Drug-resistant tuberculosis (DR TB) is a global health crisis threatening advances in TB care. In 2016, of the estimated 600 000 people with new cases of DR-TB, less than 22% were detected and enrolled onto treatment and less than 12% were cured. TB is the most prevalent among diseases affected by antimicrobial resistance (AMR), with multidrug-resistant TB (MDR TB) responsible for one-third of all deaths caused by AMR.

Even with treatment improvements due to new drugs such as bedaquiline and delamanid, expansion and use of diagnostic technologies such as GeneXpert, and updated WHO guidelines reflecting new evidence, further improvements are needed if the global goal of ending TB is to be realized.

There is commitment from countries and a broad range of stakeholders to reach the targets in the End TB Strategy – that is, a 95% reduction in TB deaths and 90% reduction in new cases by 2035, and a commitment to eliminate catastrophic expenses due to TB. The challenge is how to maximize available technologies for screening, diagnosis and treatment along the care pathway while ensuring innovations emerging from the pipeline are integrated successfully.

For MDR TB, gaps in obtaining the right diagnosis and having access to effective treatment are more critical. Recently, extensive patient pathway analyses have been published highlighting the need for access to quality and timely diagnosis, efficient and clear linkages to treatment, and affordable, simplified and more effective treatment. Unitaid supports principles of integrated diagnosis and treatment and ways to build better linkages along the care pathway.

Unitaid aims to improve cure rates for people affected by MDR TB by addressing concrete challenges where measurable impact may be achieved, using technologies that are available (or soon will be) in a targeted timeframe, and filling concrete gaps in the global response. Through extensive outreach and consultations with TB stakeholders, Unitaid has worked to understand the evolving challenges and identify potential opportunities that could align with its strategy and model – with a focus on those with potential to provide significant improvements to the lives of people affected by MDR TB.

As such, under this call, Unitaid is soliciting proposals that address one or more of the areas described below. Proposals’ scope should be carefully targeted, reflecting focused interventions to address key challenges in innovation, access, or preparing for scale-up, and demonstrating measurable impact within the time frame of the grant.

• Improved access to drug-susceptibility testing (DST), specifically using targeted gene sequencing platforms for clinical decision-making (e.g., replacing phenotypic DST), in low- and lower-middle-income countries (LMICs).

  Targeted gene sequencing platforms have the potential to guide clinical management of patients, generate data for policy-making, and improve diagnostic test development. Many high-income countries are already devoting resources to gene sequencing laboratories. To date, the complexity and costs for rolling out such platforms have been prohibitive in low-resource settings. The landscape is, however, rapidly changing and has major implications for practical use in MDR-TB and AMR more broadly.  Unitaid is interested in proposals that may include: (i) limited late-stage development to validate and/or obtain market authorization for a viable product/platform and/or (ii) targeted proof-of-concept work in high-burden settings to demonstrate the feasibility of replacing phenotypic DST by sequencing methods. Additional elements that address sample quality, such as sample transport, through innovative solutions could be included if there is clear added value with the proposal objectives. Proposals should consider addressing data validation and interpretation together with product/platform development to ensure optimal use of sequencing results (preferably in open source data information systems) for patients’ benefit.

• Targeted interventions to boost uptake of better MDR-TB regimens of commercially available drugs, subject to WHO guidance.

  The market introduction of bedaquiline in 2012 and delamanid in 2013 has opened new possibilities for better, shorter regimens for MDR TB, as supported by recent clinical studies, including the Unitaid-funded endTB Project. The bedaquiline donation program, supported by USAID in partnership with Johnson & Johnson, provides free treatment courses in over 70 LMICs, and has helped improve access to bedaquiline. However, work is needed to build on this effort and to address longer-term access and uptake of regimens incorporating the new drugs. Subject to changes in WHO policy and intended to complement ongoing work in this area, Unitaid is interested in proposals that may include targeted interventions (e.g., mapping, forecasting or supply-side work) to facilitate uptake and long-term availability of affordable, quality-assured drugs that are part of key MDR-TB regimens recommended by WHO.

  In addition, Unitaid supports the needs of children with TB.  Unitaid has invested in, and catalyzed the market for, new child-friendly formulations to treat drug-susceptible TB, and is currently supporting work to improve identification and diagnosis to find the estimated 64% of children missed annually. With increasing availability of new improved child-friendly medicines used to treat drug-resistant TB, there is an opportunity for Unitaid to complement its investments to date.  Unitaid believes that addressing specific elements of new MDR-TB regimens can accelerate access for children. Unitaid is therefore interested in activities that may include (i) targeted evidence generation (e.g., pharmacokinetic/pharmacodynamics studies) to inform better treatment for children (e.g., shorter treatments, all-oral treatments) and/or (ii) targeted work to support demand and adoption of quality-assured formulations of second-line drugs  for children.

• Improve TB treatment outcomes through targeted innovative approaches to support adherence that can be implemented within the next two years.

Recent results from clinical trials of new drugs/regimens have indicated that improvements in adherence and care of patients can lead to high cure rates, irrespective of treatment regimen. In parallel, several digital adherence technologies have become available and have been piloted with evidence of significant impact on adherence rates, yet none of these technologies has achieved global scale. WHO recently provided guidance on adherence technologies in its 2017 update of the Guidelines for treatment of drug-susceptible tuberculosis and patient care and its January 2018 Handbook for the use of digital technologies to support tuberculosis medication adherence. India with 99DOTS and China with MEMS have demonstrated some feasibility of national scale-up. Unitaid is interested in the relevance of this work in other settings, and therefore solicits targeted proposals that could demonstrate the feasibility of using innovative adherence technologies at scale to improve outcomes. Unitaid notes its interest in the value of such technologies in supporting MDR-TB treatment, as well as drug-susceptible and preventive treatment. 

All proposals received will be considered, but Unitaid reserves the right to not fund all the areas outlined in this call. Proposals submitted should clearly demonstrate the fit with one or more of the objectives set out above, the expected impact and value for money. Unitaid recognizes – and seeks to complement – the efforts of partners in this area. Proposals should therefore demonstrate how work would be coordinated with (and complementary to) ongoing efforts of Unitaid and other partners.