TY - JOUR
T1 - Model-assisted designs for early-phase clinical trials
T2 - Simplicity meets superiority
AU - Yuan, Ying
AU - Lee, J. Jack
AU - Hilsenbeck, Susan G.
N1 - Funding Information:
Supported in part by Grants No. 1P50CA217685 and 5P50CA098258 from the National Cancer Institute (Y.Y.) and in part by Grant No. CA016672 from the National Cancer Institute and Grant No. RP160668 from the Cancer Prevention and Research Institute of Texas (J.J.L.).
Publisher Copyright:
© 2019 by American Society of Clinical Oncology.
PY - 2019
Y1 - 2019
N2 - Drug development enterprise is struggling because of prohibitively high costs and slow progress. There is urgent need for adoption of novel adaptive designs to improve the efficiency and success of clinical trials. A major barrier is that many conventional designs are inadequate for modern drug development, yet most novel adaptive designs are difficult to understand, require complicated statistical modeling, demand complex computation, and need expensive infrastructure for implementation. The objective of this article is to introduce and review a class of novel adaptive designs, known as model-assisted designs, to remove this barrier and increase the use of novel adaptive designs. Model-assisted designs enjoy superior performance comparable to more complicated, model-based adaptive designs, but their decision rule can be pretabulated and included in the protocol- thus implemented as simply as the conventional designs. We review state-of-the-art model-assisted designs for phase I clinical trials for single-agent, drug-combination and late-onset toxicity scenarios. We also briefly introduce model-assisted designs for phase II trials to handle binary, coprimary endpoints and delayed response. Freely available user-friendly software and trial examples (trialdesign.org) facilitate the adoption of model-assisted designs.
AB - Drug development enterprise is struggling because of prohibitively high costs and slow progress. There is urgent need for adoption of novel adaptive designs to improve the efficiency and success of clinical trials. A major barrier is that many conventional designs are inadequate for modern drug development, yet most novel adaptive designs are difficult to understand, require complicated statistical modeling, demand complex computation, and need expensive infrastructure for implementation. The objective of this article is to introduce and review a class of novel adaptive designs, known as model-assisted designs, to remove this barrier and increase the use of novel adaptive designs. Model-assisted designs enjoy superior performance comparable to more complicated, model-based adaptive designs, but their decision rule can be pretabulated and included in the protocol- thus implemented as simply as the conventional designs. We review state-of-the-art model-assisted designs for phase I clinical trials for single-agent, drug-combination and late-onset toxicity scenarios. We also briefly introduce model-assisted designs for phase II trials to handle binary, coprimary endpoints and delayed response. Freely available user-friendly software and trial examples (trialdesign.org) facilitate the adoption of model-assisted designs.
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U2 - 10.1200/PO.19.00032
DO - 10.1200/PO.19.00032
M3 - Review article
C2 - 32923856
AN - SCOPUS:85082946482
SN - 2473-4284
VL - 3
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -