New TB regimens: What Countries Want. The Value Proposition of Existing and New First-Line Regimens for Drug-Susceptible Tuberculosis.
The design and adoption of new tuberculosis (TB) regimens requires a close understanding of the opinions of those who approve, prescribe and receive TB treatments: what they like and dislike about current regimens and what they would value, tolerate or reject with regard to a new, shorter regimen. To assess these opinions regarding first-line regimens for drug-susceptible TB, interviews were conducted with 211 stakeholders in Brazil, China, India, Kenya and South Africa - five countries with high TB burdens - and with 11 global stakeholders.
Based on these interviews, efficacy, safety and side effects of current regimens were generally judged to be acceptable. A treatment frequency of five to seven days a week was common for current regimens and preferred for new regimens, with some exceptions in China and India. Avoiding interaction with antiretroviral drugs (ARVs) was a significant priority for African and global stakeholders, as was the availability of fixed-dose combinations (FDCs) in all but China and the Indian public sector.
Two international Phase III trials are currently testing whether the substitution of a fluoroquinolone into first-line TB regimens will allow these treatments to be shortened to four months. In the current study, with the exception of some stakeholders in China, the potential for a shorter (four- or two-month) regimen was positively received. Many stakeholders noted that a shorter regimen would increase the likelihood of adherence and listed several acceptable trade-offs, including increased drug costs. Shorter regimens including moxifloxacin would be welcomed for the same reasons, although there are concerns about whether primary fluoroquinolone resistance already exists and whether fluoroquinolone use for first-line treatment would lead to the loss of the fluoroquinolones as a viable option for second-line treatment.
Before adopting a new regimen to replace an existing one, stakeholders said they would require or prefer data including results from trials in their own countries (for Brazil, China, India and South Africa), cost and real-world effectiveness data, and efficacy data for various subgroups, including patients co-infected with HIV and TB.
The findings of this study are consistent with the target product profile used by the TB Alliance and with the organization's clinical trials strategy as currently implemented. Stakeholder feedback can guide the development of new TB drugs, but the diversity of opinions underlines the challenges ahead and the need for continued exchange of data and information.
TB Alliance, New York, USA, 20 pp.