Informed consent in pragmatic trials: results from a survey of trials published 2014-2019.

OBJECTIVES: To describe reporting of informed consent in pragmatic trials, justifications for waivers of consent and reporting of alternative approaches to standard written consent. To identify factors associated with (1) not reporting and (2) not obtaining consent. METHODS: Survey of primary trial reports, published 2014-2019, identified using an electronic search filter for pragmatic trials implemented in MEDLINE, and registered in ClinicalTrials.gov. RESULTS: Among 1988 trials, 132 (6.6%) did not include a statement about participant consent, 1691 (85.0%) reported consent had been obtained, 139 (7.0%) reported a waiver and 26 (1.3%) reported consent for one aspect (eg, data collection) but a waiver for another (eg, intervention). Of the 165 trials reporting a waiver, 76 (46.1%) provided a justification. Few (53, 2.9%) explicitly reported use of alternative approaches to consent. In multivariable logistic regression analyses, lower journal impact factor (p=0.001) and cluster randomisation (p<0.0001) were significantly associated with not reporting on consent, while trial recency, cluster randomisation, higher-income country settings, health services research and explicit labelling as pragmatic were significantly associated with not obtaining consent (all p<0.0001). DISCUSSION: Not obtaining consent seems to be increasing and is associated with the use of cluster randomisation and pragmatic aims, but neither cluster randomisation nor pragmatism are currently accepted justifications for waivers of consent. Rather than considering either standard written informed consent or waivers of consent, researchers and research ethics committees could consider alternative consent approaches that may facilitate the conduct of pragmatic trials while preserving patient autonomy and the public's trust in research.

Impact of stated barriers on proposed warfarin prescription for atrial fibrillation: a survey of Canadian physicians.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia, and leading cause of ischemic stroke. Despite proven effectiveness, warfarin remains an under-used treatment in atrial fibrillation patients. We sought to study, across three physician specialties, a range of factors that have been argued to have a disproportionate effect on treatment decisions. METHODS: Cross-sectional survey of Canadian Family Doctors (FD: n = 500), Geriatricians (G: n = 149), and Internal Medicine specialists (IMS: n = 500). Of these, 1032 physicians were contactable, and 335 completed and usable responses were received. Survey questions and clinical vignettes asked about the frequency with which they see patients with atrial fibrillation, treatment practices, and barriers to the prescription of anticoagulants. RESULTS: Stated prescribing practices did not significantly differ between physician groups. Falls risk, bleeding risk and poor patient adherence were all highly cited barriers to prescribing warfarin. Fewer geriatricians indicated that history of patient falls would be a reason for not treating with warfarin (G: 47%; FD: 71%; IMS: 72%), and significantly fewer changed reported practice in the presence of falls risk (χ (2) (6) = 45.446, p < 0.01). Experience of a patient having a stroke whilst not on warfarin had a significant impact on vignette decisions; physicians who had had patients who experienced a stroke were more likely to prescribe warfarin (χ (2) (3) =10.7, p = 0.013). CONCLUSIONS: Barriers to treatment of atrial fibrillation with warfarin affect physician specialties to different extents. Prior experience of a patient suffering a stroke when not prescribed warfarin is positively associated with intention to prescribe warfarin, even in the presence of falls risk.

Audit and feedback to improve laboratory test and transfusion ordering in critical care: a systematic review.

