Cluster Randomized Trial Design Research Articles

A Scoping Review on the Attributes of Cluster Randomized Controlled Trials in Long-Term Care Facilities.

Cluster randomized trial design, where groups of participants are randomized instead of individual participants, is increasingly being used in long-term care research. The purpose of this review was to determine the characteristics of cluster randomized trials in long-term care facilities. A medical librarian conducted the literature search. Two independent reviewers reviewed each paper. Studies were included if the design was cluster randomized and participants were from long-term care facilities. For each included study, two independent data extractors captured data on study attributes, including: journal, location, year published, author discipline, funding, methodology, number of participants, and intervention target. The literature search yielded 7,679 unique studies, with 195 studies meeting the selection criteria and being included for data extraction. The included studies were published between 1976 and 2017, with 53% of studies published after 2009. The term cluster randomized was in the title of only 45% of the studies. The studies were conducted worldwide; the United States had the largest number of studies (23%), followed by the United Kingdom (18%). Ten percent of studies were published in journals with an impact factor >10. The most frequent discipline of the first and last authors was medicine (34%), followed by nursing (17%). Forty-nine percent of the studies had government funding, while only 20% had medical industry funding. In studies with <1000 residents, 85% of the studies obtained consent from the resident and/or their proxy, while in studies with ≥ 1000 residents, it was 31%. The most frequent intervention targets were infection (13%), falls/fracture (13%), and behavior/physical restraint (13%). Cluster randomized controlled trials in long-term care have a unique set of characteristics. Results of this review will provide guidance to researchers conducting studies in long-term care facilities.

Study protocol of the Healthy High School study: a school-based intervention to improve well-being among high school students in Denmark

BackgroundThe prevalence of low well-being, perceived stress and unhealthy behaviours is high among high school students, but few interventions have addressed these problems. The aim of this paper is to present a study protocol of a cluster randomised controlled trial evaluating the Healthy High School (HHS) intervention programme. The intervention programme is designed to improve well-being (primary outcome) by preventing 1) stress and promoting 2) sleep, 3) sense of community, 4) physical activity (PA) and 5) regular and healthy meals among high school students in Denmark.MethodsThe development of the HHS study was guided by the Intervention Mapping protocol. The intervention comprises four components: 1) a teaching material, 2) a smartphone app, 3) a catalogue focusing on environmental changes, and 4) a peer-led innovation workshop aiming at inspiring students to initiate and participate in various movement activities. The HHS study employs a cluster-randomised controlled trial design. Thirty-one high schools across Denmark were randomly allocated to intervention (16 schools) or control (15 schools) groups. The study included all first-year students (~ 16 years of age) (n = 5976 students). Timeline: Intervention: August 2016 – June 2017. Collection of questionnaire data: Baseline (August 2016), 1st follow-up (May 2017) and 2nd follow-up (April 2018). All students were invited to participate in a monthly sub-study about perceived stress using text messages for data collection (September 2016 – June 2017). PA was objectively assessed among a sub-sample of students using accelerometers (Axivity, AX3) in August 2016 and May 2017. Primary outcome measures: Student well-being measured by the Cantril Ladder and the five item World Health Organisation Well-being Index (individual level outcomes). Secondary outcome measures: Stress (10-item Perceived Stress Scale), sleep (quantity and quality), PA (hours of moderate-to-vigorous PA per week, hours of daily sedentary time and average daily PA), meal habits (daily intake of breakfast, lunch, snacks and water), and strong sense of community in class and at school, respectively (individual level outcomes). The study encompasses process and effect evaluation as well as health economic analyses.Trial registrationISRCTN ISRCTN43284296, 28 April 2017, retrospectively registered.

Impact of regular deworming and long term multiple micro-nutrient supplementation on nutritional status of extremely poor women and children

