Search

Background: Stepped wedge design (SWD) is a cluster randomized controlled trial (RCT) design that sequentially rolls out intervention to all clusters at varying time points. Being a relatively new design method, reporting quality has yet to be explored, and this review will seek to fill this gap in knowledge. Objectives: The objectives of this review are: 1) to assess the quality of SWD trial reports based on the CONSORT guidelines or CONSORT extension to cluster RCTs; 2) to assess the completeness of reporting of SWD trial abstracts using the CONSORT extension for abstracts; 3) to assess the reporting of sample size details in SWD trial reports or protocols; 4) to assess the completeness of reporting of SWD trial protocols according to SPIRIT guidelines; 5) to assess the consistency between the trial registration information and final SWD trial reports; and 6) to assess the consistency of what is reported in the abstracts and main text of the SWD trial reports. We will also explore factors that are associated with the completeness of reporting. Methods: We will search MEDLINE, EMBASE, Web of Science, CINAHL, and PsycINFO for all randomized controlled trials utilizing SWD. Details from eligible papers will be extracted in duplicate. Demographic statistics obtained from the data extraction will be analyzed to answer the primary objectives pertaining to the reporting quality of several aspects of a published paper, as well as to explore possible temporal trends and consistency between abstracts, trial registration information, and final published articles. Discussion: Findings from this review will establish the reporting quality of SWD trials and inform academics and clinicians on their completeness and consistency. Results of this review will influence future trials and improve the overall quality and reporting of SWD trials. [ABSTRACT FROM AUTHOR]

Background: Reducing sugar-sweetened beverage (SSB) consumption is a promising dietary target for childhood obesity prevention. This paper describes the design and methods of a cluster randomized trial of H2GO!, a youth empowerment intervention to prevent childhood obesity through reducing SSB consumption among a low-income, ethnically diverse sample of youth.Methods: This cluster randomized controlled trial is an academic-community partnership with the Massachusetts Alliance of Boys and Girls Clubs (BGC). Ten BGC sites will be randomly assigned to the H2GO! intervention or a wait-list, usual care control. Eligible study participants will be N = 450 parent-child pairs (youth ages 9-12 years and their parents/caregivers) recruited from participating BGCs. The 6-week in-person H2GO! intervention consists of 12 group-based sessions delivered by BGC staff and youth-led activities. An innovative feature of the intervention is the development of youth-produced narratives as a strategy to facilitate youth empowerment and parental engagement. Child outcomes include measured body mass index z scores (zBMI), beverage intake, and youth empowerment. Parent outcomes include beverage intake and availability of SSBs at home. Outcomes will be measured at baseline and at 2, 6, and 12 months. With a 75% retention rate, the study is powered to detect a minimum group difference of 0.1 zBMI units over 12 months.Discussion: Empowering youth may be a promising intervention approach to prevent childhood obesity through reducing SSB consumption. This intervention was designed to be delivered through BGCs and is hypothesized to be efficacious, relevant, and acceptable for the target population of low-income and ethnically diverse youth.Trial Registration: ClinicalTrials.gov NCT04265794 . Registered 11 February 2020. [ABSTRACT FROM AUTHOR]

The stepped-wedge cluster randomized trial (SW-CRT) involves the sequential transition of clusters (such as hospitals, public health units or communities) from control to intervention conditions in a randomized order. The use of the SW-CRT is growing rapidly. Yet the SW-CRT is at greater risks of bias compared with the conventional parallel cluster randomized trial (parallel-CRT). For this reason, the CONSORT extension for SW-CRTs requires that investigators provide a clear justification for the choice of study design. In this paper, we argue that all other things being equal, the SW-CRT is at greater risk of bias due to misspecification of the secular trends at the analysis stage. This is particularly problematic for studies randomizing a small number of heterogeneous clusters. We outline the potential conditions under which an SW-CRT might be an appropriate choice. Potentially appropriate and often overlapping justifications for conducting an SW-CRT include: (i) the SW-CRT provides a means to conduct a randomized evaluation which otherwise would not be possible; (ii) the SW-CRT facilitates cluster recruitment as it enhances the acceptability of a randomized evaluation either to cluster gatekeepers or other stakeholders; (iii) the SW-CRT is the only feasible design due to pragmatic and logistical constraints (for example the roll-out of a scare resource); and (iv) the SW-CRT has increased statistical power over other study designs (which will include situations with a limited number of clusters). As the number of arguments in favour of an SW-CRT increases, the likelihood that the benefits of using the SW-CRT, as opposed to a parallel-CRT, outweigh its risks also increases. We argue that the mere popularity and novelty of the SW-CRT should not be a factor in its adoption. In situations when a conventional parallel-CRT is feasible, it is likely to be the preferred design. [ABSTRACT FROM AUTHOR]

