Cluster Randomized Trial Design Research Articles

Effect of a small increase in off-premises trading hours on alcohol sales in Norway: A stepped-wedge cluster-randomized controlled trial.

Evidence of the effect of limiting off-premises alcohol trading hours is still scarce. This study tested the effect of a small extension in trading hours on alcohol sales in alcohol monopoly outlets in Norway. The extension of trading hours was implemented within a stepped-wedge cluster-randomized trial design. Eligible state monopoly outlets (n = 229) were clustered into trade districts (n = 62), which were block-randomized to one of three sequences regarding date of implementation: 1 September 2020 (n = 21 districts, 82 outlets), 1 December 2020 (n = 21 districts, 73 outlets) and 1 March 2021 (n = 20 districts, 74 outlets). Outcomes were followed-up for a 1-year period. Study participants were state monopoly outlets in urban and rural trade districts in all parts of Norway. Monthly alcohol sales in litres of pure alcohol per trade district and per outlet were measured from March 2020 to March 2022 (primary outcome). We applied a linear mixed-effect model with two-way fixed effects within a difference-in-difference framework. As a robustness check we considered the effects of cross-border trade and effects in subgroups of outlets. Trading hours in monopoly outlets were extended by 1 hour on Saturdays. The extension was permanent. Pre-intervention periods and not-yet-treated units served as control conditions. We did not find a statistically significant effect of the small extension in trading hours on monthly alcohol sales (i) per trade district [average treatment effect: -185.5litres, 95% confidence interval (CI) = -1159.9, 788.9] and (ii) per outlet (-35.3litres, 95% CI = -142.1, 72.0). These findings were consistent across estimation methods and model specifications. There is no clear evidence that a small extension in off-premises trading hours affected alcohol sales in monopoly outlets in Norway.

Remote coaching for supporting the implementation of treatment for depression in primary care in Madhya Pradesh, India: protocol for a cluster randomized controlled trial.

Upwards of ninety percent of individuals living with depression in India do not have access to evidence-based treatments, especially in rural areas. Integrating these treatments into primary care is essential for bridging this care gap. This trial aims to evaluate whether a remote coaching implementation support strategy, referred to as Enhanced Implementation Support, is superior to routine support, referred to as Routine Implementation Support, in supporting the delivery of collaborative depression care in rural primary care centers. Employing a cluster-randomized hybrid type-III implementation trial design, 14 primary care facilities in Sehore district, Madhya Pradesh, will implement a collaborative depression care package based on the WHO's mhGAP program. Facilities will be randomized to either Enhanced Implementation Support or the Routine Implementation Support control condition. Enhanced Implementation Support consists of remote coaching and technical assistance, supplemented with in-person visits, and guided by the Plan-Do-Study-Act implementation cycles. The primary implementation outcome is the proportion of outpatients screened for depression by facility staff, with secondary outcomes including the proportions of outpatients who screen positive for depression, are referred to the medical officer, and initiate treatment. Secondary patient outcomes include proportion of patients who achieve reduction in depression symptom severity at 3-month follow up. Acceptability, feasibility, and fidelity of the depression care package will be assessed through routine observations collected during field visits, facility audits, and qualitative exit interviews with facility staff. Costs of delivering the Enhanced Implementation Support strategy will also be estimated. This trial can inform efforts to integrate depression care in rural primary care facilities in a low-resource setting, and illuminate whether external coaching support is superior relative to existing implementation support for achieving these goals. NCT05264792.

Abstract A122: Predictors of mailed fecal immunochemical test return for Hispanic patients receiving care at community health centers

Abstract Background and Purpose: Mailed fecal immunochemical testing (FIT) is an evidence-based strategy to increase colorectal cancer (CRC) screening. We have previously reported that a multi-level mailed FIT intervention resulted in higher CRC screening rates compared to usual care among Hispanic patients receiving care at Community Health Centers (CHCs). The objective of this study was to assess predictors of mailed FIT completion among Hispanic individuals. Methods: The San Diego Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) project tested a multi-level mailed FIT intervention in 3 CHC systems in Southern California. Using a cluster-randomized trial design, 9 clinics were randomized to mailed FIT and 16 to usual care. The intervention was delivered in Spanish and English and included an invitation letter, a mailed FIT kit with completion instructions, and phone and text-based reminders. Multi-level implementation strategies (i.e., training, centralized facilitation, etc.) were utilized to increase uptake. For this analysis, we assessed mailed FIT completion at 1 year among Hispanic participants ages 50-75 years not up-to-date with CRC screening at baseline and who were randomized to clinics in the mailed FIT intervention. We conducted logistic regression to assess relationships between sex, language preference, health insurance and mailed FIT return. Results: Among the 9 intervention clinics, 2,199 Hispanic patients who were age-eligible and not up-to-date with CRC screening at baseline were included in the present analysis. In this group, 1,457 (66.3%) were female, 1,449 (65.9%) were Spanish-speaking, and 769 (35.0%) returned the FIT kit. Variation in FIT return for Hispanic individuals was shown across CHC systems: 53.2% in CHC1, 31.4% in CHC2, and 24.7% in CHC3. The percentage of individuals who returned the mailed FIT was highest among 55 to 59-year-olds (39.4%) and lowest among 50 to 54-year-olds (30.6%). Results from univariate logistic regression showed that individuals who preferred Spanish language had higher return rate than those who preferred English (OR=1.44; 95% CI: 1.17-1.77). FIT return was higher among participants who were privately insured compared with Medicaid-insured individuals (OR=1.57; 95% CI: 1.20-2.06). Return rate was higher among females compared to males, but the difference was not statistically significant (OR=1.13, 95% CI: 0.98-1.29). Conclusions: Among Hispanic patients who receive care at CHCs, a regional mailed FIT intervention was effective at increasing screening rates. Mailed FIT completion among participants randomized to clinics in the intervention group varied by language preference and health insurance status. These results suggest that future efforts could be tailored to increase FIT return rates among English-speaking Hispanics and those with Medicaid insurance. Citation Format: Joshua Demb, Maria Elena Martinez, Scott Roesch, Samir Gupta, Valesca Largaespada, Sheila F. Castañeda, Borsika A. Rabin, Jennifer Covin, Kristine Ortwine, Yesenia Preciado-Hidalgo, Nicole Howard, James Schultz, Nannette Stamm, Daniel Ramirez, Michael T. Halpern, Jesse Nodora. Predictors of mailed fecal immunochemical test return for Hispanic patients receiving care at community health centers [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A122.

Supportive-leadership training to improve social connection: A cluster-randomized trial demonstrating efficacy in a high-risk occupational context.

The high, and still rising, rate of loneliness is a threat to public health (Office of the Surgeon General, 2023), with negative mental and physical health consequences (e.g., Holt-Lunstad, 2021). Given that loneliness is a risk factor for poor mental health, efforts to address loneliness are urgently needed. Workplaces can facilitate an employee's social connection through supervisor support training, which can help mitigate loneliness. Among occupational groups, the military is at higher risk for mental health disorders, suicide, and loneliness (Fikretoglu et al., 2022; Naifeh et al., 2019). This study evaluated the efficacy of an evidence-based supportive-leadership training intervention targeting active-duty U.S. Army platoon leaders and targeting both proactive support behaviors that help bolster employee social connection and responsive support behaviors, including destigmatizing mental health. Ninety-nine platoon leaders (69.7% of eligible leaders) completed the 90-min training that consisted of both in-person and computer-based components. Using a cluster-randomized controlled trial design, intervention effects were tested using an intent-to-treat approach and revealed a significant effect, whereby loneliness of service members whose leaders were randomized to the intervention group (N = 118) was significantly reduced compared to loneliness reports for service members in the control group (N = 158). Additionally, service members with higher baseline loneliness were more strongly and positively impacted by the supervisor training, reporting higher levels of supportive behaviors from their leaders at 3 months postbaseline. In sum, these results suggest how workplaces, especially those that are considered high-risk occupations, and their leaders play a critical role in a national strategy to address Americans' well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Methodological progress note: Stepped-wedge cluster randomized trial design.

Methodological progress note: Stepped-wedge cluster randomized trial design.

Effectiveness of a Mobile Phone Messaging-Based Message Framing Intervention for Improving Maternal Health Service Uptake and Newborn Care Practice in Rural Jimma Zone, Ethiopia: Protocol for a Cluster Randomized Controlled Trial.

