TITE-BOIN12: A Bayesian Phase I/II Trial Design to Find the Optimal Biological Dose with Late-onset Toxicity and Efficacy

Trial Name (Optional):

Design parameters:

Type in Upload using previously saved input

Enter design parameters in the following panels.

Upload the previously saved input (a .csv file)

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Dose, Sample Size, Patient Accrual

Number of doses:

Starting dose level:

Cohort size :

Number of cohorts :

Stop the trial if the number of patients at the current dose reaches:

Warning: this number is too small. Recommended value: 9 or 12.

DLT assessment window (month):

Efficacy assessment window (month):

Accural rate (No. patients per month):

Suspend accrual if >50% safety data or >50% efficacy data are pending at the current dose.

Risk-Benefit Tradeoff

Number of toxicity level:

Number of efficacy level:

Maximize the mean utility based on the utility ascribed to each possible outcome

Maximize Pr(efficacy)-w*Pr(toxicity)

Efficacy

Toxicity

where w=

App for this option is under development...

Admissible Criteria

Upper limit for toxicity probability \(\phi_{_T}\) :

Lower limit for efficacy probability \(\phi_{_E}\):

Check to apply the 3+3 design run-in.

A dose is deemed admissible if it satisfies the following safety and efficacy criteria, where (\(\pi_{_T}\)) and (\(\pi_{_E}\)) denote the true toxicity rate and true efficacy rate, respectively.

(Safety)

(Efficacy)

Pr\((\pi_{_T}>\phi_{_T}\mid data )<C_T\), where \(C_T=\)

Pr\((\pi_{_E}<\phi_{_E}\mid data)<C_E\), where \(C_E=\)

Save Input

The TITE-BOIN12 flowchart

Scenarios

Trial Name (Optional):

Method to enter simulation scenarios:

Type in

Upload scenario file

Upload simulation scenario file with the template: csv file template

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Number of scenarios:

For each scenario, enter true dose limiting toxicity (toxicity) rate and efficacy rate.

Below are the scenarios uploaded.

Scenario 1:

Scenario 2:

Scenario 3:

Scenario 4:

Scenario 5:

Scenario 6:

Scenario 7:

Scenario 8:

Scenario 9:

Scenario 10:

Distribution of the time to toxicity/efficacy:

Uniform Weibull

Pr(DLT occurs in the late half of assessment window) =

Pr(Efficacy occurs in the late half of assessment window) =

Correlation between toxicity (\(Y_T\)) and efficacy (\(Y_E\)) to simulate data:

Number of simulations:

Set seed:

Save Scenarios

Operating Characteristics

Please make sure that you have set up Trial Setting and Simulation before generating the protocol. The protocol is provided in html format. To edit, copy and paste it into a word document.

Download trial protocol as html file

This tab is used to determine the dose assignment for the next cohort of patients, based on the interim data. Before using this function, Trial Setting must be appropriately set up.

Check the box to confirm that design parameters have been entered under Trial Setting.

Trial Name (Optional):

Upload data file using this csv file template:

Browse...

Current dose level:

Download Report

This tab is used to determine optimal dose after the trial is completed. Before using this function, Trial Setting must be appropriately set up.

Check the box to confirm that design parameters have been entered under Trial Setting.

Trial Name (Optional):

Upload data file using this csv file template:

Browse...

Download Report

1. Liu S. and Yuan, Y. (2015). Bayesian optimal interval designs for Phase I clinical trials, Journal of the Royal Statistical Society: Series C , 64, 507-523.

2. Lin R., Zhou Y., Yan, F., Li D., and Yuan, Y. (2020). BOIN12: Bayesian optimal interval Phase I/II trial design for utility-based dose finding with immunotherapy and targeted therapies, JCO Precision Oncology 4, 1393-1402.

3. Zhou Y., Lin R., Lee, J.J., and Yuan, Y. (2022). TITE-BOIN12: A Bayesian Phase I/II Trial Design to Find the Optimal Biological Dose with Late-onset Toxicity and Efficacy Statistics in Medicine 41, 1918–1931.

TITE-BOIN12: A Bayesian Phase I/II Trial Design to Find the Optimal Biological Dose with Late-onset Toxicity and Efficacy

PID: 1062 ; V1.4.2.0 ; Last Updated: 1/08/2024

Yanhong Zhou, Ruitao Lin, J.Jack Lee, and Ying Yuan

Department of Biostatistics, MD Anderson Cancer Center

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Trial Setting

Simulation

Trial Protocol

Trial Conduct

OBD Determination

Reference

Design parameters:

Enter design parameters in the following panels.

Dose, Sample Size, Patient Accrual

Warning: this number is too small. Recommended value: 9 or 12.

Risk-Benefit Tradeoff

Efficacy

Toxicity

App for this option is under development...

Admissible Criteria

A dose is deemed admissible if it satisfies the following safety and efficacy criteria, where (\(\pi_{_T}\)) and (\(\pi_{_E}\)) denote the true toxicity rate and true efficacy rate, respectively.

(Safety)

(Efficacy)

The TITE-BOIN12 flowchart

Scenarios

For each scenario, enter true dose limiting toxicity (toxicity) rate and efficacy rate.

Below are the scenarios uploaded.

Scenario 1:

Scenario 2:

Scenario 3:

Scenario 4:

Scenario 5:

Scenario 6:

Scenario 7:

Scenario 8:

Scenario 9:

Scenario 10:

Operating Characteristics

Here is the scenarios entered

Please make sure that you have set up Trial Setting and Simulation before generating the protocol. The protocol is provided in html format. To edit, copy and paste it into a word document.

This tab is used to determine the dose assignment for the next cohort of patients, based on the interim data. Before using this function, Trial Setting must be appropriately set up.

This tab is used to determine optimal dose after the trial is completed. Before using this function, Trial Setting must be appropriately set up.

1. Liu S. and Yuan, Y. (2015). Bayesian optimal interval designs for Phase I clinical trials, Journal of the Royal Statistical Society: Series C , 64, 507-523.

2. Lin R., Zhou Y., Yan, F., Li D., and Yuan, Y. (2020). BOIN12: Bayesian optimal interval Phase I/II trial design for utility-based dose finding with immunotherapy and targeted therapies, JCO Precision Oncology 4, 1393-1402.

3. Zhou Y., Lin R., Lee, J.J., and Yuan, Y. (2022). TITE-BOIN12: A Bayesian Phase I/II Trial Design to Find the Optimal Biological Dose with Late-onset Toxicity and Efficacy Statistics in Medicine 41, 1918–1931.