Andrew McRae

Inadequate Reporting of Research Ethics Review and Informed Consent in Cluster Randomised Trials: Review of Random Sample of Published Trials

Objectives To investigate the extent to which authors of cluster randomised trials adhered to two basic requirements of the World Medical Association’s Declaration of Helsinki and the International Committee of Medical Journal Editors’ uniform requirements for manuscripts (namely, reporting of research ethics review and informed consent), to determine whether the adequacy of reporting has improved over time, and to identify characteristics of cluster randomised trials associated with reporting of ethics practices. Design Review of a random sample of published cluster randomised trials from an electronic search in Medline. Setting Cluster randomised trials in health research published in English language journals from 2000 to 2008. Study sample 300 cluster randomised trials published in 150 journals. Results 77 (26%, 95% confidence interval 21% to 31%) trials failed to report ethics review. The proportion reporting ethics review increased significantly over time (P<0.001). Trials with data collection interventions at the individual level were more likely to report ethics review than were trials that used routine data sources only (79% (n=151) v 55% (23); P=0.008). Trials that accounted for clustering in the design and analysis were more likely to report ethics review. The median impact factor of the journal of publication was higher for trials that reported ethics review (3.4 v 2.3; P<0.001). 93 (31%, 26% to 36%) trials failed to report consent. Reporting of consent increased significantly over time (P<0.001). Trials with interventions targeting participants at the individual level were more likely to report consent than were trials with interventions targeting the cluster level (87% (90) v 48% (41); P<0.001). Trials with data collection interventions at the individual level were more likely to report consent than were those that used routine data sources only (78% (146) v 29% (11); P<0.001). Conclusions Reporting of research ethics protections in cluster randomised trials is inadequate. In addition to research ethics approval, authors should report whether informed consent was sought, from whom consent was sought, and what consent was for.

Researchers’ perceptions of ethical challenges in cluster randomized trials: a qualitative analysis

BackgroundCluster randomized trials (CRTs) pose ethical challenges for investigators and ethics committees. This study describes the views and experiences of CRT researchers with respect to: (1) ethical challenges in CRTs; (2) the ethics review process for CRTs; and (3) the need for comprehensive ethics guidelines for CRTs.MethodsDescriptive qualitative analysis of interviews conducted with a purposive sample of 20 experienced CRT researchers.ResultsInformants expressed concern over the potential for bias that may result from requirements to obtain informed consent from research participants in CRTs. Informants suggested that the need for informed consent ought to be related to the type of intervention under study in a CRT. Informants rarely expressed concern regarding risks to research participants in CRTs, other than risks to privacy. Important issues identified in the research ethics literature, including fair subject selection and other justice issues, were not mentioned by informants. The ethics review process has had positive and negative impacts on CRT conduct. Informants stated that variability in ethics review between jurisdictions, and increasingly stringent ethics review in recent years, have hampered their ability to conduct CRTs. Many informants said that comprehensive ethics guidelines for CRTs would be helpful to researchers and research ethics committees.ConclusionsInformants identified key ethical challenges in the conduct of CRTs, specifically relating to identifying subjects, seeking informed consent, and the use of gatekeepers. These data have since been used to identify topics for in-depth ethical analysis and to guide the development of comprehensive ethics guidelines for CRTs.

Predictors of Failure of Empiric Outpatient Antibiotic Therapy in Emergency Department Patients With Uncomplicated Cellulitis

