Clinical Trials Methodology

Fundamentals in Clinical Trials, EJP RD partners and collaborators (ECRIN, UKA and APHP) recommend the following three freely accessible online courses:

EURORDIS Medical research and development (Very Beginner level)

1. 1. 1. Short description: Many aspects of medical research concern problem solving and asking the right questions. In this course, you will be able to learn more about the process of medicine discovery, such as pre-clinical testing, clinical trials and the methodology and statistics used in medicine development, including evidence-based medicine, blinding and study protocol. This course also includes training on the development of medicines for small populations.
      2. Topics covered: Study design, controlled trial, randomisation, endpoints, criteria of inclusion, analysis of results
      3. Provider: EURORDIS
      4. Level: Very beginner
      5. Language: English
      6. Cost: Free
      7. Venue: Online
      8. Duration: 1-2 days
      9. Certificate of completion: Available/ Free

Design and Interpretation of Clinical Trials (Basic level)

1. 1. Short Description: The course will explain the basic principles for the design of randomized clinical trials and how they should be reported. In the first part of the course, students will be introduced to terminology used in clinical trials and the several common designs used for clinical trials, such as parallel and cross-over designs. The course will also explain some of the mechanics of clinical trials, like randomization and blinding of treatment. In the second half of the course, clinical trials analysis and interpretation will be explained. Finally, the course will provide a review the essential ethical consideration involved in conducting experiments on people.
   2. Topics covered: Types of Trial Designs: parallel, crossover, group allocation, factorial, large simple, equivalency, non-inferiority, and adaptive designs.
   3. Provider: Johns Hopkins University via Coursera
   4. Level: Basic
   5. Language: English
   6. Cost: Free
   7. Venue: Online
   8. Duration: 6 weeks; 2-3 h per week
   9. Certificate of Completion: Available/ Paid

Study Designs in Epidemiology (advanced level)

1. 1. Short Description: the course is an Introduction to Study Designs: Ecological and Cross-Sectional Studies
   2. Topics covered: The main epidemiological study designs, including cross-sectional and ecological studies, case-control and cohort studies, as well as the more complex nested case-control and case-cohort designs. The final module is dedicated to randomised controlled trials, which is often considered the optimal study design, especially in clinical research. You will also develop the skills to identify strengths and limitations of the various study designs. By the end of this course, you will be able to choose the most suitable study design considering the research question, the available time, and resources.
   3. Provider: Imperial College London via Coursera
   4. Level: Advanced
   5. Language: English
   6. Cost: Free
   7. Venue: Online
   8. Duration: 4 weeks; 2-4 h per week
   9. Certificate of Completion: Available/ Paid

An intermediate Course is currently under preparation to address Clinical Trials Methodologies in Rare Diseases. Stay Tuned.

In partnership with IOR (ERN-BOND), APHP (Necker) and UKA, EJP RD delivered and will continue to deliver advanced webinars addressed to people willing to conduct clinical research in rare diseases with the objective to train them in terminology, communication and understanding of RD clinical trial methodology. The webinars are organized as a series of lectures presented by experts in the specific topics.
The webinars listed below have taken place so far, covering the following topics:

Does randomization matter in Clinical Trials? (VIDEO)
Speaker’s Presentation (PDF)
Lecturer: Prof. Ralf-Dieter Hilgers- RWTH Aachen University, Germany
The objectives of the webinar are:

1. To learn about other randomization procedures beyond the most frequently applied permuted bock randomization in a fixed sample scenario,
2. To understand properties of different randomization procedures beyond balancing sample sizes,
3. To argue, which randomization procedure fits best in a particular trial setting,
4. To know about the potential advantages of randomization from design to analysis of clinical trials in RD.

Composite endpoints including patient relevant endpoints Quality of Life (VIDEO)
Speaker’s Presentation (PDF)
Lecturer: Dr. Johan Verbeeck- Hasselt University, Belgium.
The objectives of the webinar are:

1. To learn about procedures to combine multiple endpoints and its limitations,
2. To argue that generalized pairwise comparison is a suitable method to combine any number and type of endpoints (including QoL) in small samples,
3. To understand the properties and the flexibility of the class of generalized pairwise comparison tests,
4. To know the potential advantages and disadvantages of designing a clinical trial in rare disease with generalized pairwise comparisons primary analysis.

The Statistical Evaluation of Surrogate Endpoints in Clinical Trials (VIDEO)
Speaker’s Presentation (PDF)
Lecturer: Prof. Geert Molenberghs- Hasselt University and KU Leuven, Belgium
The objectives of the webinar are:

1. To get an overview of the methodological developments in surrogate endpoint evaluation over the last 30 years,
2. To understand practical use,
3. To understand promise and limitations,
4. To understand how they can be useful in the context of rare diseases

Statistical and Operational Challenges with Master Protocols (VIDEO)
Speaker’s Presentation (PDF)
Lecturer: Prof. Franz König – Medical University of Vienna.
The objectives of the webinar are:

1. To learn about master protocols and the differences between basket, umbrella and platform trials
   
2. To understand the difference between traditional drug development programs and more complex designs like platform trials using a master protocol
   
3. To understand the key statistical challenges with respect to multiplicity and sharing control data across the platform trial
   
4. To know the potential advantages and disadvantages of designing and running platform trials in rare disease
   

• The Statistical Evaluation of Surrogate Endpoints in Clinical Trials
• Composite endpoints including patient relevant endpoints Quality of Life
• Does randomization matter in Clinical Trials?
• Statistical and Operational Challenges with Master Protocols
• Replicated N of 1 Randomized Controlled Trials for Rare Diseases