Key Multiplicity Issues in Clinical Trials II


Dr. Alex Dmitrienko (Mediana Inc).

Full-day course

This Instant Short Course was released in November 2017.

Total duration: 7 hours 6 minutes.

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$1199.00 (U.S. dollars)
7-day access for up to 25 attendees

Related courses

See also Key Multiplicity Issues in Clinical Trials I.


The online training course provides a detailed survey of advanced multiplicity problems with two or more sources of multiplicity in clinical trials (traditional problems with a single source of multiplicity are presented in Part I). Examples of advanced multiplicity problems include problems related to complex clinical objectives such as the evaluation of multiple endpoints at several dose levels or in several patient populations. Multiple testing procedures, known as gatekeeping procedures, used in confirmatory trials with complex objectives are presented. The course introduces popular methods for defining gatekeeping procedures, including a novel method based on the mixture approach, and describes their applications using case studies based on Phase III trials in multiple therapeutic areas. The course also discusses methods for handling multiplicity in group-sequential and general adaptive trials with multiple endpoints. Key regulatory considerations arising in the analysis and interpretation of complex clinical objectives, e.g., evaluation of secondary endpoints, in Phase III trials are presented with numerous references to the FDA and EMA multiplicity guidance documents released in 2017. A thorough discussion of software implementation issues using SAS and R software is provided in the course.


Topics covered in this Instant Short Course:

  • Introduction. Duration: 15 minutes.
  • Module A. Clinical trial examples (Phase III trials with multiple sources of multiplicity). Duration: 22 minutes.
  • Module B. Introduction to gatekeeping strategies (General regulatory considerations,
    Classification of gatekeeping strategies, Analysis of secondary endpoints) sskip
    Secondary analyses in confirmatory trials). Duration: 1 hour 3 minutes.
  • Module C. Parallel gatekeeping strategies (Simple strategies based on nonparametric procedures, More powerful strategies based on semiparametric procedures in a parallel gatekeeping setting). Duration: 1 hour 27 minutes.
  • Module D. General gatekeeping strategies (gatekeeping strategies based on semiparametric procedures in multiplicity problems with general gatekeepers). Duration: 1 hour 15 minutes.
  • Module E. Group-sequential trials with multiple objectives (Introduction to group-sequential trials, Group-sequential trials with multiple endpoints). Duration: 1 hour 13 minutes.
  • Module F. General adaptive trials with multiple objectives (Decision rules in adaptive designs, Adaptive population selection trials). Duration: 59 minutes.
  • Module G. Power calculations in clinical trials with multiple objectives. Duration: 27 minutes.

Supplementary material

Download the handouts for this Instant Short Course (PDF document).

Download the list of references used in this Instant Short Course (PDF document).

Download the SAS and R code used in this Instant Short Course (ZIP archive).


Multiple Testing Problems in Pharmaceutical Statistics (Edited by Alex Dmitrienko, Ajit Tamhane and Frank Bretz). Chapman and Hall/CRC Press, 2009.

Analysis of Clinical Trials Using SAS (Second Edition) (Edited by Alex Dmitrienko and Gary Koch). SAS Press, 2017.

Live courses

This Instant Short Course is based on single-day or two-day live courses that have been offered at the following meetings:

  • U.S. Food and Drug Administration, Rockville, Maryland, 2008.
  • International Multiple Comparison conference, Tokyo, Japan, 2009.
  • Deming Conference, Atlantic City, NJ, 2010.
  • FDA/Industry Statistics Workshop, Washington, DC, 2011.
  • FDA/DIA Statistics Forum, Washington, DC, 2012.
  • ENAR Spring Meeting, Orlando, FL, 2013.
  • IBS German Region Meeting, Berlin, Germany, 2013.
  • U.S. Food and Drug Administration, Rockville, Maryland, 2014.

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