Jill Wechsler

Biopharmaceutical companies have joined public–private partnerships (PPPs) developing these therapies, attracted by the desire to expand sales globally while also improving the health of poor populations. In announcing quarterly earnings in July, GlaxoSmithKline Chief Andrew Witty highlighted the company's reduced reliance on "white pill/western market" sales. Pfizer has established an emerging markets business unit to build sales in Brazil, China, India, Mexico, Russia, and Turkey, and other pharma companies are taking similar tacks.

These developments are increasing the number of clinical trials being conducted outside North America and Western Europe, raising questions about how well sponsors can monitor and ensure adherence to good clinical practices (GCPs) around the world. Many PPPs are poised to harvest the fruit of over a decade of research efforts, but may be stymied by the international financial crisis, which is squeezing resources needed to underwrite the late-phase clinical trials necessary to register new treatments.

The Food and Drug Administration is encouraging development of new vaccines and drugs for global diseases by providing guidance on ways to streamline preclinical and clinical studies for third-world conditions. These initiatives may expand under Commissioner Margaret Hamburg, who has a strong background in public health and spear-headed TB control efforts when head of New York City's public health department in the 1990s.

The FDA has been particularly active in efforts to combat the resurgence in multidrug resistant (MDR) and extensively drug resistant (XDR) TB strains. An FDA advisory committee in June supported a research pathway for drugs to treat MDR TB that utilizes early endpoints of reduced bacterial count in sputum culture, followed by confirmatory trials to document low relapse rates.

This approach could accelerate the R&D process for new compounds, such as that being developed by Johnson & Johnson's Tibotec subsidiary with support from the Global Alliance for TB Drug Development (TB Alliance).

A two-day FDA workshop in July delved further into clinical trial design challenges for drug-susceptible TB. The panel weighed noninferiority study designs, combination therapy regimens, and missing data problems, as well as early study endpoints. Sequella Chief Medical Officer Gary Horwith urged consideration of Phase 0, adaptive clinical trials, and surrogate endpoints to accelerate development.

TB Alliance President Melvin Spigelman emphasized the importance of testing new combination drug regimens to combat resistance. Gail Cassell, vice president at Eli Lilly, advocated "boldness in clinical trial design," along with better postapproval adverse event monitoring.