Introduction: Growth failure among children and micronutrient deficiency among children and women is one of the major nutritional problems in Bangladesh. According to a 2011 estimate, half of the children and 40% women were anaemic, and the prevalence of stunting and underweight was 40% and 36% among children, while a quarter of non-pregnant adult women were chronically energy deficient. The problem was magnified among the extreme poor population. Previously, standalone initiatives have attempted to tackle undernutrition and micronutrient deficiency separately, but there have been few attempts to integrate these two approaches; and credible evidence from experimental studies was sought from the government and development partners to guide future policy and investment decisions.&#x0D; Aims &amp; Objectives: This study aimed to determine the effect of an intervention package, containing deworming at six-monthly intervals, daily multiple-micronutrient powder (MNP containing 15 ingredients) supplementation for twelve months, and flip flop (thong) shoes in reducing anaemia among extremely poor women and children under-five, as well as to assess the effect on growth failure.&#x0D; Methods: The study employed a two-arm cluster randomised trial design involving 537 women and 168 under-five children in 21 clusters within the intervention arm, while the comparison clusters contained a total of 503 women and 139 under-five children in another 21 clusters. The implementation took place between December 2010 and December 2011. Anaemia prevalence was the primary outcome; growth failure (measured by anthropometry), the prevalence of diarrhoea, and passed worms were assessed as secondary outcomes. The analysis was conducted based on cluster-level summaries of mean and prevalence, and the differences between groups were compared using independent sample t-tests.&#x0D; Results: The study detected a significant effect on anaemia. At endline, the prevalence of anaemia among the women in the intervention clusters was 52% less than the comparison clusters (mean difference 18.1%, 95% CI: 11.1% to 25.1%, P&lt;0.001). Among the under-fives in the intervention clusters, anaemia prevalence was 58% lower (mean difference 18.4%, 95% CI: 7.2% to 29.6%, P=0.002). Mean haemoglobin concentration was also significantly higher among the children (mean difference 7.8 g/l, 95% CI: 5.0 to 10.7, P&lt;0.001) and women (mean difference 4.8 g/l, 95% CI: 3.3 to 6.3, P&lt;0.001) in the intervention clusters. However, there was no detectable effect on child growth failure (stunting, underweight, wasting and thinness), chronic energy deficiency among women, the prevalence of diarrhoea, or passed worms.&#x0D; Conclusion: The study results suggest that the intervention package is effective in reducing anaemia among women and children under-five. However, the current evidence is insufficient to make a public health recommendation for using the intervention package, containing 15 component MNP, to replace the existing government and WHO recommendation for using 5 component MNP. Further investigation would be necessary to answer this important public health question.

Stepped-wedge trials should be classified as research for the purpose of ethical review.

All studies classified as research involving human participants require research ethics review. Most regulation and guidance on ethical oversight of research involving human participants was written for pharmacotherapy interventions. Interpretation of such guidance for cluster-randomized trials and stepped-wedge trials, which commonly evaluate complex non-therapeutic interventions such as knowledge translation, public health, or health service delivery interventions, can pose challenges to researchers and regulators. The Ottawa Statement on the Ethical Design and Conduct of Cluster-Randomized Trials provides guidance on the ethical oversight and consent procedures for cluster-randomized trials, and while not explicit, this includes stepped-wedge trials. Yet, stepped-wedge trials have unique characteristics that differentiate them from standard cluster-randomized trials. In particular, they can be used to evaluate knowledge translation interventions within the context of a routine health system rollout; they may have a non-randomized design; and the decision to implement the intervention is not always made by the researcher. Many stepped-wedge trials do not undergo ethical review and do not report trial registration. This suggests that those undertaking these studies and research ethics committees perceive them as non-research activities. Through an ethical analysis of two case studies, we argue that stepped-wedge trials, like parallel arm cluster trials, are systematic investigations designed to produce generalizable knowledge. We contend that stepped-wedge trials usually include human research participants, which may be patients, health care providers, or both. Stepped-wedge trials are therefore research involving human participants for the purpose of ethical review. Nevertheless, the use of a waiver or alteration of consent may be appropriate in many stepped-wedge trials due to the infeasibility of obtaining informed consent and the low-risk nature of the interventions. To ensure that traditional ethical principles such as respect for persons are upheld, these studies must undergo research ethics review.

Effectiveness of upgraded maternity waiting homes and local leader training in improving institutional births among women in the Jimma zone, Ethiopia: study protocol for a cluster-randomized controlled trial

