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This document reports a brief update to the previously published protocol of the MinDial study.Trial registration German Clinical Trials Register DRKS00029691. Registered on 12 Sept. 2022, https://drks.de/search/en/trial/DRKS00029691 .
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Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/diagnóstico , Factores de Riesgo , Alemania/epidemiología , Resultado del Tratamiento , Medición de Riesgo , Factores de TiempoRESUMEN
BACKGROUND: In the UK, recent evidence of young people and gambling indicates a higher prevalence of gambling in comparison to other addictive behaviours. Engaging in gambling-related behaviour at a young age is associated with short and long-term consequences, including financial, emotional, academic, interpersonal, and physical and mental health detriments; otherwise known as gambling-related harms (GRH). Given the unique vulnerability of this younger group, early interventions aimed at delaying or preventing gambling are critical. PRoGRAM-A (Preventing Gambling-Related Harm in Adolescents) is a school-based, social network intervention to protect young people from future GRH, by delaying or preventing gambling experimentation. METHODS: Pilot cluster RCT with an embedded process evaluation and health economic scoping study. PARTICIPANTS: PRoGRAM-A will be delivered in four schools, with two control schools acting as a comparator. All are secondary schools in Scotland. Baseline surveys were conducted with students in S3 (ages 13-14). Follow-up surveys were conducted with the same cohort, six months post-baseline. INTERVENTION: PRoGRAM-A trainers will deliver a 2-day, out-of-school training workshop to Peer supporters. Peer supporters will be nominated by peers among their school year group (S3, age 13-14). Workshops will provide peer supporters with information on four gambling-related topics: (1) what is gambling? (2) gambling and gaming, (3) gambling marketing, (4) identifying harm and reducing risk. Peer supporters will disseminate the information (message diffusion) they have learned among their friends and family over a 10-week period. After the 2-day workshop, PRoGRAM-A trainers will conduct × 3 in-school follow-up sessions with peer supporters to offer support, encouragement, and advice to Peer Supporters as well as monitor and explore the extent of their message diffusion. PRIMARY OUTCOME: The primary outcome of the pilot cluster RCT (cRCT) will be whether progression to a phase III RCT is justified. DISCUSSION: This will be the first pilot cluster RCT (cRCT) of an intervention to prevent gambling-related harms among young people within the UK. If findings indicate feasibility and acceptability, funding will be sought for a phase III RCT of effectiveness. TRIAL REGISTRATION: Researchregistry8699. Registered 21st February 2023.
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Background: Contact tracing was described as a key strategy to contribute to controlling the spread of severe acute respiratory syndrome of Coronavirus 2 (SARS-CoV-2) but implementing it can be a challenge. Digitalisation of contact tracing is among the proposed solutions being explored in sub-Saharan African settings. We assessed the effectiveness of a digital tool to expand SARS-CoV-2 testing in exposed individuals in Cameroon. Methods: We conducted a cluster-randomised (1:1) trial in eight health districts, including 22 facilities and SARS-CoV-2 testing units, randomly assigned to a digital (intervention) or standard (control) contact tracing approach. The intervention consisted of a contact tracing module added to the digital platform "Mamal PRO" used for monitoring and coordination of Coronavirus Disease 2019 pandemic response in Cameroon. The primary outcome was the proportion of contacts declared by SAR-CoV-2 index patients who were successfully traced and tested for SARS-CoV-2 evaluated with a Poisson regression model with cluster adjustment. This study is registered with ClinicalTrials.gov (NCT05684887). Findings: Between October 18, 2022, and March 31, 2023, we enrolled 164 index patients in the intervention arm and 149 in the control arm, who identified 854 and 849 contacts, respectively. In the intervention arm, 93.8% (801/854) of identified contacts were successfully reached by the tracing unit versus 54.5% (463/849) in the control arm. The intervention significantly increased the likelihood of successfully tracing contacts (adjusted relative risks (RR) 1.72 [95% CI: 1.00-2.95], p = 0.049). The median (interquartile range, IQR) time to successfully tracing contacts was 0 days [IQR: 0, 1] in the intervention and 1 day [IQR: 0, 2] in the control arm. In the intervention arm, 21.3% (182/854) of identified contacts received SARS-CoV-2 testing compared to 14.5% (123/849) in the control arm (adjusted RR 1.47 [95% CI: 0.44-4.90], p = 0.530). Interpretation: Digitalising the contact tracing process improved exposure notification and facilitated the tracing of a greater number of contacts of individuals infected with SARS-CoV-2 in resource-limited settings. Funding: The study was funded by FIND, United Kingdom (FCDO 40105983), Switzerland (81066910), Netherlands (SDD 4000004160), Canada (DFATD 7429348), The Kingdom of Saudi Arabia (FIND-ACT-A DX PARTNERSHIP 20.08.2020), The Rockefeller Foundation (2020 HTH 059), Germany (BMZ Covid-19 Diagnostic and Surveillance Response 27.07.2021), Australia (DFAT 76442), Kuwait (M239/2020), The Government of Portugal and Partners (ANF, BCP, CGF, APIFARMA) and The BlackRock Foundation (Grant Agreement as of April 20, 2022).
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BACKGROUND: Randomised, cluster-based study designs in schools are commonly used to evaluate children's physical activity interventions. Sample size estimation relies on accurate estimation of the intra-cluster correlation coefficient (ICC), but published estimates, especially using accelerometry-measured physical activity, are few and vary depending on physical activity outcome and participant age. Less commonly-used cluster-based designs, such as stepped wedge designs, also need to account for correlations over time, e.g. cluster autocorrelation (CAC) and individual autocorrelation (IAC), but no estimates are currently available. This paper estimates the school-level ICC, CAC and IAC for England children's accelerometer-measured physical activity outcomes by age group and gender, to inform the design of future school-based cluster trials. METHODS: Data were pooled from seven large English datasets of accelerometer-measured physical activity data between 2002-18 (> 13,500 pupils, 540 primary and secondary schools). Linear mixed effect models estimated ICCs for weekday and whole week for minutes spent in moderate-to-vigorous physical activity (MVPA) and being sedentary for different age groups, stratified by gender. The CAC (1,252 schools) and IAC (34,923 pupils) were estimated by length of follow-up from pooled longitudinal data. RESULTS: School-level ICCs for weekday MVPA were higher in primary schools (from 0.07 (95% CI: 0.05, 0.10) to 0.08 (95% CI: 0.06, 0.11)) compared to secondary (from 0.04 (95% CI: 0.03, 0.07) to (95% CI: 0.04, 0.10)). Girls' ICCs were similar for primary and secondary schools, but boys' were lower in secondary. For all ages, combined the CAC was 0.60 (95% CI: 0.44-0.72), and the IAC was 0.46 (95% CI: 0.42-0.49), irrespective of follow-up time. Estimates were higher for MVPA vs sedentary time, and for weekdays vs the whole week. CONCLUSIONS: Adequately powered studies are important to evidence effective physical activity strategies. Our estimates of the ICC, CAC and IAC may be used to plan future school-based physical activity evaluations and were fairly consistent across a range of ages and settings, suggesting that results may be applied to other high income countries with similar school physical activity provision. It is important to use estimates appropriate to the study design, and that match the intended study population as closely as possible.
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Acelerometría , Ejercicio Físico , Instituciones Académicas , Humanos , Niño , Inglaterra , Acelerometría/métodos , Acelerometría/estadística & datos numéricos , Femenino , Masculino , Ejercicio Físico/fisiología , Instituciones Académicas/estadística & datos numéricos , Análisis por Conglomerados , Adolescente , Factores Sexuales , Factores de EdadRESUMEN
Pyrethroid bednets treated with the synergist piperonyl butoxide (PBO) offer the possibility of improved vector control in mosquito populations with metabolic resistance. In 2017-2019, we conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus PBO (PBO LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda. In LLINEUP, and similar trials in Tanzania, PBO LLINs were found to provide greater protection against malaria than conventional LLINs, reducing parasitaemia and vector density. In the LLINEUP trial, we conducted cross-sectional household entomological surveys at baseline and then every 6 months for two years, which we use here to investigate longitudinal changes in mosquito infection rate and genetic markers of resistance. Overall, 5395 female Anopheles mosquitoes were collected from 5046 households. The proportion of mosquitoes infected (PCR-positive) with Plasmodium falciparum did not change significantly over time, while infection with non-falciparum malaria decreased in An. gambiae s.s., but not An. funestus. The frequency of genetic markers associated with pyrethroid resistance increased significantly over time, but the rate of change was not different between the two LLIN types. The knock-down resistance (kdr) mutation Vgsc-995S declined over time as Vgsc-995F, the alternative resistance mutation at this codon, increased. Vgsc-995F appears to be spreading into Uganda. Distribution of LLINs in Uganda was previously found to be associated with reductions in parasite prevalence and vector density, but here we show that the proportion of infective mosquitoes remained stable across both PBO and non-PBO LLINs, suggesting that the potential for transmission persisted. The increased frequency of markers of pyrethroid resistance indicates that LLIN distribution favoured the evolution of resistance within local vectors and highlights the potential benefits of resistance management strategies.Trial registration: This study is registered with ISRCTN, ISRCTN17516395. Registered 14 February 2017, http://www.isrctn.com/ISRCTN17516395 .
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Anopheles , Resistencia a los Insecticidas , Mosquiteros Tratados con Insecticida , Control de Mosquitos , Mosquitos Vectores , Piretrinas , Animales , Anopheles/parasitología , Anopheles/genética , Anopheles/efectos de los fármacos , Resistencia a los Insecticidas/genética , Uganda/epidemiología , Mosquitos Vectores/genética , Mosquitos Vectores/parasitología , Mosquitos Vectores/efectos de los fármacos , Control de Mosquitos/métodos , Humanos , Piretrinas/farmacología , Insecticidas/farmacología , Malaria/epidemiología , Malaria/prevención & control , Malaria/transmisión , Malaria/parasitología , Femenino , Plasmodium falciparum/genética , Plasmodium falciparum/efectos de los fármacos , Prevalencia , Marcadores Genéticos , Estudios Transversales , Malaria Falciparum/parasitología , Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & control , Butóxido de Piperonilo/farmacología , GenotipoRESUMEN
BACKGROUND: Early identification of patients with chronic kidney disease (CKD) and advancing kidney insufficiency, followed by specialist care, can decelerate the progression of the disease. However, awareness of the importance and possible consequences of kidney insufficiency is low among doctors and patients. Since kidney insufficiency can be asymptomatic even in higher stages, it is often not even known to those belonging to risk groups. This study aims to clarify whether, for hospitalised patients with advanced chronic kidney disease, a risk-based appointment with a nephrology specialist reduces disease progression. METHODS: The target population of the study is hospitalised CKD patients with an increased risk of end-stage renal disease (ESRD), more specifically with an ESRD risk of at least 9% in the next 5 years. This risk is estimated by the internationally validated Kidney Failure Risk Equation (KFRE). The intervention consists of a specific appointment with a nephrology specialist after the hospital stay, while control patients are discharged from the hospital as usual. Eight medical centres include participants according to a stepped-wedge design, with randomised sequential centre-wise crossover from recruiting patients into the control group to recruitment to the intervention. The estimated glomerular filtration rate (eGFR) is measured for each patient during the hospital stay and after 12 months within the regular care by the general practitioner. The difference in the change of the eGFR over this period is compared between the intervention and control groups and considered the primary endpoint. DISCUSSION: This study is designed to evaluate the effect of risk-based appointments with nephrology specialists for hospitalised CKD patients with an increased risk of end-stage renal disease. If the intervention is proven to be beneficial, it may be implemented in routine care. Limitations will be examined and discussed. The evaluation will include further endpoints such as non-guideline-compliant medication, economic considerations and interviews with contributing physicians to assess the acceptance and feasibility of the intervention. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029691 . Registered on 12 September 2022.
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Progresión de la Enfermedad , Tasa de Filtración Glomerular , Fallo Renal Crónico , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Diálisis Renal , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/diagnóstico , Fallo Renal Crónico/terapia , Factores de Riesgo , Hospitalización , Medición de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Citas y HorariosRESUMEN
Estimands can help clarify the interpretation of treatment effects and ensure that estimators are aligned with the study's objectives. Cluster-randomised trials require additional attributes to be defined within the estimand compared to individually randomised trials, including whether treatment effects are marginal or cluster-specific, and whether they are participant- or cluster-average. In this paper, we provide formal definitions of estimands encompassing both these attributes using potential outcomes notation and describe differences between them. We then provide an overview of estimators for each estimand, describe their assumptions, and show consistency (i.e. asymptotically unbiased estimation) for a series of analyses based on cluster-level summaries. Then, through a re-analysis of a published cluster-randomised trial, we demonstrate that the choice of both estimand and estimator can affect interpretation. For instance, the estimated odds ratio ranged from 1.38 (p = 0.17) to 1.83 (p = 0.03) depending on the target estimand, and for some estimands, the choice of estimator affected the conclusions by leading to smaller treatment effect estimates. We conclude that careful specification of the estimand, along with an appropriate choice of estimator, is essential to ensuring that cluster-randomised trials address the right question.
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Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Análisis por Conglomerados , Humanos , Interpretación Estadística de Datos , Modelos EstadísticosRESUMEN
BACKGROUND: The demand for mental health services in Australia is substantial and has grown beyond the capacity of the current workforce. As a result, it is currently difficult for many to access secondary healthcare providers. Within the secondary healthcare sector, however, peer workers who have lived experience of managing mental health conditions have been increasingly employed to intentionally use their journey of recovery in supporting others living with mental health conditions and their communities. Currently, the presence of peer workers in primary care has been limited, despite the potential benefits of providing supports in conjunction with GPs and secondary healthcare providers. METHODS: This stepped-wedge cluster randomised controlled trial (RCT) aims to evaluate a lived experience peer support intervention for accessing mental health care in primary care (PS-PC). Four medical practices across Australia will be randomly allocated to switch from control to intervention, until all practices are delivering the PS-PC intervention. The study will enrol 66 patients at each practice (total sample size of 264). Over a period of 3-4 months, 12 h of practical and emotional support provided by lived experience peer workers will be available to participants. Scale-based questionnaires will inform intervention efficacy in terms of mental health outcomes (e.g., self-efficacy) and other health outcomes (e.g., healthcare-related costs) over four time points. Other perspectives will be explored through scales completed by approximately 150 family members or carers (carer burden) and 16 peer workers (self-efficacy) pre- and post-intervention, and 20 medical practice staff members (attitudes toward peer workers) at the end of each study site's involvement in the intervention. Interviews (n = 60) and six focus groups held toward the end of each study site's involvement will further explore the views of participants, family members or carers, peer workers, and practice staff to better understand the efficacy and acceptability of the intervention. DISCUSSION: This mixed-methods, multi-centre, stepped-wedge controlled study will be the first to evaluate the implementation of peer workers in the primary care mental health care sector. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12623001189617. Registered on 17 November 2023, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386715.
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Trastornos Mentales , Servicios de Salud Mental , Grupo Paritario , Atención Primaria de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Trastornos Mentales/terapia , Trastornos Mentales/psicología , Salud Mental , Estudios Multicéntricos como Asunto , Apoyo Social , AustraliaRESUMEN
Background: There is a need for more sustainable interventions and for assessing the effectiveness of school-based universal anti-bullying programmes in vulnerable populations. We assessed the efficacy of a multicomponent, web-enabled, school-based intervention that aims to improve school climate and reduce bullying (LINKlusive) relative to conventional practices (control condition). Methods: We conducted a cluster randomised controlled trial in primary and secondary schools in Madrid, Spain. The primary outcome measure was peer-reported bullying victimisation after the 12-week intervention (study endpoint). We analysed data using longitudinal mixed-effects models. The trial was registered with the ISRCTN registry (15719015). Findings: We included 20 schools (10 in each group); 6542 students participated at baseline; 6403 were assessed at study endpoint. After the intervention, there was a statistically significant reduction in bullying victimisation in both the intervention (OR 0.61, 95% CI [0.41, 0.90]) and control groups (OR 0.69, 95% CI [0.51, 0.92]), with no evidence of differences in the whole sample (OR 0.89, 95% CI [0.58, 1.36]; aOR 0.89, 95% CI [0.58, 1.37]). Subgroup analyses showed a statistically significant effect of LINKlusive on bullying victimisation in primary education (aOR 0.68, 95% CI [0.47, 0.98]). In students with peer-reported bullying victimisation at baseline, LINKlusive showed a statistically significant effect on depression (-1.43, 95% CI [-2.46, -0.40], adjusted standardised mean difference (SMD) -0.41) and quality of life (2.18, 95% CI [0.80, 3.56], adjusted SMD 0.45). Interpretation: LINKlusive could be effective in reducing bullying victimisation in primary school students. Sustainable whole-school interventions to promote mental health and reduce risk factors are warranted to improve outcomes in young people, especially in the early years of education. Funding: Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation.
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OBJECTIVE: To evaluate the effectiveness of implementing the Enhanced Recovery After Surgery (ERAS) protocol in patients undergoing elective hysterectomy in a network of regional hospitals, supported by an intensive audit-and-feedback (A&F) approach. DESIGN: A multi-centre, stepped-wedge cluster randomised trial (ClinicalTrials.gov NCT04063072). SETTING: Gynaecological units in the Piemonte region, Italy. POPULATION: Patients undergoing elective hysterectomy, either for cancer or for benign conditions. METHODS: Twenty-three units (clusters), stratified by surgical volume, were randomised into four sequences. At baseline (first 3 months), standard care was continued in all units. Subsequently, the four sequences implemented the ERAS protocol successively every 3 months, after specific training. By the end of the study, each unit had a period in which standard care was maintained (control) and a period in which the protocol, supported by feedback, was applied (experimental). MAIN OUTCOME MEASURES: Length of hospital stay (LOS), without outliers (>98th percentile). RESULTS: Between September 2019 and May 2021, 2086 patients were included in the main analysis with an intention-to-treat approach: 1104 (53%) in the control period and 982 (47%) in the ERAS period. Compliance with the ERAS protocol increased from 60% in the control period to 76% in the experimental period, with an adjusted absolute difference of +13.3% (95% CI 11.6% to 15.0%). LOS, moving from 3.5 to 3.2 days, did not show a significant reduction (-0.12 days; 95% CI -0.30 to 0.07 days). No difference was observed in the occurrence of complications. CONCLUSIONS: Implementation of the ERAS protocol for hysterectomy at the regional level, supported by an A&F approach, resulted in a substantial improvement in compliance, but without meaningful effects on LOS and complications. This study confirms the effectiveness of A&F in promoting important innovations in an entire hospital network and suggests the need of a higher compliance with the ERAS protocol to obtain valuable improvements in clinical outcomes.
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Recuperación Mejorada Después de la Cirugía , Histerectomía , Tiempo de Internación , Humanos , Femenino , Histerectomía/métodos , Persona de Mediana Edad , Tiempo de Internación/estadística & datos numéricos , Italia , Procedimientos Quirúrgicos Electivos , Adulto , Complicaciones Posoperatorias/prevención & control , Auditoría Médica , RetroalimentaciónRESUMEN
BACKGROUND: Despite substantial research evidence indicating the effectiveness of a range of interventions to prevent falls, uptake into routine clinical practice has been limited by several implementation challenges. The complexity of fall prevention in municipality health care underlines the importance of flexible implementation strategies tailored both to general determinants of fall prevention and to local contexts. This cluster-randomised trial (RCT) investigates the effectiveness of a tailored intervention to implement national recommendations on fall prevention among older home-dwelling adults compared to usual practice on adherence to the recommendations in health professionals. METHODS: Twenty-five municipalities from four regions in Norway will be randomised to intervention or control arms. Each municipality cluster will recruit up to 30 health professionals to participate in the study as responders. The tailored implementation intervention comprises four components: (1) identifying local structures for implementation, (2) establishing a resource team from different professions and levels, (3) promoting knowledge on implementation and fall prevention and (4) supporting the implementation process. Each of these components includes several implementation activities. The Consolidated Framework for Implementation Research (CFIR) will be used to categorise determinants of the implementation process and the Expert Recommendations for Implementing Change (ERIC) will guide the matching of barriers to implementation strategies. The primary outcome measure for the study will be health professionals' adherence to the national recommendations on fall prevention measured by a questionnaire. Secondary outcomes include injurious falls, the feasibility of the intervention, the experiences of the implementation process and intervention costs. Measurements will be carried out at baseline in August 2023, post-intervention in May 2024 and at a follow-up in November 2024. DISCUSSION: This study will provide evidence on the effectiveness, intervention costs and underlying processes of change of tailored implementation of evidence-based fall prevention recommendations. TRIAL REGISTRATION: The trial is registered in the Open Science Registry: https://doi.org/10.17605/OSF.IO/JQ9T5 . Registered: March 03, 2023.
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Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Anciano , Ciudades , NoruegaRESUMEN
BACKGROUND: Early childhood is a critical period for child development. Effective approaches to support families in low-resource settings in the use of responsive and stimulating parenting are needed. AIM: The aim of this study was to examine the effects of the Reach Up early childhood parenting programme on children's development, parenting attitudes and practices, when delivered through early childhood development (ECD) centres in Zimbabwe. METHODS: A cluster randomised controlled trial was conducted in Sanyati, a rural district in Zimbabwe. Twenty-four of 51 available centres were randomised to intervention (n = 12) or control (n = 12) groups. Sixteen mothers with a child aged 12-30 months were recruited from each centre's catchment area (n = 189 intervention; n = 193 control). The intervention comprised two home visits per month delivered by centre teaching assistants over a period of 27 months. Primary outcomes were child Developmental Quotient (DQ), Language, Eye and Hand coordination, Performance and Practical Reasoning subscale scores assessed at follow-up. Secondary outcomes were mothers' attitudes about child development, parenting practices and maternal depressive symptoms all measured at baseline and follow-up. Intention to treat analyses was conducted using mixed-effects regression models with the standard error adjusted for cluster and inverse proportionality weights to adjust for attrition. Significance was set at P < 0.05. RESULTS: A total of 285 (74.6%) of 382 children enrolled were tested, with 97 children lost to follow-up. The intervention improved the children's DQ by 3.55 points (95% CI 0.82 to 6.28), Eye and Hand by 3.58 (95% CI 0.59 to 6.56) and Practical Reasoning by 4.19 (95% CI 0.96 to 7.42). No significant improvements to Performance or Language scores, parenting attitudes, parenting practices and depressive symptoms were identified. CONCLUSIONS: A home visiting intervention delivered by ECD teaching assistants promoted children's development. This suggests that outreach from preschools may be an effective platform for delivery of parenting interventions.
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Desarrollo Infantil , Responsabilidad Parental , Niño , Femenino , Humanos , Preescolar , Lactante , Zimbabwe , Madres/educaciónRESUMEN
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.
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Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Análisis por Conglomerados , Modelos Lineales , Probabilidad , Tamaño de la MuestraRESUMEN
BACKGROUND: Pressure ulcer prophylaxis is a central topic in clinical care. Pressure-relieving repositioning is strongly recommended for all pressure-sensitive patients. The Mobility Monitor (MoMo) is a technical device that records a patient's movements and transmits the data to a monitor. This study investigated the extent to which the MoMo sensor system, which records and visualises patients' movements in bed, supports nurses in performing pressure-relieving repositioning in neurological and neurosurgical intensive care units (ICU). METHODS: This stepped-wedge cluster-randomised trial involved two clusters: one neurological and one neurosurgical ICU. The study was carried out in two steps over three periods between November 2018 and May 2019, with a two-month interval between each step. At the beginning of the study, we equipped 33 beds across the two ICUs with a MoMo system. Our primary endpoint was the immobility rate, which is defined as the patient's inactive time in bed exceeding two hours without pressure-relieving movements divided by the time the MoMo was in the bed. The immobility rate ranges from 0 to below 1, with higher values indicating lower mobility. Secondary endpoints were the rate of new pressure ulcers and the rate of relevant pressure-relieving repositionings. Relevant repositionings are defined as the number of repositionings identified by the MoMo as a pressure-relieving repositioning divided by the total number of repositionings, RESULTS: 808 patients were included in the study, of whom 403 were in the control group and 405 were in the intervention group. The mean immobility rate was 0.171 during the control phase and 0.144 during the intervention phase. The estimated intervention effect was -0.0018 (95% confidence interval [-0.0471, 0.0436], p=0.94). The number of new pressure ulcers was 5/405 in the intervention phase and 15/403 in the control phase. We noted a small difference in the mean rate of relevant repositioningswith an estimated intervention effect of 0.046 (95% confidence interval [-0.018, 0.110], p=0.16). CONCLUSION: Our results are insufficient to recommend the standardised use of mobility monitors in neurological or neurosurgical ICUs. CLINICAL TRIAL REGISTRATION: The primary analysis was prespecified and the trial was registered in the German Clinical Trials Register (DRKS) under the reference number DRKS00015492 (31/10/2018).
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There are multiple possible cluster randomised trial designs that vary in when the clusters cross between control and intervention states, when observations are made within clusters, and how many observations are made at each time point. Identifying the most efficient study design is complex though, owing to the correlation between observations within clusters and over time. In this article, we present a review of statistical and computational methods for identifying optimal cluster randomised trial designs. We also adapt methods from the experimental design literature for experimental designs with correlated observations to the cluster trial context. We identify three broad classes of methods: using exact formulae for the treatment effect estimator variance for specific models to derive algorithms or weights for cluster sequences; generalised methods for estimating weights for experimental units; and, combinatorial optimisation algorithms to select an optimal subset of experimental units. We also discuss methods for rounding experimental weights, extensions to non-Gaussian models, and robust optimality. We present results from multiple cluster trial examples that compare the different methods, including determination of the optimal allocation of clusters across a set of cluster sequences and selecting the optimal number of single observations to make in each cluster-period for both Gaussian and non-Gaussian models, and including exchangeable and exponential decay covariance structures.
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Algoritmos , Proyectos de Investigación , Tamaño de la Muestra , Análisis por Conglomerados , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The COVID-19 pandemic disrupted the normality of daily life for many children, their families, and schools, resulting in heightened levels of anxiety, depression, social isolation, and loneliness among young people. An integrated public health model of interventions is needed to address the problem and to safeguard the mental health and wellbeing of children. The Triple P - Positive Parenting Program is one system of parenting support with a strong evidence-base and wide international reach. When implemented as a public health approach, Triple P has demonstrated population level positive effects on child wellbeing. This study will be the first large-scale, multi-site randomised controlled trial of a newly developed, low-intensity variant of Triple P, a school-based seminar series, as a response to the impacts of the pandemic. METHODS: The evaluation will employ an Incomplete Batched Stepped Wedge Cluster Randomised Trial Design. At least 300 Australian primary schools, from South Australia, Queensland, and Victoria will be recruited and randomised in three batches. Within each batch, schools will be randomly assigned to either start the intervention immediately or start in six weeks. Parents will be recruited from participating schools. The Triple P seminar series includes three seminars titled: "The Power of Positive Parenting", "Helping Your Child to Manage Anxiety", and "Keeping your Child Safe from Bullying". Parents will complete measures about child wellbeing, parenting, parenting self-regulation and other key intervention targets at baseline, six weeks after baseline, and 12 weeks after baseline. Intervention effectiveness will be evaluated with a Multilevel Piecewise Latent Growth Curve Modelling approach. Data collection is currently underway, and the current phase of the project is anticipated to be completed in January 2024. DISCUSSION: The findings from this study will extend the current knowledge of the effects of evidence-based parenting support delivered through brief, universally offered, low intensity, school-based parenting seminars in a post pandemic world. TRIAL REGISTRATION: The trial is registered at the Australian New Zealand Clinical Trials Registry (Trial Registration Number: ACTRN12623000852651).
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COVID-19 , Pandemias , Niño , Humanos , Adolescente , Pandemias/prevención & control , Padres/psicología , Responsabilidad Parental/psicología , Instituciones Académicas , Victoria , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Background: In 2017-2019, we conducted a large-scale, cluster-randomised trial (LLINEUP) to evaluate long-lasting insecticidal nets (LLINs) treated with a pyrethroid insecticide plus the synergist piperonyl butoxide (PBO LLINs), as compared to conventional, pyrethroid-only LLINs across 104 health sub-districts (HSDs) in Uganda. In LLINEUP, and similar trials in Tanzania, PBO LLINs were found to provide greater protection against malaria than conventional LLINs, reducing parasitaemia and vector density. In the LLINEUP trial, cross-sectional entomological surveys were carried out at baseline and then every 6 months for two years. In each survey, ten households per HSD were randomly selected for indoor household entomological collections. Results: Overall, 5395 female Anopheles mosquitoes were collected from 5046 households. The proportion of mosquitoes infected with Plasmodium falciparum did not change significantly over time, while infection with non-falciparum malaria decreased in An. gambiae s.s, but not An. funestus. The frequency of genetic markers associated with pyrethroid resistance increased significantly over time, but the rate of change was not different between the two LLIN types. The knock-down resistance (kdr) mutation Vgsc-995S declined over time as Vgsc-995F, the alternative resistance mutation at this codon, increased. Vgsc-995F appears to be spreading into Uganda. Conclusions: Distribution of LLINs in Uganda was associated with reductions in parasite prevalence and vector density, but the proportion of infective mosquitoes remained stable, suggesting that the potential for transmission persisted. The increased frequency of markers of pyrethroid resistance indicates that LLIN distribution favoured the evolution of resistance within local vectors and highlights the potential benefits of resistance management strategies.Trial registration:: This study is registered with ISRCTN, ISRCTN17516395. Registered 14 February 2017, http://www.isrctn.com/ISRCTN17516395.
RESUMEN
BACKGROUND: Timely detection and management of gestational diabetes mellitus (GDM) have been identified as a high priority for policymakers in low- and middle-income countries (LMICs). The GUIDES trial will evaluate a package of three interconnected film-based interventions aimed at improving the timely detection and management of GDM. The protocol for this trial has previously been published; this publication outlines the statistical analysis plan for the trial. METHODS AND DESIGN: The GUIDES study is a multi-country cluster-randomised controlled trial consisting of one trial conducted in Uganda and one in India (30 clusters in each country). Mixed effects models will be used to compare the primary study outcomes of the proportion of women who are tested for GDM between 24 and 32 weeks of pregnancy and the mean fasting blood sugar of women with GDM at 34-week follow-up while accounting for clustering. Secondary analyses will compare the proportion of women with self-reported GDM diagnosis at 32 weeks of pregnancy and the proportion of women with adverse perinatal outcomes related to GDM up to 4 weeks after birth in each trial arm. TRIAL STATUS AND DISCUSSION: Follow-up is expected to end in March 2023 in Uganda and in May 2023 in India. Analyses will be carried out following this statistical analysis plan in the month following trial completion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03937050. Registered on 3 May 2019. Clinical Trials Registry India CTRI/2020/02/023605. Registered on 26 February 2020.
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Diabetes Gestacional , Automanejo , Embarazo , Femenino , Humanos , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/terapia , Uganda , Escolaridad , India , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Vasovagal reactions (VVRs) are the most common acute complications of blood donation. Responsible for substantial morbidity, they also reduce the likelihood of repeated donations and are disruptive and costly for blood services. Although blood establishments worldwide have adopted different strategies to prevent VVRs (including water loading and applied muscle tension [AMT]), robust evidence is limited. The Strategies to Improve Donor Experiences (STRIDES) trial aims to reliably assess the impact of four different interventions to prevent VVRs among blood donors. METHODS: STRIDES is a cluster-randomised cross-over/stepped-wedge factorial trial of four interventions to reduce VVRs involving about 1.4 million whole blood donors enrolled from all 73 blood donation sites (mobile teams and donor centres) of National Health Service Blood and Transplant (NHSBT) in England. Each site ("cluster") has been randomly allocated to receive one or more interventions during a 36-month period, using principles of cross-over, stepped-wedge and factorial trial design to assign the sequence of interventions. Each of the four interventions is compared to NHSBT's current practices: (i) 500-ml isotonic drink before donation (vs current 500-ml plain water); (ii) 3-min rest on donation chair after donation (vs current 2 min); (iii) new modified AMT (vs current practice of AMT); and (iv) psychosocial intervention using preparatory materials (vs current practice of nothing). The primary outcome is the number of in-session VVRs with loss of consciousness (i.e. episodes involving loss of consciousness of any duration, with or without additional complications). Secondary outcomes include all in-session VVRs (i.e. with and without loss of consciousness), all delayed VVRs (i.e. those occurring after leaving the venue) and any in-session non-VVR adverse events or reactions. DISCUSSION: The STRIDES trial should yield novel information about interventions, singly and in combination, for the prevention of VVRs, with the aim of generating policy-shaping evidence to help inform blood services to improve donor health, donor experience, and service efficiency. TRIAL REGISTRATION: ISRCTN: 10412338. Registration date: October 24, 2019.
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Donantes de Sangre , Síncope Vasovagal , Humanos , Medicina Estatal , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/etiología , Síncope Vasovagal/prevención & control , Agua , Donación de SangreRESUMEN
BACKGROUND: Recent work has shown that cluster-randomised trials can estimate two distinct estimands: the participant-average and cluster-average treatment effects. These can differ when participant outcomes or the treatment effect depends on the cluster size (termed informative cluster size). In this case, estimators that target one estimand (such as the analysis of unweighted cluster-level summaries, which targets the cluster-average effect) may be biased for the other. Furthermore, commonly used estimators such as mixed-effects models or generalised estimating equations with an exchangeable correlation structure can be biased for both estimands. However, there has been little empirical research into whether informative cluster size is likely to occur in practice. METHOD: We re-analysed a cluster-randomised trial comparing two different thresholds for red blood cell transfusion in patients with acute upper gastrointestinal bleeding to explore whether estimates for the participant- and cluster-average effects differed, to provide empirical evidence for whether informative cluster size may be present. For each outcome, we first estimated a participant-average effect using independence estimating equations, which are unbiased under informative cluster size. We then compared this to two further methods: (1) a cluster-average effect estimated using either weighted independence estimating equations or unweighted cluster-level summaries, and (2) estimates from a mixed-effects model or generalised estimating equations with an exchangeable correlation structure. We then performed a small simulation study to evaluate whether observed differences between cluster- and participant-average estimates were likely to occur even if no informative cluster size was present. RESULTS: For most outcomes, treatment effect estimates from different methods were similar. However, differences of >10% occurred between participant- and cluster-average estimates for 5 of 17 outcomes (29%). We also observed several notable differences between estimates from mixed-effects models or generalised estimating equations with an exchangeable correlation structure and those based on independence estimating equations. For example, for the EQ-5D VAS score, the independence estimating equation estimate of the participant-average difference was 4.15 (95% confidence interval: -3.37 to 11.66), compared with 2.84 (95% confidence interval: -7.37 to 13.04) for the cluster-average independence estimating equation estimate, and 3.23 (95% confidence interval: -6.70 to 13.16) from a mixed-effects model. Similarly, for thromboembolic/ischaemic events, the independence estimating equation estimate for the participant-average odds ratio was 0.43 (95% confidence interval: 0.07 to 2.48), compared with 0.33 (95% confidence interval: 0.06 to 1.77) from the cluster-average estimator. CONCLUSION: In this re-analysis, we found that estimates from the various approaches could differ, which may be due to the presence of informative cluster size. Careful consideration of the estimand and the plausibility of assumptions underpinning each estimator can help ensure an appropriate analysis methods are used. Independence estimating equations and the analysis of cluster-level summaries (with appropriate weighting for each to correspond to either the participant-average or cluster-average treatment effect) are a desirable choice when informative cluster size is deemed possible, due to their unbiasedness in this setting.