BACKGROUND Despite several expert panel recommendations and cellulitis treatment guidelines, there are currently no clinical decision rules to assist clinicians in deciding which emergency department (ED) patients should be treated with oral antibiotics and which patients require intravenous (IV) therapy at first presentation of cellulitis amenable to outpatient treatment. OBJECTIVES The objective was to determine risk factors associated with adult patients presenting to the ED with cellulitis who fail initial antibiotic therapy as outpatients and require a change of antibiotics or admission to hospital. METHODS This was a prospective cohort study of patients 18 years of age or older presenting with cellulitis to one of two tertiary care EDs (combined annual census 140,000). Patients were excluded if they had been treated with antibiotics for the cellulitis before presenting to the ED, if they were admitted to the hospital, or if they had an abscess only. Trained research personnel administered a questionnaire at the initial ED visit with telephone follow-up 2 weeks later. Multivariable logistic regression models determined predictor variables independently associated with treatment failure (failed initial antibiotic therapy and required a change of antibiotics or admission to hospital). RESULTS A total of 598 patients were enrolled, 52 were excluded, and 49 were lost to follow-up. The mean (±standard deviation [SD]) age was 53.1 (±18.4) years and 56.4% were male. A total of 185 patients (37.2%) were given oral antibiotics, 231 (46.5%) were given IV antibiotics, and 81 patients (16.3%) received both oral and IV antibiotics in the ED. A total of 102 (20.5%, 95% confidence [CI] = 17.2% to 24.2%) patients had treatment failures. Fever (temperature > 38°C) at triage (odds ratio [OR] = 4.3, 95% CI = 1.6 to 11.7), chronic leg ulcers (OR = 2.5, 95% CI = 1.1 to 5.2), chronic edema or lymphedema (OR = 2.5, 95% CI = 1.5 to 4.2), prior cellulitis in the same area (OR = 2.1, 95% CI = 1.3 to 3.5), and cellulitis at a wound site (OR = 1.9, 95% CI = 1.2 to 3.0) were independently associated with treatment failure. CONCLUSIONS These risk factors should be considered when initiating empiric antibiotic therapy for ED patients with cellulitis amenable to outpatient treatment.

Use of prehospital ultrasound in North America: a survey of emergency medical services medical directors

BackgroundAdvances in ultrasound imaging technology have made it more accessible to prehospital providers. Little is known about how ultrasound is being used in the prehospital environment and we suspect that it is not widely used in North America at this time. We believe that EMS system characteristics such as provider training, system size, population served, and type of transport will be associated with use or non-use of ultrasound. Our study objective was to describe the current use of prehospital ultrasound in North America.MethodsThis study was a cross-sectional survey distributed to EMS directors on the National Association of EMS Physicians (NAEMSP) mailing list. Respondents had the option to complete a paper or electronic survey.ResultsOf the 755 deliverable surveys we received 255 responses from across Canada and the United states for an overall response rate of 30%. Of respondents, 4.1% of EMS systems (95% CI 1.9, 6.3) reported currently using ultrasound and an additional 21.7% (95% CI 17, 26.4) are considering implementing ultrasound. EMS services using ultrasound have a higher proportion of physicians (p < 0.001) as their highest trained prehospital providers when compared to the survey group as a whole. The most commonly cited current and projected applications are Focused Abdominal Sonography for Trauma (FAST) and assessment of pulseless electrical activity (PEA) arrest. The cost of equipment and training are the most significant barriers to implementation of ultrasound. Most medical directors want evidence that prehospital ultrasound improves patient outcomes prior to implementation.ConclusionsPrehospital ultrasound is infrequently used in North America and there are a number of barriers to its implementation, including costs of equipment and training and limited evidence demonstrating improved outcomes. A research agenda for prehospital ultrasound should focus on patient-important outcomes such as morbidity and mortality. Two commonly used indications that could be a focus of standardized training programs are the FAST exam, and assessment of PEA arrest.

Undetectable Concentrations of a Food and Drug Administration–approved High-sensitivity Cardiac Troponin T Assay to Rule Out Acute Myocardial Infarction at Emergency Department Arrival

