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Background: Clinical trials management can be studied using project management theory. The CYCLE pilot randomized controlled trial (RCT) was conducted to determine the feasibility of a future rehabilitation trial of early in-bed cycling in the intensive care unit (ICU). In-bed cycling is a novel intervention, not typically available in ICUs. Implementation of this intervention requires personnel with specialized clinical expertise caring for critically ill patients and use of the in-bed cycle. Our objective was to describe the implementation and conduct of our pilot RCT using a project management approach., Methods: We retrospectively reviewed activities, timelines, and personnel involved in the trial. We organized activities into four project management phases: initiation, planning, execution, and monitoring and controlling. Data sources included Methods Centre documents used for trial coordination and conduct, and the trial data set. We report descriptive statistics as counts and proportions and also medians and quartiles, and we summarize the lessons learned., Results: Seven ICUs in Canada participated in the trial. Time from research ethics board and contracts submission to first enrolment was a median (first quartile, third quartile) of 185 (146, 209) and 162 (114, 181) days, respectively. We trained 128 personnel on the CYCLE pilot RCT protocol, and 80 (63%) completed trial-related activities. Four sites required additional training after start-up due to staff turnover and leaves of absence. Over 15 months, we screened 864 patients: 256 were eligible and 66 were enrolled. Despite an 85% consent rate, 74% (190/256) of eligible patients were not randomized, largely (80% [152/190]) due to physiotherapist availability. Thirteen percent of recruitment weeks were lost due to physiotherapist staffing shortages. We highlight five key lessons learned: (1) prepare and anticipate site needs; (2) communicate regularly; (3) proactively analyse and act on process measure data; (4) develop contingency plans; (5) express appreciation to participating sites., Conclusions: Our analysis highlights the scope of relevant activities, rigorous training and monitoring, number and types of required personnel, and time required to conduct a multicentre ICU rehabilitation intervention trial. Our lessons learned can help others interested in implementing complex intervention trials, such as rehabilitation., Trial Registration: ClinicalTrials.gov, NCT02377830 . Registered prospectively on 4 March 2015.

Background: Successful stroke trials require adequate recruitment. In this observational study, we assessed reasons for refusal to provide informed consent in eligible patients approached for clinical trial participation at the Vancouver Stroke Program., Methods: We assessed screening logs from four trials that were actively recruiting at our center: three randomized trials, two of which investigated different antithrombotic strategies for secondary prevention (NAVIGATE-ESUS, NCT02313909 12/2014; DATAS-II, NCT02295826 11/2014) and one that investigated surgery plus medical management versus medical management alone for primary prevention (CREST-2, NCT02089217 03/2014). The fourth study was observational and non-randomized; all participants received an external monitoring device (PROPHECY, NCT03712865 10/2018). Screening logs from June 2015 to April 2017 were reviewed retrospectively. Subsequently, we used a prospective structured case report form for screening (May 2017-March 2018). We assessed and compared refusal rates between trials, demographics of those refusing consent, and their reasons for doing so. We used descriptive statistics, chi-square and Fisher's exact tests as appropriate for non-parametric data, and t-tests for parametric data. We examined likelihood of refusal by sex using multivariable logistic regression models including age and trial intervention as co-variables., Results: A total of 235 patients (43% women) were approached for consent. More patients refused the surgical (59%) and antithrombotic trials (53%) compared with the non-randomized external monitoring device study (13%) (p < 0.001). Surgical trial refusals were primarily due to a desire for certainty in receiving a particular intervention (39%), with the majority of those patients wanting surgery. Refusals for the antithrombotic trials were mainly due to concerns with the potential side effects of the study drug (41%); refusals in the device trial were mainly due to disinterest (46%). Women refused participation more often than men (48% vs 33%). Women remained less likely to consent than men, even after adjustment for age and trial intervention (OR 0.46, 95% CI 0.26-0.82, p = 0.009)., Conclusions: Concern surrounding drug safety, randomization, and disinterest were the chief deterrents to enrolment; there were also differences in rates of consent by gender. A better understanding of why patients refuse participation in stroke trials may help to develop future patient-directed communication strategies to improve enrolment. Further research is required to better understand the reasons underlying gender disparities in consent rates.