Ethiopia has high rates of maternal and neonatal mortality. In 2019 and 2020, the maternal and newborn mortality rates were estimated at 412 per 1,000,000 births and 30 per 10,000 births, respectively. While mobile health interventions to improve maternal and neonatal health management have shown promising results, there are still insufficient scientific studies to assess the effectiveness of mobile phone messaging-based message framing for maternal and newborn health. This research aims to examine the effectiveness of mobile phone messaging-based message framing for improving the use of maternal and newborn health services in the Jimma Zone, Ethiopia. A 3-arm cluster-randomized trial design was used to evaluate the effects of mobile phone-based intervention on maternal and newborn health service usage. The trial arms were (1) gain-framed messages (2) loss-framed messages, and (3) usual care. A total of 21 health posts were randomized, and 588 pregnant women who had a gestational age of 16-20 weeks, irrespective of their antenatal care status, were randomly assigned to the trial arms. The intervention consisted of a series of messages dispatched from the date of enrolment until 6-8 months. The control group received existing care without messages. The primary outcomes were maternal health service usage and newborn care practice, while knowledge, attitude, self-efficacy, iron supplementation, and neonatal and maternal morbidity were secondary outcomes. The outcomes will be analyzed using a generalized linear mixed model and the findings will be reported according to the CONSORT-EHEALTH (Consolidated Standards of Reporting Trials of Electronic and Mobile HEalth Applications and onLine TeleHealth) statement for randomized controlled trials. Recruitment of participants was conducted and the baseline survey was administered in March 2023. The intervention was rolled out from May 2023 till December 2023. The end-line assessment was conducted in February 2024. This trial was carried out to understand how mobile phone-based messaging can improve maternal and newborn health service usage. It provides evidence for policy guidelines around mobile health strategies to improve maternal and newborn health. Pan African Clinical Trials Registry PACTR202201753436676; https://tinyurl.com/ykhnpc49. DERR1-10.2196/52395.

A pragmatic randomized trial of mailed fecal immunochemical testing to increase colorectal cancer screening among low-income and minoritized populations.

Colorectal cancer (CRC) screening is underused, particularly among low-income and minoritized populations, for whom the coronavirus disease 2019 (COVID-19) pandemic has challenged progress in achieving equity. A hub-and-spoke model was used. The hub was a nonacademic organization and the spokes were three community health center (CHC) systems overseeing numerous clinic sites. Via a cluster-randomized trial design, nine clinic sites were randomized to intervention and 16 clinic sites were randomized to usual care. Patient-level interventions included invitation letters, mailed fecal immunochemical tests (FITs), and call/text-based reminders. Year 1 intervention impact, which took place during the COVID-19 pandemic, was assessed as the proportion completing screening among individuals not up to date at baseline, which compared intervention and nonintervention clinics accounting for intraclinic cluster variation; confidence intervals (CIs) around differences not including 0 were interpreted as statistically significant. Among 26,736 patients who met eligibility criteria, approximately 58% were female, 55% were Hispanic individuals, and 44% were Spanish speaking. The proportion completing screening was 11.5 percentage points (ppts) (95% CI, 6.1-16.9 ppts) higher in intervention versus usual care clinics. Variation in differences between intervention and usual care clinics was observed by sex (12.6 ppts [95% CI, 7.2-18.0 ppts] for females; 8.8 ppts [95% CI, 4.7-13.9 ppts] for males) and by racial and ethnic group (13.8 ppts [95% CI, 7.0-20.6 ppts] for Hispanic individuals; 13.0 ppts [95% CI, 3.6-22.4 ppts] for Asian individuals; 11.3 ppts [95% CI, 5.8-16.8 ppts] for non-Hispanic White individuals; 6.1 ppts [95% CI, 0.8-10.4 ppts] for Black individuals). A regional mailed FIT intervention was effective for increasing CRC screening rates across CHC systems serving diverse, low-income populations.

Evaluation of the Implementation of the FLOW Program for Increasing Access to Mental Health Care.

The FLOW program was designed to facilitate appropriate and safe transitions of patients from specialty mental health (SMH) to primary care (PC) as a method of improving access and reducing appointment burden on veterans who have improved or remitted. In this study, the team evaluated the implementation of FLOW across nine Veterans Affairs (VA) sites using a mixed-methods evaluation in a cluster-randomized stepped wedge trial design. Outcome assessments used data from VA databases, dashboards, and semi-structured interviews and were guided by the Reach, Adoption, Effectiveness, Implementation, and Maintenance (RE-AIM) framework. Across the sites, mean level reach was 1.36% of all specialty mental health patients transitioned to primary care (standard deviation [SD] = 1.05). Mean provider adoption was 10.2% (SD = 8.3%). Approximately 75% of veterans were fully satisfied with their transition and reported shared decision-making in the decision to transition. Rates of transitions did not decrease over the 6-month maintenance period following implementation. These data suggest that FLOW can be successfully implemented and maintained, although there was wide variation in implementation across sites. Future research should examine how to support sites that struggle with implementation.

