Implications of the current tuberculosis treatment landscape for future regimen change.

BACKGROUND: The current tuberculosis (TB) treatment landscape has been studied extensively, but researchers rarely consider how it creates challenges or opportunities for future regimen change. METHODS: In 166 stakeholder interviews in the TB high-burden countries (HBCs), we investigated areas of first-line TB treatment and control that would affect, and be affected by, a future TB regimen change. Responses were compared with existing standardized data. RESULTS: Public sector regimens are converging towards a single standard, which facilitates comparison with a single control arm from clinical trials. However, final product design is challenging if the goal is fixed-dose combinations and patient kits, whose current widespread use addresses continuing weaknesses in drug management. Any product must address broad groups, as relatively low levels of drug susceptibility testing (DST) do not allow for individualized therapy. Finally, the protection of new drugs from the development of resistance will be challenging, as the implementation of directly observed therapy and public-private mix programs is incomplete, and substantial private sectors have been identified as early adopters of these drugs. CONCLUSIONS: Health systems for TB treatment and control must be improved not only to allow better implementation of current treatments but also to set the stage for implementation of new, improved TB regimens.

Tuberculosis regimen change in high-burden countries.

BACKGROUND: Experience with past tuberculosis (TB) regimen changes can guide future regimen changes. METHODS: To explore the process, major players and procedural success factors for recent public sector TB regimen changes, we conducted 166 interviews of country stakeholders in 21 of the 22 TB high-burden countries (HBCs). RESULTS: Stakeholders described 40 distinct regimen changes for drug-susceptible TB. Once countries committed to considering a change, the average timing was ∼1 year for decision-making and ∼2 years for roll-out. Stakeholders more often cited concerns that were program-based (e.g., logistics and cost) rather than patient-focused (e.g., side effects), and patient representatives were seldom part of decision making. Decision-making bodies in higher-income HBCs had more formalized procedures and fewer international participants. Pilot studies focused on logistics were more common than effectiveness studies, and the evidence base was often felt to be insufficient. Once implementation started, weaknesses in drug management were often exposed, with additional complications if local manufacturing was required. Best practices for regimen change included early engagement of budgeting staff, procurement staff, regulators and manufacturers. CONCLUSIONS: Future decision makers will benefit from strengthened decision-making bodies, patient input, early and comprehensive planning, and regimens and evidence that address local, practical implementation issues.

Estimating the market for tuberculosis drugs in industrialized and developing nations.

BACKGROUND: The successful introduction of new drugs into low- and middle-income countries requires an understanding of the existing market size and market dynamics for the therapeutic area of interest. The drug markets in these countries are, however, less well understood than those in high-income countries. METHODS: The global market for tuberculosis (TB) drugs was estimated by studying in detail six high-burden countries and four high-income countries, followed by extrapolation. Data were derived from existing pharmaceutical audit databases and interviews with government officials, medical staff and suppliers. RESULTS: The use of qualitative inputs to inform the collection of quantitative information, notably to identify where the major flows of TB drugs are located, allowed a confident estimate of the global market for first-line TB drugs. Final ranges were US$261-316 million or US$310-418 million, depending on whether case notification rates or incidence were used for extrapolations. CONCLUSIONS: An estimation of the global TB drug market is made more reliable by a qualitative understanding of TB drug distribution pathways, which differ greatly among countries. The understanding of this structure in key high-burden countries provides the basis for a simpler update of the market estimate in the future.