BackgroundEthiopia is one of the ten countries in the world that together account for almost 60% of all maternal deaths. Recent reductions in maternal mortality have been seen, yet just 26% of women who gave birth in Ethiopia in 2016 reported doing so at a health facility. Maternity waiting homes (MWHs) have been introduced to overcome geographical and financial barriers to institutional births but there is no conclusive evidence as to their effectiveness. We aim to evaluate the effects of upgraded MWHs and local leader training in increasing institutional births in the Jimma zone of Ethiopia.MethodsA parallel, three-arm, stratified, cluster-randomized controlled trial design is being employed to evaluate intervention effects on institutional births, which is the primary outcome. Trial arms are: (1) upgraded MWH + religious/community leader training; (2) leader training alone; and (3) standard care. Twenty-four primary health care unit catchment areas (clusters) have been randomized and 3840 women of reproductive age who had a pregnancy outcome (livebirth, stillbirth or abortion) are being randomly recruited for each survey round. Outcome assessments will be made using repeat cross-sectional surveys at baseline and 24 months postintervention. An intention to treat approach will be used and the primary outcome analysed using generalized linear mixed models with a random effect for cluster and time. A cost-effectiveness analysis will also be conducted from a societal perspective.DiscussionThis is one of the first trials to evaluate the effectiveness of upgraded MWHs and will provide much needed evidence to policy makers about aspects of functionality and the community engagement required as they scale-up this programme in Ethiopia.Trial registrationClinicalTrial.gov, NCT03299491. Retrospectively registered on 3 October 2017.

Evaluating the Role of Parent-Child Interactive Groups in a Parent Training Program for Children with Externalizing and/or Internalizing Behavior Problems

SYNOPSISObjective: This study evaluated the role of parent-child interactive groups in a group-based parent training program for children with externalizing and/or internalizing behavior problems; Design: A cluster-randomized trial design compared two versions of delivery of the Exploring Together program, with (Exploring Together; ET) and without (Exploring Together-Adapted; ET-Adapted) the parent-child interactive component. Participants were 136 parents and their children (aged 5–10 years) with identified externalizing and/or internalizing problems, recruited from primary schools. Outcome measures were parent- and teacher-reported child externalizing and internalizing problems, assessed at post intervention and at 6- and 12-month follow-ups; Results: Significant reductions in parent- and teacher-reported child externalizing and internalizing problems were evident across both treatment groups (ET and ET-Adapted) at post intervention. At the 6- and 12-month follow-ups significant reductions were maintained across both groups on parent-reported child externalizing and internalizing problems only. No differences were found between the two treatment groups on any of the child outcome variables at any time point; Conclusions: Inclusion of parent-child interactive groups was not associated with greater improvement in child behavior outcomes. This finding suggests service providers would need to consider potential resource (i.e., staffing allocation) and clinical benefit (i.e., coaching parents through behavior management issues in vivo) associated with the two versions of the program.

Impact of a Pilot School-Based Nutrition Intervention on Fruit and Vegetable Waste at School Lunches

ObjectiveTo determine the preliminary impact of the Brighter Bites nutrition intervention on decreasing fruit and vegetable (F&V) waste at school lunches among fourth- and fifth-grade children. MethodThis was a nonrandomized pre–post-controlled study in Houston and Dallas, TX. Two schools received the Brighter Bites intervention (n = 76), and 1 comparison school (n = 39), during the 2017-2018 school year. Brighter Bites is a 16-week school-based nutrition intervention providing weekly distribution of fresh F&V plus nutrition education. Main outcome measures were direct observation and weights to measure the number of F&V dishes selected at school lunches, amount of F&V wasted (gm), and related nutrient waste (4 time points/child). Mixed-effects linear regression analysis was used to determine change in F&V selection and waste over time. ResultsThere was a significant decrease over time in proportion of F&V selected among those in the comparison school, but not the intervention schools (P < .001). Compared with children in the comparison group, those receiving Brighter Bites showed a significant decrease in the amount of F&V wasted at each meal (P < .001) and per item (P < .05) at the end of both 8 and 16 weeks of intervention. There were significant decreases in waste of energy (kcal); dietary fiber (gm); vitamins B1, B3, and B6 (mg); total folate (µg); and B12 (µg) among those receiving Brighter Bites (P < .05). Conclusions and ImplicationsAlthough absolute food or nutrient changes were small even when significant, programs such as Brighter Bites may contribute to a healthy intake. Future studies are warranted that include a larger sample size with a stringent, cluster-randomized control trial design and consideration for other covariates.

An evaluation of the effectiveness of a community-based parenting empowerment program to improve nurturing care of young children in Kenya and Zambia

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Investing in parents and children during the critical period between birth and five years of a child’s life can have long-lasting benefits in the life of the child. Recently, the 2016 Lancet Series estimated that 250 million children aged less than five years in low- and middle-income countries (LMICs) are at risk of not reaching their developmental potential. Over 66 % of these, who live in sub-Saharan Africa and are at risk due to poor nutrition, exposure to poverty, high HIV prevalence as well as under stimulation in the home environment.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; The study will employ a cluster-randomized control trial design and will use a mixed-methods approach combining quantitative and qualitative methodologies &lt;strong&gt;(&lt;/strong&gt;Concurrent Triangulation Design).&lt;strong&gt; &lt;/strong&gt;This will be a two-arm study, where the first arm will participate in the parenting empowerment program implemented by the faith-based organizations, while the second (control) will not receive the parenting interventions. A total of 510 mother/primary caregiver-child dyads will be recruited into this study. We will estimate the causal effect of the intervention using mixed linear models and the Difference-in-Differences (DID) estimator.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt; This implementation research will provide greater scientific rigor and a deeper process and outcome evaluation including measurement of child development outcomes. The findings will be useful for early childhood practitioners, multilateral stakeholders and funders as they provide information on the factors to consider in the implementation of high quality ECD interventions.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Trial Registration: &lt;/strong&gt;Ethical approval: ESRC P467/2018 and IRB No.00005948).&lt;/p&gt;

SAT-037 STUDY PROTOCOL FOR THE SYMPTOM MONITORING WITH FEEDBACK TRIAL (SWIFT): A NOVEL REGISTRY-BASED CLUSTER RANDOMISED TRIAL AMONG ADULTS WITH END-STAGE KIDNEY DISEASE MANAGED ON HAEMODIALYSIS

Women and men on haemodialysis frequently experience symptoms of severe or overwhelming pain, fatigue, nausea, cramping, itching, trouble sleeping, and depression that contribute to poor quality of life. A focus on laboratory biomarkers of lower relevance to patients, may have resulted in missed opportunities to intervene and reduce symptoms and improve health-related quality of life. Recent trials in other clinical settings have shown that active symptom management can improve overall survival. The aim of this trial is to determine whether regular symptom monitoring with feedback to the renal team can improve health-related quality of life and overall survival among adults with end-stage kidney disease (ESKD) managed with facility-haemodialysis. Using a novel ANZDATA registry-based cluster randomised trial design, with adults receiving haemodialysis, the proposed trial will test the hypothesis that: 1) three-monthly symptom monitoring using the IPOS-Renal tool with feedback to clinicians improves health-related quality of life (measured by the EQ-5D), dialysis duration and frequency, and cause-specific mortality compared with usual care; and 2) electronic capture of patient-reported outcomes within a clinical quality registry is cost-effective. A two-arm design of 160 clusters (~3072 individuals) has 90% power to detect a 7% clinically meaningful increase in health-related quality of life (primary endpoint); and 80% power to detect an 11% reduction in deaths from dialysis withdrawal (secondary endpoint). The SWIFT pilot study commencing in December 2018 will assess the feasibility and acceptability of the intervention to patients and clinicians including feedback of how data was used. Funding for the SWIFT pilot study was awarded from Kidney Health Australia in July 2018. Ethics approval was received in August 2018, and the electronic patient reported outcome measures were developed in Qualtrics software, with a novel QR reader interface to link with the ANZDATA registry. Preliminary user testing suggested the recording of quality of life and symptom scores within defined response categories is straight forward, however has identified issues with the touch screen interface on tablet computers for the EQ-5D visual analogue scale. The findings from SWIFT may result in improved quality of life, lower symptom burden (both severity and number of symptoms), and lower rates of dialysis withdrawal with the potential to change practice in haemodialysis care. Of significance, SWIFT provides a template for registry-based randomised trial of health services interventions; ongoing bi-national monitoring of patient-reported outcome measures; and infrastructure for economic evaluation of subsequent interventions.

