A cost-effectiveness analysis of early detection and bundled treatment of postpartum hemorrhage alongside the E-MOTIVE trial.

Timely detection and treatment of postpartum hemorrhage (PPH) are crucial to prevent complications or death. A calibrated blood-collection drape can help provide objective, accurate and early diagnosis of PPH, and a treatment bundle can address delays or inconsistencies in the use of effective interventions. Here we conducted an economic evaluation alongside the E-MOTIVE trial, an international, parallel cluster-randomized trial with a baseline control phase involving 210,132 women undergoing vaginal delivery across 78 secondary-level hospitals in Kenya, Nigeria, South Africa and Tanzania. We aimed to assess the cost-effectiveness of the E-MOTIVE intervention, which included a calibrated blood-collection drape for early detection of PPH and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination and escalation), compared with usual care. We used multilevel modeling to estimate incremental cost-effectiveness ratios from the perspective of the public healthcare system for outcomes of cost per severe PPH (blood loss ≥1,000 ml) avoided and cost per disability-adjusted life-year averted. Our findings suggest that the use of a calibrated blood-collection drape for early detection of PPH and bundled first-response treatment is cost-effective and should be perceived by decision-makers as a worthwhile use of healthcare budgets. ClinicalTrials.gov identifier: NCT04341662 .

Statistical analysis plan for the NU IMPACT stepped-wedge cluster randomized trial.

BACKGROUND: As part of the IMPACT Consortium of three effectiveness-implementation trials, the NU IMPACT trial was designed to evaluate implementation and effectiveness outcomes for an electronic health record (EHR)-embedded symptom monitoring and management program for outpatient cancer care. NU IMPACT uses a unique stepped-wedge cluster randomized design, involving six clusters of 26 clinics, for evaluation of implementation outcomes with an embedded patient-level randomized trial to evaluate effectiveness outcomes. Collaborative, consortium-wide efforts to ensure use of the most robust and recent analytic methodologies for stepped-wedge trials motivated updates to the statistical analysis plan for implementation outcomes in the NU IMPACT trial. METHODS: In the updated statistical analysis plan for NU IMPACT, the primary implementation outcome patient adoption, as measured by clinic-level monthly proportions of patient engagement with the EHR-based cancer symptom monitoring system, will be analyzed using generalized least squares linear regression with auto-regressive errors and adjustment for cluster and time effects (underlying secular trends). A similar strategy will be used for secondary patient and provider implementation outcomes. DISCUSSION: The analytic updates described here resulted from highly iterative, collaborative efforts among statisticians, implementation scientists, and trial leads in the IMPACT Consortium. This updated statistical analysis plan will serve as the a priori specified approach for analyzing implementation outcomes for the NU IMPACT trial.

What type of cluster randomized trial for which setting?

The cluster randomized trial allows a randomized evaluation when it is either not possible to randomize the individual or randomizing individuals would put the trial at high risk of contamination across treatment arms. There are many variations of the cluster randomized design, including the parallel design with or without baseline measures, the cluster randomized cross-over design, the stepped-wedge cluster randomized design, and more recently-developed variants such as the batched stepped-wedge design and the staircase design. Once it has been clearly established that there is a need for cluster randomization, one ever important question is which form the cluster design should take. If a design in which time is split into multiple trial periods is to be adopted (e.g. as in a stepped-wedge), researchers must decide whether the same participants should be measured in multiple trial periods (cohort sampling); or if different participants should be measured in each period (continual recruitment or cross-sectional sampling). Here we outline the different possible options and weigh up the pros and cons of the different design choices, which revolve around statistical efficiency, study logistics and the assumptions required.

Why and when should we cluster randomize?