BACKGROUND: Laboratory tests and transfusions are sometimes ordered inappropriately, particularly in the critical care setting, which sees frequent use of both. Audit and Feedback (A&F) is a potentially useful intervention for modifying healthcare provider behaviors, but its application to the complex, team-based environment of critical care is not well understood. We conducted a systematic review of the literature on A&F interventions for improving test or transfusion ordering in the critical care setting. METHODS: Five databases, two registries, and the bibliographies of relevant articles were searched. We included critical care studies that assessed the use of A&F targeting healthcare provider behaviors, alone or in combination with other interventions to improve test and transfusion ordering, as compared to historical practice, no intervention, or another healthcare behaviour change intervention. Studies were included only if they reported laboratory test or transfusion orders, or the appropriateness of orders, as outcomes. There were no restrictions based on study design, date of publication, or follow-up time. Intervention characteristics and absolute differences in outcomes were summarized. The quality of individual studies was assessed using a modified version of the Effective Practice and Organisation of Care Cochrane Review Group's criteria. RESULTS: We identified 16 studies, including 13 uncontrolled before-after studies, one randomized controlled trial, one controlled before-after study, and one controlled clinical trial (quasi-experimental). These studies described 17 interventions, mostly (88%) multifaceted interventions with an A&F component. Feedback was most often provided in a written format only (41%), more than once (53%), and most often only provided data aggregated to the group-level (41%). Most studies saw a change in the hypothesized direction, but not all studies provided statistical analyses to formally test improvement. Overall study quality was low, with studies often lacking a concurrent control group. CONCLUSIONS: Our review summarizes characteristics of A&F interventions implemented in the critical care context, points to some mechanisms by which A&F might be made more effective in this setting, and provides an overview of how the appropriateness of orders was reported. Our findings suggest that A&F can be effective in the context of critical care; however, further research is required to characterize approaches that optimize the effectiveness in this setting alongside more rigorous evaluation methods. TRIAL REGISTRATION: PROSPERO CRD42016051941.

Ethical Issues in the Design and Conduct of Pragmatic Cluster Randomized Trials in Hemodialysis Care: An Interview Study With Key Stakeholders.

BACKGROUND: Pragmatic cluster randomized trials (CRTs) offer an opportunity to improve health care by answering important questions about the comparative effectiveness of treatments using a trial design that can be embedded in routine care. There is a lack of empirical research that addresses ethical issues generated by pragmatic CRTs in hemodialysis. OBJECTIVE: To identify stakeholder perceptions of ethical issues in pragmatic CRTs conducted in hemodialysis. DESIGN: Qualitative study using semi-structured interviews. SETTING: In-person or telephone interviews with an international group of stakeholders. PARTICIPANTS: Stakeholders (clinical investigators, methodologists, ethicists and research ethics committee members, and other knowledge users) who had been involved in the design or conduct of a pragmatic individual patient or cluster randomized trial in hemodialysis, or their role would require them to review and evaluate pragmatic CRTs in hemodialysis. METHODS: Interviews were conducted in-person or over the telephone and were audio-recorded with consent. Recorded interviews were transcribed verbatim prior to analysis. Transcripts and field notes were analyzed using a thematic analysis approach. RESULTS: Sixteen interviews were conducted with 19 individuals. Interviewees were largely drawn from North America (84%) and were predominantly clinical investigators (42%). Six themes were identified in which pragmatic CRTs in hemodialysis raise ethical issues: (1) patients treated with hemodialysis as a vulnerable population, (2) appropriate approaches to informed consent, (3) research burdens, (4) roles and responsibilities of gatekeepers, (5) inequities in access to research, and (6) advocacy for patient-centered research and outcomes. LIMITATIONS: Participants were largely from North America and did not include research staff, who may have differing perspectives. CONCLUSIONS: The six themes reflect concerns relating to individual rights, but also the need to consider population-level issues. To date, concerns regarding inequity of access to research and the need for patient-centered research have received less coverage than other, well-known, issues such as consent. Pragmatic CRTs offer a potential approach to address equity concerns and we suggest future ethical analyses and guidance for pragmatic CRTs in hemodialysis embed equity considerations within them. We further note the potential for the co-creation of health data infrastructure with patients which would aid care but also facilitate patient-centered research. These present results will inform planned future guidance in relation to the ethical design and conduct of pragmatic CRTs in hemodialysis. TRIAL REGISTRATION: Registration is not applicable as this is a qualitative study.

