title: Adaptive dose insertion in early phase clinical trials.
abstract: OBJECTIVE
  We propose to adaptively insert new doses during the course of a dose-finding trial when none of the prespecified doses in the trial are acceptable, for example, have tolerable toxicity.
  
  
  METHODS
  Our procedure uses an activation rule to determine whether a new dose is needed and an inverse dose-response algorithm to estimate new doses to be inserted into the trial.
  
  
  RESULTS
  The proposed method can be applied to both one-agent and two-agent trials. In application to a Phase I trial about advanced ovarian cancer, our method selected a new dose that is better than all prespecified doses in at least 44% simulations. The effectiveness of the procedure was also demonstrated in a simulation study.
  
  
  CONCLUSIONS
  The proposed method is applicable to dose-finding trials with binary responses.
  
  
  CONCLUSIONS
  We believe that with the added adaptive dose insertion, traditional dose-finding trials will have better chances of locating desirable doses. In addition, by allowing for dose insertion, unnecessary trial suspension due to lack of acceptable doses can be avoided.
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: B Nebiyou
authors.initials: BN
authors.lastname: Bekele
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000465:Algorithms; D002986:Clinical Trials as Topic / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic / Q000379:methods; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015233:Models, Statistical; D010051:Ovarian Neoplasms / Q000188:drug therapy; D012107:Research Design