A cluster randomized trial is defined as a randomized trial in which intact social units of individuals are randomized rather than individuals themselves. Outcomes are observed on individual participants within clusters (such as patients). Such a design allows assessing interventions targeting cluster-level participants (such as physicians), individual participants or both. Indeed, many interventions assessed in cluster randomized trials are actually complex ones, with distinct components targeting different levels. For a cluster-level intervention, cluster randomization is an obvious choice: the intervention is not divisible at the individual-level. For individual-level interventions, cluster randomization may nevertheless be suitable to prevent group contamination, for logistical reasons, to enhance participants' adherence, or when objectives pertain to the cluster level. An unacceptable reason for cluster randomization would be to avoid obtaining individual consent. Indeed, participants in cluster randomized trials have to be protected as in any type of trial design. Participants may be people from whom data are collected, but they may also be people who are intervened upon, and this includes both patients and physicians (for example, physicians receiving training interventions). Consent should be sought as soon as possible, although there may exist situations where participants may consent only for data collection, not for being exposed to the intervention (because, for instance, they cannot opt-out). There may even be situations where participants are not able to consent at all. In this latter situation a waiver of consent must be granted by a research ethics committee.

Practical considerations for sample size calculation for cluster randomized trials.

Cluster randomized trials are an essential design in public health and medical research, when individual randomization is infeasible or undesirable for scientific or logistical reasons. However, the correlation among observations within clusters leads to a decrease in statistical power compared to an individually randomised trial with the same total sample size. This correlation - often quantified using the intra-cluster correlation coefficient - must be accounted for in the sample size calculation to ensure that the trial is adequately powered. In this paper, we first describe the principles of sample size calculation for parallel-arm CRTs, and explain how these calculations can be extended to CRTs with cross-over designs, with a baseline measurement and stepped-wedge designs. We introduce tools to guide researchers with their sample size calculation and discuss methods to inform the choice of the a priori estimate of the intra-cluster correlation coefficient for the calculation. We also include additional considerations with respect to anticipated attrition, a small number of clusters, and use of covariates in the randomisation process and in the analysis.

Leveraging baseline covariates to analyze small cluster-randomized trials with a rare binary outcome.

Cluster-randomized trials (CRTs) involve randomizing entire groups of participants-called clusters-to treatment arms but are often comprised of a limited or fixed number of available clusters. While covariate adjustment can account for chance imbalances between treatment arms and increase statistical efficiency in individually randomized trials, analytical methods for individual-level covariate adjustment in small CRTs have received little attention to date. In this paper, we systematically investigate, through extensive simulations, the operating characteristics of propensity score weighting and multivariable regression as two individual-level covariate adjustment strategies for estimating the participant-average causal effect in small CRTs with a rare binary outcome and identify scenarios where each adjustment strategy has a relative efficiency advantage over the other to make practical recommendations. We also examine the finite-sample performance of the bias-corrected sandwich variance estimators associated with propensity score weighting and multivariable regression for quantifying the uncertainty in estimating the participant-average treatment effect. To illustrate the methods for individual-level covariate adjustment, we reanalyze a recent CRT testing a sedation protocol in 31 pediatric intensive care units.

Intensified screening for SARS-CoV-2 in 18 emergency departments in the Paris metropolitan area, France (DEPIST-COVID): A cluster-randomized, two-period, crossover trial.

BACKGROUND: Asymptomatic and paucisymptomatic infections account for a substantial portion of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions. The value of intensified screening strategies, especially in emergency departments (EDs), in reaching asymptomatic and paucisymptomatic patients and helping to improve detection and reduce transmission has not been documented. The objective of this study was to evaluate in EDs whether an intensified SARS-CoV-2 screening strategy combining nurse-driven screening for asymptomatic/paucisymptomatic patients with routine practice (intervention) could contribute to higher detection of SARS-CoV-2 infections compared to routine practice alone, including screening for symptomatic or hospitalized patients (control). METHODS AND FINDINGS: We conducted a cluster-randomized, two-period, crossover trial from February 2021 to May 2021 in 18 EDs in the Paris metropolitan area, France. All adults visiting the EDs were eligible. At the start of the first period, 18 EDs were randomized to the intervention or control strategy by balanced block randomization with stratification, with the alternative condition being applied in the second period. During the control period, routine screening for SARS-CoV-2 included screening for symptomatic or hospitalized patients. During the intervention period, in addition to routine screening practice, a questionnaire about risk exposure and symptoms and a SARS-CoV-2 screening test were offered by nurses to all remaining asymptomatic/paucisymptomatic patients. The primary outcome was the proportion of newly diagnosed SARS-CoV-2-positive patients among all adults visiting the 18 EDs. Primary analysis was by intention-to-treat. The primary outcome was analyzed using a generalized linear mixed model (Poisson distribution) with the center and center by period as random effects and the strategy (intervention versus control) and period (modeled as a weekly categorical variable) as fixed effects with additional adjustment for community incidence. During the intervention and control periods, 69,248 patients and 69,104 patients, respectively, were included for a total of 138,352 patients. Patients had a median age of 45.0 years [31.0, 63.0], and women represented 45.7% of the patients. During the intervention period, 6,332 asymptomatic/paucisymptomatic patients completed the questionnaire; 4,283 were screened for SARS-CoV-2 by nurses, leading to 224 new SARS-CoV-2 diagnoses. A total of 1,859 patients versus 2,084 patients were newly diagnosed during the intervention and control periods, respectively (adjusted analysis: 26.7/1,000 versus 26.2/1,000, adjusted relative risk: 1.02 (95% confidence interval (CI) [0.94, 1.11]; p = 0.634)). The main limitation of this study is that it was conducted in a rapidly evolving epidemiological context. CONCLUSIONS: The results of this study showed that intensified screening for SARS-CoV-2 in EDs was unlikely to identify a higher proportion of newly diagnosed patients. TRIAL REGISTRATION: Trial registration number: ClinicalTrials.gov NCT04756609.

