Randomized Clinical Trials: General Concepts and Statistical Aspects

Prerequisites (knowledge of topic)
This course gives an introduction to randomized clinical trials including basic concepts and more advanced statistical considerations. It provides guidance on how to design, conduct, analyze and interpret randomized clinical trials.
- Students should have some experience in the health sector
- Basic knowledge on clinical trials (such as guidelines for good clinical practice / principles for medical research) is recommended.
- Basic knowledge on statistics/biostatistics, data analysis and/or epidemiology is a plus
- Knowledge about the R statistical software would be an asset

Hardware
- Laptop (Linux / macOS / Windows)

Software
- R-statistical software, R-studio, with the possibility to install additional extension packages

Course content
This course gives an introduction to randomized clinical trials, and various related concepts including designs of experiment, conduct, implementation and analysis of trials. The statistical aspects will be emphasized.

Students following the course should be able to critically assess the design of a clinical trial, decide of the choice of the population. He or she will be able to define the appropriate intervention, determine a sample size, identify and correct bias, confounding factors. The role played by randomization and blinding will be detailed. Randomization strategies will be discussed and students will be able to appraise critically published clinical trials.

Structure
Day 1
- General considerations about clinical trials
- Statistics in good clinical practice
- Ethics and statistics
- Introduction to R / R-studio
- Practical R-sessions (afternoon)

Day 2
- Randomization
- Statistical hypothesis testing
- Study designs
- Nature of endpoints and associated statistical methodology
- Bias and confounding factors
- Power analysis, sample size calculation, effect size, simulations
- Interim analysis, missing values
- Practical R-sessions (afternoon)

Day 3
- Case study
- Practical R-sessions (afternoon)

Day 4
- Advanced study designs
- Meta-analyses
- Practical R-sessions (afternoon)

Day 5
- Working with their own data
- Practical R-sessions (afternoon)

Literature
Randomized Controlled Trials: Questions, Answers and Musings
Mandatory
by A.R. Jadad and M.W. Enkin
https://www.wiley.com/en-us/Randomized+Controlled+Trials%3A+Questions%2C+Answers+and+Musings%2C+2nd+Edition-p-9780470766163

CRAN Task View: Clinical Trial Design, Monitoring, and Analysis
https://cran.r-project.org/web/views/ClinicalTrials.html

CRAN Task View: Design of Experiments (DoE) & Analysis of Experimental Data
Supplementary / voluntary

https://cran.r-project.org/web/views/ExperimentalDesign.html

Ethical Guidelines for Statistical Practice
https://www.amstat.org/asa/files/pdfs/EthicalGuidelines.pdf

Examination part

Students will be required to submit a written assignment within 3 weeks. Performance of the participant’s assignment at the final exam (100%).

Examination content
What the student should know?
The student should understand the principles of randomized clinical trials.

The student should be able to critically evaluate existing clinical trials (e.g. published trial or ethical application) and develop their own research proposal.

The students should be able to choose the most appropriate study design that will successfully answer a research question.

The students will better understand the concepts associated with:
- Study designs, study phases
- Inclusion/exclusion criteria
- Study objectives
- Appropriate endpoints, and associated statistical methodology
- Appropriate sample size, power analysis
- Method dealing with missing values (incl. Imputations)
- Interim analyses
- Ethical aspects, incl. the preparation of an ethical proposal
- Statistical analysis plans
- Reporting of findings from randomized trials

The student should be able to use the R statistical software as a helping tool to evaluate existing clinical trials or design new clinical trials.

Literature
None.