Module 2-1 – Design Foundations for Pragmatic Clinical Trials (17-min video)

• The module starts by emphasizing the importance of clearly defining the intent of a trial—whether the goal is to show one intervention is better (superiority), no worse (non-inferiority), or essentially the same (equivalence) compared to current standards. This intent directly shapes every aspect of trial design, from randomization and structure to analysis methods. Learners will also explore various trial designs, including parallel, factorial, crossover, stratified, and cluster trial designs. We walk through each design’s applications, strengths, and limitations.

** The content, slides, and narrator's voice were generated with the assistance of artificial intelligence, with human guidance and oversight throughout the process.

Selecting the Right Trial Design - Superiority, Non-Inferiority, and Equivalence (PDF)

• Key differences between superiority, non-inferiority, and equivalence trial designs.

Common Design Structures (PDF)

• Overview of parallel, factorial, crossover, stratified, cluster randomized, and stepped‑wedge CRT—summarizing when each is most appropriate, its impact on sample size, and key implementation and analysis considerations.

Estimand Frameworks and Analysis Units in Cluster Randomized Trials (PDF)

• The first table provides a comparison of marginal versus conditional treatment‐effect estimands in cluster randomized trials, detailing the modelling approach (population‐average vs cluster‐specific), common analytical methods, interpretation of the effect, and implications for answering questions about the overall population versus individual clusters.

• The second table provides a comparison of individual‑level versus cluster‑level units of analysis in cluster randomized trials, summarizing how outcomes are handled, the interpretation of the treatment effect (on individuals vs on clusters), and the resulting trade‑offs in precision and variability. 

Key considerations for designing, conducting and analysing a cluster randomized trial (PDF) 

• Pragmatic clinical trials rely heavily on engaging the right partners (e.g., patients, caregivers, healthcare professionals, system leaders, insurers, regulators, funders, researchers, and manufacturers). These partners can help develop the research question, trial design, overcome challenges, and ensure the findings matter to those who will use or be impacted by the trial. Through inclusive collaboration, pragmatic trials produce valuable evidence that benefits patients and healthcare providers, making research more relevant and effective in real-world settings.