Design and rationale of the cardiometabolic health program linked with community health workers and mobile health telemonitoring to reduce health disparities (LINKED-HEARTS) program

Hypertension and diabetes are major risk factors for cardiovascular diseases, stroke, and chronic kidney disease (CKD). Disparities in hypertension control persist among Black and Hispanic adults and persons living in poverty in the United States. The "LINKED-HEARTS Program" (a Cardiometabolic Health Program LINKED with Community Health WorkErs and Mobile HeAlth TelemonitoRing To reduce Health DisparitieS"), is a multi-level intervention that includes home blood pressure (BP) monitoring (HBPM), blood glucose telemonitoring, and team-based care. This study aims to examine the effect of the LINKED-HEARTS Program intervention in improving BP control compared to enhanced usual care (EUC) and to evaluate the reach, adoption, sustainability, and cost-effectiveness of the program. Using a hybrid type I effectiveness-implementation design, 428 adults with uncontrolled hypertension (systolic BP ≥ 140 mm Hg) and diabetes or CKD will be recruited from 18 primary care practices, including community health centers, in Maryland. Using a cluster-randomized trial design, practices are randomly assigned to the LINKED-HEARTS intervention arm or EUC arm. Participants in the LINKED-HEARTS intervention arm receive training on HBPM, BP and glucose telemonitoring, and community health worker and pharmacist telehealth visits on lifestyle modification and medication management over 12 months. The primary outcome is the proportion of participants with controlled BP (<140/90 mm Hg) at 12 months. The study tests a multi-level intervention to control multiple chronic diseases. Findings from the study may be leveraged to reduce disparities in the management and control of chronic diseases and make primary care more responsive to the needs of underserved populations. ClinicalTrials.gov. Identifier: NCT05321368.

Reconsidering stepped wedge cluster randomized trial designs with implementation periods: Fewer sequences or the parallel-group design with baseline and implementation periods are potentially more efficient.

When designing a cluster randomized trial, advantages and disadvantages of tentative designs must be weighed. The stepped wedge design is popular for multiple reasons, including its potential to increase power via improved efficiency relative to a parallel-group design. In many realistic settings, it will take time for clusters to fully implement the intervention. When designing the HEALing (Helping to End Addiction Long-termSM) Communities Study, implementation time was a major consideration, and we examined the efficiency and practicality of three designs. Specifically, a three-sequence stepped wedge design with implementation periods, a corresponding two-sequence modified design that is created by removing the middle sequence, and a parallel-group design with baseline and implementation periods. In this article, we study the relative efficiencies of these specific designs. More generally, we study the relative efficiencies of modified designs when the stepped wedge design with implementation periods has three or more sequences. We also consider different correlation structures. We compare efficiencies of stepped wedge designs with implementation periods consisting of three to nine sequences with a variety of corresponding designs. The three-sequence design is compared to the two-sequence modified design and to the parallel-group design with baseline and implementation periods analysed via analysis of covariance. Stepped wedge designs with implementation periods consisting of four or more sequences are compared to modified designs that remove all or a subset of 'middle' sequences. Efficiencies are based on the use of linear mixed effects models. In the studied settings, the modified design is more efficient than the three-sequence stepped wedge design with implementation periods. The parallel-group design with baseline and implementation periods with analysis of covariance-based analysis is often more efficient than the three-sequence design. With respect to stepped wedge designs with implementation periods that are comprised of more sequences, there are often corresponding modified designs that improve efficiency. However, use of only the first and last sequences has the potential to be either relatively efficient or inefficient. Relative efficiency is impacted by the strength of the statistical correlation among outcomes from the same cluster; for example, the relative efficiencies of modified designs tend to be greater for smaller cluster auto-correlation values. If a three-sequence stepped wedge design with implementation periods is being considered for a future cluster randomized trial, then a corresponding modified design using only the first and last sequences should be considered if sole focus is on efficiency. However, a parallel-group design with baseline and implementation periods and analysis of covariance-based analysis can be a practical, efficient alternative. For stepped wedge designs with implementation periods and a larger number of sequences, modified versions that remove 'middle' sequences should be considered. Due to the potential sensitivity of design efficiencies, statistical correlation should be carefully considered.