Optimal study designs for cluster randomised trials: An overview of methods and results.

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.

Protocol for a cluster randomised waitlist-controlled trial of a goal-based behaviour change intervention for employees in workplaces enrolled in health and wellbeing initiatives.

Many workplaces offer health and wellbeing initiatives to their staff as recommended by international and national health organisations. Despite their potential, the influence of these initiatives on health behaviour appears limited and evaluations of their effectiveness are rare. In this research, we propose evaluating the effectiveness of an established behaviour change intervention in a new workplace context. The intervention, 'mental contrasting plus implementation intentions', supports staff in achieving their health and wellbeing goals by encouraging them to compare the future with the present and to develop a plan for overcoming anticipated obstacles. We conducted a systematic review that identified only three trials of this intervention in workplaces and all of them were conducted within healthcare organisations. Our research will be the first to evaluate the effectiveness of mental contrasting outside a solely healthcare context. We propose including staff from 60 organisations, 30 in the intervention and 30 in a waitlisted control group. The findings will contribute to a better understanding of how to empower and support staff to improve their health and wellbeing. Trial registration: ISRCTN17828539.

Evaluation of an organisational-level monetary incentive to promote the health and wellbeing of workers in small and medium-sized enterprises: A mixed-methods cluster randomised controlled trial.

We conducted an independent evaluation on the effectiveness of an organisational-level monetary incentive to encourage small and medium-sized enterprises (SMEs) to improve employees' health and wellbeing. This was A mixed-methods cluster randomised trial with four arms: high monetary incentive, low monetary incentive, and two no monetary incentive controls (with or without baseline measurements to examine 'reactivity' The consequence of particpant awareness of being studied, and potential impact on participant behavior effects). SMEs with 10-250 staff based in West Midlands, England were eligible. We randomly selected up to 15 employees at baseline and 11 months post-intervention. We elicited employee perceptions of employers' actions to improve health and wellbeing; and employees' self-reported health behaviours and wellbeing. We also interviewed employers and obtained qualitative data. One hundred and fifty-two SMEs were recruited. Baseline assessments were conducted in 85 SMEs in three arms, and endline assessments in 100 SMEs across all four arms. The percentage of employees perceiving "positive action" by their employer increased after intervention (5 percentage points, pp [95% Credible Interval -3, 21] and 3pp [-9, 17], in models for high and low incentive groups). Across six secondary questions about specific issues the results were strongly and consistently positive, especially for the high incentive. This was consistent with qualitative data and quantitative employer interviews. However, there was no evidence of any impact on employee health behaviour or wellbeing outcomes, nor evidence of 'reactivity'. An organisational intervention (a monetary incentive) changed employee perceptions of employer behaviour but did not translate into changes in employees' self-reports of their own health behaviours or wellbeing. Trial registration: AEARCTR-0003420, registration date: 17.10.2018, retrospectively registered (delays in contracts and identfying a suitable trial registry). The authors confirm that there are no ongoing and related trials for this intervention.

A re-analysis of 150 women's health trials to investigate how the Bayesian approach may offer a solution to the misinterpretation of statistical findings.

OBJECTIVE: To investigate whether a Bayesian interpretation might help prevent misinterpretation of statistical findings and support authors to differentiate evidence of no effect from statistical uncertainty. DESIGN: A Bayesian re-analysis to determine posterior probabilities of clinically important effects (e.g., a large effect is set at a 4 percentage point difference and a trivial effect to be within a 0.5 percentage point difference). Posterior probabilities greater than 95% are considered as strong statistical evidence, and less than 95% as inconclusive. SAMPLE: 150 major women's health trials with binary outcomes. MAIN OUTCOME MEASURES: Posterior probabilities of large, moderate, small and trivial effects. RESULTS: Under frequentist methods, 48 (32%) were statistically significant (p-value ≤ 0.05) and 102 (68%) statistically non-significant. The frequentist and Bayesian point estimates and confidence intervals showed strong concordance. Of the statistically non-significant trials (n = 102), the Bayesian approach classified the majority (94, 92%) as inconclusive, neither able to confirm or refute effectiveness. A small number of statistically non-significant findings (8, 8%) were classified as having strong statistical evidence of an effect. CONCLUSIONS: Whilst almost all trials report confidence intervals, in practice most statistical findings are interpreted on the basis of statistical significance, mostly concluding evidence of no effect. Findings here suggest the majority are likely uncertain. A Bayesian approach could help differentiate evidence of no effect from statistical uncertainty.

Permutation-based multiple testing corrections for P $$ P $$ -values and confidence intervals for cluster randomized trials.

In this article, we derive and compare methods to derive P-values and sets of confidence intervals with strong control of the family-wise error rates and coverage for estimates of treatment effects in cluster randomized trials with multiple outcomes. There are few methods for P-value corrections and deriving confidence intervals, limiting their application in this setting. We discuss the methods of Bonferroni, Holm, and Romano and Wolf and adapt them to cluster randomized trial inference using permutation-based methods with different test statistics. We develop a novel search procedure for confidence set limits using permutation tests to produce a set of confidence intervals under each method of correction. We conduct a simulation-based study to compare family-wise error rates, coverage of confidence sets, and the efficiency of each procedure in comparison to no correction using both model-based standard errors and permutation tests. We show that the Romano-Wolf type procedure has nominal error rates and coverage under non-independent correlation structures and is more efficient than the other methods in a simulation-based study. We also compare results from the analysis of a real-world trial.

Estimating intra-cluster correlation coefficients for planning longitudinal cluster randomized trials: a tutorial.

It is well-known that designing a cluster randomized trial (CRT) requires an advance estimate of the intra-cluster correlation coefficient (ICC). In the case of longitudinal CRTs, where outcomes are assessed repeatedly in each cluster over time, estimates for more complex correlation structures are required. Three common types of correlation structures for longitudinal CRTs are exchangeable, nested/block exchangeable and exponential decay correlations-the latter two allow the strength of the correlation to weaken over time. Determining sample sizes under these latter two structures requires advance specification of the within-period ICC and cluster autocorrelation coefficient as well as the intra-individual autocorrelation coefficient in the case of a cohort design. How to estimate these coefficients is a common challenge for investigators. When appropriate estimates from previously published longitudinal CRTs are not available, one possibility is to re-analyse data from an available trial dataset or to access observational data to estimate these parameters in advance of a trial. In this tutorial, we demonstrate how to estimate correlation parameters under these correlation structures for continuous and binary outcomes. We first introduce the correlation structures and their underlying model assumptions under a mixed-effects regression framework. With practical advice for implementation, we then demonstrate how the correlation parameters can be estimated using examples and we provide programming code in R, SAS, and Stata. An Rshiny app is available that allows investigators to upload an existing dataset and obtain the estimated correlation parameters. We conclude by identifying some gaps in the literature.

Key considerations for designing, conducting and analysing a cluster randomized trial.

