title: Integrated phase II/III clinical trials in oncology: a case study.
abstract: BACKGROUND
  Integrated phase II/III trial designs implement the phase II and phase III aspects of oncology studies into a single trial. Despite a body of literature discussing the merits of integrated phase II/III clinical trial designs within the past two decades, implementation of this design has been limited in oncology studies.
  
  
  OBJECTIVE
  We provide a brief discussion of the potential advantages and disadvantages of integrated phase II/III clinical trial designs in oncology and provide an example of the operating characteristics of a Radiation Therapy Oncology Group (RTOG) trial.
  
  
  METHODS
  We review the differences among proposed integrated phase II/III designs. Then, we illustrate the use of the design in a brain tumor trial to be conducted by the RTOG and examine the impact of association between endpoints on design performance in terms of type I error, power, study duration, and expected sample size.
  
  
  RESULTS
  Although integrated phase II/III designs should not be used in all situations, under appropriate conditions, significant gains can be achieved when using integrated phase II/III designs, including smaller sample size, time and resources savings, and shorter study duration.
  
  
  CONCLUSIONS
  Data submission without delay and sufficient evaluation of intermediate endpoints are assumed.
  
  
  CONCLUSIONS
  Although there are potential benefits in using phase II/III designs, there also may be disadvantages. We recommend running design simulations incorporating theoretical and practical issues before implementing an integrated phase II/III design.
authors.affiliation: Department of Statistics, Radiation Therapy Oncology Group, American College of Radiology, Philadelphia, PA, USA. sumswang@yahoo.com
authors.forename: Meihua
authors.initials: M
authors.lastname: Wang
authors.forename: James J
authors.initials: JJ
authors.lastname: Dignam
authors.forename: Qiang E
authors.initials: QE
authors.lastname: Zhang
authors.forename: John F
authors.initials: JF
authors.lastname: DeGroot
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.forename: Sally
authors.initials: S
authors.lastname: Hunsberger
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D015982:Bias; D001932:Brain Neoplasms / Q000188:drug therapy; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D005910:Glioma / Q000188:drug therapy; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D012107:Research Design; D018401:Sample Size; D013997:Time Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D008130:Lomustine