Key Multiplicity Issues in Clinical Trials (Part II)

An 8-part online training course on advanced multiplicity problems in clinical trials:

  • Introduction.
  • Module A. Clinical trial examples (Phase III trials with multiple sources of multiplicity).
  • Module B. Introduction to gatekeeping strategies (General regulatory considerations, Classification of gatekeeping strategies, Analysis of secondary endpoints).
  • Module C. Parallel gatekeeping strategies (Simple strategies based on nonparametric procedures, More powerful strategies based on semiparametric procedures in a parallel gatekeeping setting).
  • Module D. General gatekeeping strategies (Gatekeeping strategies based on semiparametric procedures in multiplicity problems with general gatekeepers).
  • Module E. Group-sequential trials with multiple objectives (Introduction to group-sequential trials, Group-sequential trials with multiple endpoints).
  • Module F. General adaptive trials with multiple objectives (Decision rules in adaptive designs, Adaptive population selection trials).
  • Module G. Power calculations in clinical trials with multiple objectives.

Clinical trial simulation software

The R package (Mediana) is used in this training course to implement the multiple testing procedures and perform power calculations for Phase II and Phase III trials. For more information on this package, see the online manual. The latest stable version of this package can be downloaded from CRAN.

The R and SAS code used in the training course can be downloaded from GitHub.

References

Key papers and books used in the training course:

  • Alosh, M., Bretz, F., Huque, M. (2014). Advanced multiplicity adjustment methods in clinical trials. Statistics in Medicine. 33, 693-713.
  • Dmitrienko, A., Tamhane, A.C., Bretz, F. (editors) (2009). Multiple Testing Problems in Pharmaceutical Statistics. Chapman and Hall/CRC Press, New York.
  • Dmitrienko, A., D’Agostino, R.B., Huque, M.F. (2013). Key multiplicity issues in clinical drug development. Statistics in Medicine. 32, 1079-1111.
  • Dmitrienko, A., D’Agostino, R.B. (2013). Tutorial in Biostatistics: Traditional multiplicity adjustment methods in clinical trials. Statistics in Medicine. 32, 5172-5218.
  • Huque, M.F., Dmitrienko, A., D’Agostino, R.B. (2013). Multiplicity issues in clinical trials with multiple objectives. Statistics in Biopharmaceutical Research. 5, 321-337.