TOP: Time-to-Event Bayesian Optimal Phase II Trial Design

Endpoints:

Binary Efficacy

Efficacy & Toxicity

Multiple Efficacy

Interims:

Sample sizes when interim analyses to be performed, seperated by space. The last number must be the total sample size.

Accrual Rate (number of patients / month)

Null Hypothesis:

Response rate

Null Hypothesis:

Pr(Eff1)

Pr(Eff2)

Pr(Eff1 & Eff2)

Null Hypothesis:

Pr(Eff)

Pr(Tox)

Pr(Eff & Tox)

Alternative Hypothesis:

Response rate

Alternative Hypothesis:

Pr(Eff1)

Pr(Eff2)

Pr(Eff1 & Eff2)

Alternative Hypothesis:

Pr(Eff)

Pr(Tox)

Pr(Eff & Tox)

Outcome Assessment:

Efficacy assessment window

Use the default uniform prior for the time to efficacy

Prior efficacy probabilities in the assessment period (sum to 1)

Trimester 1

Trimester 2

Assessment Setting:

Eff1 assessment window

Use the default uniform prior for the time to efficacy 1

Prior efficacy 1 probabilities in the assessment period (sum to 1)

Trimester 1

Trimester 2

Eff2 assessment window

Use the default uniform prior for the time to efficacy 2

Prior efficacy 2 probabilities in the assessment period (sum to 1)

Trimester 1

Trimester 2

Assessment Setting:

Eff assessment window

Use the default uniform prior for the time to efficacy

Prior efficacy probabilities in the assessment period (sum to 1)

Trimester 1

Trimester 2

Tox assessment window

Use the default uniform prior for the time to toxicity

Prior toxicity probabilities in the assessment period (sum to 1)

Trimester 1

Trimester 2

Type I Error Rate:

Stopping Boundaries

Note: Calculate the stopping boundaries and run the simulation using the same endpoint before downloading the protocol template; otherwise, the download button is disabled.

Download protocol template

Response assessment window (days):

Prior for time to response:

Uniform Informative

Prior response probabilities in the assessment period (sum to 1)

Trimester 1

Trimester 2

Number of non-pending patients

Number of pending patients

Pending patient

Follow-up time (days)

ESS/WESS calculation result

Lin, R., Coleman, R. L., & Yuan, Y. (2019). TOP: Time-to-event Bayesian optimal phase II trial design for cancer immunotherapy. JNCI: Journal of the National Cancer Institute.

Zhou, H., Lee, J. J., & Yuan, Y. (2017). BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints. Statistics in Medicine, 36(21):3302-3314

Version: V1.0.4.0 ; Last Updated: 02/23/2022

TOP: Time-to-Event Bayesian Optimal Phase II Trial Design

PID: 960; Version: V1.0.4.0 ; Last Updated: 02/23/2022

Ruitao Lin and Ying Yuan

Department of Biostatistics,MD Anderson Cancer Center

Trial Setting

Simulation

Protocol

ESS Calculator

Reference

Endpoints:

Interims:

Sample sizes when interim analyses to be performed, seperated by space. The last number must be the total sample size.

Null Hypothesis:

Null Hypothesis:

Null Hypothesis:

Alternative Hypothesis:

Alternative Hypothesis:

Alternative Hypothesis:

Outcome Assessment:

Prior efficacy probabilities in the assessment period (sum to 1)

Assessment Setting:

Prior efficacy 1 probabilities in the assessment period (sum to 1)

Prior efficacy 2 probabilities in the assessment period (sum to 1)

Assessment Setting:

Prior efficacy probabilities in the assessment period (sum to 1)

Prior toxicity probabilities in the assessment period (sum to 1)

Type I Error Rate:

Stopping Boundaries

Example

Simulation Setup

Degree of late-onset

Simulation Scenarios:

Scenario 3

Scenario 4

Scenario 5

Scenario 6

Scenario 7

Scenario 8

Scenario 9

Scenario 10

The maximum number of scenarios you can enter is 10

Simulation Setup

Degree of late-onset

Degree of late-onset

Simulation scenarios:

Scenario 3

Scenario 4

Scenario 5

Scenario 6

Scenario 7

Scenario 8

Scenario 9

Scenario 10

The maximum number of scenarios you can enter is 10

Simulation Setup

Degree of late-onset

Degree of late-onset

Simulation scenarios:

Scenario 3

Scenario 4

Scenario 5

Scenario 6

Scenario 7

Scenario 8

Scenario 9

Scenario 10

The maximum number of scenarios you can enter is 10

Operating characteristics

Note: Calculate the stopping boundaries and run the simulation using the same endpoint before downloading the protocol template; otherwise, the download button is disabled.

Prior response probabilities in the assessment period (sum to 1)

Pending patient

Follow-up time (days)

ESS/WESS calculation result

Lin, R., Coleman, R. L., & Yuan, Y. (2019). TOP: Time-to-event Bayesian optimal phase II trial design for cancer immunotherapy. JNCI: Journal of the National Cancer Institute.

Zhou, H., Lee, J. J., & Yuan, Y. (2017). BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints. Statistics in Medicine, 36(21):3302-3314