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. But applying the Ottawa Statement recommendations to CRTs in the hemodialysis setting is complicated by the unique features of the setting and population. Here, with the help of content experts and patient partners, we co-developed this implementation guidance document to provide research teams, research ethics committees, and other stakeholders with detailed guidance on how to apply the Ottawa Statement recommendations to CRTs in the hemodialysis setting, the result of a 4-year research project. Thus, our work demonstrates how the voices of patients, caregivers, and all stakeholders may be included in the development of research ethics guidance.

Safer Bars: A cluster-randomized effectiveness evaluation of alcohol-related sexual violence prevention through bar staff bystander training

BackgroundSexual assault is consistently associated with social contexts that support high levels of alcohol consumption such as alcohol-serving establishments (i.e., bars). The significant rates of alcohol-involved sexual assault among college students demonstrate the critical need for evidence-based efforts to reduce alcohol-involved sexual assault in this population. Although bystander approaches have demonstrated some promise for reducing alcohol-involved sexual assault, to date no published studies have examined the effectiveness of implementing bystander prevention approaches with bar staff. Given the robust evidence indicating that bars serve as hot spots for sexual aggression, interventions that improve bar staff's ability to identify and intervene in sexually aggressive situations may offer a useful approach for reducing rates of alcohol-involved sexual assault. MethodsThe Safer Bars study utilizes a cluster-randomized trial design that randomizes participants at the bar level into intervention and waitlist control arms. The sample includes bars (Nbars = 56) within a three-mile proximity to the three major public Arizona universities, with an average of 10 staff members per bar (Nstaff = 564). Assessments of individual-level and bar-level outcomes occur at baseline, training completion, and 3-months post-training, with an additional individual-level assessment at 6 months. Community-level effects are assessed using GIS data regarding police dispatches. ConclusionSafer Bars represents a novel, theory-driven approach to promote effective bystander behavior among bar staff working in close proximity to university campuses to reduce rates of alcohol-involved sexual assault.

A Bayesian adaptive design approach for stepped-wedge cluster randomized trials.

The Bayesian group sequential design has been applied widely in clinical studies, especially in Phase II and III studies. It allows early termination based on accumulating interim data. However, to date, there lacks development in its application to stepped-wedge cluster randomized trials, which are gaining popularity in pragmatic trials conducted by clinical and health care delivery researchers. We propose a Bayesian adaptive design approach for stepped-wedge cluster randomized trials, which makes adaptive decisions based on the predictive probability of declaring the intervention effective at the end of study given interim data. The Bayesian models and the algorithms for posterior inference and trial conduct are presented. We present how to determine design parameters through extensive simulations to achieve desired operational characteristics. We further evaluate how various design factors, such as the number of steps, cluster size, random variability in cluster size, and correlation structures, impact trial properties, including power, type I error, and the probability of early stopping. An application example is presented. This study presents the incorporation of Bayesian adaptive strategies into stepped-wedge cluster randomized trials design. The proposed approach provides the flexibility to stop the trial early if substantial evidence of efficacy or futility is observed, improving the flexibility and efficiency of stepped-wedge cluster randomized trials.

Improving access to family planning for women with disabilities in Kaduna city, Nigeria: study protocol for a pragmatic cluster-randomized controlled trial with integrated process evaluation

BackgroundGlobally, women with disabilities are less likely to have access to family planning services compared to their peers without disabilities. However, evidence of effective interventions for promoting their sexual and reproductive health and rights remains limited, particularly in low- and middle-income settings. To help address disparities, an inclusive sexual and reproductive health project was developed to increase access to modern contraceptive methods and reduce unmet need for family planning for women of reproductive age with disabilities in Kaduna city, Nigeria. The project uses demand-side, supply-side and contextual interventions, with an adaptive management approach. This protocol presents a study to evaluate the project’s impact.MethodsA pragmatic cluster-randomized controlled trial design with surveys at baseline and endline will be used to evaluate interventions delivered for at least 1 year at health facility and community levels in comparison to ‘standard’ state provision of family planning services, in the context of state-wide and national broadcast media and advocacy. Randomization will be conducted based on the health facility catchment area, with 19 clusters in the intervention arm and 18 in the control arm. The primary outcome measure will be access to family planning. It was calculated that at least 950 women aged 18 to 49 years with disabilities (475 in each arm) will be recruited to detect a 50% increase in access compared to the control arm. For each woman with disabilities enrolled, a neighbouring woman without disabilities in the same cluster and age group will be recruited to assess whether the intervention has a specific effect amongst women with disabilities. The trial will be complemented by an integrated process evaluation. Ethical approval for the study has been given by the National Health Research Ethics Committee of Nigeria and London School of Hygiene & Tropical Medicine.DiscussionDefining access to services is complex, as it is not a single variable that can be measured directly and need for family planning is subjectively defined. Consequently, we have conceptualized ‘access to family planning’ based on a composite of beliefs about using services if needed.Trial registrationISRCTN registry ISRCTN12671153. Retrospectively registered on 17/04/2023.

