The rate of failure in phase III oncology trials is surprisingly high, partly due to inadequate phase II studies. Recently, the use of randomized designs in phase II is being increasingly recommended, to avoid the limits of studies that use a historical control. We propose a two-arm two-stage design based on a Bayesian-predictive approach. The idea is to ensure a large probability, expressed in terms of the prior predictive probability of the data, of obtaining a substantial posterior evidence in favour of the experimental treatment, under the assumption that it is actually more effective than the standard agent. This design is a randomized version of the two-stage design that has been proposed for single-arm phase II trials by Sambucini. We examine the main features of our novel design as all the parameters involved vary and compare our approach to Jung's minimax and optimal designs. An illustrative example is also provided online as supplementary material to this article.

A randomized two-stage design for phase II clinical trials based on a Bayesian predictive approach / Cellamare, Matteo; Sambucini, Valeria. - In: STATISTICS IN MEDICINE. - ISSN 0277-6715. - 34(6):(2015), pp. 1059-1078. [10.1002/sim.6396]

A randomized two-stage design for phase II clinical trials based on a Bayesian predictive approach

CELLAMARE, MATTEO;SAMBUCINI, Valeria
2015

Abstract

The rate of failure in phase III oncology trials is surprisingly high, partly due to inadequate phase II studies. Recently, the use of randomized designs in phase II is being increasingly recommended, to avoid the limits of studies that use a historical control. We propose a two-arm two-stage design based on a Bayesian-predictive approach. The idea is to ensure a large probability, expressed in terms of the prior predictive probability of the data, of obtaining a substantial posterior evidence in favour of the experimental treatment, under the assumption that it is actually more effective than the standard agent. This design is a randomized version of the two-stage design that has been proposed for single-arm phase II trials by Sambucini. We examine the main features of our novel design as all the parameters involved vary and compare our approach to Jung's minimax and optimal designs. An illustrative example is also provided online as supplementary material to this article.
2015
analysis and design priors; bayesian predictive approach; phase ii clinical trials; randomized trials; two-stage designs
01 Pubblicazione su rivista::01a Articolo in rivista
A randomized two-stage design for phase II clinical trials based on a Bayesian predictive approach / Cellamare, Matteo; Sambucini, Valeria. - In: STATISTICS IN MEDICINE. - ISSN 0277-6715. - 34(6):(2015), pp. 1059-1078. [10.1002/sim.6396]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/667833
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