1. What is the EGAPP initiative?
The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) initiative was established in October 2004 by the Office of Public Health Genomics (OPHG) at the Centers for Disease Control and Prevention (CDC). The goal of EGAPP is to develop a systematic, evidence-based process for evaluating genetic tests and other applications of genomic technology that are rapidly moving from research to use in clinical practice. A key objective of this process is to provide objective, timely, and credible information that is clearly linked to the scientific evidence on specific applications of genetic and genomic tests.
The primary focus of EGAPP activities is an independent, nonfederal expert panel, the EGAPP Working Group. Other components of the EGAPP initiative include a federal interagency, the CDC staff and consultants, and an EGAPP initiative evaluation team.Links for more information
2. Why is CDC supporting the EGAPP initiative?
The EGAPP initiative was launched to respond to the need for a coordinated approach for effective translation of new applications of genomics into clinical practice and health policy. Reliable and objective information on emerging genomic applications will allow health care providers and payers, consumers, and policy makers to distinguish tests that are safe and effective, and will provide guidance on their appropriate use.
Although most genetic tests currently available in clinical practice are used to diagnose rare single gene disorders, a growing number have the potential for broad public health impact. Examples include tests that predict risk of common diseases, provide information on prognosis or therapeutic options, or help physicians determine the right drug and dosage for individual patients.
4. Does CDC or EGAPP have any regulatory authority over genetic testing?
No. CDC has no regulatory authority with regard to genetic testing. EGAPP is a non-regulatory process for knowledge synthesis and critical review, and dissemination of information to stakeholders.
5. Who does have regulatory oversight of genetic testing?
In the United States, genetic tests are subject to federal regulatory oversight through two mechanisms. The first mechanism is U.S. Food and Drug Administration (FDA) regulation of test kits sold to laboratories by commercial manufacturers as diagnostic devices. To date more than 50 tests have been cleared or approved by FDA. However, most genetic tests currently offered by laboratories in the U.S. do not involve the use of commercially available FDA reviewed kits. Instead, laboratories develop and offer tests as a clinical service; such tests are known as laboratory developed tests or LDTs. The FDA also regulates "analyte specific reagents," component reagents that are used by laboratories as part of genetic LDTs.
The FDA has the ability and authority under existing statutes and regulations to provide oversight for all genetic based testing. However, for many reasons, the FDA has chosen to apply enforcement discretion and not to actively regulate tests developed at a single site for use at that single site (so-called LDTs) These tests are subject to indirect regulation at the time of their laboratory inspections mandated by the Clinical Laboratory Improvement Act 1988 (CLIA). CLIA certification and inspection addresses a range of general and subspecialty laboratory standards (e.g., personnel qualifications, quality control, sample handling); subspecialty standards specific to genetic testing have not been implemented.
6. What is the role of other Health and Human Services (HHS) agencies in EGAPP?
Other HHS agencies have provided representation on the EGAPP Steering Committee throughout the development and implementation of the initiative. Founding Steering Committee members included representatives from CDC, the Agency for Healthcare Research and Quality (AHRQ), the Centers for Medicare and Medicaid Services, the Food and Drug Administration, the Health Resources and Service Administration, and the National Human Genome Research Institute (National Institutes of Health). AHRQ Evidence-based Practice Centers are also being commissioned by CDC to conduct some evidence reviews.
Current EGAPP Steering Committee membership also includes the Veterans Administration;, broader representation from the National Institutes of Health; and liaisons from the HHS Secretary’s Personalized Healthcare Initiative, the Secretary’s Advisory Committee on Genetics, Health and Society; and the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children. These agencies are monitoring the EGAPP process and products, and provide feedback to CDC on the value of the information developed from their perspectives.
7. Is EGAPP connected with the Secretary’s Personalized Health Care Initiative?
The Department of Health and Human Services (HHS) Secretary's Personalized Health Care (PHC) Initiative supports long-term improvements in patient care through the use of genetics in medicine, adoption of health information technology, and improved development of evidence-based care. PHC goals include helping to coordinate related activities among HHS agencies, providing an HHS contact point for the private and academic sectors, and addressing cross-cutting issues of high priority.
The PHC initiative recognizes the need for reliable processes to determine the clinical utility of specific genetic tests and to inform health professionals and consumers. EGAPP is the primary effort within HHS for developing such processes. EGAPP's activities call on the resources of the CDC and other HHS agencies. For these reasons, the activities and success of EGAPP are of special interest and importance for the initiative.
1. What is the EGAPP Working Group?
The EGAPP Working Group is an independent panel established in April 2005 to lead the development of a process for evidence-based assessment that is specifically focused on genetic tests and other applications of genomic technology. The multidisciplinary panel was orginally composed of 13 experts from areas such as evidence-based review, clinical practice, public health, laboratory practice, genomics, epidemiology, economics, ethics, policy, and health technology assessment. Key objectives of the panel are to:
2. How are EGAPP Working Group members selected?
In 2005, CDC solicited nominations for this independent panel from a wide range of organizations and individuals. Thirteen Working Group members were selected from the pool of nominees by the Health and Human Services interagency EGAPP Steering Committee.
In 2008, the EGAPP Working Group will expand from 13 to 16 members, and begin a planned regular rotation of members on the panel. As before, the nomination and selection process will include a broad solicitation of nominations, and review and selection by the EGAPP Steering Committee.
