Web Application for simulating operating characteristics of the Wages and Fadul (2019) design

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 feasibility 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 minimum acceptable probability of feasibility that defines the threshold for desireable feasibility

5. Specify the probability cutoff for defining the set of feasible dose levels.

6. Specify the probability cutoff for defining the safety stopping rule based on an unacceptable high DLT rate.

7. Enter the maximum number of participants who will be infused at some dose level and evaluated for toxicity.

8. Enter the maximum target accrual for the study. This is the number of participants who will have cells extracted.

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

10. 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.)


11. Set the seed of the random number generator.

        

          

            This application simulates operating characteristics for the early-phase method of Wages and Fadul [1].
          

          References:
          

            [1] Wages NA, Fadul CE (2019). Adaptive dose finding based on safety and feasibility in early-phase clinical trials of adoptive cell immunotherapy.
            Clin Trials;
            [epub ahead of print] Dec 20.
          

        

        
      

      

        
Web Application for implementation of the Wages and Fadul (2019) method

        

          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 minimum acceptable probability of feasibility that defines the threshold for desireable feasibility

        

          
          
        

        

        

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

        

          3. 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.
        

        

          
          
        

        

        

          4. 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.
        

        

          
          
        

        

        

          5. Enter number of patients feasible to receive each dose level. If none have been observed, enter '0'.
          Note:
          The length of this set should be equal to the number of possible study dose levels.
        

        

          
          
        

        

        

          6. Enter the number of patients accrued to the study that have had cells obtained.
          Note:
          The length of this set should be equal to the number of possible study dose levels.
        

        

          
          
        

        

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

        

          
          
        

        

        
8. Specify the threshold for defining the safety stopping rule based on an unacceptable high DLT rate at the lowest study dose level.

        

          
          
        

        

        
9. Specify the threshold for defining the feasbility stopping rule based on an unacceptable low feasibility rate at the lowest study dose level.

        

          
          
        

        

          
        

        

        

          

            This application computes an updated planned dose level for the next patient in a phase I trial according to the Wages and Fadul method [1].
          

          References:
          

            [1] Wages NA, Fadul CE (2019). Adaptive dose finding based on safety and feasibility in early-phase clinical trials of adoptive cell immunotherapy.
            Clin Trials;
            [epub ahead of print] Dec 20.
          

        

        
      

      

        
Web Application for generating safety stopping bounds at the lowest study dose level computed from the posterior distribution of the DLT rate at the lowest dose level based on a beta prior distribution.

        

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

        

        
1. Specify the threshold for defining the safety stopping rule based on an unacceptable high DLT rate at the lowest study dose level.

        

          
          
        

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

        

          
          
        

        
3. Enter the maximum sample size for the study.

        

          
          
        

        

          
        

        

        

          

            This application computes the safety stopping bounds for the lowest study dose level computed from the posterior distribution of the DLT rate at the lowest dose level based on a beta prior distribution.
          

        

        
      

      

        
Web Application for generating feasibility stopping bounds at the lowest study dose level computed from the posterior distribution of the feasibility rate at the lowest dose level based on a beta prior distribution.

        

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

        

        

        
1. Specify the probability cutoff for defining the set of feasible dose levels.

        

          
          
        

        
2. Enter the minimum acceptable probability of feasibility that defines the threshold for desireable feasibility

        

          
          
        

        
3. Enter the maximum target sample size for the study.

        

          
          
        

        

          
        

        

        

          

            This application computes the feasibility stopping bounds computed from the posterior distribution of the feasbility rate at the lowest dose level based on a beta prior distribution.