Background: Cluster randomized trials are common in health research in low- and middle-income countries raising issues that challenge interpretation of standard ethical guidelines. While the Ottawa Statement on the ethical design and conduct of cluster randomized trials provides guidance for researchers and research ethics committees, it does not explicitly focus on low- and middle-income settings.Main Body: In this paper, we use the lens of the Ottawa Statement to analyze two cluster randomized trials conducted in low- and middle-income settings in order to identify gaps or ethical issues requiring further analysis and guidance. The PolyIran trial was a parallel-arm, cluster trial examining the effectiveness of a polypill for prevention of cardiovascular disease in Golestan province, Iran. The PASTAL trial was an adaptive, multistage, parallel-arm, cluster trial evaluating the effect of incentives for human immunodeficiency virus self-testing and follow-up on male partners of pregnant women in Malawi. Through an in-depth case analysis of these two studies we highlight several issues in need of further exploration. First, standards for verbal consent and waivers of consent require methods for operationalization if they are to be employed consistently. Second, the appropriate choice of a control arm remains contentious. Particularly in the case of implementation interventions, locally available care is required as the comparator to address questions of comparative effectiveness. However, locally available care might be lower than standards set out in national guidelines. Third, while the need for access to effective interventions post-trial is widely recognized, it is often not possible to guarantee this upfront. Clarity on what is required of researchers and sponsors is needed. Fourth, there is a pressing need for ethics education and capacity building regarding cluster randomized trials in these settings.Conclusion: We identify four issues in cluster randomized trials conducted in low- and middle-income countries for which further ethical analysis and guidance is required. [ABSTRACT FROM AUTHOR]

Background: The purpose of this paper is to describe the Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS) study, a cooperative implementation science initiative involving the National Institute on Drug Abuse, six research centers, a coordinating center, and Juvenile Justice Partners representing seven US states. While the pooling of resources across centers enables a robust implementation study design involving 36 juvenile justice agencies and their behavioral health partner agencies, co-producing a study protocol that has potential to advance implementation science, meets the needs of all constituencies (funding agency, researchers, partners, study sites), and can be implemented with fidelity across the cooperative can be challenging. This paper describes (a) the study background and rationale, including the juvenile justice context and best practices for substance use disorders, (b) the selection and use of an implementation science framework to guide study design and inform selection of implementation components, and (c) the specific study design elements, including research questions, implementation interventions, measurement, and analytic plan.Methods/design: The JJ-TRIALS primary study uses a head-to-head cluster randomized trial with a phased rollout to evaluate the differential effectiveness of two conditions (Core and Enhanced) in 36 sites located in seven states. A Core strategy for promoting change is compared to an Enhanced strategy that incorporates all core strategies plus active facilitation. Target outcomes include improvements in evidence-based screening, assessment, and linkage to substance use treatment.Discussion: Contributions to implementation science are discussed as well as challenges associated with designing and deploying a complex, collaborative project.Trial Registration: NCT02672150 . [ABSTRACT FROM AUTHOR]