3. How does the EGAPP Working Group function?
Two-day Working Group meetings are held three times per year, and the work of subcommittees continues between meetings through teleconferencing. Based on the agenda and specific tests under consideration or review, members are asked to declare any potential conflicts of interest prior to each meeting.
Specific roles of the Working Group include:
4. What are the roles of the EGAPP Working Group Subcommittees?
5. What are the products of the EGAPP Working Group?
Products resulting from the Working Group’s efforts include
6. Is the EGAPP Working Group a Federal Advisory Committee?
No. The EGAPP Working Group is an independent expert panel supported by CDC’s EGAPP initiative, not a Federal Advisory Committee. The panel does not have Federal Advisory Committee Act (FACA) status.
7. Do EGAPP Working Group recommendation statements represent the views of CDC?
No. EGAPP Working Group recommendation statements represent the views of the independent EGAPP Working Group, not CDC.
1. What are evidence reviews and why are they important?
Increasingly, the health care provider and payer communities consider evidence review to be the preferred method for evaluating a new test, technology, or intervention. Also referred to as “evidence-based” or “systematic,” such reviews involve:
Most commonly, “evidence” is defined as peer-reviewed publications of original data or systematic review or meta-analysis of such studies. Editorials and expert opinion pieces are not included. In some cases, reviews allow for inclusion of some unpublished literature, and for consideration on a case-by-case basis of other sources of information.
The product of an evidence review is an evidence report that provides detailed documentation on the test, the rationale and clinical scenario for testing, key questions addressed in the review, methods used for review and analysis, and the conclusions and identified gaps in knowledge.
2. How does the EGAPP Working Group define a genetic test?
The definition of a “genetic test” is variable, and often the subject of debate. Due to the rapid evolution of genomic technology, the EGAPP Working Group has not adopted a specific definition of this term, but rather has taken a broad view that includes analysis of genes for heritable or acquired variations, or of gene products (e.g., proteins), when the tests’ intended uses relate to disease or health. This approach could also include as “tests” questions about personal or family health history that are used to assess risk.
3. How does the EGAPP Working Group select tests for review?
Since it was clearly not feasible to immediately address the “universe” of genetic and genomic testing, the EGAPP Working Group has focused on tests recognized as having wider potential population application, greater potential to impact clinical practice and the public’s health, and those for which there is demand for information. Tests currently of highest priority for EGAPP review include those used in specific clinical scenarios:
Categories of tests less likely to be considered by EGAPP at this time include diagnostic tests for rare single gene disorders, and prenatal or newborn screening tests.
During the review and selection process, topics (tests) are carefully defined based on the medical disorder, the specific test(s) to be used, and the specific clinical scenario in which the test will be used.
See the EGAPP Working Group’s web site for more information on test selection
4. Can outside groups or individuals make suggestions about genetic tests that should be considered for evidence review?
Yes. Suggestions and comments can be made via the “Contact us” section on the EGAPP Working Group web site. EGAPP encourages submission of suggested topics for review, preferably accompanied by a brief rationale explaining why the test should be considered as a high priority.
5. What are some of the EGAPP Working Group’s primary considerations in evaluating a genetic test?
The Working Group bases their recommendations on the quality and certainty of the available data on the analytic validity, clinical validity, and clinical utility of tests used in specific clinical scenarios. The main focus of review is clinical outcomes: Do interventions or actions based on genetic testing results improve health outcomes, compared with not testing?
The panel also considers specific family or societal outcomes of genetic testing, such as the impact of a genetic test on decision making by healthcare providers and patients, psychosocial benefits and harms to the patient and family, and potential public health impact. Other issues considered may include the availability or access to testing, adequacy of consumer and healthcare provider knowledge, and resources and infrastructure for delivering tests. Throughout the review process, the Working Group identifies gaps in knowledge and priority areas for research that can provide the additional evidence needed to better establish the validity and utility of tests.
6. What is the difference between an “EGAPP-commissioned evidence report” and an “EGAPP Working Group recommendation statement?”
An EGAPP-commissioned evidence report is a detailed, systematic, objective assessment of the available scientific and clinical evidence on a specific topic. Evidence reports for EGAPP are conducted by contracted review groups or Agency for Healthcare Research and Quality Evidence-based Practice Centers. The evidence review is an independent process that is not conducted by the EGAPP Working Group. The Working Group’s involvement in the review is generally limited to development of key questions to be addressed, participation by 2-3 members on a Technical Expert Panel convened by the reviewers, reviewer presentations to the Working Group at meetings, and Working Group review of the draft evidence report. Evidence reports represent the first step in the EGAPP evaluation process.
An EGAPP Working Group recommendation statement is based on the commissioned evidence report, other review of evidence as needed, the quality of available data, and the potential clinical and social impact of using the test in practice (i.e., contextual issues), with input on the draft document from a range of outside peer reviewers. The statement is intended to provide guidance to healthcare providers, policymakers, payers and healthcare purchasers, and consumers on the use of specific genetic tests.
1. What mechanisms exist for interaction between EGAPP and the wide range of stakeholders in genetic testing?
2. Who can answer my questions about EGAPP?
Please submit questions through the Contact Us web page.
Page last updated: May 15, 2013
Page last reviewed: December 23, 2008
Content Source: OPHG Staff