title: Early Biomarkers and Regulatory Innovation in Multidrug-Resistant Tuberculosis.
abstract: Biomarkers play an essential role in accelerating drug development. Sputum culture conversion using solid medium is the best-characterized tuberculosis biomarker, having been examined at the patient and trial levels in studies with thousands of subjects, and having recently been validated using data from 3 unsuccessful phase 3 trials. We presently are poised at the threshold of regulatory innovation for antibacterials to treat drug-resistant infections, in which Special Medical Use authorization restricted to patients with limited options could be based on the results of small clinical trials. Patients worldwide would be well served by licensing of new regimens for multidrug-resistant tuberculosis based on biomarker evidence commensurate with the urgency of the current global crisis.
authors.affiliation: Aurum Institute, Johannesburg, South Africa.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wallis
authors.affiliation: Certara, LP, St Louis, Missouri.
authors.forename: Thomas
authors.initials: T
authors.lastname: Peppard
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D017326:Clinical Trials, Phase III as Topic; D057069:Diagnostic Test Approval; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D013183:Sputum / Q000382:microbiology; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis* / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D015415:Biomarkers
keywords: biomarkers; drug resistance; regulatory innovation; sputum culture; tuberculosis