R2D2-xDRTB

The challenge

Every year, around 400,000 people develop tuberculosis infections resistant to commonly used drugs. These multidrug-resistant infections require longer and more intensive treatments, although new drugs have significantly shortened treatment duration and reduced toxicity. 

However, less than half of patients with drug-resistant TB infections receive the appropriate treatment. Only around 50% are tested for the most common type of resistance, to rifampicin, and a much smaller number are tested for resistance to other key TB drugs, even though resistance levels are showing a worrying increase.

The main bottleneck is the availability of tests to assess drug susceptibility. Low-complexity molecular testing platforms exist but are primarily used to test for rifampicin resistance. Genome sequencing can provide information on multiple resistance genes, but requires complex infrastructure and is costly. Culture methods can provide comprehensive information on the drug susceptibility of infections but take weeks to complete. 

To overcome this barrier, rapid, affordable and accessible drug susceptibility tests are needed. Multiple such tests are in development, but they must be clinically evaluated and validated.

The project

The R2D2-xDRTB project is building on an existing international platform for tuberculosis diagnostic evaluation to accelerate the assessment of new TB drug susceptibility tests.

The NIH-funded R2D2 TB Network has established an adaptive international platform for testing a variety of TB tests (for example, for diagnosis across different groups, for screening or drug susceptibility testing). It has established standard protocols across a network of sites in six countries, generating comparable data on more than 40 products, helping to advance products beyond the proof-of-principle stage. 

In the R2D2-xDRTB project, the team is expanding on this approach by creating a platform specifically designed to evaluate the performance and validate drug-susceptibility tests for TB. It will focus on one specific use case – further testing of patients who have received a positive rifampicin resistance test. A total of 500 such adults and adolescents, as well as 100 patients with rifampicin-sensitive infections, will be enrolled in two high-burden countries (Georgia and South Africa). Results from the candidate tests will be compared with those from gold-standard drug-susceptibility testing to assess the accuracy of each test. 

In addition to technical performance, the project will provide a platform for assessing the usability, acceptability, and feasibility of each product. This will be based on systematic consultation with end-users and an analysis of how well new tools would integrate into existing clinical pathways.

To provide policymakers with additional valuable evidence, the project will also develop models to estimate the potential epidemiological, health, and health-economic impacts of different implementation scenarios. These will provide insights into the likely cost-effectiveness of tools and the budgetary implications of their introduction. 

Impact

The R2D2-xDRTB project will ensure that emerging tuberculosis drug-susceptibility testing tools receive a comprehensive and consistent evaluation. It will:

• Provide a rigorous assessment of the technical performance of TB drug-susceptibility testing tools.
• Assess their usability and compatibility with existing health system TB care pathways.
• Deliver a standardised analysis of their likely cost-effectiveness.
• Create a platform that can add new devices for evaluation as soon as they reach the appropriate point of development.

The R2D2-xDRTB project will accelerate the introduction of new TB drug-susceptibility testing tools, ensuring that patients more rapidly receive the most appropriate treatment, improving health outcomes and reducing disease transmission and wasteful use of health service resources on ineffective treatments.