Understanding Regimen Change
TB Alliance investigated health systems to understand the regimen change process, in order to accelerate and maximize the uptake of new products.
Learning from Past Regimen Change
Experience with past TB regimen changes can guide future regimen changes. To explore the process, the TB Alliance and Management Sciences for Health conducted 166 interviews of country stakeholders in 21 of the TB high burden countries (HBCs). Stakeholders described 40 distinct regimen changes for drug-sensitive TB.
Major findings included:
- Once countries committed to consider a change, average timing was ~1 year for decision-making and ~2 years for roll-out.
- Stakeholders more often cited concerns about regimen change 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 high-burden countries had more formalized procedures and fewer international participants.
- Pilot studies of changes 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.
Regimen change would benefit from strengthened decision-making bodies, patient input, as well as early and comprehensive planning. Country decision-makers would benefit from regimens and evidence that address local, practical implementation issues.
The paper was published in the International Journal of Tuberculosis and Lung Disease analyzing past regimen changes.
Implications of Current Treatment Landscape on Regimen Change
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. This study also used interviews with stakeholders in high-burden countries to identify actions that would facilitate introduction of new TB regimens. Major findings included:
- 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 can 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 private sector study). Efforts are needed to strengthen both DOT and PPM, and thus lessen the threat that further drug resistance will emerge.
This analysis 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.
The paper, published in the International Journal of Tuberculosis and Lung Disease, explores the implications of current treatment practices on future regimen change.