A trial design should not be implemented before being evaluated through simulation. Tessella and Berry Consultants have formed a strategic alliance to produce a powerful tool to help Biostatisticians to rapidly design, compare and simulate both fixed and adaptive trial designs.
This trial design software is called FACTSTM V2 and provides Biostatisticians the following capabilities.
Supports clinical trial design process
- Enables swift high level decisions on the trial design through being able to swiftly specify designs (no programming) and run simulations (the simulations run very quickly)
- Makes successive refinement of the trial design easy, allowing the design to be optimized in terms of its key operating characteristics
- Provides data for inclusion in a Simulation Report
Provides the following trial designs
- Dose Escalation Designs: Phase 1/2a trials that are based on the CRM (Continuous Reassessment Method) and extensions:
- The use of CRM designs with an efficacy endpoint, and designs with both an efficacy and toxicity endpoint
- Allows a dichotomous co-variate (splitting the population into to populations or “samples”) to be included in the model
- The use of an ordinal endpoint, 3 or 4 levels of toxicity.
- An options for a ‘single-patient run-in’ then applying the standard CRM after the first toxicity
- Bayesian Dose Finding Designs: Phase 2a/b trials where the endpoint is continuous, dichotomous or time-to-event. For each endpoint the following features are available
- Fixed or adaptive designs
- Both Bayesian and Frequentist final analysis
- Options to include dose response modeling and longitudinal modeling
- Data can be simulated within the tool, or generated externally and supplied as a datafile of patient responses (e.g. from a PK-PD model)
- Timing of interims (if any)
- Time to endpoint and intermediate visits
- If adaptive a range of adaptive strategies – early stopping, arm dropping, adaptive randomization
- Bayesian Dose Finding Designs: Phase 2a/b trials with two endpoints either continuous or dichotomous. This has all the features of the single endpoint designs but allows the trial decisions to be driven by a utility function that can be defined to combine the two endpoints. Allowing trials combining two efficacy endpoints or an efficacy and safety endpoint to be designed.
Prototypes for Future Designs
The following design is available as prototype for potential completion.
- Combination designs: Phase 1 trials which vary the dose of two drugs given in combination.
- can be used on with NMEs or existing treatments
- can include ‘prior’ data
- can exclude specific combinations and ensure higher combinations are only ‘opened up’ when sufficient data has been collected on lower combinations
- supports a variety of strategies for the ‘initial run-in’ and subsequent MTD combination finding stage