Table 2.

Summary findings for key variables, per country

	Belarus	France	Georgia	South Africa	Swaziland
Year and conditions of first BDQ use	2015, program use	2011, CU/EA	2011, CU/EA	2012, CU/EA	2014, CU/EA
Impetus for wider use	High rates of MDR-TB and second-line drug resistance Poor treatment outcomes Safety and efficacy of BDQ reported in other settings	Migrant population with high rates of MDR-TB and second-line drug resistance Safety and efficacy of BDQ seen in CU/EA program	Poor treatment outcomes Concerns over amplification of drug resistance Green Light Committee recommendations Safety and efficacy of BDQ seen in the CU/EA program	High rates of second-line drug resistance Poor treatment outcomes Safety and efficacy of BDQ seen in CU/EA program	Hopes to implement an oral MDR-TB treatment regimen using new DR-TB drugs
Planned annual patient population to receive BDQ and location of care	250 patients annually at a centralized in-patient center	50 patients annually at in-patient and out-patient centers throughout the country	200 patients annually at in-patient and out-patient sites throughout the country	3000 patients annually at in-patient and out-patient sites throughout the country down to district level	200 patients annually at 6 in-patient and out-patient public MDR-TB treatment initiation sites
Clinical indications	Patients with resistance to an FQ, an injectable or both Patients in whom a WHO-recommended regimen with 4 effective drugs cannot be constructed due to resistance or intolerance to medications, including drug substitution for hearing loss	Patients in whom a WHO-recommended regimen with 4 effective drugs cannot be constructed due to resistance or intolerance to medications, including drug substitution for hearing loss	Patients with resistance to an FQ, an injectable or both Previous treatment failures Intolerance to two or more second-line drugs, including drug substitution for hearing loss	Patients with resistance to an FQ, an injectable or both Patients with intolerance to two or more second-line drugs, including drug substitution for hearing loss	Patients with resistance to an FQ, an injectable or both Patients with intolerance to two or more second-line drugs, including drug substitution for hearing loss
Special populations	Children as young as 14 years included	Extra-pulmonary cases, children and pregnant women included BDQ treatment courses beyond 24 weeks, BDQ in combination with DLM		Patients with both inhA and katG mutations HIV-infected patients included and efavirenz changed to nevirapine or lopinavir/ritonavir for the duration of BDQ treatment Children as young as 14 years of age included	HIV-infected patients included and efavirenz changed to nevirapine or lopinavir/ritonavir for the duration of BDQ treatment Children as young as 12 years of age included
Number of initial implementing sites	1	1	1	4	2
Number of implementing sites in 2015	1	3	2	12	6
Hospitalization required for BDQ initiation?	Yes	Yes	Yes	No	Yes
Number of clinical review committees and their scope	One national review committee, reviews all BDQ patients	One national review committee,13,14 reviews all BDQ patients, but national coverage is not complete	One national review committee, reviews all BDQ patients	One national review committee and 10 provincial review committees National committee reviews all complicated cases	One national review committee and two district review committees National committee reviews all complicated cases
Planned monitoring as per country guidelines	Monthly culture and DST, ECG and renal/liver function tests per national guidelines for patients on BDQ Currently available for all patients on BDQ per NTP reports	Monthly culture and DST, ECG and renal/liver function tests per national guidelines for patients on BDQ Currently available for all patients on BDQ per NTP reports	Monthly culture and DST, ECG and renal/liver function tests per national guidelines for patients on BDQ Currently available for all patients on BDQ per NTP reports	Monthly culture and DST, ECG and renal/liver function tests per national guidelines for patients on BDQ Currently available for all patients on BDQ per NTP reports	Monthly culture and DST, ECG and renal/liver function tests per national guidelines for patients on BDQ Currently available for all patients on BDQ per NTP reports
Registration, supply and import	Waiver program, as BDQ is not yet registered BDQ supplied by Pharmastandard and the GDF via a donation program (at no cost)	Waiver program, as BDQ is not yet registered (registration due in 2016) BDQ supplied by Janssen directly to country (cost is approximately 27 137 USD [25 000€] per 6-month course)	Waiver program, as BDQ is not yet registered BDQ supplied by the GDF via the USAID donation program at no cost after initial supply from MSF	BDQ registered in 2014 by the MCC: ‘Section 21 waiver’ prior to registration; BDQ supplied by Janssen directly to country (cost is approximately 700 USD per 6-month course)	Waiver program, as BDQ is not yet registered, although its registration in South Africa allows it to be imported into Swaziland: regulatory activities performed by the Office of the Chief Pharmacist; Oversight by Central Medical Stores BDQ supplied by the GDF via the USAID donation program at no cost after initial supply from MSF
