ADDPLAN Adaptive Designs - Plans and Analyses was first released in 2002. Since then, interest in performing clinical trials with flexible (adaptive) designs has been permanently growing. The availability of a reliable, comprehensive, user-friendly and professionally validated statistical planning and analysis software package has never been so important before. We developed ADDPLAN along these lines and the new Release 4 was considerably enhanced and improved. Many recent developments in statistical theory were considered in the development process. As before, ADDPLAN lays special emphasis on adaptive group sequential test designs but also offers a much broader range of applicability.

The planning of a controlled clinical trial requires the knowledge of some basic characteristics. For example, for comparing means in a two-group parallel design the knowledge of the effect size and its variability are required to calculate the sample size needed for achieving a specified power when using a test at a given significance level. Misspecification of the designing parameters yields an underpowered or an overpowered study.

ADDPLAN provides the comprehensive toolbox for the design, simulation, and analysis (including sample size reassessment) for group sequential studies. Specifically, designs and sample size planning facilities include the following designs:

• one-sided and two-sided testing of means (paired and unpaired samples)
• one-sided and two-sided testing of proportions (paired and unpaired samples)
• noninferiority and equivalence (TOST) testing of means (difference and ratio specified)
• noninferiority and equivalence (TOST) testing of proportions (difference or relative risk specified)
• survival analysis
• non-inferiority and equivalence (TOST) for survival analysis

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

• one-sided and two-sided testing of means (paired and unpaired samples)
• one-sided and two-sided testing of proportions (paired and unpaired samples)
• noninferiority and equivalence (TOST) testing of means (difference and ratio specified)
• noninferiority and equivalence (TOST) testing of proportions (difference or relative risk specified)

In addition to the planning and simulation features ADDPLAN allows for a convenient 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. The recalculation will follow various methods. ADDPLAN will output relevant summary data in the form of spreadsheets and graphs. The user will have the choice between various forms of interim analysis including:

• hypothesis testing
• sample size recalculation based on various reassessment methods
• computation of overall conditional and predictive power
• computation of maximum likelihood estimates and confidence intervals, or RCIs, respectively

The graphical user interface of ADDPLAN 5 MC was consistently developed according to modern Microsoft® Windows software. Some of the new features of ADDPLAN MC (which is fully integrated in the ADDPLAN package) are

• Specific options for performing multi-armed designs including treatment arm selection
  • Confirmatory analysis for multi-armed trial with selection of treatment arms
  • Closed testing procedure (CTP)
  • Powerful simulation engine for performing multiarmed designs
  • Assess the power and ASN of adaptive designs
  • Choice of intersection tests: Dunnett, Bonferroni, Sidák, Simes, hierarchical testing
  • Comparison of selection rules
  • Comparison of dose-response shapes, e.g., linear, logistic, Emax, sigmoid Emax, exponential,...