Constructing Oversight

of Genetic Testing
in the USA

D. Joe Boone, Ph.D.

Acting Director,
Division of Laboratory Systems
Centers for Disease Control and Prevention (CDC)
Kitasato University
Tokyo, Japan
16 March, 2008
 Outline

• Background
 Genetic Exceptionalism
 Scope: Laboratory versus Care Providers
 Advisory Committees

• Current Oversight
 Role in research and test development
 Role in laboratory practice
 Role in access and reimbursement
 Role in surveillance

• Possible changes in future oversight

 Background

• Are genetic tests different from other laboratory tests?

 Can predict individual’s and family members’ future health
 Germline mutations do not change during lifetime
 Can be used to discriminate against an individual

• Who is and who is not covered by US regulation?

 Manufacturers of in vitro Diagnostic (IVD) kits and Instruments
 Laboratory practice for those offering tests for clinical use - >200,000
laboratories
 Not clinical care provider practices

• Who are the regulators?

 US government
o CMS – laboratories
o FDA – R&D IDE, RUO, IVD’s, and IVDMIA’s
 Bodies with delegated authority – states (NY,WA) The Joint Commission,
CAP, COLA

• US Advisory Committees
 Secretary’s Advisory Committee on Genetics, Health, and Society (SACGHS)
 Clinical Laboratory Improvement Advisory Committee (CLIAC)
 Current Oversight
Research and Development

• Research Phase
 Gene – Disease association (FDA, NIH)
 Prototype/design (FDA design control)
 Preclinical development (FDA IDE)

• Clinical Development Phase

 Testdevelopment - FDA (IVD/IVDMIA)
 FDA Clearance (Class I,II,III)

• Laboratory Developed Tests - LDT

 CLIA (CMS or agent)
 FDA (Analyte Specific Reagents – ASRs)
 Current Oversight
Laboratory Practice

• CLIA – all clinical tests (Industry and LDTs)

 Administered by Centers for Medicare and Medicaid
Services (CMS) or CMS approved agents
 Includes: Inspections every 2 years, personnel, QA,
QC, PT
 Tests regulated on the basis of test complexity – high,
moderate, waived
 Tests regulated by specialty – none for genetics
 Tests must have analytical validity
 CMS approved agents can have more stringent
requirements than CMS
 Current Oversight
Access and Reimbursement

• All Industry developed IVDs cleared by FDA performed in

CLIA certified laboratories
 Clinical validity claims reviewed
• All LDTs performed in CLIA certified laboratories
 No exemption for research laboratories performing clinical tests
 Clinical validity claims not explicitly required

• Direct-to-Consumer tests for clinical purposes must be

performed in CLIA certified laboratories

• Tests performed in CLIA-certified laboratories are

generally eligible to receive Medicare (CMS), Medicaid
(States), Private Insurance, other reimbursements
 Current Oversight
Surveillance

• FDA monitors the field for violations of its requirements and

conducts a limited amount of post-market surveillance

• CMS responds to complaint-based violations of its requirements by

certified and non-certified laboratories
 No exemption for research laboratories performing clinical tests

• The Federal Trade Commission can penalize marketers for false

advertising and has taken action to warn the public about Direct-to-
Consumer vendors of genetic tests.

• The Clinical Utility of selected genetic tests has been reviewed by the
CDC (Evaluation of Genomics Applications in Practice and
Prevention (EGAPP), the NIH Collaboration, Education, and Test
Translation (CETT) program, and the US Preventive Services Task
Force.
 Oversight
Future Activities

• Adherence to International Guidelines and Standards

such as OECD and ISO 15189
• PT for all non-waived genetic tests?
• Genetic testing training for CLIA inspectors
• More reference and QC materials (GeT-RM)
• Enhanced data and information sharing
 Oversight
Future Activities

• More standards and guidelines from professional

groups
• US registry for all genetic tests with data on
analytical and clinical validity, and clinical utility –
start with GeneTests
• All LDTs addressed by FDA?
• Good laboratory practices MMWR publication
• Clinical validity – risk management approach to tests
 Oversight
Future Activities

• Enforcement focused on laboratories who seem to be

avoiding oversight
• DTC for health-related purposes deserves increased scrutiny
• Increase the quality and amount of clinical utility information –
what is the standard of evidence required?
• Surveillance of health outcomes to determine what works and
what does not
• Define and address knowledge gaps
• Clinical decision support systems need to be developed
• Better collaboration, communication, and coordination of the
limited resources available
 Direct-to-Consumer Tests Offered on the Internet

gastrointestinal disease
heart disease / stroke
myocardial infraction

athletic performance

periodontal disease
hemochromatosis
glaucoma / AMD

metabolic health
Type 2 diabetes
Type 1 diabetes

general nutrition

multipe sclerosis

bipolar disorder
pregnancy loss
drug response
celiac disease

HIV response
cystic fibrosis
osteoporosis

fetal gender

Parkinson's
thrombosis

narcolepsy
skin profile
RPL (FVL)
Alzheimer

addiction
infertility

asthma
obesity

arthritis
cancer
23andMe X X X X X X X X X X X
Acu-gen Biolabs X
Consumer Genetics, Inc. X X
CyGene Direct X X X X X
DeCode X X X X X X X X X X X
Dermagenetics X
DNA Direct X X X X X X X X X
G-nostics X
Genelex X X X X X X X X
Genetic Health X X X X X X X
Graceful Earth X
Health Check USA X X X
Health Tests Direct X X X
Holistic Heal X
MediChecks X X X
Medigenomix X X X
My Genome X X X X X X
Navigenetics
Psynomics X
Quixtar - Interleukin Genetics X X
Salugen X X
Scientific Match X
Sciona X X X
Smart Genetics X
Suracell X

Dr. Kathy Hudson, Genetics and Public Policy Center, Johns Hopkins Univ., USA
 Oversight must be Global

• Requires collaboration, coordination

• Country differences must be respected
• We all need reliable decision support tools
• We all have limited resources
• We are all accountable to the public
 Thank you
Questions/Comments