title: A comparison of a new multinomial stopping rule with stopping rules of fleming and gehan in single arm phase II cancer clinical trials.
abstract: BACKGROUND
  Response rate (RR) alone may be insensitive to drug activity in phase II trials. Early progressive disease (EPD) could improve sensitivity as well as increase stage I stopping rates. This study compares the previously developed dual endpoint stopping rule (DESR), which incorporates both RR and EPD into a two-stage, phase II trial, with rules using only RR.
  
  
  METHODS
  Stopping rules according to the DESR were compared with studies conducted under the Fleming (16 trials) or Gehan (23 trials) designs. The RR hypothesis for the DESR was consistent with the comparison studies (ralt = 0.2, rnul = 0.05). Two parameter sets were used for EPD rates of interest and disinterest respectively (epdalt, epdnul): (0.4, 0.6) and (0.3, 0.5).
  
  
  RESULTS
  Compared with Fleming, the DESR was more likely to allow stage two of accrual and to reject the null hypothesis (Hnul) after stage two, with rejection being more common with EPD parameters (0.4, 0.6) than (0.3, 0.5). Compared with Gehan, both DESR parameter sets accepted Hnul in 15 trials after stage I compared with 8 trials by Gehan, with consistent conclusions in all 23 trials after stage II.
  
  
  CONCLUSIONS
  The DESR may reject Hnul when EPD rates alone are low, and thereby may improve phase II trial sensitivity to active, cytostatic drugs having limited response rates. Conversely, the DESR may invoke early stopping when response rates are low and EPD rates are high, thus shortening trials when drug activity is unlikely. EPD parameters should be chosen specific to each trial.
authors.affiliation: McMaster University, Juravinski Cancer Centre, 699 Concession St,, Hamilton, Ontario, L8V 5C2, Canada. john.goffin@medportal.ca
authors.forename: John R
authors.initials: JR
authors.lastname: Goffin
authors.forename: Greg R
authors.initials: GR
authors.lastname: Pond
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Tu
mesh_terms: D017322:Clinical Trials, Phase II as Topic; D023381:Endpoint Determination / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D004364:Pharmaceutical Preparations; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome
chemical_list: D004364:Pharmaceutical Preparations