These concerns have been recognized and discussed, particularly at the May 2004 "Promoting Quality Laboratory Testing for Rare Diseases: Key to Ensuring Quality Genetic Testing for Rare Diseases" meeting in Atlanta, GA and the September 2005 "Access to Quality Testing for Rare Diseases" national conference in Rockville, MD Both meetings were collaboratively organized by the Centers for Disease Control and Prevention (CDC), the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH), the American Society for Human Genetics (ASHG), the American College of Medical Genetics (ACMG), the Health Resources and Services Administration (HRSA), the Genetic Alliance, Emory University, and several other key groups. Among the major actions recommended by conference participants was to convene a working meeting, to specifically address the public concerns in the biochemical genetic testing area and to develop recommendations for practical solutions.

II. Meeting Overview

The "Quality, Access, and Sustainability of Biochemical Genetic Testing" working meeting was held on Oct. 6-7, 2006, in Atlanta, GA, as the third collaborative effort organized by CDC, NIH ORD, ACMG, SIMD, ASHG, the Genetic Alliance, HRSA, and Emory University. About 50 representatives and experts in biochemical genetic testing and inherited metabolic diseases from professional organizations, laboratories, academic institutions, proficiency testing programs, disease-specific advocacy groups, industry, and government agencies participated in the meeting. The objectives of the meeting were to 1) discuss problems and concerns raised in previous meetings and the community, regarding availability, quality, access, sustainability, test development, and resources in biochemical genetic testing; 2) identify areas of need; 3) discuss applicability of current models and approaches; and 4) develop recommendations for action items and strategies for moving forward.

The meeting began with welcoming remarks and charge to the group by Drs. Joe Boone, CDC, and Steve Groft, NIH ORD. Subsequent plenary presentations included an overview and outlook of biochemical genetic testing by Dr. Mike Watson, ACMG; results of a recent SIMD laboratory survey by Drs. Carol Greene and Bruce Barshop; European efforts on information resources for genetic testing by Dr. Valerie Thibaudeau, Orphanet and Eurogentest; updates on the Collaboration, Education, and Test Translation (CETT) Program for Rare Genetic Diseases by Dr. Giovanna Spinella, ORD, NIH; and examples of coordination between biochemical and molecular genetic testing in improving diagnosis and patient management by Drs. David Ledbetter, Art Beaudet, and Andy Faucett. Participants then formed three breakout groups: Access and Sustainability, Quality Assurance, and Information Resources, to specifically address issues in each of the focus areas.

III. Recommendations

Dynamic discussion at both the breakout and the general sessions led to recommendations on needs, opportunities, and actions to improve the quality, availability, sustainability, access, and information resources of biochemical genetic testing, in the following major areas:

1. The CETT pilot program should be extended to support the translation and implementation of new biochemical genetic tests, as well as tests that are needed in patient care but are only available in non-U.S. laboratories. To apply the CETT model to biochemical genetic tests, a scientific advisor with biochemical experience and Review Board members with biochemical testing experience should be recruited as soon as possible. It was also suggested that applications proposing appropriate use and coordination of multiple test methods, such as biochemical and molecular genetic tests, be encouraged on a disease-specific basis, to provide broad-spectrum testing (e.g., proband diagnosis, carrier testing, and prenatal diagnosis) needed for disease diagnosis and management.

2. A laboratory consortium should be established to monitor, determine, and coordinate tests that must be available to meet the standards of care. The advantages of the consortium strategy include facilitation of the development of a comprehensive test directory, acceleration of the pace of test translation, improvement of financial viability by specialization of testing among consortium laboratories, and coordination between biochemical and molecular genetic testing when needed. Financial support should be provided for the infrastructure of the consortium and to create regional or national reference laboratories with specialized testing expertise. It was emphasized that the consortium should include international laboratories offering critical and high quality testing and could facilitate these laboratories in applying for CLIA certification.

3. Training of both laboratory and clinical personnel should be encouraged in the area of biochemical genetic testing, to alleviate the current shortage in biochemical genetic specialists and trainees in training programs and to sustain critical testing services and expertise. It would be helpful to document the value of the services provided by specialized geneticists to improve the demand for these services. In addition, dual training in clinical biochemical and molecular genetics should be encouraged, and incentives should be provided for entry into clinical and laboratory genetics training programs.

4. Guidelines should be developed to ensure the quality of testing, result interpretation, and diagnosis for inherited metabolic disorders and other genetic diseases. It was suggested that both general practice guidelines and disease-specific guidelines should be developed, to provide test strategies and algorithms, quality assurance (QA) measures, and guidance on interpretation and use of test results in diagnosis and management. Participants identified the following specific needs related to guideline development:

1. Identifying diseases for which testing guidelines are needed and developing a priority listing.
2. Developing guidance or guidelines for the use and coordination of biochemical and molecular genetic testing for the purposes of proband diagnosis, carrier testing, and prenatal diagnosis of specific diseases.
3. Developing coordination and collaboration among professional organizations and groups leading or involved in guideline development. It was suggested that ACMG and SIMD take the lead with other professional organizations, patient advocacy groups, and payers involved in the activities.

1. Establishing an information resource for biochemical genetic tests to complement GeneTests, which currently emphasizes DNA-based genetic testing. This could be accomplished by expanding GeneTests to enrich information on biochemical genetic testing, or by developing a companion site with links to GeneTests.
2. Developing a test strategy portal to provide information on the use of appropriate testing, test algorithm, result interpretation, and application of test results in patient diagnosis and management.
3. Providing a symptom-based entry portal to help users of biochemical genetic laboratory services with disease recognition and test utilization. It was suggested that the European-based information resource Orphanet be publicized in the U.S. to help serve the current needs, while unmet and future needs be monitored and addressed through international collaboration.
4. Improving information resources that primary care providers and the patient community know and use, on inherited metabolic disorders and other genetic diseases and utilization of biochemical genetic testing.

1. Evaluating the needs/demand for and the availability of biochemical genetic tests both at present and in the near future.
2. Determining QA and QC needs for biochemical genetic testing, including the needs for QC and PT materials and for alternative approaches to PT.
3. Monitoring the development of new tests and testing technology.
4. Collecting and documenting outcome-oriented data on the quality, analytical validity, clinical validity, and utility of existing genetic tests in a uniform way, to help with the translation and evaluation of potential tests.
5. Monitoring the needs of the healthcare and patient communities for guidance development and information resources.
6. Assessing international laboratory standards and monitoring the development of international harmonization.

IV. Outcomes

The meeting concluded with the following immediate outcomes:

1. NIH ORD is expanding the CETT program to support translation of biochemical genetic tests from research to practice.
2. GeneTests is willing to provide more specific information on biochemical genetic testing, either by expanding the current capacity or by setting up a companion site through subcontracting. GeneTests will also host some disease-based testing algorithm models developed at this meeting.
3. Both ACMG and SIMD are committed to developing testing guidelines needed by users and providers of biochemical genetic testing services in collaboration with other professional organizations.
4. CDC will prepare a report of this meeting and will post information on this meeting (background information, presentations and discussion, and meeting report) on our Division's website.
5. Once the recommendations developed at this meeting are summarized, the steering committee will review the recommendations, to refine roles and responsibilities and to engage efforts and additional collaborations as needed.
6. Based on the meeting report, one or more manuscripts will be prepared for peer-reviewed publication.
7. A follow-up meeting is planned in one year to review development and formulate further recommendations.