Tuberculosis Trials Consortium (TBTC)
Background and Infrastructure
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Background
The United
States Public Health Service (USPHS) and the Veterans Administration
(VA) have a distinguished history of conducting clinical trials
to evaluate new drug regimens for both the treatment and prevention
of tuberculosis.1,2,3,4 In 1960, the Centers for Disease Control and Prevention (CDC) assumed a major role in these studies when the USPHS Tuberculosis Division was transferred to CDC.
Subsequently, CDC coordinated a series of multi-center clinical trials that helped to establish rifampin-based, short-course therapy as the standard for tuberculosis treatment. It also conducted studies to provide the scientific basis for preventive chemotherapy, which remains a major component of our tuberculosis elimination strategy.
Support for the infrastructure required for these studies gradually diminished, so that USPHS Study 21 was nearly terminated several times during its course for lack of adequate funding. With the infusion of federal support for tuberculosis control and elimination in the early 1990s, CDC established a consortium of clinical investigators for the specific purpose of conducting USPHS Study 22, a trial of once-weekly isoniazid and rifapentine in the continuation phase of therapy for pulmonary TB.5This consortium, whose sites include public health departments, academic medical centers, and VA medical centers (VAMCs), required both time and substantial financial resources to establish and support and is now functioning efficiently. Currently new drugs and regimens for both tuberculosis treatment and prevention, new diagnostic tests, and new vaccine candidates are becoming available for clinical investigation. Concurrently, the challenges posed by the goal of TB elimination are increasing, as rates of drug resistance increase 6and as the costs associated with assuring high rates of adherence rise.7The consortium now provides a unique and important resource for further clinical studies, and has demonstrated its ability to play an important role in TB treatment and prevention.8
Infrastructure
The original group of clinical sites included 12 academic centers and health departments (7 contracts issued in 1993, and 5 more in 1994), and 15 VAMCs (funded through a Memorandum of Agreement with the Washington, D.C., VAMC). Enrollment into USPHS Study 22 began in April 1995, and continued to completion in November 1998. In 1997 CDC began working with the USPHS Study 22 investigators to develop a structure that would engage more fully the capacities of the study investigators in the work of the group. The TBTC was thus organized, with formal by-laws adopted in 1998. Several working committees were established, composed of elected Consortium investigators and coordinators, in collaboration with CDC staff. One committee (Core Science) develops the scientific program of research, a second (Implementation and Quality) supervises the conduct and quality of ongoing studies, and a third (Executive Affairs) serves as the executive arm of the steering committee. This structure is modeled on the Community Programs for Clinical Research on AIDS (CPCRA), which is supported by the National Institute of Allergy and Infectious Diseases (NIAID) 9, 10,
11.
In 1999 the TBTC underwent a formal external re competition. New 10-year contracts were awarded to 13 offerors (7 prior TBTC members and 6 new sites) 10. The VA side of the consortium underwent a similar process, and funded 10 VA Medical Centers to continue as members of the TBTC. The current infrastructure of the TB Trials Consortium includes:
- A network of 28 clinical sites worldwide whose principal investigators are recognized experts in tuberculosis treatment and prevention
- Experienced clinical coordinators and outreach workers at each of the 28 funded sites
- Extensive communications systems, including biannual conferences
- Close and collaborative relationships with local TB control programs to facilitate the recruitment and management of trial patients
- An expert Data & Safety Monitoring Board, which reviews active protocols
- Coordination with the CDC IRB, the central IRB process, and local IRBs
- A Data and Coordinating Center at CDC
- Cooperative relationships with key manufacturers of TB drugs
- Support for monitoring, training, and protocol development from leading contract research organizations
- Laboratory support from the CDC/DTBE Microbiology Laboratory Branch
Funding
The Division of TB Elimination at CDC supports all 28 clinical sites through 10 contracts and the Memorandum of Agreement with the Washington, D.C., VAMC. The approximate extramural cost is $9.2 million per year. Intramural resources are required to support project officers and staff (about 10 FTE) for the TBTC Data and Coordinating Center at CDC.
For further information, contact the Clinical and Health Systems Research Branch, Division of TB Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control & Prevention, Mailstop E-10, Atlanta GA 30333.
Tel: (404) 639-8123
Fax: (404) 639-8961
Email: tbtc@cdc.gov
Internet: http://www.cdc.gov/tb/
References
- Streptomycin Committee, Central Office, Veterans
Administration. The effect of streptomycin upon pulmonary tuberculosis.
Preliminary report of a cooperative study of 223 patients by the
Army, Navy, and Veterans Administration. Am Rev Tuberc 1947; 56:485-507.
- United States Public Health Service
Cooperative Investigation of Antimicrobial Therapy of Tuberculosis:
V: Report on thirty-two week observations on combinations of isoniazid,
streptomycin, and para-amino salicylic acid. Am Rev Tuberc 1954;70:521-526.
- Ferebee SH. Controlled chemoprophylaxis
trials in tuberculosis. A general review. Adv Tuberc Res 1970;17:28-106.
- Combs DL, O’Brien RJ, Geiter LJ.
USPHS Tuberculosis Short-Course Chemotherapy Trial 21: Effectiveness,
toxicity, and acceptability. The report of final results. Ann
Intern Med 1990;112:397-406.
- Benator D, Bhattacharya M, Bozeman L,
at al., Rifapentine and isoniazid once a week versus rifampicin
and isoniazid twice a week for treatment of drug-susceptible pulmonary
tuberculosis in HIV-negative patients: a randomised clinical trial.
Lancet. 2002 Aug 17;360(9332):528-34.
- WHO/IUATLD Global Project on Anti-Tuberculosis
Drug Resistance Surveillance. Anti-tuberculosis drug resistance
in the world: third global report of the WHO/IUATLD Global Project
on Anti-Tuberculosis Drug Resistance Surveillance, 1999-2002.
Geneva, 2004.
- Burman WJ, Cohn DL, Rietmeijer CA, Judson
FN, Sbarbaro JA, Reves RR. Noncompliance with directly observed
therapy for tuberculosis. Epidemiology and effect on the outcome
of treatment. Chest 1997;111:1168-1173.
- www.cdc.gov/tb/pubs/mmwrhtml/Maj_guide/Treatment.htm
- www.clinicalresearchnetworks.org
- TB Trials Consortium. The Tuberculosis
Trials Consortium: a model for clinical trials collaborations.
Public Health Reports, 2001, 116 (Supplement 1): 41-49.
- www.niaid.nih.gov
Contact Us:
- Centers for Disease Control and Prevention
Division of Tuberculosis Elimination (DTBE)
1600 Clifton Rd., NE
MS E10
Atlanta, GA 30333 - 800-CDC-INFO
(800-232-4636)
TTY: (888) 232-6348
24 Hours/Every Day - cdcinfo@cdc.gov