Comparing theory and non-theory based implementation approaches to improving referral practices in cancer genetics: a cluster randomised trial protocol

BackgroundLynch syndrome (LS) is an inherited, cancer predisposition syndrome associated with an increased risk of colorectal, endometrial and other cancer types. Identifying individuals with LS allows access to cancer risk management strategies proven to reduce cancer incidence and improve survival. However, LS is underdiagnosed and genetic referral rates are poor. Improving LS referral is complex, and requires multisystem behaviour change. Although barriers have been identified, evidence-based strategies to facilitate behaviour change are lacking. The aim of this study is to compare the effectiveness of a theory-based implementation approach against a non-theory based approach for improving detection of LS amongst Australian patients with colorectal cancer (CRC).MethodsA two-arm parallel cluster randomised trial design will be used to compare two identical, structured implementation approaches, distinguished only by the use of theory to identify barriers and design targeted intervention strategies, to improve LS referral practices in eight large Australian hospital networks. Each hospital network will be randomly allocated to a trial arm, with stratification by state. A trained healthcare professional will lead the following phases at each site: (1) undertake baseline clinical practice audits, (2) form multidisciplinary Implementation Teams, (3) identify target behaviours for practice change, (4) identify barriers to change, (5) generate intervention strategies, (6) support staff to implement interventions and (7) evaluate the effectiveness of the intervention using post-implementation clinical data. The theoretical and non-theoretical components of each trial arm will be distinguished in phases 4–5. Study outcomes include a LS referral process map for each hospital network, with evaluation of the proportion of patients with risk-appropriate completion of the LS referral pathway within 2 months of CRC resection pre and post implementation.DiscussionThis trial will determine the more effective approach for improving the detection of LS amongst patients with CRC, whilst also advancing understanding of the impact of theory-based implementation approaches in complex health systems and the feasibility of training healthcare professionals to use them. Insights gained will guide the development of future interventions to improve LS identification on a larger scale and across different contexts, as well as efforts to address the gap between evidence and practice in the rapidly evolving field of genomic research.Trial registrationANZCTR, ACTRN12618001072202. Registered on 27 June 2018.

A pilot and feasibility study of the effectiveness of care mapping on person-centred care in neurorehabilitation settings

ABSTRACT Dementia care mapping for neurorehabilitation (DCM-NR) is a tool designed to increase person-centred care (PCC) in neurorehabilitation settings. This paper reports pilot and feasibility testing of a cluster-randomized controlled trial assessing the effectiveness of DCM-NR at increasing PCC. Forty-one staff members, from four neurorehabilitation wards, were cluster-randomized to receive DCM-NR (experimental group) or care as usual (control). Measures of PCC, attitudes to people with brain injury, and PCC self-efficacy were taken at baseline and follow-up. The experimental group were also interviewed about their experiences of the trial. Twenty-nine participants completed the study. Participants generally found the intervention and trial to be acceptable. PCC was significantly higher in the experimental than the control group at follow-up, despite levels of exposure to the intervention being low. PCC self-efficacy increased in the control group, but not in the experimental group, perhaps reflecting an initial reduction in perceived competence following feedback. Neither group showed a change in attitudes to people with brain injury. The findings suggest that this cluster-randomized trial design is acceptable; that DCM-NR shows promise as a tool for increasing PCC; and highlight modifications to the protocol that could increase the success and theoretical value of a future large-scale study.

Does Early Algebra Matter? The Effectiveness of an Early Algebra Intervention in Grades 3 to 5

A cluster randomized trial design was used to examine the effectiveness of a Grades 3 to 5 early algebra intervention with a diverse student population. Forty-six schools in three school districts participated. Students in treatment schools were taught the intervention by classroom teachers during regular mathematics instruction. Students in control schools received only regular mathematics instruction. Using a three-level longitudinal piecewise hierarchical linear model, the study explored the impact of the intervention in terms of both performance (correctness) and strategy use in students’ responses to written algebra assessments. Results show that during Grade 3, treatment students, including those in at-risk settings, improved at a significantly faster rate than control students on both outcome measures and maintained their advantage throughout the intervention.

Mixed-methods approach to evaluate an mHealth intervention to increase adherence to triage of human papillomavirus-positive women who have performed self-collection (the ATICA study): study protocol for a hybrid type I cluster randomized effectiveness-implementation trial

BackgroundCervical cancer is one of the leading causes of cancer death among women worldwide, with more than 85% of cases occurring in low- and middle-income countries. Human papillomavirus (HPV) screening allows for self-collection with the potential to increase coverage, but still requires triage to identify which HPV+ women need diagnostic and treatment procedures. However, achieving high levels of triage adherence can be challenging, especially among socially vulnerable women. This paper describes the ATICA protocol (Application of Communication and Information Technologies to Self-Collection, for its initials in Spanish), aimed at evaluating the implementation strategy and the effectiveness of a multi-component mobile health (mHealth) intervention to increase adherence to triage among women with HPV+ self-collected tests.MethodsWe will use an effectiveness-implementation hybrid type I trial with a mixed-methods evaluation approach. A cluster randomized trial design including 200 community health workers (CHWs) will evaluate whether the mHealth intervention increases adherence to triage among HPV+ women who self-collected at home during a CHW visit within 120 days after a positive result. The intervention includes an initial mobile phone text message (SMS) alert and subsequent reminders sent to HPV+ women. For those who do not adhere to triage within 60 days of a positive HPV test, an email and SMS will be sent to the CHWs to promote contact with these women during home visits.We will use the Consolidated Framework for Implementation Research (CFIR) as an organizing and analytic framework to evaluate the implementation of the intervention while also drawing on Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM). We will conduct a self-administered, semi-structured survey of CHWs, semi-structured interviews with local health authorities, and a survey of HPV+ women. Combining both qualitative and quantitative data will provide rich insights into local implementation challenges and successes.DiscussionFindings from the implementation evaluation will be applicable to programs that use or are planning to incorporate HPV self-collection and/or mHealth interventions in different settings and countries. This innovative study will also serve as a model for using implementation science in the region.Trial registrationClinicalTrials.gov, NCT03478397. Registered on 20 March 2018.

Study protocol for a pragmatic trial of the Consult for Addiction Treatment and Care in Hospitals (CATCH) model for engaging patients in opioid use disorder treatment

BackgroundTreatment for opioid use disorder (OUD) is highly effective, yet it remains dramatically underutilized. Individuals with OUD have disproportionately high rates of hospitalization and low rates of addiction treatment. Hospital-based addiction consult services offer a potential solution by using multidisciplinary teams to evaluate patients, initiate medication for addiction treatment (MAT) in the hospital, and connect patients to post-discharge care. We are studying the effectiveness of an addiction consult model [Consult for Addiction Treatment and Care in Hospitals (CATCH)] as a strategy for engaging patients with OUD in treatment as the program rolls out in the largest municipal hospital system in the US. The primary aim is to evaluate the effectiveness of CATCH in increasing post-discharge initiation and engagement in MAT. Secondary aims are to assess treatment retention, frequency of acute care utilization and overdose deaths and their associated costs, and implementation outcomes.MethodsA pragmatic trial at six hospitals, conducted in collaboration with the municipal hospital system and department of health, will be implemented to study the CATCH intervention. Guided by the RE-AIM evaluation framework, this hybrid effectiveness-implementation study (Type 1) focuses primarily on effectiveness and also measures implementation outcomes to inform the intervention’s adoption and sustainability. A stepped-wedge cluster randomized trial design will determine the impact of CATCH on treatment outcomes in comparison to usual care for a control period, followed by a 12-month intervention period and a 6- to 18-month maintenance period at each hospital. A mixed methods approach will primarily utilize administrative data to measure outcomes, while interviews and focus groups with staff and patients will provide additional information on implementation fidelity and barriers to delivering MAT to patients with OUD.DiscussionBecause of their great potential to reduce the negative health and economic consequences of untreated OUD, addiction consult models are proliferating in response to the opioid epidemic, despite the absence of a strong evidence base. This study will provide the first known rigorous evaluation of an addiction consult model in a large multi-site trial and promises to generate knowledge that can rapidly transform practice and inform the potential for widespread dissemination of these services.Trial registration: NCT03611335

Training professionals in a recovery-oriented methodology: a mixed method evaluation.

Several studies have reported difficulties concerning the implementation of recovery-oriented interventions. In this study, the effect of training in the Comprehensive Approach to Rehabilitation (CARe) on daily practice was evaluated. Additionally, we aimed to acquire insight into the experiences with the implementation process involving professionals, management and trainers. Fourteen teams for sheltered and supported housing in the Netherlands participated in this study. As part of a cluster-randomised controlled trial (RCT) design, eight teams received training in the CARe methodology. Model fidelity (using the CARe fidelity audit) and professionals' knowledge of recovery (using the Recovery Knowledge Inventory) were measured for all teams until 20months after the start. Afterwards, an evaluation meeting with participating stakeholders was organised in which barriers and facilitators of the implementation of the CARe methodology were inventoried. Ten months after the training, the intervention teams scored higher than the control teams on the fidelity subscales: 'recovery', 'strengths orientation' and 'amount of training and coaching'. Twenty months after the training, only the effect of 'amount of coaching and training' remained. Additionally, 'methodological working' clearly differed between the groups after 20months in favour of the intervention teams. In all teams, model fidelity was moderate at both measurements. The knowledge of recovery of the trained teams was slightly and significantly higher at 10 and 20months after training. Although professionals were positive about recovery and strength-oriented working, they experienced several organisational and societal barriers. Training in the CARe methodology improved the fidelity and knowledge of recovery among professionals. However, the differences were small, and fidelity decreased over time. More in-depth knowledge is needed on which barriers professionals experience in practice so that tailored training and implementation strategies can be developed. Furthermore, more attention is needed for professional development and the translation of theory into practice.