A mixed method evaluation of a theory based intervention to reduce sedentary behaviour in contact centres- the stand up for health stepped wedge feasibility study

Introduction Contact centres have higher levels of sedentary behaviour than other office-based workplaces. Stand Up for Health (SUH) is a theory-based intervention developed using the 6SQuID framework to reduce sedentary behaviour in contact centre workers. The aim of this study was to test acceptability and feasibility of implementing SUH in UK contact centres. Methods The study was conducted in 2020–2022 (pre COVID and during lockdown) and used a stepped-wedge cluster randomised trial design including a process evaluation. The intervention included working with contact centre managers to develop and implement a customised action plan aligning with SUH’s theory of change. Workplace sedentary time, measured using activPAL™ devices, was the primary outcome. Secondary outcomes included productivity, mental wellbeing, musculoskeletal health and physical activity. Empirical estimates of between-centre standard deviation and within-centre standard deviation of outcomes from pre-lockdown data were calculated to inform sample size calculations for future trials. The process evaluation adopted the RE-AIM framework to understand acceptability and feasibility of implementing the intervention. Interviews and focus groups were conducted with contact centre employees and managers, and activity preferences were collected using a questionnaire. Results A total of 11 contact centres participated: 155 employees from 6 centres in the pre-lockdown data collection, and 54 employees from 5 centres post-lockdown. Interviews and focus groups were conducted with 33 employees and managers, and 96 participants completed an intervention activity preference questionnaire. Overall, the intervention was perceived as acceptable and feasible to deliver. Most centres implemented several intervention activities aligned with SUH’s theory of change and over 50% of staff participated in at least one activity (pre-lockdown period). Perceived benefits including reduced sedentary behaviour, increased physical activity, and improved staff morale and mood were reported by contact centre employees and managers. Conclusions SUH demonstrates potential as an appealing and acceptable intervention, impacting several wellbeing outcomes. Trial registration The trial has been registered on the ISRCTNdatabase: http://www.isrctn.com/ISRCTN11580369.

Implementation strategies for hospital-based probiotic administration in a stepped-wedge cluster randomized trial design for preventing hospital-acquired Clostridioides difficile infection

BackgroundClostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +).MethodsWe used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research.ResultsA total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals.ConclusionsUse of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

The staircase cluster randomised trial design: A pragmatic alternative to the stepped wedge.

This article introduces the 'staircase' design, derived from the zigzag pattern of steps along the diagonal of a stepped wedge design schematic where clusters switch from control to intervention conditions. Unlike a complete stepped wedge design where all participating clusters must collect and provide data for the entire trial duration, clusters in a staircase design are only required to be involved and collect data for a limited number of pre- and post-switch periods. This could alleviate some of the burden on participating clusters, encouraging involvement in the trial and reducing the likelihood of attrition. Staircase designs are already being implemented, although in the absence of a dedicated methodology, approaches to sample size and power calculations have been inconsistent. We provide expressions for the variance of the treatment effect estimator when a linear mixed model for an outcome is assumed for the analysis of staircase designs in order to enable appropriate sample size and power calculations. These include explicit variance expressions for basic staircase designs with one pre- and one post-switch measurement period. We show how the variance of the treatment effect estimator is related to key design parameters and demonstrate power calculations for examples based on a real trial.

A multi-dimensional incomplete stepped-wedge trial design to estimate the impact of standards-based audit.

