Report of Expert Consultations on Rapid Molecular Testing to Detect Drug-Resistant Tuberculosis in the United States

Recommendations

1. CDC should develop a system with sufficient testing capacity to enable molecular DR testing for one AFB smear-positive or NAA-positive respiratory specimen or one M. tuberculosis culture from each TB patient or TB suspect andspecimens or isolates from persons that the local or state TB Control Program designates as high priority for testing.
2. CDC should evaluate existing molecular DR testing services to identify best practices.
3. CDC should use a phased approach to implementing a universal molecular DR testing service.
4. CDC should immediately establish an interim service to provide molecular DR testing for persons at high-risk of having MDR TB and those deemed high priority by the local TB program. CDC is encouraged to explore using supplements to existing cooperative agreements to provide sufficient new funds to existing, proficient molecular DR testing laboratories to allow them to expand their capacities to meet this need. The interim service could serve as a pilot project to inform the development of a universal molecular DR testing service.
5. CDC should establish and fund regional laboratories to provide molecular DR testing for state and local TB programs. Funds in the current TB Elimination Cooperative Agreements should not be redirected to the molecular DR testing program. The molecular DR testing laboratories should
   1. coordinate molecular DR testing services with the medical consultation and training services of the TB Regional Training and Medical Consultation Centers (RTMCCs),
   2. provide six-day-a-week service,
   3. use validated molecular methods to detect rifampin and isoniazid resistance,
   4. implement molecular DR testing for anti-TB drugs other than rifampin and isoniazid (e.g., fluoroquinolones) as the tests are developed and validated,
   5. report results electronically within two business days of specimen receipt,
   6. report detection of drug resistance in specimen or isolate by telephone to facilitate prompt action by the program and clinician,
   7. ensure notification of appropriate individuals (e.g., local program, laboratory, clinician) of the need for expedited testing of rifampin-resistant samples for susceptibility to first-line and second-line anti-TB drugs, and
   8. participate in an external quality assurance program.
6. CDC should work with TB partners and state and local TB programs and laboratories to identify and overcome potential obstacles and barriers to implementing a regional molecular DR testing service, such as local regulations regarding out-of-state testing, certification of laboratories, reporting requirements, and need for memoranda of agreement.
7. CDC and partners should develop clear policies and standard operating procedures for referring specimens to the molecular DR testing laboratories.
   1. CDC should develop and fund a process for shipping M. tuberculosis cultures to the molecular DR testing laboratories.
   2. CDC should develop and fund a process for shipping specimens to the molecular DR testing laboratories for TB laboratories or programs that can not afford the cost of shipping.
8. CDC should coordinate, and possibly integrate, activities of the molecular DR testing and genotyping laboratories to avoid unnecessary duplication of efforts and shipment of isolates.
9. CDC should work with partners to develop external quality assurance, proficiency testing, and rechecking programs for the molecular DR testing service.
10. CDC should develop a robust process for monitoring and evaluating the performance of the molecular DR testing laboratories. This should include post-market surveillance to determine the performance, cost, and benefit of the molecular DR tests as performed in a regional testing service.
11. CDC should work with partners to develop protocols to analyze discrepancies in the results of molecular DR and conventional tests. CDC should collect data on and investigate discrepancies to better understand the performance of molecular and conventional DS testing.
12. CDC, NTCA, and APHL should convene a work group to develop guidelines, templates, and models for programs to use in developing their systems to access the molecular DR testing service and receive reports.
13. CDC should work with partners such as APHL and NTCA to assess training needs, develop training materials, and establish an education program for TB control officials, laboratorians, clinicians, and policy makers on the appropriate use and interpretation of molecular DR tests for TB.
14. CDC should work with partners such as APHL and NTCA to develop a process for providing guidance, technical assistance, and consultation on clinical, programmatic, and laboratory aspects of the appropriate use and interpretation of molecular DR tests for TB in the United States.
15. CDC should develop a broader evidence base to support changes in recommendations and practices and investigate the economic implications of molecular DR testing.
16. CDC should develop and promote a research agenda for molecular DR testing for TB.
17. CDC should work with private- and public-sector partners to increase the number and types of molecular DR tests, commercial sources, FDA-approved tests, and validated tests.
    1. CDC and FDA should encourage manufacturers to develop molecular DR tests for TB and submit to FDA for review and approval.
    2. CDC should assist manufacturers with regulatory quality trials of molecular DR tests aimed at receiving FDA approval.
    3. CDC should establish a repository of well-characterized isolates for use in developing, evaluating, and validating molecular DR tests for TB.
18. CDC should disseminate the panel report and any resulting CDC recommendations in multiple media, in order to reach clinicians, TB control officials, laboratorians, regulatory agencies, policy makers, and other TB partners. This may include publication in scientific or medical journals or MMWR, posting on the CDC website, use of electronic mail lists, and direct distribution to key stakeholders.
19. CDC should monitor and evaluate the implementation of the recommendations. CDC should periodically, perhaps annually, provide progress reports to ACET.