Attribute | Minimum# | Optimum¶ | |
1 | Indication | The RR-TB regimen is indicated for patients infected with RR strains (including MDR-TB) Indication may be contingent upon additional resistance to existing first- or second-line drugs, and supported by appropriate DST | The RR-TB regimen is indicated for all patients infected with RR-TB strains, with usage consistent with principles of good antibiotic stewardship |
2 | Efficacy and duration of treatment | A 6–12-month treatment regimen Efficacy (bacteriological cure without relapse in at least 1-year follow-up, among patients who are not lost to follow up) should be not inferior to the WHO recommended standard of care for MDR-TB | Less than or equal to 6-month treatment regimen Efficacy should be >90% |
3 | Target population in respect to age | At least adolescent (age 12–19 years) and adults | All age groups irrespective of severity of disease, pulmonary or extrapulmonary TB, or HIV status |
4 | Safety and tolerability | SAEs no more than 5% and treatment discontinuation due to TEAEs no more than 2.5% QT prolongation and proarrhythmic effects of the regimen would not put the patient at a moderate or high risk of arrhythmias or sudden death | SAEs are no more than 2% and treatment discontinuation due to TEAEs no more than 2% The regimen would have no or insignificant QT prolongation or proarrhythmic effects |
5 | DDI and metabolism | Ability to adjust dosing or perform safe monitoring for DDIs with: At least one first-line ART regimen Drugs that induce or inhibit P450 liver enzymes Pro-arrhythmic QT prolonging drugs | No dose adjustment with other medications and ability to safely use without active laboratory tests monitoring with: ART regimens and co-trimoxizole Drugs that induce or inhibit P450 liver enzymes Pro-arrhythmic QT prolonging drugs |
6 | Formulation dosage, route of administration and dosing (including schedule) | Formulation to be oral for all drugs in regimen Ability to deliver paediatric dosing of the regimen Twice-daily dosing and manageable food restrictions | Formulation to be oral. FDC formulations available (desirable to have no weight adjustment for adults) Paediatric (oral) and i.v. formulations must also be available Once-daily or intermittent dosing (preference for once-weekly or only monthly as the intermittency) |
7 | Stability/shelf-life | 3 years for all drugs in the regimen No cold chain requirements | 5 years for all drugs in the regimen No cold chain requirements |
8 | Special populations | Adults and women of childbearing potential Increased acceptable risk (benefits outweigh the risk in most cases) for pregnancy women, paediatrics and those with significant renal or hepatic disease Inclusions of patients with comorbidities including: HIV Diabetes Alcoholism Viral hepatitis | Adults, paediatrics, women of childbearing potential and pregnant women Ability to use the regimen with patients with significant renal disease Inclusions of patients with comorbidities including: HIV Diabetes Alcoholism Viral hepatitis Opiate addiction |
9 | Barrier to emergence of drug resistance (propensity to develop resistance, generation of cross-resistance) | New resistance to one or more drugs in the regimen emerges in <2% of treatment courses when taken as prescribed and when no pre-existing resistance to the drugs in the regimen exists | Essentially no acquired resistance (<0.1%) when regimen is taken as prescribed and no pre-existing resistance to the drugs in the regimen exists |
MDR: multidrug-resistant; DST: drug-susceptibility testing; WHO: World Health Organization; SAE: serious adverse event; TEAE: treatment-emergent adverse event; DDI: drug–drug interaction; ART: antiretroviral therapy; FDC: fixed-dose combination; i.v.: intravenous. #: should be considered as a potential go/no go decision point; ¶: should reflect what is needed to achieve broader, deeper, quicker global health impact.