1. Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2017.8
Figure 1 Patient randomization in the continuum of drug and/or biomarker development
Figure 1 | Patient randomization in the continuum of drug and/or biomarker development. Blue bars indicate control treatment (Table 1), and their shading denotes the possibility of changing the control arm as the trial progresses, in which case the statistical analyses should be adjusted accordingly. Red bars indicate cohorts of patients treated with different doses and/or schedules of the experimental agent; bar length represents the number of patients enrolled at different phases. Phase I testing starts with allocation of patients to treatment groups according to a model-based dose-escalation strategy. A seamless transition between trial phases is represented by dotted vertical lines. The grey arrow indicates the stage of biomarker development. In the design depicted in the top half of the figure, randomization is retained throughout trial phases through expansion of patient accrual to relevant treatment arms; whereas in the bottom half, the phase III trial uses a biomarker-stratified design in independent cohorts of patients (rather than expansion of existing cohorts from earlier phases), with strata of different sizes and follow-up durations. The biomarker-negative stratum is needed to rule out a treatment effect in this patient subset and to test for a treatment-by-biomarker interaction.
Saad, E. D. et al. (2017) Precision medicine needs randomized clinical trials
Nat. Rev. Clin. Oncol. doi: /nrclinonc