Background: Malawi introduced an ambitious public health program known as "Option B+" which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy, regardless of WHO clinical stage or CD4 cell count. The PMTCT Uptake and REtention (PURE) study aimed at evaluating the effect of peer-support on care-seeking and retention in care. Methods/design: PURE Malawi was a three-arm cluster randomized controlled trial that compared facility-based and community-based models of peer support to standard of care under Option B+ strategy. Each arm was expected to enroll a minimum of 360 women with a total minimum sample size of 1080 participants. 21 sites (clusters) were selected for inclusion in the study. This paper describes the site selection, recruitment, enrollment process and baseline characteristics of study sites and women enrolled in the trial. Results: Study implementation was managed by 3 partner organizations; each responsible for 7 study sites. The trial was conducted in the South East, South West, and Central West zones of Malawi, the zones where the implementing partners operate. Study sites included 2 district hospitals, 2 mission hospitals, 2 rural hospitals, 13 health centers and 1 private clinic. Enrollment occurred from November 2013 to November 2014, over a median period of 31 weeks (range 17-51) by site. A total of 1269 HIV-infected pregnant (1094) and breastfeeding (175) women, who were eligible to initiate ART under Option B+, were enrolled. Each site reached or surpassed the minimum sample size. Comparing the number of women enrolled versus antenatal cohort reports, sites recruited a median of 90% (IQR 75-100) of eligible reported women. In the majority of sites the ratio of pregnant and lactating women enrolled in the study was similar to the ratio of reported pregnant and lactating women starting ART in the same sites. The median age of all women was 27 (IQR 22-31) years. All women have ≥20 months of possible follow-up time; 96% ≥ 2 years (24-32 months). Conclusion: The PURE Malawi study showed that 3 implementing partner organizations could successfully recruit a complex cohort of pregnant and lactating women across 3 geographical zones in Malawi within a reasonable timeline. Trial registration: This study is registered at clinicaltrials.gov - ID Number NCT02005835. Registered 4 December, 2013. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a debilitating disease. Adequate calcium consumption and physical activity are the two major modifiable risk factors. This paper describes the major outcomes and efficacy of a workplace-based targeted behaviour change intervention to improve the dietary and physical activity behaviours of working women in sedentary occupations in Singapore.Methods: A cluster-randomized design was used, comparing the efficacy of a tailored intervention to standard care. Workplaces were the units of randomization and intervention. Sixteen workplaces were recruited from a pool of 97, and randomly assigned to intervention and control arms (eight workplaces in each). Women meeting specified inclusion criteria were then recruited to participate. Workplaces in the intervention arm received three participatory workshops and organization-wide educational activities. Workplaces in the control/standard care arm received print resources. Outcome measures were calcium intake (milligrams/day) and physical activity level (duration: minutes/week), measured at baseline, 4 weeks and 6 months post intervention. Adjusted cluster-level analyses were conducted comparing changes in intervention versus control groups, following intention-to-treat principles and CONSORT guidelines.Results: Workplaces in the intervention group reported a significantly greater increase in calcium intake and duration of load-bearing moderate to vigorous physical activity (MVPA) compared with the standard care control group. Four weeks after intervention, the difference in adjusted mean calcium intake was 343.2 mg/day (95 % CI = 337.4 to 349.0, p < .0005) and the difference in adjusted mean load-bearing MVPA was 55.6 min/week (95 % CI = 54.5 to 56.6, p < .0005). Six months post intervention, the mean differences attenuated slightly to 290.5 mg/day (95 % CI = 285.3 to 295.7, p < .0005) and 50.9 min/week (95 % CI =49.3 to 52.6, p < .0005) respectively.Conclusion: This workplace-based intervention substantially improved calcium intake and load-bearing moderate to vigorous physical activity 6 months after the intervention began.Trial Registration: Australia New Zealand Clinical Trial Registry ACTRN12616000079448 . Registered 25 January 2016 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Background: Various papers have addressed pros and cons of the stepped wedge cluster randomized trial design (SWD). However, some issues have not or only limitedly been addressed. Our aim was to provide a comprehensive overview of all merits and limitations of the SWD to assist researchers, reviewers and medical ethics committees when deciding on the appropriateness of the SWD for a particular study.Methods: We performed an initial search to identify articles with a methodological focus on the SWD, and categorized and discussed all reported advantages and disadvantages of the SWD. Additional aspects were identified during multidisciplinary meetings in which ethicists, biostatisticians, clinical epidemiologists and health economists participated. All aspects of the SWD were compared to the parallel group cluster randomized design. We categorized the merits and limitations of the SWD to distinct phases in the design and conduct of such studies, highlighting that their impact may vary depending on the context of the study or that benefits may be offset by drawbacks across study phases. Furthermore, a real-life illustration is provided.Results: New aspects are identified within all disciplines. Examples of newly identified aspects of an SWD are: the possibility to measure a treatment effect in each cluster to examine the (in)consistency in effects across clusters, the detrimental effect of lower than expected inclusion rates, deviation from the ordinary informed consent process and the question whether studies using the SWD are likely to have sufficient social value. Discussions are provided on e.g. clinical equipoise, social value, health economical decision making, number of study arms, and interim analyses.Conclusions: Deciding on the use of the SWD involves aspects and considerations from different disciplines not all of which have been discussed before. Pros and cons of this design should be balanced in comparison to other feasible design options as to choose the optimal design for a particular intervention study. [ABSTRACT FROM AUTHOR]

