Evaluation of Viable Dynamic Treatment Regimes in a Sequentially Randomized Trial of Advanced Prostate Cancer

TitleEvaluation of Viable Dynamic Treatment Regimes in a Sequentially Randomized Trial of Advanced Prostate Cancer
Publication TypePresentation
Year of Publication2014
AuthorsWang, L
KeywordsSymposium III

In this talk, we present new statistical analyses of data arising from a clinical trial designed to compare two-stage dynamic treatment regimes (DTRs) for advanced prostate cancer. The trial protocol mandated that patients be initially randomized among four chemotherapies, and that those who responded poorly be re-randomized to one of the remaining candidate therapies. Of the 150 study participants, 47 did not complete their therapy as per the algorithm. However, 35 of them did so for reasons that precluded further chemotherapy, that is, toxicity and/or progressive disease. Consequently, we conducted an analysis that compared viable switch rules defined by the per-protocol rules but with the additional provision that patients who developed toxicity or progressive disease switch to a non-prespecified therapeutic or palliative strategy. This modification involved consideration of bivariate per-course outcomes encoding both efficacy and toxicity. We used numerical scores elicited from the trial’s principal investigator to quantify the clinical desirability of each bivariate per-course outcome, and defined one endpoint as their average over all courses of treatment. Two other simpler sets of scores as well as log survival time were also used as endpoints. Estimation of each DTR-specific mean score was conducted using inverse probability weighted methods, which assumed that missingness in the 12 remaining dropouts was informative but explainable in that it only depended on past recorded data. We conducted additional worst- and best-case analyses to evaluate sensitivity of our findings to extreme departures from the explainable dropout assumption.