Final published version
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - The role of minimal sets in dose finding studies
AU - Clertant, Matthieu
AU - O'Quigley, John
PY - 2018
Y1 - 2018
N2 - In view of the impossibility theorem of Azriel et al., the Maximum Tolerated Dose (MTD), as currently defined in Phase I and Phase I/II trials, cannot be consistently estimated without making some very strong parametric assumptions. Experimentation carried out at a single dose will fail to provide a consistent estimator of the MTD. We require that information be obtained on a subset of the doses which we describe as the ‘minimal set’. We provide a definition of this set and study its role in semiparametric inference concerning the MTD. Focusing inference on the minimal set, and only indirectly on the MTD, has important consequences. Among these is consistency of estimators for both the minimal set and the MTD, in completely general conditions. Even when the goal is only to estimate the MTD, we do no worse, and often better than other methods and without making any sacrifice in terms of safety for the patient. © 2018, © American Statistical Association and Taylor & Francis 2018.
AB - In view of the impossibility theorem of Azriel et al., the Maximum Tolerated Dose (MTD), as currently defined in Phase I and Phase I/II trials, cannot be consistently estimated without making some very strong parametric assumptions. Experimentation carried out at a single dose will fail to provide a consistent estimator of the MTD. We require that information be obtained on a subset of the doses which we describe as the ‘minimal set’. We provide a definition of this set and study its role in semiparametric inference concerning the MTD. Focusing inference on the minimal set, and only indirectly on the MTD, has important consequences. Among these is consistency of estimators for both the minimal set and the MTD, in completely general conditions. Even when the goal is only to estimate the MTD, we do no worse, and often better than other methods and without making any sacrifice in terms of safety for the patient. © 2018, © American Statistical Association and Taylor & Francis 2018.
KW - clinical trial
KW - continual reassessment method
KW - dose finding methodology
KW - hierarchical model
KW - Sequential design
U2 - 10.1080/10485252.2018.1515430
DO - 10.1080/10485252.2018.1515430
M3 - Journal article
VL - 30
SP - 1016
EP - 1031
JO - Journal of Nonparametric Statistics
JF - Journal of Nonparametric Statistics
SN - 1048-5252
IS - 4
ER -