Integrated phase II/III clinical trials in oncology: a case study.

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.
PURPOSE: 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. LIMITATIONS: 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.