title: Medium matters: modeling the impact of solid medium performance on tuberculosis trial sample size requirements.
abstract: METHODS
  Two-month solid medium culture conversion is a commonly used, if suboptimal, endpoint for phase 2 anti-tuberculosis treatment trials.
  
  
  OBJECTIVE
  To model the effect of the performance characteristics (sensitivity and contamination rate) of solid medium on required sample size for a two-arm clinical trial with 85% true (gold standard) culture conversion in the control and 95% in the experimental arm.
  
  
  RESULTS
  Increasing sensitivity and decreasing contamination reduced the sample size from 239 subjects/arm (60% sensitivity, 30% contamination) to 138 subjects/arm (95% sensitivity, 1% contamination).
  
  
  CONCLUSIONS
  Optimizing solid medium has significant potential to reduce sample size and increase the efficiency of tuberculosis clinical trials.
authors.affiliation: Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Johnson
authors.affiliation: Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Stout
authors.affiliation: Infectious Diseases Section, Veterans Affairs Medical Center and the George Washington University Medical Center, Washington DC, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Benator
authors.affiliation: Clinical Research Branch, Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Whitworth
authors.affiliation: Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, USA; Division of Infectious Diseases, Emory University, Atlanta, Georgia, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Holland
mesh_terms: D000995:Antitubercular Agents / Q000627:therapeutic use*; D001431:Bacteriological Techniques; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D018849:Controlled Clinical Trials as Topic / Q000379:methods*; D003470:Culture Media; D023381:Endpoint Determination; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018401:Sample Size; D013997:Time Factors; D016896:Treatment Outcome; D014376:Tuberculosis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D003470:Culture Media