CONTEXTE: Les essais pragmatiques randomisés par grappes fournissent une occasion d'améliorer les soins parce qu'ils répondent à des questions importantes sur l'efficacité comparative des traitements en utilisant des modèles pouvant être intégrés aux soins courants. On constate toutefois un manque de recherche empirique abordant les questions éthiques générées par ces essais en contexte d'hémodialyse. OBJECTIF: Connaître le point de vue d'intervenants sur les questions éthiques liées aux essais pragmatiques randomisés par grappes en contexte d'hémodialyse. TYPE D'ÉTUDE: Étude qualitative sous forme d'interviews semi-structurées. CADRE: Interviews téléphoniques ou en personne avec des intervenants internationaux. PARTICIPANTS: Des intervenants (chercheurs cliniciens, spécialistes de la méthodologie, éthiciens, membres de comités d'éthique de la recherche et autres utilisateurs de connaissances) impliqués dans la conception ou la conduite d'essais pragmatiques randomisés menés sur un patient individuel, ou un groupe de patients, en contexte d'hémodialyse; ou des individus dont le rôle pourrait les amener à réviser et à évaluer ce type d'essais cliniques. MÉTHODOLOGIE: Les interviews ont été menées en personne ou au téléphone, et ont été enregistrées avec le consentement des intervenants. Les enregistrements ont été transcrits verbatim pour l'analyse. Les transcriptions et les notes ont été analysées par une approche d'analyse thématique. RÉSULTATS: Seize interviews ont été menées auprès de 19 intervenants, principalement des chercheurs cliniciens (42%) provenant en grande majorité d'Amérique du Nord (84 %). Ces discussions ont dégagé six thèmes pour lesquels les essais pragmatiques randomisés par grappes soulèvent des questions éthiques en contexte d'hémodialyse: 1) les patients hémodialysés en tant que population vulnérable; 2) les approches appropriées en matière de consentement éclairé; 3) la charge de la recherche; 4) les rôles et responsabilités des personnes responsables; 5) les inégalités dans l'accès à la recherche, et; 6) la promotion de la recherche et des résultats axés sur les patients. LIMITES: Les participants provenaient très majoritairement d'Amérique du Nord et aucun membre du personnel de recherche n'a été questionné, ceux-ci auraient pu fournir un point de vue différent. CONCLUSIONS: Les six thèmes rendent compte de préoccupations relatives aux droits individuels, mais indiquent également la nécessité de se pencher sur les enjeux relatifs à la population. À ce jour, les questions concernant l'inégalité dans l'accès à la recherche et la nécessité de faire de la recherche axée sur les patients ont reçu moins d'attention que d'autres enjeux notoires comme le consentement. Les essais pragmatiques randomisés par grappes constituent une approche susceptible d'aborder les questions d'équité; nous suggérons que les futures analyses et orientations éthiques intègrent des considérations d'équité à ce type d'essais en contexte d'hémodialyse. Nous notons également un potentiel pour la co-création d'une infrastructure de données sur la santé avec les patients, ce qui améliorerait les soins tout en facilitant la recherche axée sur les patients. Ces résultats éclaireront les orientations futures pour la conception et la conduite éthique d'essais pragmatiques randomisés par grappes menés en contexte d'hémodialyse.L'enregistrement n'est pas nécessaire puisqu'il s'agit d'une étude qualitative.

The cumulative effects of intravenous antibiotic treatments on hearing in patients with cystic fibrosis.

BACKGROUND: Aminoglycosides (AGs) and glycopeptides are antibiotics essential for treating life-threatening respiratory infections in patients with cystic fibrosis (CF). The goal of this study was to examine the effects of cumulative intravenous (IV)-AG (amikacin and/or tobramycin) and/or glycopeptide (vancomycin) dosing on hearing status in patients with CF. METHODS: Hearing thresholds were measured from 0.25 to 16.0kHz, in 81 participants with CF. Participants were categorized into two groups: normal hearing in both ears (≤25dB HL for all frequency bands) or hearing loss (>25dB HL for any frequency band in either ear). Participants were also characterized into quartiles by their cumulative IV-AG (with or without vancomycin) exposure. Dosing was calculated using two strategies: (i) total number of lifetime doses, and (ii) total number of lifetime doses while accounting for the total doses per day. This was referred to as the "weighted" method. RESULTS: Participants in the hearing loss group were significantly older than those in the normal-hearing group. After adjusting for gender and age at the time of hearing test, participants in the two highest-quartile exposure groups were almost 5 X more likely to have permanent sensorineural hearing loss than those in the two lowest-quartile exposure groups. There was a small group of CF patients who had normal hearing despite high exposure to IV-antibiotics. CONCLUSIONS: Cumulative IV-antibiotic dosing has a significant negative effect on hearing sensitivity in patients with CF, when controlling for age and gender effects. A trend for increasing odds of hearing loss was associated with increasing cumulative IV-antibiotic dosing.