Title: Improving phase II oncology trials using best observed RECIST response as an endpoint by modelling continuous tumour measurements,
Abstract: In many phase II trials in solid tumours, patients are assessed using
endpoints based on the Response Evaluation Criteria in Solid Tumours (RECIST)
scale. Often, analyses are based on the response rate. This is the proportion
of patients who have an observed tumour shrinkage above a pre-defined level and
no new tumour lesions. The augmented binary method has been proposed to improve
the precision of the estimator of the response rate. The method involves
modelling the tumour shrinkage to avoid dichotomising it. However, in many
trials the best observed response is used as the primary outcome. In such
trials, patients are followed until progression, and their best observed RECIST
outcome is used as the primary endpoint. In this paper, we propose a method
that extends the augmented binary method so that it can be used when the
outcome is best observed response. We show through simulated data and data from
a real phase II cancer trial that this method improves power in both single-arm
and randomised trials. The average gain in power compared to the traditional
analysis is equivalent to approximately a 35% increase in sample size. A
modified version of the method is proposed to reduce the computational effort
required. We show this modified method maintains much of the efficiency
advantages.