Objective:: Trial results are usually given in terms of end point confidence intervals, the data concerning the participating patients being not available. Sometimes, it would be useful or necessary to obtain derived quantities, such as dose-response relationships, from the known information. In this work, we describe a methodology that allows to do that and illustrate it by analyzing the UK standardization of breast radiotherapy (START) trials.
Methods:: Using Monte Carlo techniques, virtual data sets were generated by sampling trial outcome distributions in terms of the tumor control probability (described by means of a logistic dose response and the equations of isoeffect in the linear-quadratic model). After fitting the available experimental data, the radiobiological parameters of interest and their confidence intervals were obtained from the TCP vs 'EQD2 curve in which the surgery effect is also taken into account.
Results:: The value of [Formula: see text] obtained for breast cancer was 3.6 Gy, with a 95% confidence interval of (1.5,15.5) Gy, in agreement with the one estimated by the START group. The time factor, referred to a scheme of 2 Gy per fraction, was 0.74 (0.41,2.67) Gy day-1, of the same order than that estimated for head and neck cancers.
Conclusion:: A methodology permitting an analysis of trial results was developed and tested with the results of the START trials. The procedure does not require detailed knowledge of the distributions actually found in the trials. The values obtained for the parameters are similar to those of the START estimations and this can be considered an independent confirmation of their validity, thus showing the model usefulness. The methodology presented here relies on basic statistical methods that are general enough to permit it to be applied to any kind of trial. This may be particularly interesting when the original data are no longer available.
Advances in knowledge:: The main novelty of this paper is to provide with a Monte Carlo based tool that permits an independent analysis of published trial results in order to obtain radiobiological parameters without a detailed knowledge of the data corresponding to the participating patients.