ADDPLAN 6 BASE is the comprehensive toolbox for the design, simulation, and analysis for one or two sample clinical trials.
ADDPLAN allows to select between commonly used group sequential designs including the designs proposed by O’Brien and Fleming (1979), Pocock (1977), Wang and Tsiatis (1987), Pampallona and Tsiatis (1994), and alpha and beta spending function designs. Binding and non-binding stopping for futility bounds are defined either by design, or can be directly entered by the user.
Power calculation and sample size planning facilities are included for the following designs:
- one-sided and two-sided testing of means (paired or unpaired samples)
- one-sided and two-sided testing of proportions (paired or unpaired samples)
- survival analysis
- non-inferiority and equivalence (TOST) testing of means (difference or ratio specified)
- non-inferiority and equivalence (TOST) testing of proportions (difference or relative risk specified)
- non-inferiority and equivalence (TOST) for survival analysis
- general design, which is used as a synonym for a (group sequential) test situation which is not covered by the above designs and sample size calculation for the group sequential test is calculated based on the design specifications and a fixed sample size design only
Output in the planning phase is comprised of the total sample size in a comparable fixed sample design, total maximum sample size according to the group sequential plan, average sample size (ASN), as well as power achieved, alpha spent, and beta spent if early rejection of the alternative is possible.
Graphical output comprised of plots of stopping boundaries, power, ASN and maximum sample size.
Adaptive designs allow the use of data from an interim analysis to recalculate the sample size for the ongoing trial. The recalculation can follow various methods that differ in the conditional power arguments on which they are based. The simulation module in ADDPLAN includes the assessment of different sample size recalculation methods.
Simulations are available for all designs (with the exception of the general design) that are available in the planning phase.
Once a design is specified, the user can study the impact of
- the conditional power
- the bounds for the minimum and maximum sample size per stage
- the stopping for futility bound, overall or by stage, binding or non-binding, as required
- the choice of boundaries and planned information rates
- the sample size allocation ratio
- the survival time distribution
- the accrual and drop-out pattern in survival designs
on the performance of the trial in terms of power and ASN in case of testing of means, rates, or expected number of events/expected duration in case of survival designs.
ADDPLAN allows for the convenient interactive analysis of user supplied data within an adaptive design. ADDPLAN enables the user to utilize data from an interim analysis to recalculate the sample size of an ongoing trial.
In the analysis phase, the user specifies which design will be used for data analysis and sample size recalculation/adaptive redesign. All designs that were available in the planning phase are also available for analysis.
Upon choosing a design, the user has the choice between various forms of interim analysis including:
- hypothesis testing
- sample size recalculation based on various reassessment methods (precision of repeated confidence interval (RCI), conditional power for next stage, overall conditional power)
- computation of overall conditional and predictive power
- computation of maximum likelihood estimates, confidence intervals, and/or RCIs
- computation of overall p-values and final analysis adjusted p-values
- recursive combination test designs.
Graphical output comprises plots of stopping boundaries along with test statistics, and plots of the conditional power and likelihood vs effect.