Not only do cluster randomized trials require a larger sample size than individually randomized trials, they also face many additional complexities. The potential for contamination is the most commonly used justification for using cluster randomization, but the risk of contamination should be carefully weighed against the more serious problem of questionable scientific validity in settings with post-randomization identification or recruitment of participants unblinded to the treatment allocation. In this paper we provide some simple guidelines to help researchers conduct cluster trials in a way that minimizes potential biases and maximizes statistical efficiency. The overarching theme of this guidance is that methods that apply to individually randomized trials rarely apply to cluster randomized trials. We recommend that cluster randomization be only used when necessary-balancing the benefits of cluster randomization with its increased risks of bias and increased sample size. Researchers should also randomize at the lowest possible level-balancing the risks of contamination with ensuring an adequate number of randomization units-as well as exploring other options for statistically efficient designs. Clustering should always be allowed for in the sample size calculation; and the use of restricted randomization (and adjustment in the analysis for covariates used in the randomization) should be considered. Where possible, participants should be recruited before randomizing clusters and, when recruiting (or identifying) participants post-randomization, recruiters should be masked to the allocation. In the analysis, the target of inference should align with the research question, and adjustment for clustering and small sample corrections should be used when the trial includes less than about 40 clusters.

Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage.

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28). CONCLUSIONS: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).

Impact assessment of a raw coal ban on maternal and child health outcomes in Ulaanbaatar: a protocol for an interrupted time series study.

INTRODUCTION: Despite a decade of policy actions, Ulaanbaatar's residents continue to be exposed to extreme levels of air pollution, a major public health concern, especially for vulnerable populations such as pregnant women and children. In May 2019, the Mongolian government implemented a raw coal ban (RCB), prohibiting distribution and use of raw coal in households and small businesses in Ulaanbaatar. Here, we present the protocol for an interrupted time series (ITS; a strong quasi-experimental study design for public health interventions) that aims to assess the effectiveness of this coal ban policy on environmental (air quality) and health (maternal and child) outcomes. METHODS AND ANALYSIS: Routinely collected data on pregnancy and child respiratory health outcomes between 2016 and 2022 in Ulaanbaatar will be collected retrospectively from the four main hospitals providing maternal and/or paediatric care as well as the National Statistics Office. Hospital admissions data for childhood diarrhoea, an unrelated outcome to air pollution exposure, will be collected to control for unknown or unmeasured coinciding events. Retrospective air pollution data will be collected from the district weather stations and the US Embassy. An ITS analysis will be conducted to determine the RCB intervention impact on these outcomes. Prior to the ITS, we have proposed an impact model based on a framework of five key factors, which were identified through literature search and qualitative research to potentially influence the intervention impact assessment. ETHICS AND DISSEMINATION: Ethical approval has been obtained via the Ministry of Health, Mongolia (No.445) and University of Birmingham (ERN_21-1403). To inform relevant stakeholders of our findings, key results will be disseminated on both (inter)national and population levels through publications, scientific conferences and community briefings. These findings are aimed to provide evidence for decision-making in coal pollution mitigation strategies in Mongolia and similar settings throughout the world.

Protocol for a parallel group, two-arm, superiority cluster randomised trial to evaluate a community-level complementary-food safety and hygiene and nutrition intervention in Mali: the MaaCiwara study (version 1.3; 10 November 2022).

BACKGROUND: Diarrhoeal disease remains a significant cause of morbidity and mortality among the under-fives in many low- and middle-income countries. Changes to food safety practices and feeding methods around the weaning period, alongside improved nutrition, may significantly reduce the risk of disease and improve development for infants. We describe a protocol for a cluster randomised trial to evaluate the effectiveness of a multi-faceted community-based educational intervention that aims to improve food safety and hygiene behaviours and enhance child nutrition. METHODS: We describe a mixed-methods, parallel group, two-arm, superiority cluster randomised controlled trial with baseline measures. One hundred twenty clusters comprising small urban and rural communities will be recruited in equal numbers and randomly allocated in a 1:1 ratio to either treatment or control arms. The community intervention will be focussed around an ideal mother concept involving all community members during campaign days with dramatic arts and pledging, and follow-up home visits. Participants will be mother-child dyads (27 per cluster period) with children aged 6 to 36 months. Data collection will comprise a day of observation and interviews with each participating mother-child pair and will take place at baseline and 4 and 15 months post-intervention. The primary analysis will estimate the effectiveness of the intervention on changes to complementary-food safety and preparation behaviours, food and water contamination, and diarrhoea. Secondary outcomes include maternal autonomy, enteric infection, nutrition, child anthropometry, and development scores. A additional structural equation analysis will be conducted to examine the causal relationships between the different outcomes. Qualitative and health economic analyses including process evaluation will be done. CONCLUSIONS: The trial will provide evidence on the effectiveness of community-based behavioural change interventions designed to reduce the burden of diarrhoeal disease in the under-fives and how effectiveness varies across different contexts. TRIAL REGISTRATION: ISRCTN14390796. Registration date December 13, 2021.

Minimisation for the design of parallel cluster-randomised trials: An evaluation of balance in cluster-level covariates and numbers of clusters allocated to each arm.

BACKGROUND: Cluster-randomised trials often use some form of restricted randomisation, such as stratified- or covariate-constrained randomisation. Minimisation has the potential to balance on more covariates than blocked stratification and can be implemented sequentially unlike covariate-constrained randomisation. Yet, unlike stratification, minimisation has no inbuilt guard to maintain close to a 1:1 allocation. A departure from a 1:1 allocation can be unappealing in a setting with a small number of allocation units such as cluster randomisation which typically include about 30 clusters. METHODS: Using simulation (10,000 per scenario), we evaluate the performance of a range of minimisation procedures on the likelihood of a 1:1 allocation of clusters (10-80 clusters) to treatment arms, along with its performance on covariate imbalance. The range of minimisation procedures includes varying: the proportion of clusters allocated to the least imbalanced arm (known as the stochastic element) - between 0.7 and 1, percentage of first clusters allocated completely at random (known as the bed-in period) - between 0% and 20% and adding 'number of clusters allocated to each arm' as a covariate in the minimisation algorithm. We additionally include a comparison of stratifying and then minimising within key strata (such as country within a multi country cluster trial) as a potential aid to increasing balance. RESULTS: Minimisation is unlikely to result in an exact 1:1 allocation unless the stochastic element is set higher than 0.9. For example, with 20 clusters, 2 binary covariates and setting the stochastic element to 0.7: only 41% of the possible randomisations over the 10,000 simulations achieved a 1:1 allocation. While typical sizes of imbalance were small (a difference of two clusters per arm), allocations as extreme as of 10:10 were observed. Adding the 'number of clusters' into the minimisation algorithm reduces this risk slightly, but covariate imbalance increases slightly. Stratifying and then minimising within key strata improve balance within strata but increase imbalance across all clusters, both on the number of clusters and covariate imbalance. CONCLUSION: In cluster trials, where there are typically about 30 allocation units, when using minimisation, unless the stochastic element is set very high, there is a high risk of not achieving a 1:1 allocation, and a small but nonetheless real risk of an extreme departure from a 1:1 allocation. Stratification with minimisation within key strata (such as country) improves the balance within strata although compromises overall balance.

Retrospective evaluation of an intervention based on training sessions to increase the use of control charts in hospitals.

BACKGROUND: Statistical process control charts (SPCs) distinguish signal from noise in quality and safety metrics and thus enable resources to be targeted towards the most suitable actions for improving processes and outcomes. Nevertheless, according to a recent study, SPCs are not widely used by hospital boards in England. To address this, an educational training initiative with training sessions lasting less than one and a half days was established to increase uptake of SPCs in board papers. This research evaluated the impact of the training sessions on the inclusion of SPCs in hospital board papers in England. METHODS: We used a non-randomised controlled before and after design. Use of SPCs was examined in 40 publicly available board papers across 20 hospitals; 10 intervention hospitals and 10 control hospitals matched using hospital characteristics and time-period. Zero-inflated negative binomial regression models and t-tests compared changes in usage by means of a difference in difference approach. RESULTS: Across the 40 board papers in our sample, we found 6287 charts. Control hospitals had 9/1585 (0.6%) SPCs before the intervention period and 23/1900 (1.2%) after the intervention period, whereas intervention hospitals increased from 89/1235 (7%) before to 328/1567 (21%) after the intervention period; a relative risk ratio of 9 (95% CI 3 to 32). The absolute difference in use of SPCs was 17% (95% CI 6% to 27%) in favour of the intervention group. CONCLUSIONS: The results suggest that a scalable educational training initiative to improve use of SPCs within organisations can be effective. Future research could aim to overcome the limitations of observational research with an experimental design or seek to better understand mechanisms, decision-making and patient outcomes.