Drug resistance is a major threat to global tuberculosis (TB) care and control. WHO estimates that around 480,000 new multidrug-resistant tuberculosis (MDR-TB) cases occured in 2013. Current treatment regimens for drug-resistant TB are complex, lengthy, toxic and expensive. Only about one half of MDR-TB patients started on treatment globally are reported to be treated successfully, largely due to a high frequency of death and loss to follow-up, commonly associated with adverse drug reactions and high costs of treatment. In addition, it is estimated that up to a third of MDR-TB cases may have strains with additional resistance to fluoroquinolones and/or injectable second-line drugs (aminoglycosides or capreomycin), rendering their treatment even more difficult, with recourse only to highly toxic drugs.

The landscape of drug development for treatment of TB has evolved over the past ten years and novel drugs are presently or soon entering Phase III trials for the treatment of MDR-TB. Considering the global MDR-TB crisis, the limited therapeutic options available for this life-threatening condition, and the need to promote safe and responsible use of TB drugs, WHO convened an Expert Group in April 2014 to review the available evidence on the efficacy, safety and effectiveness of delamanid, a new drug for the treatment of MDR-TB, with the view to issue interim recommendations on its use in conjunction with WHO-recommended MDR-TB treatment.

Contents

• Abbreviations
• Acknowledgements
• Executive summary
• 1. Background
• 2. Guideline purpose and target audience
  • 2.1 Purpose
  • 2.2 Target audience
• 3. Guideline development process
  • 3.1 Expert Group meeting
  • 3.2 Management of conflicts of interest
  • 3.3 Review of evidence
  • 3.4 Decision-making during the Expert Group meeting
  • 3.5 External peer review
  • 3.6 Financial support
• 4. Evidence base for policy formulation
  • 4.1 Evidence for the efficacy of delamanid in the treatment of MDR-TB
  • 4.2 Evidence for the safety of delamanid in the treatment of MDR-TB
  • 4.3 Cost-effectiveness
• 5. Expert Group recommendations
  • 5.1 Summary of evidence for the recommendation
  • 5.2 Expert Group recommendations
• 6. WHO interim policy recommendations
• 7. Further research
• 8. Dissemination and implementation
• References
• Annex 1 List of WHO guideline Steering Group members
• Annex 2 List of Expert Group members
• Annex 3 Expert Group meeting on interim guidance for the use of delamanid in the treatment of multidrug-resistant tuberculosis
• Annex 4 Declarations of interest
• Annex 5 GRADE glossary
• Annex 6 List of Expert Review Panel members

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