Point-of-care molecular testing and antiviral treatment of influenza in residents of homeless shelters in Seattle, WA: study protocol for a stepped-wedge cluster-randomized controlled trial

Abstract Introduction Influenza is an important public health problem, but data on the impact of influenza among homeless shelter residents are limited. The primary aim of this study is to evaluate whether on-site testing and antiviral treatment of influenza in residents of homeless shelters reduces influenza spread in these settings. Methods and analysis This study is a stepped-wedge cluster-randomized trial of on-site testing and antiviral treatment for influenza in nine homeless shelter sites within the Seattle metropolitan area. Participants with acute respiratory illness (ARI), defined as two or more respiratory symptoms or new or worsening cough with onset in the prior 7 days, are eligible to enroll. Approximately 3200 individuals are estimated to participate from October to May across two influenza seasons. All sites will start enrollment in the control arm at the beginning of each season, with routine surveillance for ARI. Sites will be randomized at different timepoints to enter the intervention arm, with implementation of a test-and-treat strategy for individuals with two or fewer days of symptoms. Eligible individuals will be tested on-site with a point-of-care influenza test. If the influenza test is positive and symptom onset is within 48 h, participants will be administered antiviral treatment with baloxavir or oseltamivir depending upon age and comorbidities. Participants will complete a questionnaire on demographics and symptom duration and severity. The primary endpoint is the incidence of influenza in the intervention period compared to the control period, after adjusting for time trends. Trial registration ClinicalTrials.gov NCT04141917. Registered 28 October 2019. Trial sponsor: University of Washington.

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Impact of Routine Point-of-Care Versus Laboratory Testing for Early Infant Diagnosis of HIV: Results From a Multicountry Stepped-Wedge Cluster-Randomized Controlled Trial

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/qai.0000000000002383 ◽

2020 ◽

Vol 84 (1) ◽

pp. S5-S11

Author(s):

Emma Sacks ◽

Jennifer Cohn ◽

Bernard Ochuka ◽

Haurovi Mafaune ◽

Addmore Chadambuka ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Laboratory Testing ◽

Point Of Care ◽

Controlled Trial ◽

Cluster Randomized Controlled Trial ◽

Early Infant Diagnosis ◽

Stepped Wedge ◽

Randomized Controlled ◽

Early Infant ◽

Cluster Randomized

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Atmiyata, a community led intervention to address common mental disorders: Study protocol for a stepped wedge cluster randomized controlled trial in rural Gujarat, India

10.21203/rs.2.12186/v2 ◽

2019 ◽

Author(s):

Kaustubh Joag ◽

Jasmine Kalha ◽

Deepa Pandit ◽

Susmita Chatterjee ◽

Sadhvi Krishnamoorthy ◽

...

Keyword(s):

Mental Health ◽

Common Mental Disorders ◽

Controlled Trial ◽

Mixed Effects ◽

Stepped Wedge ◽

Linear Mixed Effects ◽

Lay Health Worker ◽

Randomized Controlled ◽

Cluster Randomized ◽

The Impact

Abstract Background: While lay-health worker models for mental health care have proven to be effective in controlled trials, there is limited evidence on the effectiveness and scalability of these models in rural communities in low- and middle-income countries (LMICs). Atmiyata is a rural community-led intervention using local community volunteers, called Champions, to identify and provide evidence-based counselling for persons with common mental disorders (CMD) as part of a package of community-based interventions for mental health. Methods: The impact of the Atmiyata intervention is evaluated through a stepped wedge cluster randomized controlled trial (SW-CRCT) with a nested economic evaluation. The trial spans across 10 sub-blocks (645 villages) in Mehsana district with 1.52 million rural adult population. There are 56Primary Health Centers (PHCs) in Mehsana district and villages covered under these PHCs are equally divided into four groups of clusters of 14 PHCs each, and the intervention is rolled out in a staggered manner in these groups of villages at an interval of 5 months. The primary outcome is symptomatic improvement measured through the GHQ-12 at 3-month follow-up. Secondary outcomes include: quality of life using the EURO-QoL (EQ- 5D), symptom improvement measured by the Self-Reporting Questionnaire-20 (SRQ-20), functioning using the WHO Disability Assessment Scale (WHO-DAS-12), depression symptoms using the Patient Health Questionnaire, (PHQ-9), anxiety symptoms using Generalized Anxiety Disorder Questionnaire, (GAD-7) and social participation using the Social Participation Scale (SPS). Generalized linear mixed effects model are employed for binary outcomes and linear mixed effects models for continuous outcomes. A Return on investment (ROI) analysis of the intervention will be conducted to understand whether the intervention generates any return on financial investments made into the project. Discussion: Stepped wedge designs are progressively being used to evaluate real-life effectiveness of interventions. To the best of our knowledge, this is the first SW-CRCT in a LMIC evaluating the impact of implementation of a psychosocial mental health intervention. The results of this study will contribute to the evidence on scaling-up lay health worker models for mental health interventions and contribute to the SW-CRCT literature in LMICs.