Active pharmacovigilance	Initially cohort event monitoring; currently aDSM in accordance with WHO recommendations When BDQ use started, Belarus was using a cohort event monitoring protocol it had developed for patients on linezolid. This required the pharmacovigilance center to be notified of all adverse events, regardless of severity. This protocol was time-consuming and required substantial resources, and was phased out to focus only on serious, severe, and targeted events, such as QTc prolongation	aDSM in accordance with WHO recommendations through the national regulatory agency (ANSM)	aDSM core and advanced packages in accordance with WHO recommendations In this model, all serious and severe adverse events are reported to the national pharmacovigilance center, as are targeted events of any severity, including QTc prolongation, peripheral neuropathy, and hypokalemia	Targeted spontaneous reporting of all serious adverse events at a provincial level as required by the MCC In this model, all serious and severe adverse events are reported to provincial pharmacovigilance centers. These are then collated and sent to the national pharmacovigilance center	aDSM in line with WHO recommendations per National Pharmacovigilance Center policies When BDQ use started, there was limited pharmacovigilance available in Swaziland. BDQ use thus helped develop the national system for TB pharmacovigilance. In this system, providers report all serious and severe adverse events to the national pharmacovigilance center
BDQ resistance testing available?	Via supranational reference laboratory for research purposes only	Via national laboratory for routine patient management since 2014. BDQ resistance testing is performed for all patients started on BDQ at baseline and in case of treatment failure	Via supranational reference laboratory for research purposes only	Via national laboratory for research purposes only All patients started on BDQ have a sample taken at baseline, week 8, and week 24, with specimens saved for BDQ resistance surveillance	Via supranational reference laboratory for research purposes only
Key implementing partners	National TB Program, Global Fund, National Pharmacovigilance Center, WHO	ANSM, National Reference Center for Mycobacteria	National Center for TB and Lung Disease; MSF France; National Center for Disease Control; Ministry of Labor, Health, and Social Assistance; USAID/SIAPS	National Department of Health, MSF, Right to Care	National TB and Leprosy Program, MSF Holland, MSF Swiss, MSH/SIAPS, URC, ICAP, EGPAF and CHAI, WHO
Financing	National budget, GF grant	National budget	National budget, GF grant, USAID/SIAPS, MSF (BDQ and companion drugs)	National budget	National budget, GF grant, USAID/SIAPS, MSF (companion drugs)
Early implementation challenges	Clinical protocol development Concerns about safety Procuring equipment to monitor ECGs Initial process for importation	Concerns about safety Development of national implementation framework	Initial process for importation Concerns about safety Lack of a developed pharmacovigilance system Clinical protocol development Concomitant use of imipenem	Selection of initial implementing sites Concerns about safety Use of high-cost companion drugs, especially linezolid Concomitant use with ART	Clinical protocol development Concerns about safety Concomitant use with ART Procuring equipment to monitor ECGs Lack of a developed pharmacovigilance system
Possible challenges to scale-up	Drug supply Decentralized treatment Inclusion of children and adolescents Management of patients in whom BDQ-containing treatment has failed	Decentralized treatment Definition of BDQ treatment duration Inclusion of children, adolescents, and pregnant women	Decentralized treatment Management of patients in whom BDQ-containing treatment has failed Inclusion of children and adolescents	Management of patients in whom BDQ-containing treatment has failed Quality monitoring and consistency in care in large-scale program Optimizing use in shorter regimens	Management of patients in whom BDQ-containing treatment has failed Management of patients in whom shortened regimen (which are being piloted in the country) has failed Maintaining quality during ambulatory treatment

BDQ = bedaquiline; CU = compassionate use; EA = expanded access; MDR-TB = multidrug-resistant tuberculosis; FQ = fluoroquinolone; WHO = World Health Organization; DLM = delamanid; HIV = human immunodeficiency virus; DST =drug susceptibility testing; ECG =electrocardiography; NTP = National TB Control Program; GDF =Global Drug Facility; USAID = United States Agency for International Development; MSF = Médecins Sans Frontières; MCC = Medicines Control Council; aDSM = active drug safety monitoring and management; ANSM = Agence Nationale de Sécurité du Médicament et des produits de Santé; MSH = Management Sciences for Health; ISIAPS = Systems for Improved Access to Pharmaceuticals and Services; URC = University Research Corporation; CAP = International Center for AIDS Care and Treatment Program; EGPAF = Elizabeth Glaser Pediatric AIDS Foundation; CHAI = Clinton Health Access Initiative; GF = Global Fund to Fight AIDS, Tuberculosis, and Malaria; ART = antiretroviral therapy.