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.
CONCLUSIONS: 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.

To investigate if a prospective feedback loop that flags older patients at risk of death can reduce non-beneficial treatment at end of life.
Prospective stepped-wedge cluster randomised trial with usual care and intervention phases.
Three large tertiary public hospitals in south-east Queensland, Australia.
14 clinical teams were recruited across the three hospitals. Teams were recruited based on a consistent history of admitting patients aged 75+ years, and needed a nominated lead specialist consultant. Under the care of these teams, there were 4,268 patients (median age 84 years) who were potentially near the end of life and flagged at risk of non-beneficial treatment.
The intervention notified clinicians of patients under their care determined as at-risk of non-beneficial treatment. There were two notification flags: a real-time notification and an email sent to clinicians about the at-risk patients at the end of each screening day. The nudge intervention ran for 16-35 weeks across the three hospitals.
The primary outcome was the proportion of patients with one or more intensive care unit (ICU) admissions. The secondary outcomes examined times from patients being flagged at-risk.
There was no improvement in the primary outcome of reduced ICU admissions (mean probability difference [intervention minus usual care] = -0.01, 95% confidence interval -0.08 to 0.01). There were no differences for the times to death, discharge, or medical emergency call. There was a reduction in the probability of re-admission to hospital during the intervention phase (mean probability difference -0.08, 95% confidence interval -0.13 to -0.03).
This nudge intervention was not sufficient to reduce the trial\'s non-beneficial treatment outcomes in older hospital patients.
Australia New Zealand Clinical Trial Registry, ACTRN12619000675123 (registered 6 May 2019).

BACKGROUND: Despite increasing morbidity and mortality from non-communicable diseases (NCD) globally, health systems in low- and middle-income countries (LMICs) have limited capacity to address these chronic conditions, particularly in sub-Saharan Africa (SSA). There is an urgent need, therefore, to respond to NCDs in SSA, beginning by applying lessons learned from the first global response to any chronic disease-HIV-to tackle the leading cardiometabolic killers of people living with HIV (PLHIV). We have developed a feasible and acceptable package of evidence-based interventions and a multi-faceted implementation strategy, known as \"TASKPEN,\" that has been adapted to the Zambian setting to address hypertension, diabetes, and dyslipidemia. The TASKPEN multifaceted implementation strategy focuses on reorganizing service delivery for integrated HIV-NCD care and features task-shifting, practice facilitation, and leveraging HIV platforms for NCD care. We propose a hybrid type II effectiveness-implementation stepped-wedge cluster randomized trial to evaluate the effects of TASKPEN on clinical and implementation outcomes, including dual control of HIV and cardiometabolic NCDs, as well as quality of life, intervention reach, and cost-effectiveness.
METHODS: The trial will be conducted in 12 urban health facilities in Lusaka, Zambia over a 30-month period. Clinical outcomes will be assessed via surveys with PLHIV accessing routine HIV services, and a prospective cohort of PLHIV with cardiometabolic comorbidities nested within the larger trial. We will also collect data using mixed methods, including in-depth interviews, questionnaires, focus group discussions, and structured observations, and estimate cost-effectiveness through time-and-motion studies and other costing methods, to understand implementation outcomes according to Proctor\'s Outcomes for Implementation Research, the Consolidated Framework for Implementation Research, and selected dimensions of RE-AIM.
CONCLUSIONS: Findings from this study will be used to make discrete, actionable, and context-specific recommendations in Zambia and the region for integrating cardiometabolic NCD care into national HIV treatment programs. While the TASKPEN study focuses on cardiometabolic NCDs in PLHIV, the multifaceted implementation strategy studied will be relevant to other NCDs and to people without HIV. It is expected that the trial will generate new insights that enable delivery of high-quality integrated HIV-NCD care, which may improve cardiovascular morbidity and viral suppression for PLHIV in SSA. This study was registered at ClinicalTrials.gov (NCT05950919).

BACKGROUND: Falls are the leading cause of injury, disability, premature institutionalization, and injury-related mortality among older adults. Home hazard removal can effectively reduce falls in this population but is not implemented as standard practice. This study translated an evidence-based home hazard removal program (HARP) for delivery in low-income senior apartments to test whether the intervention would work in the \"real world.\"
METHODS: From May 1, 2019 to December 31, 2020, a stepped-wedge cluster-randomized trial was used to implement the evidence-based HARP among residents with high fall risk in 11 low-income senior apartment buildings. Five clusters of buildings were randomly assigned an intervention allocation sequence. Three-level negative-binomial models (repeated measures nested within individuals, individuals nested within buildings) were used to compare fall rates between treatment and control conditions (excluding a crossover period), controlling for demographic characteristics, fall risk, and time period.
RESULTS: Among 656 residents, 548 agreed to screening, 435 were eligible (high fall risk), and 291 agreed to participate and received HARP. Participants were, on average, 72 years, 67% female, and 76% Black. Approximately 95.4% of fall prevention strategies and modifications implemented were still used 3 months later. The fall rate (per 1000 participant-days) was 4.87 during the control period and 4.31 during the posttreatment period. After adjusting for covariates and secular trend, there was no significant difference in fall rate (incidence rate ratio [IRR] 0.97, 95% CI 0.66-1.42). After excluding data collected during a hiatus in the intervention due to COVID-19, the reduction in fall rate was not significant (IRR 0.93, 95% CI 0.62-1.40).
CONCLUSIONS: Although HARP did not significantly reduce the rate of falls, this pragmatic study showed that the program was feasible to deliver in low-income senior housing and was acceptable among residents. There was effective collaboration between researchers and community agency staff.

Tuberculosis(TB) is among the leading causes of infectious death worldwide. Contact investigation is an evidence-based, World Health Organisation-endorsed intervention for timely TB diagnosis, treatment, and prevention but has not been widely and effectively implemented.
We are conducting a stepped-wedge, cluster-randomised, hybrid Type III implementation-effectiveness trial comparing a user-centred to a standard strategy for implementing TB contact investigation in 12 healthcare facilities in Uganda. The user-centred strategy consists of several client-focused components including (1) a TB-education booklet, (2) a contact-identification algorithm, (3) an instructional sputum-collection video, and (4) a community-health-rider service to transport clients, CHWs, and sputum samples, along with several healthcare-worker-focused components, including (1) collaborative improvement meetings, (2) regular audit-and-feedback reports, and (3) a digital group-chat application designed to develop a community of practice. Sites will cross-over from the standard to the user-centred strategy in six, eight-week transition steps following a randomly determined site-pairing scheme and timeline. The primary implementation outcome is the proportion of symptomatic close contacts completing TB evaluation within 60 days of TB treatment initiation by the index person with TB. The primary clinical effectiveness outcomes are the proportion of contacts diagnosed with and initiating active TB disease treatment and the proportion initiating TB preventative therapy within 60 days. We will assess outcomes from routine source documents using intention-to-treat analyses. We will also conduct nested mixed-methods studies of implementation fidelity and context and perform cost-effectiveness and impact modelling. The Makerere School of Public Health IRB(#554), the Uganda National Council for Science and Technology(#HS1720ES), and the Yale Institutional Review Board(#2000023199) approved the study and waived informed consent for the main trial implementation-effectiveness outcomes. We will submit results for publication in peer-reviewed journals and disseminate findings to local policymakers and representatives of affected communities.
This pragmatic, quasi-experimental implementation trial will inform efforts to find and prevent undiagnosed persons with TB in high-burden settings using contact investigation. It will also help assess the suitability of human-centred design and communities of practice for tailoring implementation strategies and sustaining evidence-based interventions in low-and-middle-income countries.
The trial was registered(ClinicalTrials.gov Identifier NCT05640648) on 16 November 2022, after the trial launch on 7 March 2022.

BACKGROUND: While community-based eldercare has proven to be effective in qualitative studies, there is limited evidence on the effectiveness of this geriatric care model in rural communities where caring for older people is traditionally the responsibility of family members, but a formal long-term care was recently introduced in China. CIE is a rural community-embedded intervention using multidisciplinary team, to provide evidenced-based integrated care services for frail older people including social care services and allied primary healthcare and community-based rehabilitation services.
METHODS: CIE is a prospective stepped-wedge cluster randomized trial conducted at 5 community eldercare centers in rural China. The multifaceted CIE intervention, guided by chronic care model and integrated care model, consists of five components: comprehensive geriatric assessment, individualized care planning, community-based rehabilitation, interdisciplinary case management, and care coordination. The intervention is rolled out in a staggered manner in these clusters of centers at an interval of 1 month. The primary outcomes include functional status, quality of life, and social support. Process evaluation will also be conducted. Generalized linear mixed model is employed for binary outcomes.
CONCLUSIONS: This study is expected to provide important new evidence on clinical effectiveness and implementation process of an integrated care model for frail older people. The CIE model is also unique as the first registered trial implementing a community-based eldercare model using multidisciplinary team to promote individualized social care services integrated with primary healthcare and community-based rehabilitation services for frail older people in rural China, where formal long-term care was recently introduced. TRIAL REGISTRATION {2A}: China Clinical Trials Register ( http://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR2200060326 ). May 28th, 2022.

BACKGROUND: Antenatal clinical practice guidelines recommend routine assessment of weight and provision of advice on recommended weight gain during pregnancy and referral to additional services when appropriate. However, there are barriers to clinicians adopting such best-practice guidelines. Effective, cost-effective, and affordable implementation strategies are needed to ensure the intended benefits of guidelines are realised. This paper describes the protocol for evaluating the efficiency and affordability of implementation strategies compared to the usual practice in public antenatal services.
METHODS: The prospective trial-based economic evaluation will identify, measure, and value key resource and outcome impacts arising from the implementation strategies compared with usual practice. The evaluation will comprise of (i) costing, (ii) cost-consequence analyses, where a scorecard approach will be used to show the costs and benefits given the multiple primary outcomes included in the trial, and (iii) cost-effectiveness analysis, where the primary outcome will be incremental cost per percent increase in participants reporting receipt of antenatal care for gestational weight gain consistent with the guideline recommendations. Affordability will be evaluated using (iv) budget impact assessment and will estimate the financial implications of adoption and diffusion of this implementation strategy from the perspective of relevant fund-holders.
CONCLUSIONS: Together with the findings from the effectiveness trial, the outcomes of this economic evaluation will inform future healthcare policy, investment allocation, and research regarding the implementation of antenatal care to support healthy gestational weight gain.
BACKGROUND: Trial Registration: Australian and New Zealand Clinical Trials Registry, ACTRN12621000054819 (22/01/2021) http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380680&isReview=true .

