title: Use of nonlinear mixed-effects analysis for improved precision of early pharmacodynamic measures in tuberculosis treatment.
abstract: Nonlinear mixed-effects analysis of serial sputum colony-counting data supports the existence of two bacillary subpopulations in sputum, eliminated at different rates. It distinguishes between combination regimens, removes bias, and greatly improves precision, with significant implications for the analysis of surrogate endpoints of "sterilization" in the development of new antituberculosis regimens.
authors.affiliation: Wellcome Trust Centre for Clinical Tropical Medicine, University of Liverpool, UK. gerrydavies@doctors.org.uk
authors.forename: Geraint R
authors.initials: GR
authors.lastname: Davies
authors.forename: Richard
authors.initials: R
authors.lastname: Brindle
authors.forename: Saye H
authors.initials: SH
authors.lastname: Khoo
authors.forename: Leon J
authors.initials: LJ
authors.lastname: Aarons
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use; D008954:Models, Biological; D017711:Nonlinear Dynamics; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D013183:Sputum / Q000382:microbiology; D013307:Streptomycin / Q000627:therapeutic use; D013828:Thioacetazone / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D013828:Thioacetazone; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin