U-BOIN: A Utility-Based Bayesian Phase I/II Design to Identify the Optimal Biological Dose for Targeted and Immune Therapies

Dose & Sample Size

Number of doses:

Starting dose level:

Error: Starting dose level must be less than the number of doses

Cohort size :

Number of cohorts :

Stage I is completed if the number of patients treated at any dose reaches \(s_1\), where \(s_1=\)

Apply the 3+3 design run-in:

Yes No

Perform accelerated titration in Stage I:

No Yes

Stage II is completed if the number of patients treated at any dose reaches \(s_2\), where \(s_2=\)

Utility for Risk-Benefit Tradeoff

Number of toxicity level:

Number of efficacy level:

Toxicity

Efficacy

Method for patient assignment based on utility in stage II

Pick-the-winner Adaptive randomization Equal randomization

App for this option is under development...

Admissible Criteria

Maximum tolerable toxicity rate (\(\bar{\pi}_{_T}\)) :

Minimum acceptable efficacy rate (\(\underline{\pi}_{_E}\)):

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

A dose is deemed admissible if none of the following conditions hold for the true toxicity rate (\(\pi_{_T}\)) and true efficacy rate (\(\pi_{_E}\)).

A dose is considered admissible if it satisfies none of the "(Toxic)", "(Futile)", and "(Insufficient activity)" critera below.

(Toxicity)

(Futility)

Pr\((\pi_{_T}>\bar{\pi}_{_T}\mid data )>C_T\), where \(C_T=\)

Pr\((\pi_{_E}<\underline{\pi}_{_E}\mid data)>C_E\), where \(C_E=\)

Use immune response? (check the box if immune response is used).

Minimum acceptable immune response (\(\mu_{min}\)):

(Insufficient activity) Pr\((\mu_{_I}>\mu_{min})>C_I, C_I=\)

App considering the immune response is under development...

The U-BOIN flowchart
Decision Tables

Scenarios

Number of scenarios:

Accrual rate (number of patients per month):

Time required to assess efficacy (in month)

For each scenario, enter true dose limiting toxicity (toxicity) rate, efficacy rate, and immune response mean (immume.M) and corresponding variance for the immune response (immune.var).

For each scenario, enter true dose limiting toxicity (toxicity) 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:

Association parameter between toxicity (\(Y_T\)) and efficacy (\(Y_E\)) in Gumbel model for simulating data:

Number of simulations:

Set seed:

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

Appendix: utility table

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.

"Yes" is selected under "Perform accelerated titration in Stage I:". Use this tab only when titration stage is completed.

Please upload interim data using this csv file template:

Browse...

This tab allows user to calculate the utility of a dose, based on the efficacy and toxicity data observed in that dose. Before using this function, Trial Setting must be appropriately set up.

Number of doses for utility calculation

Error:You already reached the maximum number of doses you can enter!

Please enter the trial data:

Note. #(Eff=0,Tox=1) is the number of patients who do not experience efficacy (Eff=0) but experience toxicity (Tox=1). The other columns are defined in a similar way.

1. Zhou, Y., Lee, J. J., & Yuan, Y. (2019). A utility-based Bayesian optimal interval (U-BOIN) phase I/II design to identify the optimal biological dose for targeted and immune therapies. Statistics in Medicine, 38(28), 5299-5316.

2. Zhou, Y., Lin, R., Kuo, Y., Lee, J. J, & Yuan, Y. (2021). BOIN suite: a software platform to design and implement novel early phase clinical trials. JCO Clinical Cancer Informatics, 5, 91-101.