The \"Diabetes: Community-led Awareness, Response and Evaluation\" (D:Clare) trial aims to scale up and replicate an evidence-based participatory learning and action cycle intervention in Bangladesh, to inform policy on population-level T2DM prevention and control.The trial was originally designed as a stepped-wedge cluster randomised controlled trial, with the interventions running from March 2020 to September 2022. Twelve clusters were randomly allocated (1:1) to implement the intervention at months 1 or 12 in two steps, and evaluated through three cross-sectional surveys at months 1, 12 and 24. However, due to the COVID-19 pandemic, we suspended project activities on the 20th of March 2020. As a result of the changed risk landscape and the delays introduced by the COVID-19 pandemic, we changed from the stepped-wedge design to a wait-list parallel arm cluster RCT (cRCT) with baseline data. We had four key reasons for eventually agreeing to change designs: equipoise, temporal bias in exposure and outcomes, loss of power and time and funding considerations.Trial registration ISRCTN42219712 . Registered on 31 October 2019.

The stepped-wedge design has been extensively studied in the setting of the cluster randomized trial, but less so for the individually randomized trial. This article derives the optimal allocation of individuals to treatment sequences. The focus is on designs where all individuals start in the control condition and at the beginning of each time period some of them cross over to the intervention, so that at the end of the trial all of them receive the intervention.
The statistical model that takes into account the nesting of repeated measurements within subjects is presented. It is also shown how possible attrition is taken into account. The effect of the intervention is assumed to be sustained so that it does not change after the treatment switch. An exponential decay correlation structure is assumed, implying that the correlation between any two time point decreases with the time lag. Matrix algebra is used to derive the relation between the allocation of units to treatment sequences and the variance of the treatment effect estimator. The optimal allocation is the one that results in smallest variance.
Results are presented for three to six treatment sequences. It is shown that the optimal allocation highly depends on the correlation parameter ρ and attrition rate r between any two adjacent time points. The uniform allocation, where each treatment sequence has the same number of individuals, is often not the most efficient. For 0.1≤ρ≤0.9 and r=0,0.05,0.2, its efficiency relative to the optimal allocation is at least 0.8. It is furthermore shown how a constrained optimal allocation can be derived in case the optimal allocation is not feasible from a practical point of view.
This article provides the methodology for designing individually randomized stepped-wedge designs, taking into account the possibility of attrition. As such it helps researchers to plan their trial in an efficient way. To use the methodology, prior estimates of the degree of attrition and intraclass correlation coefficient are needed. It is advocated that researchers clearly report the estimates of these quantities to help facilitate planning future trials.

Hospitalisation rates for older people are increasing, with end-of-life care becoming a more medicalised experience. Innovative approaches are warranted to support early identification of the end-of-life phase, communicate prognosis, provide care consistent with people\'s preferences, and improve the use of healthcare resources. The Intervention for Appropriate Care and Treatment (InterACT) trial aimed to increase appropriate care and treatment decisions for older people at the end of life, through implementation of a prospective feedback loop. This paper reports on the care review outcomes.
A stepped-wedge randomised controlled trial was conducted in three large acute hospitals in Queensland, Australia between May 2020 and June 2021. The trial identified older people nearing the end of life using two validated tools for detecting deterioration and short-term death. Admitting clinical teams were provided with details of patients identified as at-risk with the goal of increasing awareness that end of life was approaching to facilitate appropriate patient centred care and avoid non-beneficial treatment. We examined the time between when the patient was identified as \'at-risk\' and three outcomes: clinician-led care review discussions, review of care directive measures and palliative care referrals. These were considered useful indicators of appropriate care at the end of life.
In two hospitals there was a reduction in the review of care directive measures during the intervention compared with usual care at 21 days (reduced probability of - 0.08; 95% CI: - 0.12 to - 0.04 and - 0.14; 95% CI: - 0.21 to - 0.06). In one hospital there was a large reduction in clinician-led care review discussions at 21 days during the intervention (reduced probability of - 0.20; 95% CI: - 0.28 to - 0.13). There was little change in palliative care referrals in any hospital, with average probability differences at 21 days of - 0.01, 0.02 and 0.04.
The results are disappointing as an intervention designed to improve care of hospitalised older people appeared to have the opposite effect on care review outcomes. The reasons for this may be a combination of the intervention design and health system challenges due to the pandemic that highlight the complexity of providing more appropriate care at the end of life.
Australia New Zealand Clinical Trial Registry, ACTRN12619000675123 (registered 6 May 2019).