Abstract Background The objective of this study was to quantify the sensitivity of very low concentrations of high‐sensitivity cardiac troponin T (hsTnT) at ED arrival for acute myocardial infarction (AMI) in a large cohort of chest pain patients evaluated in real‐world clinical practice. Methods This retrospective study included consecutive ED patients with suspected cardiac chest pain evaluated in four urban EDs, excluding those with ST‐elevation AMI, cardiac arrest or abnormal kidney function. The primary outcomes were AMI at 7, 30, and 90 days. Secondary outcomes included major adverse cardiac events (MACE; all‐cause mortality, AMI, and revascularization) and the individual MACE components. Test characteristics were calculated for hsTnT values from 3 to 200 ng/L . Results A total of 7,130 patients met inclusion criteria. AMI incidences at 7, 30, and 90 days were 5.8, 6.0, and 6.2%. When the hsTnT assay was performed at ED arrival, the limit of blank of the assay (3 ng/L) ruled out 7‐day AMI in 15.5% of patients with 100% sensitivity and negative predictive value (NPV). The limit of detection of the assay (5 ng/L) ruled out AMI in 33.6% of patients with 99.8% sensitivity and 99.95% NPV for 7‐day AMI. The limit of quantification (the Food and Drug Administration [FDA]‐approved cutoff for lower the reportable limit) of 6 ng/L ruled out AMI in 42.2% of patients with 99.8% sensitivity and 99.95% NPV. The sensitivities of the cutoffs of <3, <5, and <6 ng/L for 7‐day MACE were 99.6, 97.4, and 96.6%, respectively. The NPVs of the cutoffs of <3, <5, and <6 ng/L for 7‐day MACE were 99.8, 99.5, and 99.4%, respectively. A secondary analysis was performed in a subgroup of 3,549 higher‐risk patients who underwent serial troponin testing. In this subgroup, a cutoff of 3 ng/L ruled out 7‐day AMI in 9.6% of patients with 100% sensitivity and NPV, a cutoff of 5 ng/L ruled out 7‐day AMI in 23.3% of patients with 99.7% sensitivity and 99.9% NPV, and a cutoff of 6 ng/L ruled out 7‐day AMI in 29.8% of patients with 99.7 and 99.9% NPV. In the higher‐risk subgroup, the sensitivities of cutoffs of <3, <5, and <6 ng/L for 7‐day MACE were 99.8, 97.4, and 96.6%, respectively. In this higher‐risk subgroup, the NPV of cutoffs of <3, <5, and <6 ng/L for 7‐day MACE were 99.7, 98.5, and 98.4%, respectively. Conclusions When used in real‐world clinical practice conditions, hsTnT concentrations < 6 ng/L (below the lower reportable limit for an FDA‐approved assay) at the time of ED arrival can rule out AMI with very high sensitivity and NPV. The sensitivity for MACE is unacceptably low, and thus a single‐troponin rule‐out strategy should only be used in the context of a structured risk evaluation.

Canadian Association of Emergency Physicians Position Statement on Acute Ischemic Stroke

The CAEP Stroke Practice Committee was convened in the spring of 2013 to revisit the 2001 policy statement on the use of thrombolytic therapy in acute ischemic stroke. The terms of reference of the panel were developed to include national representation from urban academic centres as well as community and rural centres from all regions of the country. Membership was determined by attracting recognized stroke leaders from across the country who agreed to volunteer their time towards the development of revised guidance on the topic. The guideline panel elected to adopt the GRADE language to communicate guidance after review of existing systematic reviews and international clinical practice guidelines. Stroke neurologists from across Canada were engaged to work alongside panel members to develop guidance as a dyad-based consensus when possible. There was no unique systematic review performed to support this guidance, rather existing efficacy data was relied upon. After a series of teleconferences and face to face meetings, a draft guideline was developed and presented to the CAEP board in June of 2014. The panel noted the development of significant new evidence to inform a number of clinical questions related to acute stroke management. In general terms the recommendations issued by the CAEP Stroke Practice Committee are supportive of the use of thrombolytic therapy when treatment can be administered within 3 hours of symptom onset. The committee is also supportive of system-level changes including pre-hospital interventions, the transport of patients to dedicated stroke centers when possible and tele-health measures to support thrombolytic therapy in a timely window. Of note, after careful deliberation, the panel elected to issue a conditional recommendation against the use of thrombolytic therapy in the 3–4.5 hour window. The view of the committee was that as a result of a narrow risk benefit balance, one that is considerably narrower than the same considerations under 3 hours, a significant number of informed patients and families would opt against the risk of early intracranial hemorrhage and the possibility of increased 90-day mortality that is not seen for more timely treatment. Furthermore, the frequently impaired nature of patients suffering an acute stroke and the difficulties in asking families to make life and death decisions in a highly time-sensitive context led the panel to restrict a strong endorsement of thrombolytic to the 3 hour outermost limit. The committee noted as well that Health Canada has not approved a thrombolytic agent beyond a three hour window in acute ischemic stroke.