2157. Design, Implementation, and Analysis Considerations for Cluster Randomized Trials in Infection Control and Hospital Epidemiology: A Systematic Review

BackgroundA cluster randomized trial (CRT) is a comparative study in which clusters or groups rather than individuals are randomized to interventions or treatments. CRT are being utilized with increasing frequency in the study of interventions in infection control and hospital epidemiology. The aims of this study were (1) to identify critical design, implementation, and analysis principles to consider when planning a CRT of interventions in the healthcare setting and (2) to review published CRT in infection control and hospital epidemiology and synthesize key characteristics of these published studies using the principles identified above.MethodsAuthors reviewed articles and book chapters to identify key methodological principles relative to the design, implementation, and analysis of CRT. We undertook a systematic review of studies conducted between 1997 and 2017 in infection control and hospital epidemiology that used a CRT design, and evaluated each study on those key principles.ResultsSeven epidemiological principles were identified as most critical (Figure 1). Among the 44 studies included in the review, the most commonly used design was a CRT with cross-over (n = 15, 34%), followed by a parallel CRT (n = 11, 25%), and a stratified CRT design (n = 7, 16%). Twenty-two (50%) offered justification for their use of a CRT. Twenty (45%) accounted for clustering at the design phase when estimating sample size. Only 15 (34%) reported the intraclass correlation coefficient, coefficient of variation, or design effect. Fifteen studies (34%) obtained waived consent, 14 (32%) did not report how they dealt with consent, 8 (18%) studies obtained consent from individuals, and 7 (16%) sought consent at the cluster level. Seventeen studies (39%) matched or stratified at time of randomization, while 27 (61%) did not employ either of these techniques. Notably, 10 (23%) studies did not report any efforts to reduce the potential for bias and/or contamination. Twenty-seven (61%) accounted for clustering in their analyses.ConclusionCRT in infection control and hospital epidemiology are common but are still lacking in methodological rigor. It is crucial to continue improving the design and reporting of these studies to better evaluate the effectiveness of interventions. Disclosures All authors: No reported disclosures.

Admissible multiarm stepped-wedge cluster randomized trial designs.

Numerous publications have now addressed the principles of designing, analyzing, and reporting the results of stepped‐wedge cluster randomized trials. In contrast, there is little research available pertaining to the design and analysis of multiarm stepped‐wedge cluster randomized trials, utilized to evaluate the effectiveness of multiple experimental interventions. In this paper, we address this by explaining how the required sample size in these multiarm trials can be ascertained when data are to be analyzed using a linear mixed model. We then go on to describe how the design of such trials can be optimized to balance between minimizing the cost of the trial and minimizing some function of the covariance matrix of the treatment effect estimates. Using a recently commenced trial that will evaluate the effectiveness of sensor monitoring in an occupational therapy rehabilitation program for older persons after hip fracture as an example, we demonstrate that our designs could reduce the number of observations required for a fixed power level by up to 58%. Consequently, when logistical constraints permit the utilization of any one of a range of possible multiarm stepped‐wedge cluster randomized trial designs, researchers should consider employing our approach to optimize their trials efficiency.

Comparing evidence of selection bias between cluster-randomised and individually randomised controlled trials: a systematic review and meta-analysis