A clinical audit is a low-cost process used for quality improvement in healthcare. Such audits are however infrequently used in resource poor countries, where the need for and potential impact of quality improvement is higher. Sets of standards for use in maternal and newborn care have been established based on internal guidelines and evidence. The before-after design of a clinical audit is prone to bias in the estimation of the impact of conducting a clinical audit. A trial design that would provide an unbiased estimate of the impact of implementing a clinical audit process on the attainment of standards selected (a standards-based audit) was needed. The aim of this paper is to introduce and describe the design of trials we developed to meet this need. A novel randomised stepped-wedge trial design to estimate the impact of conducting standards-based audits is presented. A multi-dimensional incomplete stepped-wedge cluster randomised trial design suitable for estimation of the impact of Standards-based audits on compliance with standard is proposed; two variants are described in detail. A method for sample size estimation is described. Analyses can be performed for the binary outcome using a generalised linear mixed model framework to estimate the impact of the approach on compliance with standards subjected to a standards-based audit; additional terms to consider including in sensitivity analyses are considered. The design presented has the potential to estimate the impact of introducing the standards-based audit process on compliance with standard, while providing participating healthcare providers opportunity to gain experience of implementing the standards-based audit process. The design may be applicable in other areas in which multiple processes are to be studied.

Protocol and Statistical Analysis Plan for the Mode of Ventilation During Critical Illness (MODE) Trial

For every critically ill adult receiving invasive mechanical ventilation, clinicians must select a mode of ventilation. The mode of ventilation determines whether the ventilator directly controls the tidal volume or the inspiratory pressure. Newer hybrid modes allow clinicians to set a target tidal volume; the ventilator controls and adjusts the inspiratory pressure. A strategy of low tidal volumes and low plateau pressure improves outcomes, but the optimal mode to achieve these targets is not known. Can a cluster-randomized trial design be used to assess whether the mode of mandatory ventilation affects the number of days alive and free of invasive mechanical ventilation among critically ill adults? The Mode of Ventilation During Critical Illness (MODE) trial is a cluster-randomized, multiple-crossover pilot trial being conducted in the medical ICU at an academic center. The MODE trial compares the use of volume control, pressure control, and adaptive pressure control. The study ICU is assigned to a single-ventilator mode (volume control vs pressure control vs adaptive pressure control) for continuous mandatory ventilation during each 1-month study block. The assigned mode switches every month in a randomly generated sequence. The primary outcome is ventilator-free days to study day 28, defined as the number of days alive and free of invasive mechanical ventilation from the final receipt of mechanical ventilation to 28 days after enrollment. Enrollment began November 1, 2022, and will end on July 31, 2023. This manuscript describes the protocol and statistical analysis plan for the MODE trial of ventilator modes comparing volume control, pressure control, and adaptive pressure control. Prespecifying the full statistical analysis plan prior to completion of enrollment increases rigor, reproducibility, and transparency of the trial results. The trial was registered with clinicaltrials.gov on October 3, 2022, before initiation of patient enrollment on November 1, 2022 (ClinicalTrials.gov identifier: NCT05563779).

The Me and the Us of Emotions: a cluster-randomized controlled trial of the feasibility and efficacy of a compassion-based social-emotional learning program for children.

There are well-established benefits of social and emotional learning (SEL) programs for children within educational contexts. Combining social-emotional skills and compassion abilities has been seldomly done, and it may be valuable at individual and societal levels, for resilient, empathetic, and inclusive societies. This study explored the feasibility and efficacy of a program designed to promote socioemotional and compassion skills in children attending the 3rd and 4th grades, by using in-class dynamics complemented with serious games. This program, named "The Me and the Us of Emotions," is part of the Gulbenkian Knowledge Academies 2020 and consists of 10 group sessions embedded in the school curriculum. Using a cluster-randomized controlled trial design, school classes were allocated to intervention (classes, n = 8; children, n = 163) and control groups (classes, n = 6; children, n = 132). During the program, facilitators assessed adherence to the sessions' plan, attendance, dosage (i.e., how many sessions were delivered), and participant responsiveness. Children completed self-report measures of social-emotional skills and emotional climate at pre-, post-intervention, 3-month, and 6-month follow-ups. Results indicate that the program is feasible, with high adherence, high attendance rate, and participant responsiveness. Results also indicate empathy, soothing, and drive feelings to change from pre-intervention to all other assessment moments, for the intervention group only. Moreover, cooperation and threat changed over time for participants in both the control and the intervention groups. The current study offers empirical support for the feasibility and utility of a compassion-based social-emotional learning program on promoting children's empathy, and emotions of soothing and vitality in the school context. Thus, these findings contribute to recent research on the potential added value of compassion practices within an SEL program.