Canadian Institutes of Health Research dissemination grant on high-sensitivity cardiac troponin

a McMaster University, Hamilton, Ontario, Canada b Mayo Clinic, Rochester, MN, USA c Australian National University Medical School, Canberra, Australian Capital Territory, Australia d BHF/University Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK e University of British Columbia, Vancouver, British Columbia, Canada f Department of Emergency Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

Computerized physician order entry and decision support improves ED analgesic ordering for renal colic

OBJECTIVES Computerized physician order entry (CPOE) offers the potential for safer, faster patient care, as well as greater use of evidence-based therapy via built-in decision support. However, the effectiveness of CPOE in yielding these benefits has shown mixed results in the emergency department (ED) setting. Our objective was to evaluate the impact of CPOE implementation on analgesic prescribing and dosing practices for renal colic presentations. METHODS This retrospective pre/post comparative study was conducted in 3 tertiary hospitals that implemented CPOE in 2010. Two patient groups were compared: prior to (pre-CPOE) and after (post-CPOE) CPOE implementation. Each group consisted of 230 randomly selected, high-acuity patients presenting to the ED with renal colic. The primary outcome was the proportion of patients receiving ketorolac in the ED. Secondary outcomes included choice of analgesic and average morphine dose. RESULTS The proportion of patients receiving ketorolac significantly increased after CPOE implementation (65.6% pre-CPOE vs 76.5% post-CPOE, P = .015), as did the proportion of patients receiving fentanyl (pre, 9.7%; post, 16.7%; P = .047). Differences in morphine use (pre, 66.0%; post, 69.1%) and average morphine dose (pre, 10.09 mg; post, 12.28 mg) did not reach statistical significance. CONCLUSIONS The introduction of CPOE is associated with an increase in ketorolac use for ED renal colic visits. This may reflect the inclusion of ketorolac in the renal colic order set. Computerized physician order entry implementation with condition-specific electronic order sets and decision support may improve evidence-based practice.

The impact of high-sensitivity troponin implementation on hospital operations and patient outcomes in 3 tertiary care centers ☆,☆☆

OBJECTIVE High-sensitivity troponin T (hs-TnT) assays detect myocardial injury sooner, possibly improving throughput times for emergency department (ED) assessment of suspected acute myocardial infarction (AMI). This study evaluates the influence of hs-TnT implementation on ED length of stay (LOS), consultations and admissions, as well as ED revisits with cardiology admissions for patients undergoing testing for suspected AMI. METHODS This control pre-post design analysis included patients evaluated using hs-TnT or conventional troponin T. Data were collected from 3 ED databases for patients who had a troponin assay for suspected AMI for the periods February 12, 2011-April 22, 2011 (Ctrl); November 20, 2011-January 28, 2012 (Pre); and February 12, 2012-April 21, 2012 (Post). The primary outcome was ED LOS; secondary outcomes included the proportions of patients who received ED cardiology consultations, patients who were admitted to hospital, and discharged patients who revisited the ED within 30 days. RESULTS Data were analyzed from 6650 (Ctrl), 6866 (Pre), and 5754 (Post) patients. Median ED LOS decreased following hs-TnT implementation (6.60 hours in Ctrl and Pre vs 6.10 hours in Post, P < .001). There was no change in cardiology consultations or admissions following hs-TnT implementation. Fewer ED revisits occurred within 30 days in Post (16.0% Ctrl, 16.5% Pre vs 14.9% Post; P < .01). These results were preserved after adjusting for age and Canadian Triage Acuity Score. CONCLUSIONS This hs-TnT implementation strategy, using an equivalent cutoff for the conventional troponin T and hs-TnT assays, decreased ED LOS for patients with suspected AMI and did not increase cardiology resource utilization or ED revisits.

Reporting of patient consent in healthcare cluster randomised trials is associated with the type of study interventions and publication characteristics

Objective Cluster randomised trial (CRT) investigators face challenges in seeking informed consent from individual patients (cluster members). This study examined associations between reporting of patient consent in healthcare CRTs and characteristics of these trials. Study design Consent practices and study characteristics were abstracted from a random sample of 160 CRTs performed in primary or hospital care settings that were published from 2000 to 2008. Multivariable logistic regression was used to examine associations between reporting of patient consent and methodological characteristics, as well as publication features such as date and journal of publication. Results 82 (53.8%) of 160 studies reported obtaining informed consent from individual patients. Reporting of patient consent was independently and positively associated with: smaller cluster size, the evaluation of experimental interventions targeted at patients, data collection from individual patients, publication later than 2004 and publication in higher-impact journals. Conclusions Reporting of consent practices in published CRTs should be improved. Consent practices in published CRTs appear to be related to the type of interventions under study, as well as journal impact and trends in research ethics practices. These findings will inform best practices in trial conduct and ethics review, remediation of errors in consent practices and ethics review and the development of regulatory guidance for CRTs.