Data collected on barriers to use of new drugs that were discussed during DR-TB STAT meetings revealed a variety of reported challenges to using new drugs under programmatic conditions. In general, the problems reported fell into 10 areas: 1) lack of awareness of drug availability and procurement process; 2) limited availability of adequate technical expertise; 3) confusion around WHO “requirements,” most notably pharmacovigilance; 4) limited availability of quality clinical trials data supporting the use of new drugs under programmatic conditions; 5) challenges in sharing rapidly changing information about new drugs with key stakeholders and incorporating such information into national guidelines; 6) concerns that the process of new drug introduction is “too complicated” under programmatic conditions; 7) prolonged turnaround time for drug procurement; 8) difficulties in import and customs clearance; 9) limited access to companion MDR TB medications, especially linezolid and clofazimine; and 10) lack of high-level national government support.

Many of the goals toward achieving the targets in the global call to action have been met for BDQ. However, the goals set for DLM are unlikely to be met (Table 5).

Although MDR TB is treatable and curable, managing it under program conditions has long been characterized by a host of problems. These include challenges in the detection of resistance, especially to second-line drugs; delays in prompt initiation of appropriate therapy; and insufficient mechanisms for ongoing monitoring for toxicity and continued engagement of patients throughout the 18–24-month course of treatment. Furthermore, challenges exist to staff training and retention, information management, and infection control. Access to new drugs will not erase these barriers, but access does offer hope for improving individual patient outcomes and decreasing the transmission of MDR TB. Uptake of BDQ and DLM under programmatic conditions, however, has not kept pace with need. According to WHO recommendations for the use of these medications, 25%–50% of MDR TB patients meet criteria to receive these drugs because of their high-level resistance, intolerance to drugs currently used to treat MDR TB, or risks for poor outcomes (20). The occurrence of ≈500,000 new cases of MDR TB each year means that 125,000–250,000 new patients would benefit from the use of either of these drugs each year, a number that does not include the large number of prevalent MDR TB patients who might benefit from new treatment options. More conservative estimates of the need for new drugs using the actual numbers of MDR TB patients placed on treatment each year show that 24,250–48,500 of the 96,000 persons started on treatment (21) would benefit from access. Even using these less ambitious numbers, it is clear that more work needs to be done to improve access to BDQ and DLM.

The findings of DR-TB STAT show that more persons with MDR TB who have an indication for new drugs have access to BDQ than to DLM. Wider access to BDQ is occurring even though the WHO recommendations for DLM use are broader and despite the association of BDQ with a higher death rate in its phase IIB trial. For several reasons, access might be greater to BDQ than to DLM. BDQ was conditionally approved by a stringent regulatory authority and recommended by WHO >1 year before DLM was approved (22); over time, access to both drugs might become more comparable. However, several other possible explanations exist. First, the compassionate use/expanded access program for BDQ started nearly 3 years earlier and was more extensive and systematic than that for DLM. As a result, multiple countries and clinical providers have had experience with BDQ and thus might be more comfortable using it on a broader scale (23). Second, BDQ is registered in more countries than DLM; thus programmatic use might be more straightforward. Third, BDQ also is available through the GDF, whereas DLM can be obtained directly only from the company, although the company’s website contains no information about how the drug can be purchased (24). Finally, in March 2015, USAID began implementing a BDQ donation program in which 30,000 treatment courses are provided free of charge for 4 years, along with the technical assistance that countries might need to implement the drug (25). Although Otsuka Pharmaceuticals announced a “20 by 2020” access initiative—meaning 20% of MDR TB patients worldwide would receive DLM by 2020 (26)—the company has not provided information about how this program will work.

Stakeholders participating in the DR-TB STAT meetings discussed multiple barriers and challenges to new drug implementation that also appear to be slowing new drug introduction. Several of these seem to be misconceptions about how to access or use the drugs, including confusion about processes for procurement and import, the specific WHO recommendations—especially around pharmacovigilance—for the use of new drugs, and beliefs that the drugs cannot be used under programmatic conditions. Indeed, all stakeholders participating in DR-TB STAT listed lack of access to technical assistance from experienced providers, including provision of rapidly changing information about new drug introduction, as a major challenge. These challenges could be addressed by providing global training for programs and their implementing partners. One approach to filling this gap would be using innovative training tools, including Web-based training. Plans for offering such training globally are now being coordinated by the DR-TB STAT participants with the hope that much of the confusion about how to optimally use BDQ and DLM under programmatic conditions can be eased.

Other challenges in new drug implementation stem from lack of access to BDQ and DLM and the other drugs needed to form complete treatment regimens. Increased registration and additional experience importing the medications also should help the drugs clear customs more rapidly. The inclusion of both drugs, along with linezolid, on the WHO Model Essential Drugs List in April 2015 might help boost country confidence and registration for their use in additional countries.

Finally, improved access to companion drugs used with BDQ and DLM, especially linezolid and clofazimine, is urgently needed. Until sufficient evidence enables BDQ and DLM to be combined, linezolid and clofazimine (and other “group 5” drugs) are used to ensure that the new drugs are not added singly to a failing regimen. These companion drugs are expensive—in the case of linezolid, more so than BDQ—and are not registered with an MDR TB indication in most of the countries using BDQ and DLM. Similar attention needs to be given to these drugs, and countries need to be supported in accessing them. DR-TB STAT is likely to begin formally monitoring and assisting countries with access to these medications in 2016.

Access to new drugs alone will not solve the ongoing crisis of MDR TB, and much more comprehensive action is needed to improve care for persons with this disease on a global level (27). These medications, however, are one of the few current hopes for more effective and less toxic therapy for MDR TB–affected persons worldwide (28). Coordinated efforts can help ensure timely and equitable access to BDQ and DLM for persons who need them most.