Phase II/III Clinical Trials

Clinical trials are conducted to demonstrate the efficacy and safety of new interventions (e.g. drugs, medical devices, surgical procedures, or public health changes) in a predefined target population. The efficacy is the therapeutic effect measured by a relevant clinical outcome (e.g. improve life expectancy, cure the disease, increase quality of life) and safety is possibly measured by side effects and evaluated in relation to the therapeutic effect. Introducing new interventions requires in principle three phases of clinical trials before it can be approved by the appropriate authorities. This course focuses mainly on the methodology for the second and third phase of clinical trials.

Learning objectives

• At the end of the course, participants can:
• Describe the different phases in clinical drug development (day 1)
• Explain the difference between uncontrolled, externally controlled, and randomized controlled clinical trials (day 1)
• Explain the difference between superiority and non-inferiority testing (day 1)
• Explain the difference between fixed-sample and group-sequential designs (day 2)
• Perform sample size calculations for one-stage uncontrolled trials with a binary outcome variable (day 2)
• Interpret sample size calculations for Simon’s optimal and minimax designs for two-stage uncontrolled clinical trials with a binary outcome variable (day 2)
• Explain how randomization and blinding can help prevent selection bias, performance bias, and detection bias in parallel-group designs (day 3)
• Describe different allocation strategies for randomized controlled trials, including complete randomization, random allocation rule, permuted-block randomization, and stratified randomization (day 3)
• Explain the role of primary, secondary, and exploratory endpoints in confirmatory phase III trials (day 3)
• Set-up basic Bonferroni-based chain procedures to adjust for multiplicity in confirmatory phase III trials with at-least-one win criteria (day 3)
• Perform basic sample-size calculations for parallel group designs (day 4)
• Interpret sample size calculations for group sequential designs with a Pocock or O’Brien-Fleming alpha spending function (day 4)

Literature
The course literature consists of a series of articles. Links to these articles are made available via Brightspace.

Software
During the course, we will make use of G*Power to perform sample size calculations for various clinical trial designs (both controlled and uncontrolled). This tool can freely be downloaded from: https://www.psychologie.hhu.de/arbeitsgruppen/allgemeine-psychologie-und-arbeitspsychologie/gpower

Elective exam (for students who require a grade) / Attendance
Research protocol (excerpt) for a controlled clinical trial to assess the efficacy of a (hypothetical) new treatment. More information about this assignment is available on Brightspace.

The number of ECTS for this course will be 1 ECTS for those who take the course and attend at least 80% of the lectures. Only those who deliver an individual research protocol at the end of the course can receive 1.5 ECTS.