Use of nonlinear mixed-effects analysis for improved precision of early pharmacodynamic measures in tuberculosis treatment.
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.
Davies
Geraint R
GR
Wellcome Trust Centre for Clinical Tropical Medicine, University of Liverpool, UK. gerrydavies@doctors.org.uk
Brindle
Richard
R
Khoo
Saye H
SH
Aarons
Leon J
LJ
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*
D000995:Antitubercular Agents; D011718:Pyrazinamide; D013828:Thioacetazone; D007538:Isoniazid; D012293:Rifampin; D013307:Streptomycin