BOIN12: Bayesian Optimal Interval Phase I/II Trial Design for Utility-Based Dose Finding

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

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.

When the current dose's observed toxicity rate falls within the stay interval, stop exploring higher doses if its number of patients >= N*, where N* =

Warning: this number is too large. Recommended value: 0 to 6.

Impose extra dose exploration when the number of patients treated at the current dose >=

Use a two-stage design: Stage 1 uses toxicity only for fast dose escalation, and Stage 2 considers both toxicity and efficacy for dose optimization.

Stage 2 begins once the number of patients at one or more doses >= S, where S =

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.

Use the default value of 0.05 for \(\delta\) to determine \(\pi^*_{_T}=\bar{\pi}_{_T}-\delta\).

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

BOIN12 Flowchart
Rank-based Desirability Score (RDS) Table

Scenarios

Trial Name (Optional):

Method to enter simulation scenarios:

Type in

Upload scenario file

Number of scenarios:

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

wrong input

Scenario 1:

Scenario 2:

Scenario 3:

Scenario 4:

Scenario 5:

Scenario 6:

Scenario 7:

Scenario 8:

Scenario 9:

Scenario 10:

Upload simulation scenario file with the template: csv file template

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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):

Please 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):

Please upload data file using this csv file template:

Browse...

Download Report

A trial animiation using the BOIN12 design is provided on the right. The trial settings are illustrated under the "Animation document" tab.

Animiation video
Animiation document

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.

BOIN12: Bayesian Optimal Interval Phase I/II Trial Design for Utility-Based Dose Finding

PID: 1048 ; V2.1.1.0 ; Last Updated: 1/14/2024

Ruitao Lin, Yanhong Zhou, and Ying Yuan

Department of Biostatistics, MD Anderson Cancer Center

(Best viewed in Google Chrome & Safari browers)

Trial Setting

Simulation

Trial Protocol

Trial Conduct

OBD Determination

Animation

Reference

Design parameters:

Enter design parameters in the following panels.

Dose & Sample Size

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

Warning: this number is too large. Recommended value: 0 to 6.

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)

BOIN12 Flowchart

Rank-based Desirability Score (RDS) Table

Scenarios

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

Scenario 1:

Scenario 2:

Scenario 3:

Scenario 4:

Scenario 5:

Scenario 6:

Scenario 7:

Scenario 8:

Scenario 9:

Scenario 10:

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.

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.

A trial animiation using the BOIN12 design is provided on the right. The trial settings are illustrated under the "Animation document" tab.

Animiation video

Animiation document

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.