Research Article: Building Clinical Trials Capacity for Tuberculosis Drugs in High-Burden Countries

Date Published: November 6, 2007

Publisher: Public Library of Science

Author(s): Neil Schluger, Unni Karunakara, Christian Lienhardt, Thomas Nyirenda, Richard Chaisson

Abstract: The long duration of TB therapy, the high prevalence of HIV coinfection, and the growing prevalence of drug-resistant TB underscore the urgent need for more effective treatments.

Partial Text: The standard preferred regimen for the treatment of drug-susceptible tuberculosis (TB) around the world consists of a two-month induction phase of isoniazid, rifampin, pyrazinamide, and ethambutol followed by a continuation phase of four months of isoniazid and rifampin. This regimen has several advantages: (1) it is essentially completely effective in achieving sputum culture conversion; (2) it is relatively inexpensive and universally available; (3) the relapse rate is low, at 3%–5%; and (4) it can be administered largely intermittently. But the regimen has significant limitations, listed in Box 1.

The experience of the British Medical Research Council’s TB research units provides a useful template for planning the renewal of capacity for clinical trials in TB [1]. Over 40 years, the Medical Research Council evaluated all the drugs currently in use for the treatment of TB. To do this, they tested roughly 250 different regimens, enrolling over 25,000 patients in trials. Why so many? Patients with TB are treated with regimens, not individual drugs. Even if a single new drug is approved for the treatment of TB, finding its optimal dosage, dosing frequency, and companion drugs will require several trials.

An urgent and massive expansion of clinical trials capacity is needed to carry out vital research to accelerate the development and evaluation of new TB drugs, including those active against MDR-TB. To conduct the clinical trials agenda described above, including the evaluation of new drugs, funding of at least US$300–US$500 million annually is needed. It is also important to make direct investment in the infrastructure needed to conduct trials, rather than taking a product-by-product approach. Current global plans for TB drug development assume that specific funding is tied to individual drugs in the pipeline and does not take into account the need for trials for MDR-TB. We believe that this product-by-product approach will lead to inefficiency, redundancy, and wasted time, and will fail to address the important question of how to construct regimens. Independent support for clinical trial sites that are prepared to undertake a variety of studies is essential to ensure that new regimens are developed as quickly as possible. A strategy where strong clinical trial sites are funded to build capacity to support weaker centers will ensure increased and sustained capacity to conduct more trials in less time.



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