Promoting Safe and Effective Genetic Testing in the United States

EDITORS
Neil A. Holtzman, M.D., MPH
Michael S. Watson, Ph.D.

ACKNOWLEDGEMENTS

EXECUTIVE SUMMARY

Origin and Work of the Task Force
Definition of Genetic Tests
The Need for Recommendations
Need for an Advisory Committee on Genetic Testing
Overarching Principles
Informed Consent
Test Development
Testing in Clinical Practice
Newborn Screening
Prenatal and Carrier Testing
Testing of Children
Confidentiality
Discrimination
Consumer Involvement in Policy Making
ENSURING THE SAFETY AND EFFECTIVENESS OF NEW GENETIC TESTS

Ensuring Compliance with Criteria for Safety and Effectiveness
Conflict of Interest
Enforcement
Data Collection
The Need for Post-market Surveillance
Evidence-based Entry of New Genetic Tests into Clinical Practice
Local Review
National Review
ENSURING THE QUALITY OF LABORATORIES PERFORMING GENETIC TESTS

Principles for Laboratories Adopting New Genetic Tests
Requirements Under CLIA
Complexity Ratings
CLIA Specialties
Laboratory Personnel
Monitoring Laboratory Performance
Proficiency Testing (PT)
Onsite Inspection
Making Laboratory Performance Assessments Public
A Central Repository of Cell Lines and DNA
The Importance of the Pre- and Post-analytic Phases of Testing
Direct Marketing of Genetic Tests to the Public
International Harmonization
IMPROVING PROVIDERS' UNDERSTANDINGS OF GENETIC TESTING

A Role for Non-genetic Health Care Professionals
Policies for Improving the Abilities of Non-genetic Health Care Professionals
Greater Public Knowledge of Genetics
Undergraduate and Graduate Medical Education
Licensure and Certification
Continuing Medical Education
Demonstrating Provider Competence
Other Models
Nursing
Community and Public Health
GENETIC TESTING FOR RARE INHERITED DISORDERS

Dissemination of Information About Rare Diseases
Ensuring Continuity and Quality of Tests for Rare Diseases
Ensuring the Quality of Genetic Tests for Rare Diseases
Chapter 1: INTRODUCTION

ORIGIN AND WORK OF THE TASK FORCE
DEFINITION OF GENETIC TESTS
REVIEW OF GENETIC TESTING
THE NEED FOR RECOMMENDATIONS
SCOPE OF THE REPORT
NEED FOR AN ADVISORY COMMITTEE ON GENETIC TESTING
OVERARCHING PRINCIPLES
Informed Consent
Test Development
Testing in Clinical Practice
Newborn Screening
Prenatal and Carrier Testing
Testing of Children
Confidentiality
Discrimination
Consumer Involvement in Policy Making
Issues Not Covered
Chapter 2: ENSURING THE SAFETY AND EFFECTIVENESS OF NEW

GENETIC TESTS
CRITERIA FOR DEVELOPING GENETIC TESTS
Establishing Associations Between a Disease, Genes, and Inherited Mutations
Analytical Validity
Clinical Validity
Heterogeneity
Penetrance
Clinical Utility
ENSURING COMPLIANCE WITH CRITERIA
Institutional Review Board (IRB) Review
Is Review of the Scientific Merit of Genetic Test Protocols Within the
Purview of IRBs?
Improving IRB's Ability to Review Genetic Test Protocols
Conflict of Interest
Enforcement
Data Collection
The Need for Post-market Surveillance
EVIDENCE-BASED ENTRY OF NEW GENETIC TESTS INTO CLINICAL PRACTICE
Local Review
National Review
Chapter 3: ENSURING THE QUALITY OF LABORATORIES PERFORMING GENETIC TESTS

PRINCIPLES FOR LABORATORIES ADOPTING NEW GENETIC TESTS
CLINICAL LABORATORY IMPROVEMENT AMENDMENTS OF 1988 (CLIA)
Complexity Ratings
CLIA Specialties
LABORATORY PERSONNEL
Laboratory Director
Testing Personnel
MONITORING LABORATORY PERFORMANCE
Proficiency Testing
Onsite Inspection
Making Laboratory Performance Assessments Public
A CENTRAL REPOSITORY OF CELL LINES AND DNA
THE IMPORTANCE OF THE PRE- AND POST-ANALYTIC PHASES OF TESTING
Pre-analytic Phase
Post-analytic Phase
Ensuring the Quality of Pre- and Post-analytic Phases
DIRECT MARKETING OF GENETIC TESTS TO THE PUBLIC
INTERNATIONAL HARMONIZATION
Chapter 4: IMPROVING PROVIDERS' UNDERSTANDINGS OF GENETIC TESTING

A ROLE FOR NON-GENETIC HEALTH CARE PROFESSIONALS
Eliciting Risks of Genetic Disease in Healthy People
Family History
Past History
Genetic Testing
The Role of Non-genetic Health Care Providers
OBSTACLES TO THE INVOLVEMENT OF NON-GENETIC PROFESSIONALS
POLICIES FOR IMPROVING THE ABILITY OF NON-GENETIC HEALTH
CARE PROFESSIONALS TO BE INVOLVED IN GENETIC TESTING
Greater Public Knowledge of Genetics
Professional Education
Undergraduate and Graduate Medical Education
Licensure and Certification
Continuing Medical Education
Demonstrating Provider Competence
Prerequisites
Enforcement
Assisting Providers in Gaining Competence in Genetics
OTHER MODELS
Nursing
Community and Public Health
Chapter 5: GENETIC TESTING FOR RARE INHERITED DISORDERS

DISSEMINATION OF INFORMATION ABOUT RARE DISEASES
Research Activity
Finding Information on the Interpretation of Clinical Findings
Finding Clinical Diagnostic Laboratories
Need for Coordination
ENSURING CONTINUITY AND QUALITY OF TESTS FOR RARE DISEASES
ENSURING THE QUALITY OF GENETIC TESTS FOR RARE DISEASES
Chapter 6: SUMMARY AND CONCLUSIONS

Appendix 1: Individuals and Organizations Who Provided Comments to the Task Force

Appendix 2: Response of the Task Force to the Food and Drug Administration's Proposed Rule on Analyte Specific Reagents

Appendix 3: State of the Art of Genetic Testing in the United States: Survey of Biotechnology Companies and Nonprofit Clinical Laboratories and Interviews of Selected Organizations

Appendix 4: Informational Materials about Genetic Tests

Appendix 5: The History of Newborn Phenylketonuria Screening in the U.S.

Appendix 6: Scientific Advances and Social Risks: Historical Perspectives of Genetic Screening Programs for Sickle Cell Disease, Tay-Sachs Disease, Neural Tube Defects and Down Syndrome, 1970-1997

GLOSSARY

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