New Study: Drivers of TB Regimen Change in High-Burden Countries

Stakeholders cite key actions critical to maximize uptake and impact of new TB regimen introductions

May 8, 2011

New TB drugs are critically important for TB elimination. Introduction of future TB treatments is more likely to be a success, according to a new study, if certain key areas of TB control are attacked now. The study, published today in the International Journal of Tuberculosis and Lung Disease (IJTLD), was conducted by the TB Alliance and Management Sciences for Health (MSH) in the 22 high TB burden countries (HBCs). Within these countries, a survey of 203 stakeholders identified actions that would facilitate introduction of new TB regimens such as the improvement of drug management, expansion of programs to link public and private TB providers, and a dramatic increase in drug-sensitivity testing resulting in evidence-informed treatment.

Based on data from the same survey, the TB Alliance and MSH published initial results in IJTLD in 2010, which analyzed decision-making processes, major players, and procedural success factors for 40 distinct TB treatment regimen changes that occurred in the past. The earlier publication focused attention on the practical concerns of stakeholders, and was a reminder that any new TB regimen must be adapted to local practice and delivery systems.

The newly released publication builds on those concepts by identifying key issues that will influence the introduction of future TB drug regimens. Major findings of the study include the following

  • The use of fixed-dose combinations (FDCs)
    Among the National TB Programmes (NTPs) in HBCs, 20 out of 22 report using fixed-dose combinations (FDCs) – formulations that combine multiple drugs into a single pill — as their preferred dosing formulation. The exceptions are India and China – two countries with very large TB burdens – although China is now introducing FDCs. Meanwhile, 8 HBCs covering 42% of the global TB burden are using patient kits, which contain an entire TB regimen for one patient. Both FDCs and patient kits help address continuing weaknesses in drug management. Suitability for FDC formulation and simple drug management will be important considerations for new TB therapies.
  • Limited capacity to conduct drug-sensitivity testing (DST)
    Many HBCs are especially plagued by a lack of capacity to perform DST and, as a result, patients may receive ineffective regimens, leading to the generation of drug resistance. In the past, the TB community did not emphasize widespread DST. because TB drug resistance was at a low level, all newly infected patients were presumed to have drug-sensitive disease and thus require only a single first-line treatment option, and drug-sensitivity tests were expensive and slow. As all three of these conditions change, however, it is becoming critical for TB programs to consider DST as a requirement. Only in this way can programs provide an informed treatment that will protect both the drugs from resistance development and the patients from ineffective therapy and worsening disease. Fortunately, this issue is now being addressed as the relative ease of use and speed of line probe assays and the GeneXpert has made DST more appealing to health systems and is leading to broader use.
  • Protection of new drugs against the development of resistance
    Not all health systems can ensure delivery of complete regimens, thus increasing the risk of drug resistance emerging. For example, in the public sector of many HBCs, patient contact with the health system occurs not daily but once a week or once a month. This can be a positive trend if backed up by other, reliable forms of ensuring directly observed treatment (DOT), but in many cases DOT was reportedly deputized to family or even "self." Meanwhile, interviewee and WHO data showed that large parts of the private sector are not yet matched with public-private mix (PPM) programs that bring the required quality standards to private sector TB treatment. In 6 HBCs, around one third or more of TB treatment occurs in the non-PPM private sector (see a recent study from the TB Alliance on private sector size). Efforts are needed to strengthen both DOT and PPM, and thus lessen the threat that further drug resistance will emerge.

By considering key characteristics of the current health systems used for TB treatment, drug developers can prioritize products more likely to meet the needs of TB programs, physicians, and patients. The same analysis also highlights areas of health systems strengthening that should be undertaken now in order to facilitate future regimen changes. Improvement of drug management, expansion of PPM and DST, and strengthening of DOT and related adherence measures are all initiatives that have been shown to benefit the delivery of current treatment regimens. As shown in the current study, the case for these actions is further strengthened by considering their impact on the introduction of new TB regimens.