac/Agenda/2-Dec-2009

definition of field

• Worked on definition of field; realized molecular diagnostics may be best name for industry. concept hierarchy:
  • Dx
    • In-Vitro Diagnostics (IVD)
      • Molecular Diagnostics
        • Genetic (Molecular) Diagnostics

• defining genetic tests:
  • kind of molecular dx
    • which are a kind of IVD (see FDA definition)
  • genetic tests are analyzed in CLIA lab
  • some are sold directly to consumers, but most are ordered by physicians and require a physicians involvement
  • regulated as ASR or medical device (what about DTC tests like counsyl?)
  • examine genetic variation to diagnose disease, predict disease progression or recurrence, predict drug response, and measure other health states.
  • most genetic diagnostics focus on single diseases, usually measuring a single genetic variant or a small number of variants known to cause the disease state. Increasingly, improvements in DNA sequencing technology are enabling hundreds or thousands of variants to be measured in a single test; these are IVDMIAs and are somewhat unique to genetic tests; other kinds of molecular diagnostics will probably not evolve into IVDIMIAs (what about proteomics).

Working Definition

Genetic Tests are clinical diagnostics based on the analysis of human DNA to determine genotype and corresponding health states, such as disease diagnosis, prognosis, recurrence, and differential drug response. (see SACGHS Patent report, pg 5).

Currently there are genetic tests clinically available for over 1574 diseases according to genetests.org.

The SACGHS Oversight report (pg 65) describes the two paths genetic diagnostics typically follow from research bench to clinical practice: a complete in vitro diagnostic kit may be developed and sold commercially to multiple laboratories, or laboratories may develop and validate a test solely for use internally, often with the use of analyte-specific reagents; these tests are called laboratory-developed tests (LDTs). The two paths are subject to different regulatory requirements; generally, IVD kits are more stringently regulated by FDA, which considers kits as in vitro diagnostic devices and may require premarket review or approval.

Both types of diagnostic, IVDs and LDTs, must be analyzed in CLIA-certified labs.

Genetic diagnostics are usually classified as "esoteric tests" along with other molecular tests based on non-genetic biomarkers. Esoteric tests, contrasted with routine tests, typically test for rare or unusual health conditions and are more sophisticated or involve increased complexity and human involvement.

Although market data is readily available for molecular and esoteric diagnostics, it usually is not broken into further sub-categories, making it difficult to find market information specifically for genetic tests.

The two largest national independent clinical laboratories, Quest Diagnostics and LabCorp, sold 2.78 billion worth of genetic & esoteric tests in 2008 (from annual reports; not clear if that revenue is from IVDs or LDTs or both).

Excluded from FD

Protein-based genetic tests. (see SACGHS Patent report, pg 5).

General

• read SACGHS Gene Patents and Licensing Practices Final Report

• interviewed Jason Bobe (personal genome project; church lab)

• introduced to Misha Angrist for interview (Duke Institute for Genomes... SACGHS author)

• looked through last 6 archives of the Journal of Molecular Diagnostics

• added Kling. Diagnosis or drug? Will pharmaceutical companies or diagnostics manufacturers earn more from personalized medicine? to bibliography

• added [[Diagnostic Kits/Direct-to-consumer genetic testing- two sides of the coin

From Commons Based Research|Direct-to-consumer genetic testing: two sides of the coin. The Journal of molecular diagnostics]] to bibliography.]

• • includes links in references to 3 fulltext New England Journal of Medicine papers about elusive genotype/phenotype correlations

• read Who Regulates Genetic Tests, which explains the regulatory forces on genetic diagnostics
  • notes that there is no uniform or comprehensive system to assess the analytic and clinical validity of tests.
  • However, based on my brief interview w/ Jason Bobe, successful test developers need to demonstrate clinical validity to get into medical guidelines.

Genetic Association Studies

• HGVbaseG2P - 12,000,000+ marker records, 305 studies, 543 phenotypes.
  • HGVbaseG2P: a central genetic association database
• NIH Genetic Association Database

Reference Labs market data

Researched top three diagnostic firms ("reference labs):

• Quest (DGX)

• LabCorp (LH)

• Bio-Reference Laboratories (BRLI)

Found Standard Industrial Classification for LabCorp: 8071: Services - medical laboratories. Also includes Quest, Bio-Reference, Athena, and ~120 others

Found SEC Edgar search for finding annual reports

• Quest Diagnostics INC (CIK: [http://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0001022079&owner=include&count=40
  • 2008 10-K - Annual Report
    • Net Sales of gene-based & esoteric tests: 1,400 Million (20% of total revenue).

• Laboratory Corp of America Holdings (CIK: 0000920148
  • 2008 10-K - Annual Report
    • Net Sales of Genomic & Esoteric tests: $1,478.3 Million (+5.9% from 2007)
    • Volume of Genomic & Esoteric tests: 23.7 Million
    • Patents, licences, and technology "2008 gross carrying amount": 94.7 million

• Bio-Reference Laboratories INC (CIK: 00000792641
  • 2008 10-K - Annual Report
    • Net revenue from esoteric tests (50%): $150.5 Million

• Athena Diagnostics INC (CIK: 0001161704

IVD companies

According to Kalorama Information's "The Worldwide Market for In Vitro Diagnostic Tests, 6th ed, the top 16 IVD companies make 76% of the market revenue (IVDBundle pg. 181). They are: Roche, Abbott, Siemens Medical, J&J Ortho/Lifescan, Beckman Coulter, Becton Dickinson, Bayer Healthcare, etc.