TY - JOUR
T1 - Adaptive design improvements in the continual reassessment method for phase I studies
AU - Heyd, Julie M.
AU - Carlin, Bradley P.
PY - 1999/6/15
Y1 - 1999/6/15
N2 - The continual reassessment method (CRM) enables full and efficient use of all data and prior information available in a phase I study. However, despite a number of recent enhancements to the method, its acceptance in actual clinical practice has been hampered by several practical difficulties. In this paper, we consider several further refinements in the context of phase I oncology trials. In particular, we allow the trial to stop when the width of the posterior 95 per cent probability interval for the maximum tolerated dose (MTD) becomes sufficiently narrow (that is, when the information accumulating from the trial data reaches a prespecified level). We employ a simulation study to evaluate five such stopping rules under three alternative states of prior knowledge regarding the MTD (accurate, too low and too high). Our results suggest our adaptive designs preserve the CRM's estimation ability while offering the possibility of earlier stopping of the trial.
AB - The continual reassessment method (CRM) enables full and efficient use of all data and prior information available in a phase I study. However, despite a number of recent enhancements to the method, its acceptance in actual clinical practice has been hampered by several practical difficulties. In this paper, we consider several further refinements in the context of phase I oncology trials. In particular, we allow the trial to stop when the width of the posterior 95 per cent probability interval for the maximum tolerated dose (MTD) becomes sufficiently narrow (that is, when the information accumulating from the trial data reaches a prespecified level). We employ a simulation study to evaluate five such stopping rules under three alternative states of prior knowledge regarding the MTD (accurate, too low and too high). Our results suggest our adaptive designs preserve the CRM's estimation ability while offering the possibility of earlier stopping of the trial.
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U2 - 10.1002/(SICI)1097-0258(19990615)18:11<1307::AID-SIM128>3.0.CO;2-X
DO - 10.1002/(SICI)1097-0258(19990615)18:11<1307::AID-SIM128>3.0.CO;2-X
M3 - Article
C2 - 10399198
AN - SCOPUS:0033564086
SN - 0277-6715
VL - 18
SP - 1307
EP - 1321
JO - Statistics in Medicine
JF - Statistics in Medicine
IS - 11
ER -