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A Stepped Wedge Cluster-Randomized Trial Assessing the Impact of a Riverbank Filtration Intervention to Improve Access to Safe Water on Health in Rural India

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.19-0260 ◽

2020 ◽

Vol 102 (3) ◽

pp. 497-506 ◽

Cited By ~ 2

Author(s):

Sarah L. McGuinness ◽

Joanne O’Toole ◽

Andrew B. Forbes ◽

Thomas B. Boving ◽

Kavita Patil ◽

...

Keyword(s):

Randomized Trial ◽

Cluster Randomized Trial ◽

Riverbank Filtration ◽

Rural India ◽

Stepped Wedge ◽

Safe Water ◽

Cluster Randomized ◽

The Impact ◽

Improve Access

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Impact of Introducing Hepatitis B Birth Dose Vaccines into the Infant Immunization Program in Burkina Faso: Study Protocol for a Stepped Wedge Cluster Randomized Trial (NéoVac Study)

Vaccines ◽

10.3390/vaccines9060583 ◽

2021 ◽

Vol 9 (6) ◽

pp. 583

Author(s):

Haoua Tall ◽

Pierrick Adam ◽

Abdoul Salam Eric Tiendrebeogo ◽

Jeanne Perpétue Vincent ◽

Laura Schaeffer ◽

...

Keyword(s):

Hepatitis B ◽

Burkina Faso ◽

Health Center ◽

Sub Saharan Africa ◽

Stepped Wedge ◽

Immunization Program ◽

Birth Dose ◽

Sub Saharan ◽

Cluster Randomized ◽

The Impact

To achieve global hepatitis elimination by 2030, it is critical to prevent the mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Since 2009, the WHO has recommended administering hepatitis B vaccine to all neonates within 24 h of birth to prevent MTCT. However, many countries in sub-Saharan Africa only provide hepatitis B immunization at the age of 6, 10, and 14 weeks or 8, 12, and 16 weeks using a combined vaccine. To accelerate the introduction of the hepatitis B birth dose vaccine (HepB-BD) into sub-Saharan Africa, it is critical to establish to what extent the addition of HepB-BD can further reduce HBV transmission in areas where three-dose infant vaccination has been implemented. We therefore designed a study to evaluate the impact, acceptability, and cost-effectiveness of incorporating the HepB-BD into the routine immunization program in a real-life field condition in Burkina Faso, where the hepatitis B vaccination is currently scheduled at 8-12-16 weeks. Through a multidisciplinary approach combining epidemiology, anthropology, and health economics, the Neonatal Vaccination against Hepatitis B in Africa (NéoVac) study conducts a pragmatic stepped wedge cluster randomized controlled trial in rural areas of the Hauts-Bassins Region. The study was registered in ClinicalTrials.gov (identifier: NCT04029454). A health center is designated as a cluster, and the introduction of HepB-BD will be rolled out sequentially in 24 centers. Following an initial period in which no health center administers HepB-BD, one center will be randomly allocated to incorporate HepB-BD. Then, at a regular interval, another center will be randomized to cross from the control to the intervention period, until all 24 centers integrate HepB-BD. Pregnant women attending antenatal care will be systematically invited to participate. Infants born during the control period will follow the conventional immunization schedule (8-12-16 weeks), while those born in the interventional period will receive HepB-BD in addition to the routine vaccines (0-8-12-16 weeks). The primary outcome, the proportion of hepatitis B surface antigen (HBsAg) positivity in infants aged at 9 months, will be compared between children born before and after HepB-BD introduction. The study will generate data that may assist governments and stakeholders in sub-Saharan Africa to make evidence-based decisions about whether to add HepB-BD into the national immunization programs.

