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. 2013 Apr 5:7:8-17.
doi: 10.2174/1874431101307010008. Print 2013.

Interactive Software "Isotonic Design using Normalized Equivalent Toxicity Score (ID-NETS©TM)" for Cancer Phase I Clinical Trials

Zhengjia Chen  1 , Zhibo Wang, Haibin Wang, Taofeek K Owonikoko, Jeanne Kowalski, Fadlo R Khuri
Affiliations

Interactive Software "Isotonic Design using Normalized Equivalent Toxicity Score (ID-NETS©TM)" for Cancer Phase I Clinical Trials

Zhengjia Chen et al. Open Med Inform J. .

Abstract

Isotonic Design using Normalized Equivalent Toxicity Score (ID-NETS) is a novel Phase I design that integrates the novel toxicity scoring system originally proposed by Chen et al. [1] and the original Isotonic Design proposed by Leung et al. [2]. ID-NETS has substantially improved the accuracy of maximum tolerated dose (MTD) estimation and trial efficiency in the Phase I clinical trial setting by fully utilizing all toxicities experienced by each patient and treating toxicity response as a quasi-continuous variable instead of a binary indicator of dose limiting toxicity (DLT). To facilitate the incorporation of the ID-NETS method into the design and conduct of Phase I clinical trials, we have designed and developed a user-friendly software, ID-NETS(©TM), which has two functions: 1) Calculating the recommended dose for the subsequent patient cohort using available completed data; and 2) Performing simulations to obtain the operating characteristics of a trial designed with ID-NETS. Currently, ID-NETS(©TM)v1.0 is available for free download at http://winshipbbisr.emory.edu/IDNETS.html.

Keywords: Isotonic design; cancer phase I clinical trial; dose limiting toxicity; maximum tolerated dose; normalized equivalent toxicity score; software..

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Figures

Fig. (1)
Fig. (1)
Interface for selecting function.
Fig. (2)
Fig. (2)
Interface for calculation of the recommended next dose level based on existing data.
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Interface for importing data into the program.
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Data showing ETS and NETS for each patient.
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Summary of the calculation results based on completed data.
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Study flow chart.
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Fig. (7)
User interface of simulation functions to obtain operating characteristics of a trial designed with ID-NETS.
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Table to set the probability of DLT for each dose level.
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Fig. (9)
Probability of DLT and corresponding NETS at each dose level.
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Summary of the simulation results.
Fig. (11)
Fig. (11)
Probability of each dose level recommended as MTD.
Fig. (12)
Fig. (12)
Proportion of patients treated at each dose level.
See this image and copyright information in PMC

References

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    1. Leung DH, Wang Y. Isotonic designs for phase I trials. Control Clin Trials. 2001;22(2 ):126–38. - PubMed
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    1. Yuan Z, Chappell R, Bailey H. The continual reassessment method for multiple toxicity grades: a Bayesian quasi-likelihood approach. Biometrics journal. 2007;63(1 ):173–9. - PubMed

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