Background: Inappropriate staff behaviour during surgical procedures may disrupt the surgical performance and compromise patient safety. We developed an innovative monitoring and feedback system combined with an adaptive approach to optimise staff behaviour intraoperatively and prevent post-operative complications (POC) in orthopaedic surgery., Methods/design: This protocol describes a parallel-group, cluster randomised, controlled trial with orthopaedic centre as the unit of randomisation. The intervention period will last 6 months and will be based on the monitoring of two surrogates of staff behaviour: the frequency of doors opening and the level of noise. Both will be collected from incision to wound closure, using wireless sensors and sonometers, and recorded and analysed on a dedicated platform (Livepulse®). Staff from centres randomised to the intervention arm will be informed in real time on their own data through an interactive dashboard available in each operating room (OR), and a posteriori for hip and knee replacement POC. Aggregated data from all centres will also be displayed for benchmarking. A lean method will be applied in each centre by a local multidisciplinary team to analyse baseline situations, determine the target condition, analyse the root cause(s), and take countermeasures. The education and awareness of participants on the impact of their behaviour on patient safety will assist the quality improvement process. The control centres will be blinded to monitoring data and quality improvement approaches. The primary outcome will be any POC occurring during the 30 days post operation. We will evaluate this outcome using local and national routinely collected data from hospital discharge and disease databases. Thirty orthopaedic centres will be randomised for a total of 9945 hip and knee replacement surgical procedures., Discussion: The field of human factors and behaviour in the OR seems to offer potential room for improvement. An intervention providing goal-setting, monitoring, feedback and action planning may reduce the traffic flow and interruptions/distractions of the surgical team during procedures, preventing subsequent POCs. The results of this trial will provide important data on the impact of OR staff behaviour on patient safety, and promote best practice during surgical procedures., Trial Registration: ClinicalTrials.gov, NCT03158181 .

Background: Eligibility criteria that result in the exclusion of a substantial number of patients from randomized trials jeopardize the generalizability of treatment effect to much of the clinical population. This is important when evaluating opioid substitution and antagonist therapies (OSATs), especially given the challenges associated with treating the opioid-dependent population. We aimed to identify OSAT trials' eligibility criteria, quantify the percentage of the clinical population excluded by these criteria, and determine how OSAT guidelines incorporate evidence from these trials., Methods: We performed a systematic review to identify the eligibility criteria used across trials. We searched Medline, EMBASE, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry (CTR), World Health Organization International CTR Platform Search Portal, and the National Institutes of Health CTR databases from inception to January 1, 2014. To quantify the effect of trials' eligibility criteria on generalizability, we applied these criteria to data from an observational study of opioid-dependent patients (n = 394). We then accessed the Canadian, American, British, and World Health Organization (WHO) OSAT guidelines to evaluate how evidence is used in the recommendations., Results: Among the 60 trials identified the majority (≥50 % of trials) exclude patients with psychiatric (60 %) and physical comorbidity (51.7 %). Additionally, we found 19 trials exclude patients with current alcohol/substance-use problems (31.7 %), and 29 (48.3 %) exclude patients taking psychotropic medications. These criteria were restrictive and in some cases rendered 70 % of the observational sample ineligible. North American OSAT guidelines made strong recommendations supported by evidence with poor generalizability. National Institute of Health and Care Excellence (NICE) and WHO guidelines for opioid misuse provide a critical assessment of the literature used to inform their recommendations., Conclusions: Trials assessing OSATs often exclude patients with concurrent disorders. If the excluded patients respond differently to treatment, results from these trials are likely to overestimate the true effectiveness of OSATs. North American guidelines should consider these limitations when drafting clinical recommendations.