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Point-of-care ultrasound-guided regional anaesthesia in older ED patients with hip fractures: a study to test the feasibility of a training programme and time needed to complete nerve blocks by ED physicians after training

BMJ Open ◽

10.1136/bmjopen-2020-047113 ◽

2021 ◽

Vol 11 (7) ◽

pp. e047113

Author(s):

Jacques Simon Lee ◽

Tina Bhandari ◽

Robert Simard ◽

Marcel Emond ◽

Claude Topping ◽

...

Keyword(s):

Hip Fractures ◽

Regional Anaesthesia ◽

Point Of Care ◽

Secondary Outcome ◽

Point Of Care Ultrasound ◽

Emergency Physicians ◽

Stepped Wedge ◽

Ultrasound Guided ◽

Cluster Rct ◽

The Impact

ObjectivesPoint-of-care ultrasound-guided regional anaesthesia (POCUS-GRA) provides safe, rapid analgesia for older people with hip fractures but is rarely performed in the emergency department (ED). Self-perceived inadequate training and time to perform POCUS-GRA are the two most important barriers. Our objective is to assess the feasibility of a proposed multicentre, stepped-wedge cluster randomised clinical trial (RCT) to assess the impact of a knowledge-to-practice (KTP) intervention on delirium.DesignOpen-label feasibility study.SettingAn academic tertiary care Canadian ED (annual visits 60 000).ParticipantsEmergency physicians working at least one ED shift per week, excluding those already performing POCUS-GRA more than four times per year.InterventionA KTP intervention, including 2-hour structured training sessions with procedure bundle and email reminders.Primary and secondary outcome measuresThe primary feasibility outcome is the proportion of eligible physicians that completed training and subsequently performed POCUS-GRA. Secondary outcome is the time needed to complete POCUS-GRA. We also test the feasibility of the enrolment, consent and randomisation processes for the future stepped-wedge cluster RCT (NCT02892968).ResultsOf 36 emergency physicians, 4 (12%) were excluded or declined participation. All remaining 32 emergency physicians completed training and 31 subsequently treated at least one eligible patient. Collectively, 27/31 (87.1%) performed 102 POCUS-GRA blocks (range 1–20 blocks per physician). The median (IQR) time to perform blocks was 15 (10–20) min, and reduction in pain was 6/10 (3–7) following POCUS-GRA. There were no reported complications.ConclusionOur KTP intervention, consent process and randomisation were feasible. The time to perform POCUS-GRA rarely exceeded 30 min, Our findings reinforce the existing data on the safety and effectiveness of POCUS-GRA, mitigate perceived barriers to more widespread adoption and demonstrate the feasibility of trialling this intervention for the proposed stepped-wedge cluster RCT.Trial registration numberClinicaltrials.gov #02892968

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Inference for the treatment effect in longitudinal cluster randomized trials when treatment effect heterogeneity is ignored

Statistical Methods in Medical Research ◽

10.1177/09622802211041754 ◽

2021 ◽

pp. 096228022110417

Author(s):

Rhys Bowden ◽

Andrew B Forbes ◽

Jessica Kasza

Keyword(s):

