Web Application for simulating operating characteristics of the Phase I/II method of Wages and Tait (2015)

Division of Translational Research & Applied Statistics, University of Virginia; nwages@virginia.edu


1. Enter an assumed set of true DLT probabilities, separated by commas. Note: The length of this set should be equal to the number of possible study dose levels.

2. Enter an assumed set of true activity probabilities, separated by commas. Note: The length of this set should be equal to the number of possible study dose levels.

3. Enter the target DLT probability that defines the MTD for the study.

4. Enter the lower limit for the probability of activity that defines the threshold for futility

5. Enter the cohort size required before the next model-based update. Cohort size may be 1, 2, or 3 patients.

4. Enter the maximum sample size for the study. This number should be a multiple of the cohort size entered above.

7. Enter the number of simulations. A minimum of 1000 is recommended.

8. Enter the index of the starting dose level. Note: Index of lowest dose level is always 1. If the design allows for 'minus' dose levels (i.e. -2, -1, etc.), then the index of the starting dose should account for these lower levels (i.e. if -1 dose level allowed, index of starting dose is 2.)


9. Enter the total number of patients treated on any dose required to stop the trial. At any point in the trial, if the recommendation is to assign the next cohort to a dose that already has the entered number of patients treated on the dose, the study is stopped and the recommended dose is declared the optimal dose. If the entered number is larger than the maximum sample size, each trial will accrue to the maximum sample size.

10. Set the seed of the random number generator.

        

          

            This application simulates operating characteristics for the early-phase method of Wages and Tait [1] with the following practical modifications.
          

          

            1.
            Dose-finding algorithm:
            The trial does not skip over an untried dose level.
          

          

            2.
            Safety Stopping Rule:
            Stop the trial for safety if the lower limit of a 90% probability interval exceeds the target DLT rate.
          

          

            3.
            Futility Stopping Rule:
            Stop the trial for futility if the upper limit of a 90% probability interval is lower than the minimum acceptable efficacy rate.
          

          References:
          

            [1] Wages NA, Tait C (2015). Seamless phase I/II adaptive design for oncology trials of molecularly targeted agents, 
            Journal of Biopharmaceutical Statistics;
            25:
            903-920.
          

        

        
      

      

        
Web Application for implementation of the Phase I/II method of Wages and Tait (2015)

        

          Division of Translational Research & Applied Statistics, University of Virginia;
          nwages@virginia.edu
        

        

        

          Design / Protocol Information
        

        
1. Enter the target DLT rate probability that defines the MTD for the study.

        

          
          
        

        

        
2. Enter the lower limit for the probability of activity that defines the threshold for futility

        

          
          
        

        

        

          Observed Trial Data (do not count 'replaced' patients)
        

        

          1. Enter number of observed DLTs at each dose level. If none have been observed or a dose level has not yet been tried, enter '0'.
          Note:
          The length of this set should be equal to the number of possible study dose levels.
        

        

          
          
        

        

        

          2. Enter the number of patients evaluated for DLT at each dose level. If a dose level has not yet been tried, enter '0'.
          Note:
          The length of this set should be equal to the number of possible study dose levels.
        

        

          
          
        

        

        

          3. Enter number of observed activity responses at each dose level. If none have been observed or a dose level has not yet been tried, enter '0'.
          Note:
          The length of this set should be equal to the number of possible study dose levels.
        

        

          
          
        

        

        

          4. Enter the number of patients evaluated for response at each dose level. If a dose level has not yet been tried, enter '0'.
          Note:
          The length of this set should be equal to the number of possible study dose levels.
        

        

          
          
        

        

        
5. Enter the most recent dose level administered in the study.

        

          
          
        

        

          
        

        

        

          

            This application computes a recommended dose level for the next patient in an early-phase trial according to the method of Wages and Tait [1] with the following practical modifications.
          

          

            1.
            Dose-finding algorithm:
            The trial does not skip over an untried dose level.
          

          

            2.
            Safety Stopping Rule:
            Stop the trial for safety if the lower limit of a 90% probability interval exceeds the target DLT rate.
          

          

            3.
            Futility Stopping Rule:
            Stop the trial for futility if the upper limit of a 90% probability interval is lower than the minimum acceptable efficacy rate.
          

          References:
          

            [1] Wages NA, Tait C (2015). Seamless phase I/II adaptive design for oncology trials of molecularly targeted agents, 
            Journal of Biopharmaceutical Statistics;
            25:
            903-920.