Tuberculosis Trials Consortium (TBTC)
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Introduction | Background
| TBTC Infrastructure | Funding
The TBTC is a collaboration of North American and international
clinical investigators whose mission is to conduct programmatically
relevant research concerning the diagnosis, clinical management,
and prevention of tuberculosis (TB) infection and disease. The purposes
of the TBTC are to conduct research that expands clinical and epidemiologic
knowledge of TB and facilitates the diagnosis, clinical management,
and prevention of tuberculosis infection and disease; to integrate
research into the care of persons with TB infection and disease;
to develop research questions that are relevant to program settings
in general; to promote research within local TB control programs
through collaboration on clinical research of relevance to public
health settings; and to provide a forum for international collaborative
research of importance to both domestic and international TB control.
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
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
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.5 This 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 6
and as the costs associated with assuring high rates of adherence
rise. 7 The 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
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,
In 1999 the TBTC underwent a formal external recompetition. 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
- An expert Data & Safety Monitoring Board, which reviews
- Coordination with the CDC IRB, the central IRB process, and
- 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
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
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
- 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.
- 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.
- TB Trials Consortium. The Tuberculosis
Trials Consortium: a model for clinical trials collaborations.
Public Health Reports, 2001, 116 (Suplement 1): 41-49.
Last Modified: 04/27/2007
Last Reviewed: 05/18/2008
Content Source: Division of Tuberculosis Elimination
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention