Barriers and facilitators to early access of bedaquiline and delamanid for MDR-TB: a mixed-methods study

Abstract

Setting: Phase II trials for bedaquiline (BDQ) and delamanid (DLM) were completed by 2011 and the drugs were approved by stringent regulatory authorities for the treatment of multidrug-resistant tuberculosis (MDR-TB) between 2012 and 2014. Manufacturers established 'early access' mechanisms to provide drugs before local registration. Objective: To inform improvements in early access, we explored experiences of providers and advocates in accessing BDQ and DLM before the end of 2015 using a mixed-methods design. Design: We examined barriers and facilitators to early access through an electronic survey. Barriers and facilitators were classified as occurring at the manufacturer-or country-level. We identified themes using inductive content analysis and illustrated themes through case studies. Results: We analysed 41 survey responses from 36 respondents reporting on 22 countries; early access was attempted in 30 (73%) survey responses. Eligibility restrictions (11/30, 37%) and complicated and slow processes (8/30, 27%) were manufacturer-level barriers; access to companion drugs (10, 33%) and importation difficulties (4, 13%) were country-level barriers. Previous experience with manufacturer (3/30, 10%) and country processes (2/30, 7%) facilitated access. Eight case studies show the human impact of barriers and facilitators. Conclusion: Manufacturers and countries should develop transparent processes to permit early access, particularly for diseases that largely affect the poor, such as MDR-TB. Developers should plan for this need and rapidly register drugs with proven benefit, prioritizing high-burden settings.

Bedaquiline resistance probability to guide treatment decision making for rifampicin-resistant tuberculosis: insights from a qualitative study

“…Access to companion drugs also influenced the interpretation of the BDQ resistance probability, especially when it narrows down the options to replace or protect BDQ. This confirms the findings of a study on early access to BDQ performed in 2015, where lack of access to companion drugs was the most commonly reported country-level barrier [ 8 ]. Guaranteeing adequate procurement of affordable RR-TB drugs is thus essential to translate new policies and guidelines into practice and to accelerate the adoption of new advancements in TB care [ 53 , 54 ].…”

“…Despite the endorsement of BDQ ten years ago, access to BDQ-containing regimens still varies across countries and is impacted by multi-level factors. Structural barriers to BDQ access include the lag in BDQ registration with national regulatory bodies, difficulties in setting up the required pharmacovigilance system, lack of access to companion drugs, and restriction of BDQ to in-patient settings [6][7][8]. The cost of BDQ also plays a role, especially in high-income countries, with a cost of €23,000 per 6-month course in European countries as compared to €340 in low-and middle-income countries [9,10].…”

Management of childhood MDR-TB in Europe and Central Asia: report of a Regional WHO meeting

“…Both manufacturer-and country-level barriers to their use have been identified and partnerships with industry through compassionate use programmes have been initiated to permit ready access to these two drugs. 21,22 The practice of lengthy hospitalisation of children and adolescents with MDR-TB is controversial and usually unnecessary. The hospital payment mechanisms may explain this in places where hospitals and departments are reimbursed at higher inpatient treatment rates than ambulatory care.…”

The coming-of-age of bedaquiline: a tale with an open ending

“…[1,2] After being developed in 2005, [3] bedaquiline showed promising results in Phase II trials [4,5], and was granted accelerated approval in 2012 by the FDA in the United States and conditional approval in 2014 by the EMA in the European Union. In the following years, the access to bedaquiline has progressively increased, from compassionate to programmatic use, [6,7] although at an insufficient pace. Between July 2015 and December 2019, 51,098 patients received bedaquiline worldwide: although remarkable, this figure only represents 11% of those who are estimated to need it according to the most recent recommendations by the World Health Organization (WHO).…”