BackgroundCluster-randomised controlled trials require different methodology from individually randomised controlled trials and have unique vulnerabilities to bias. We aimed to compare selection bias between samples of these two types of trials published in four high-impact journals. MethodsThe JAMA archives and OVID Medline were searched by single selection by one of us (JB) for cluster-randomised and individually randomised controlled trials published in four journals (BMJ, The Lancet, JAMA, and The New England Journal of Medicine). Two of us (JB and NM) independently double-extracted data from the 20 most recently published trials of each type up to July 3, 2017. Fixed-effects forest plots were generated to show any imbalances in baseline mean participant age between trial arms for each trial. Pooled imbalance was calculated for each trial type. The characteristic of age was chosen because it is reported universally, in standard units (years). FindingsFor individually randomised controlled trials, age imbalance between trial arms was not statistically significant (0·005 years, 95% CI −0·026 to 0·035). For cluster-randomised controlled trials, age imbalance was ten times greater and was statistically significant (−0·050, −0·057 to −0·043). InterpretationRandomisation distributes participant characteristics equally between trial arms except when baseline imbalances occur at random. When studies are pooled, such random imbalances cancel out to become negligible: if imbalance is not negligible across pooled trials, it indicates compromised randomisation or that selection bias has acted on the sample. The significant age imbalance in the cluster-randomised but not the individually randomised trials suggests that cluster-randomised trials are more vulnerable to selection bias. This imbalance might not affect trial outcomes since age in the control group was not substantially greater than in the intervention group. However, it indicates that selection bias can enter though the design of cluster-randomised controlled trials—possibly during the widespread practice of post-randomisation recruitment—and is therefore concerning. One limitation is that selection bias levels may be different in a more general sample of trials than one from four high-impact journals. Our method of examining selection bias has indicated that cluster-randomised controlled trials may require a more robust approach. We recommend taking steps to minimise selection bias in this type of trial. FundingNone.

Reducing contamination risk in cluster-randomized infectious disease-intervention trials.

Infectious disease interventions are increasingly tested using cluster-randomized trials (CRTs). These trial settings tend to involve a set of sampling units, such as villages, whose geographic arrangement may present a contamination risk in treatment exposure. The most widely used approach for reducing contamination in these settings is the so-called fried-egg design, which excludes the outer portion of all available clusters from the primary trial analysis. However, the fried-egg design ignores potential intra-cluster spatial heterogeneity and makes the outcome measure inherently less precise. Whereas the fried-egg design may be appropriate in specific settings, alternative methods to optimize the design of CRTs in other settings are lacking. We present a novel approach for CRT design that either fully includes or fully excludes available clusters in a defined study region, recognizing the potential for intra-cluster spatial heterogeneity. The approach includes an algorithm that allows investigators to identify the maximum number of clusters that could be included for a defined study region and maintain randomness in both the selection of included clusters and the allocation of clusters to either the treatment group or control group. The approach was applied to the design of a CRT testing the effectiveness of malaria vector-control interventions in southern Malawi. Those planning CRTs to evaluate interventions should consider the approach presented here during trial design. The approach provides a novel framework for reducing the risk of contamination among the CRT randomization units in settings where investigators determine the reduction of contamination risk as a high priority and where intra-cluster spatial heterogeneity is likely. By maintaining randomness in the allocation of clusters to either the treatment group or control group, the approach also permits a randomization-valid test of the primary trial hypothesis.

Improving cooperation between general practitioners and dermatologists via telemedicine: study protocol of the cluster-randomized controlled TeleDerm study

BackgroundInternationally, teledermatology has proven to be a viable alternative to conventional physical referrals. Travel cost and referral times are reduced while patient safety is preserved. Especially patients from rural areas benefit from this healthcare innovation. Despite these established facts and positive experiences from EU neighboring countries like the Netherlands or the United Kingdom, Germany has not yet implemented store-and-forward teledermatology in routine care.MethodsThe TeleDerm study will implement and evaluate store-and-forward teledermatology in 50 general practitioner (GP) practices as an alternative to conventional referrals. TeleDerm aims to confirm that the possibility of store-and-forward teledermatology in GP practices is going to lead to a 15% (n = 260) reduction in referrals in the intervention arm. The study uses a cluster-randomized controlled trial design. Randomization is planned for the cluster “county”. The main observational unit is the GP practice. Poisson distribution of referrals is assumed. The evaluation of secondary outcomes like acceptance, enablers and barriers uses a mixed-methods design with questionnaires and interviews.DiscussionDue to the heterogeneity of GP practice organization, patient management software, information technology service providers, GP personal technical affinity and training, we expect several challenges in implementing teledermatology in German GP routine care. Therefore, we plan to recruit 30% more GPs than required by the power calculation. The implementation design and accompanying evaluation is expected to deliver vital insights into the specifics of implementing telemedicine in German routine care.Trial registrationGerman Clinical Trials Register, DRKS00012944. Registered prospectively on 31 August 2017.