Navigating the consent river: questions to consider before waiving consent requirements in pragmatic cluster randomised trials.

The robust design and conduct of pragmatic cluster randomised trials may be in tension with the ethical requirement to obtain written informed consent from prospective research participants. In our experience, researchers tend to focus on whether a waiver of consent is appropriate for their studies. However, pragmatic cluster randomised trials raise other important questions that have direct implications for determining when an alteration or waiver of consent is permissible.

Are pragmatism and ethical protections in clinical trials a zero-sum game?

Background: Randomized controlled trials with pragmatic intent aim to generate evidence that directly informs clinical decisions. Some have argued that the ethical protection of informed consent can be in tension with the goals of pragmatism. But the impact of other ethical protections on trial pragmatism has yet to be explored.

Systematic scoping review of cluster randomised trials conducted exclusively in low-income and middle-income countries between 2017 and 2022.

Objective: Cluster randomised trials (CRTs) are used for evaluating health-related interventions in low-income and middle-income countries (LMICs) but raise complex ethical issues. To inform the development of future ethics guidance, we aim to characterise CRTs conducted exclusively in LMICs by examining the types of clusters, settings, author affiliations and primary clinical focus and to evaluate adherence to trial registration and ethics reporting requirements over time.

Design: A systematic scoping review using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews.

Ethical Issues in Normothermic Regional Perfusion in Controlled Organ Donation After Determination of Death by Circulatory Criteria: A Scoping Review.

Normothermic regional perfusion (NRP) is a surgical technique that can improve the quality and number of organs recovered for donation after the determination of death by circulatory criteria. Despite its promise, adoption of NRP has been hindered because of unresolved ethical issues. To inform stakeholders, this scoping review provides an impartial overview of the major ethical controversies surrounding NRP.

The Ottawa Statement implementation guidance document for cluster randomized trials in the hemodialysis setting.

Research teams are increasingly interested in using cluster randomized trial (CRT) designs to generate practice-guiding evidence for in-center maintenance hemodialysis. However, CRTs raise complex ethical issues. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, published in 2012, provides 15 recommendations to address ethical issues arising within 7 domains: justifying the CRT design, research ethics committee review, identifying research participants, obtaining informed consent, gatekeepers, assessing benefits and harms, and protecting vulnerable participants.

Why and when should we cluster randomize?

A cluster randomized trial is defined as a randomized trial in which intact social units of individuals are randomized rather than individuals themselves. Outcomes are observed on individual participants within clusters (such as patients). Such a design allows assessing interventions targeting cluster-level participants (such as physicians), individual participants or both.

Patient and public involvement in pragmatic trials: online survey of corresponding authors of published trials.

Background: There are few data on patient and public involvement (PPI) in pragmatic trials. We aimed to describe the prevalence and nature of PPI within pragmatic trials, describe variation in prevalence of PPI by trial characteristics and compare prevalence of PPI reported by trial authors to that reported in trial publications.

Methods: We applied a search filter to identify pragmatic trials published from 2014 to 2019 in MEDLINE.

Ethics of Controlled Human Infection Studies With Hepatitis C Virus.

Global elimination of hepatitis C virus (HCV) will be difficult to attain without an effective HCV vaccine. Controlled human infection (CHI) studies with HCV were not considered until recently, when highly effective treatment became available. However, now that successful treatment of a deliberate HCV infection is feasible, it is imperative to evaluate the ethics of establishing a program of HCV CHI research.

Neurologic Physiology after Removal of Therapy (NeuPaRT) study: study protocol of a multicentre, prospective, observational, pilot feasibility study of neurophysiology after withdrawal of life-sustaining measures.

Introduction: In donation after circulatory determination of death, death is declared 5 min after circulatory arrest. This practice assumes, but does not explicitly confirm, permanent loss of brain activity. While this assumption is rooted a strong physiological rationale, paucity of direct human data regarding temporal relationship between cessation of brain activity and circulatory arrest during the dying process threatens public and healthcare provider trust in deceased organ donation.

Health equity considerations in pragmatic trials in Alzheimer's and dementia disease: Results from a methodological review.

Introduction: To improve dementia care delivery for persons across all backgrounds, it is imperative that health equity is integrated into pragmatic trials.

Methods: We reviewed 62 pragmatic trials of people with dementia published 2014 to 2019. We assessed health equity in the objectives; design, conduct, analysis; and reporting using PROGRESS-Plus which stands for Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, and other factors such as age and disability.

FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer's lactate.

Objectives: Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids used for fluid therapy. Despite evidence of possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function and death), few large multi-centre randomised trials have evaluated the effect of these fluids on clinically important outcomes. We conducted a pilot trial to explore the feasibility of a large trial powered for clinically important outcomes.

Reporting of and explanations for under-recruitment and over-recruitment in pragmatic trials: a secondary analysis of a database of primary trial reports published from 2014 to 2019.

Objectives: To describe the extent to which pragmatic trials underachieved or overachieved their target sample sizes, examine explanations and identify characteristics associated with under-recruitment and over-recruitment.

Study Design And Setting: Secondary analysis of an existing database of primary trial reports published during 2014-2019, registered in ClinicalTrials.gov, self-labelled as pragmatic and with target and achieved sample sizes available.

Ethical analysis of vulnerabilities in cluster randomized trials involving people living with dementia in long-term care homes.

Cluster randomized trials (CRT) of non-pharmacological interventions are an important means of improving the quality of care and quality of life of people living with dementia (PLWD) in long-term care (LTC) homes. PLWD in LTC homes are, however, vulnerable in manifold ways. Therefore, researchers require guidance to ensure that the rights and welfare of PLWD are protected in the course of this valuable research.

Use of functional magnetic resonance imaging to assess cognition and consciousness in severe Guillain-Barré syndrome.

Objective: Functional neuroimaging may provide a viable means of assessment and communication in patients with Guillain-Barré Syndrome (GBS) mimicking the complete locked-in state. Functional neuroimaging has been used to assess residual cognitive function and has allowed for binary communication with other behaviourally non-responsive patients, such as those diagnosed with unresponsive wakefulness syndrome. We evaluated the potential application of functional neuroimaging using a clinical-grade scanner to determine if individuals with severe GBS retained auditory function, command following, and communication.

Heterogeneity in pragmatic randomised trials: sources and management.

Background: Pragmatic trials aim to generate evidence to directly inform patient, caregiver and health-system manager policies and decisions. Heterogeneity in patient characteristics contributes to heterogeneity in their response to the intervention. However, there are many other sources of heterogeneity in outcomes.

Protocol for a qualitative pilot study to explore ethical issues and stakeholder trust in the use of normothermic regional perfusion in organ donation in Canada.

Introduction: The process of controlled organ donation after circulatory determination of death (cDCDD) results in ischaemic injury to organs and leads to poorer outcomes in organ recipients. Although not yet used in Canada, normothermic regional perfusion (NRP) is a perfusion technology used postmortem with cDCDD donors to selectively restore perfusion of oxygenated blood to target organs in situ, reversing ischaemic injury and improving organ viability and post-transplant outcomes. However, NRP poses significant ethical challenges.