Table 5.

Recommendations to facilitate conduct of pragmatic trials in acute care

	Rationale
Assess the risk of research relative to the risk of routine clinical care	Critically ill patients are at risk of serious outcomes, including death, as a consequence of their acute illness and comorbidities; human research protections should focus on additional risk created by study interventions or other study procedures; inappropriately attributing risks arising from a patient's acute clinical scenario to interventions provided in research studies prevents potentially beneficial research and could harm patients
Allow alteration or waiver of consent for trials comparing therapies that patients would receive as part of routine clinical care	If all trial interventions are commonly used in usual care and patients are likely to be exposed to a therapy regardless of trial participation, randomisation represents a minimal incremental risk to participants
Define usual care on the basis of provider practice for similar patients or settings at a population level	If there is no evidence of superiority between two given interventions and there is provider practice variability at the population level for similar patients in similar settings, this would represent sufficient equipoise to allow enrolment at any site, not just those already using a mix of the studied therapies
Develop new methods of demonstrating respect for patients and families in pragmatic trials with greater than minimal risk where consent is impractical	Protecting patients might require novel methods to show respect for people when consent cannot be obtained without impeding potentially beneficial research; these methods could include community consultation, public disclosure, and patient or family notification58
Invest in bioinformatics tools for electronic health system interoperability and automated information technology tools within electronic health records to facilitate screening, enrolment, and data abstraction	Improving the efficiency of pragmatic trials will facilitate the generation of evidence to improve the care of future patients
Create incentives for health systems and researchers to improve patient outcomes through the conduct of embedded pragmatic trials evaluating interventions commonly used in clinical care	Investments will be needed to engage all stakeholders to show that arbitrary variation in the absence of evidence hurts patients, whereas structured variation through pragmatic trials holds the potential to help patients