Welcome from the Dean (Schulich School of Medicine & Dentistry): 2-min video. 

• Summary: Dr. John Yoo (Schulich School of Medicine & Dentistry) welcomes learners to the program.

Welcome from a Senior Scientist & CEO (ICES): 1-min video.

• Summary: Dr. Michael Schull (ICES, HDRN Canada member organization) welcomes learners to the program.

KCE Belgian Health Care Knowledge Centre - How are pragmatic trials different from the usual kind of explanatory trial? (September 25, 2017): 5-minute webinar.

• Summary: Dr. Sandra Eldridge overviews differing objectives of explanatory (“traditional”) vs. pragmatic trials. Discusses a hypothetical example of an explanatory drug trial (with highly controlled trial implementation/management to maximize adherence to the treatment) vs. a pragmatic trial (allowing for deviations in how treatments would be used in the real-world). Emphasizes how pragmatic trials are often not drug trials (e.g., other interventions may include reorganization of health services, education for patients) and how there is often not a “placebo” comparator group. Highlights the potential of novel statistical analyses and ethical considerations in explanatory vs. pragmatic trials. 

HRB Trials Methodology Research Network (HRB-TMRN & UCC CRF-C Study Day) - Explanatory and pragmatic attitudes to trials (September 8, 2021): 14-min webinar.

• Summary: Dr. Merrick Zwarenstein discusses the importance of identifying the intention of the clinical trial (i.e., intended use of the findings) before designing the trial. Overviews randomization and internal validity. Contrasts external validity in the context of explanatory (“traditional”) trials with highly-selected patients, highly controlled care delivery, short-term (non-patient-centered) outcomes vs. external validity in the context of pragmatic trials that are embedded in routine care. Emphasizes that internal and external validity are independent (increasing or decreasing internal validity does not impact external validity, or vice versa). Introduces the seminal paper describing explanatory and pragmatic attitudes, or intentions, towards trials (Schwartz D, Lellouch J. Explanatory and pragmatic attitudes in therapeutical trials. J Chronic Dis. 1967 Aug;20(8):637-48.)

Zwarenstein M. 'Pragmatic' and 'explanatory' attitudes to randomised trials. J R Soc Med. 2017 May;110(5):208-218. (11-page paper)

• Summary: Historical overview of the conceptualization of two types of randomized trials (explanatory vs. pragmatic), implications of explanatory and pragmatic objectives for choice of controls, and discussion of the ideas introduced in the seminal Schwartz D, Lellouch J. (1967) paper (i.e., choices of controls, intention-to-treat analyses). Discusses explanatory vs. pragmatic attitudes to trial design (e.g., contrasting efficacy vs. effectiveness research questions, strictness of eligibility criteria, participant compliance with interventions, and follow-up intensity) and introduces the “pragmatic-explanatory” continuum and the PRECIS (Pragmatic Explanatory Continuum Indicator Summary) tool.

NIH Pragmatic Trials Collaboratory (Living Textbook): Section 3 - Differentiating between randomized clinical trials, pragmatic clinical trials, and quality improvement activities (Chapter: Design - What is a pragmatic clinical trial?): 1-page website.

• Summary: Summarizes differences between explanatory (“traditional”) trials, pragmatic trials, and quality improvement initiatives. Provides answers to the following for each study type: Who develops the study questions? What is the purpose? What type of question does it answer? What types of participants are enrolled? Who (predominantly) collects the data? What is compared? What is the randomization approach? What is the setting? How is adherence to the intervention monitored and/or enforced? How are outcomes selected? 

NIH Pragmatic Trials Collaboratory - Promoting Both Internal and External Validity: Designing the Trial to Match Its Intention (August 11, 2021): 4-page document.

• Summary: Discusses internal and external validity and the two distinct purposes that a randomized trial can serve: (1) explanatory: generalizations regarding the existence of a causal mechanism or (2) pragmatic: specific findings on effect size within a real-world context that, with caution, can be directly applied to a decision in another context. Summarizes key design choices associated with explanatory vs. pragmatic trials and emphasizes the need to focus on the trials intention as a first step to ensure the trial successfully answers its intended primary research question. 

Saloni Dattani (2022) - “Why randomized controlled trials matter and the procedures that strengthen them” Published online at OurWorldInData.org: 1-page website.

• Summary: For those who are unfamiliar with clinical trials in general, this page provides an overview of the “fundamental problem of causal inference” in the context of observational studies vs. studies that involve randomization. Discusses confounding bias and layers of protection against various biases, including but not limited to confounding, in trials (e.g., randomization, concealment, blinding, and pre-registration).