Partner Introduction (CHEER): 2-min video. 

• Summary: Miranda Miller (Project Manager) introduces the Canadian Collaboration for Child Health: Efficiency and Excellence in the Ethics Review of Research (CHEER), a Canada-wide initiative on a mission to improve child health by streamlining research ethics review for child health research. CHEER is led by Clinical Trials Ontario and the Maternal Infant Youth Research Network, in partnership with the Queen’s University Faculty of Health Sciences, Office for Professional Development and Educational Scholarship, and investigators and collaborators across the country.

NIH Pragmatic Trials Collaboratory - Living Textbook Grand Rounds Series: Choosing What to Measure and Making it Happen: Your Keys to Pragmatic Trial Success (July 17, 2020): 26-min presentation & 31-min Q&A (53-slide presentation)

• Summary: Drs. Devon Check and Rachel Richesson define endpoints and outcomes and contrast the types of outcomes that are typically analyzed in explanatory trials (i.e., short-term surrogates from data collected outside of routine care) vs. pragmatic trials (i.e., outcomes that are more meaningful to clinicians and patients, and measures that can be readily derived from routinely collected data). When considering whether the outcome measure(s) can be derived from routinely collected data sources, it is emphasized that such data (e.g., data from an electronic health record, administrative health data/claims data, disease registries) are not collected for research. e.g., If a researcher wants to derive an outcome from hospitalizations data, one must consider whether a given outcome would in fact be captured in such data. The complexities of linking together routinely collected longitudinal data sources, the need for data quality assessment, and the fact that some outcomes will never rarely be available through existing data sources (hence the need for the collection of patient-reported outcomes in the trial) are also discussed. * Note: Patient-reported outcomes will be discussed in greater detail in a future module.

Welsing PM, et al. Series: Pragmatic trials and real world evidence: Paper 6. Outcome measures in the real world. J Clin Epidemiol. 2017 Oct;90:99-107. (9-page paper)

• Summary: This article provides guidance for selecting the most appropriate outcomes in pragmatic trials and provides guidance on measuring them with minimal impact on routine clinical care. Key takeaways are: 1. Outcomes should be relevant for patients and clinicians, and they should inform clinical decision making; surrogate endpoints should generally be avoided. 2. Common outcomes in pragmatic trials include mortality, morbidity, functional status, wellbeing, and resource use (measured over a relevant time horizon irrespective of whether the treatment protocol is followed). 3. As pragmatic trials are often open label, the inclusion of objective outcome measures can reduce the risk of bias; routinely collected outcomes should be prioritized.

NIH Pragmatic Trials Collaboratory (Living Textbook): Section 2 - Meaningful Endpoints (Chapter: Design - Choosing and Specifying Endpoints and Outcomes): 1-page website.

• Summary: A notable feature of pragmatic trials is a focus on outcomes that are directly relevant to patients, funders, communities, and clinicians. According to the PRECIS-2 criteria, “as the primary outcome becomes less recognizably important to patients, or is assessed on criteria seldom used in usual care, the trial becomes more explanatory [and less pragmatic].” It is emphasized that determining what is important to patients, funders, clinicians, and community members should be done through collaborations and partnerships.

Sundbøll J, Adelborg K. Pragmatic Trial End Point Capture: Making Sure Makes the Difference. Circ Cardiovasc Qual Outcomes. 2021 Dec;14(12):e008615. (2-page paper)

• Summary: This brief editorial introduces the importance of validity (and the consequences of misclassification) in the context of defining outcomes using routinely collected data. It is argued that with the ever-increasing generation of routinely collected health data (e.g., electronic health records, administrative health data), and concordant use of such data in pragmatic trials, validation studies have never been more important. * Note: Future modules will further discuss the use of routinely collected data in trials, and unpack validity metrics (e.g., sensitivity, specificity, positive and negative predictive values) in the context of algorithms used to define study variables, including outcomes.

NIH Pragmatic Trials Collaboratory - What Do Endpoints and Outcomes Look Like in Pragmatic Trials? (October 16, 2023): 2-min video (1-page transcript)

• Summary: Dr. Devon Check briefly contrasts endpoints and outcomes commonly examined in explanatory trials (i.e., short-term surrogates from data collected outside of routine care) vs. trials that are more pragmatic in nature (i.e., outcomes that are more meaningful to clinicians and patients, and measures that can be readily derived from routinely collected data).

Nevins P, et al. Review of pragmatic trials found that multiple primary outcomes are common but so too are discrepancies between protocols and final reports. J Clin Epidemiol. 2022 Mar;143:149-158. (10-page paper)

• Summary: Given that a single primary outcome may not always be adequate to capture all the important aspects of an intervention’s effect, examining multiple primary outcomes may be advisable in pragmatic trials. However, if co-primary outcomes are deemed necessary, failure to be explicit about whether a trial has a single or multiple primary outcomes in the protocol increases concerns about preferential outcome selection in the final paper. This review concludes that one in five pragmatic trials lacks clarity in the primary outcome definition and that use of co-primary outcomes may increase the risk of outcome selection/deviations from the protocol. It is recommended that researchers register their trials and make their trial protocols available.