Treatment Effect ◽

Randomized Trials ◽

Error Rates ◽

Type I ◽

Cluster Randomized Trials ◽

Stepped Wedge ◽

Treatment Effect Heterogeneity ◽

Cluster Randomized ◽

Effect Heterogeneity ◽

The Impact

In cluster-randomized trials, sometimes the effect of the intervention being studied differs between clusters, commonly referred to as treatment effect heterogeneity. In the analysis of stepped wedge and cluster-randomized crossover trials, it is possible to include terms in outcome regression models to allow for such treatment effect heterogeneity yet this is not frequently considered. Outside of some simulation studies of specific cases where the outcome is binary, the impact of failing to include terms for treatment effect heterogeneity on the variance of the treatment effect estimator is unknown. We analytically examine the impact of failing to include terms for treatment effect heterogeneity on the variance of the treatment effect estimator, when outcomes are continuous. Using analysis of variance and feasible generalized least squares we provide expressions for this variance. For both the cluster-randomized crossover design and the stepped wedge design, our analytic derivations indicate that failing to include treatment effect heterogeneity results in the estimates for variance of the treatment effect that are too small, leading to inflation of type I error rates. We therefore recommend assessing the sensitivity of sample size calculations and conclusions drawn from the analysis of cluster randomized trials to the inclusion of treatment effect heterogeneity.

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Information growth for sequential monitoring of clinical trials with a stepped wedge cluster randomized design and unknown intracluster correlation

Clinical Trials ◽

10.1177/1740774520901488 ◽

2020 ◽

Vol 17 (2) ◽

pp. 176-183

Author(s):

Siobhan P Brown ◽

Abigail B Shoben

Keyword(s):

Study Design ◽

Type I Error ◽

Type I ◽

Intracluster Correlation ◽

Stepped Wedge ◽

Group Sequential ◽

New Therapy ◽

Cluster Randomized ◽

The Impact ◽

Information Growth

Background/aims In a stepped wedge study design, study clusters usually start with the baseline treatment and then cross over to the intervention at randomly determined times. Such designs are useful when the intervention must be delivered at the cluster level and are becoming increasingly common in practice. In these trials, if the outcome is death or serious morbidity, one may have an ethical imperative to monitor the trial and stop before maximum enrollment if the new therapy is proven to be beneficial. In addition, because formal monitoring allows for the stoppage of trials when a significant benefit for new therapy has been ruled out, their use can make a research program more efficient. However, use of the stepped wedge cluster randomized study design complicates the implementation of standard group sequential monitoring methods. Both the correlation of observations introduced by the clustered randomization and the timing of crossover from one treatment to the other impact the rate of information growth, an important component of an interim analysis. Methods We simulated cross-sectional stepped wedge study data in order to evaluate the impact of sequential monitoring on the Type I error and power when the true intracluster correlation is unknown. We studied the impact of varying intracluster correlations, treatment effects, methods of estimating the information growth, and boundary shapes. Results While misspecified information growth can impact both the Type I error and power of a study in some settings, we observed little inflation of the Type I error and only moderate reductions in power across a range of misspecified information growth patterns in our simulations. Conclusion Taking the study design into account and using either an estimate of the intracluster correlation from the ongoing study or other data in the same clusters should allow for easy implementation of group sequential methods in future stepped wedge designs.

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Permutation tests for stepped-wedge cluster-randomized trials

The Stata Journal Promoting communications on statistics and Stata ◽

10.1177/1536867x19893624 ◽

2019 ◽

Vol 19 (4) ◽

pp. 803-819 ◽

Cited By ~ 2

Author(s):

Jennifer Thompson ◽

Calum Davey ◽

Richard Hayes ◽

James Hargreaves ◽

Katherine Fielding

Keyword(s):

Statistical Tests ◽

Permutation Tests ◽

Weighted Average ◽

Stepped Wedge ◽

Intervention Effect ◽

Trial Testing ◽

Stepped Wedge Trials ◽

Using Data ◽

Cluster Randomized ◽

The Impact

Permutation tests are useful in stepped-wedge trials to provide robust statistical tests of intervention-effect estimates. However, the permute command does not produce valid tests in this setting because individual observations are not exchangeable. We introduce the swpermute command, which permutes clusters to sequences to maintain exchangeability. The command provides additional functionality for performing analyses of stepped-wedge trials. In particular, we include the withinperiod option, which performs the specified analysis separately in each period of the study with the resulting period-specific intervention-effect estimates combined as a weighted average. We also include functionality to test nonzero null hypotheses to aid in the construction of confidence intervals. Examples of the application of swpermute are given using data from a trial testing the impact of a new tuberculosis diagnostic test on bacterial confirmation of a tuberculosis diagnosis.

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