Introduction: This paper examines the cost-effectiveness of achieving increases in the use of oral rehydration solution and zinc supplementation in the management of acute diarrhea in children under 5 years through social franchising. The study uses cost and outcome data from an initiative by Population Services International (PSI) in 3 townships of Myanmar in 2010 to promote an ORS-Zinc product called ORASEL. Background: The objective of this study was to determine the incremental cost-effectiveness of a strategy to promote ORS-Z use through private sector franchising compared to standard government and private sector practices. Methods: Costing from a societal perspective included program, provider, and household costs for the 2010 calendar year. Program costs including ORASEL program launch, distribution, and administration costs were obtained through a retrospective review of financial records and key informant interviews with staff in the central Yangon office. Household out of pocket payments for diarrheal episodes were obtained from a household survey conducted in the study area and additional estimates of household income lost due to parental care-giving time for a sick child were estimated. Incremental cost-effectiveness relative to status quo conditions was calculated per child death and DALY averted in 2010. Health effects included deaths and DALYs averted; the former modeled based on coverage estimates from a household survey that were entered into the Lives Saved Tool (LiST). Uncertainty was modeled with Monte Carlo methods. Findings: Based on the model, the promotional strategy would translate to 2.85 (SD 0.29) deaths averted in a community population of 1 million where there would be 81,000 children under 5 expecting 48,373 cases of diarrhea. The incremental cost effectiveness of the franchised approach to improving ORASEL coverage is estimated at a median $5,955 (IQR: $3437-$7589) per death averted and $214 (IQR: $127-$287) per discounted DALY averted. Interpretation: Investing in developing a network of private sector providers and keeping them stocked with ORS-Z as is done in a social franchise can be a highly cost-effective in terms of dollars per DALY averted. [ABSTRACT FROM AUTHOR]

Background: Ongoing high neonatal mortality rates (NMRs) represent a global challenge. In 2021, of the 5 million deaths reported worldwide for children under five years of age, 47% were newborns. Pakistan has one of the five highest national NMRs in the world, with an estimated 39 neonatal deaths per 1,000 live births. Reducing newborn deaths requires sustainable, evidence-based, and cost-effective interventions that can be integrated within existing community healthcare infrastructure across regions with high NMR. Methods: This pragmatic, community-based, parallel-arm, open-label, cluster randomized controlled trial aims to estimate the effect of Lady Health Workers (LHWs) providing an integrated newborn care kit (iNCK) with educational instructions to pregnant women in their third trimester, compared to the local standard of care in Gilgit-Baltistan, Pakistan, on neonatal mortality and other newborn and maternal health outcomes. The iNCK contains a clean birth kit, 4% chlorhexidine topical gel, sunflower oil emollient, a ThermoSpot™ temperature monitoring sticker, a fleece blanket, a click-to-heat reusable warmer, three 200 μg misoprostol tablets, and a pictorial instruction guide and diary. LHWs are also provided with a handheld scale to weigh the newborn. The primary study outcome is neonatal mortality, defined as a newborn death in the first 28 days of life. Discussion: This study will generate policy-relevant knowledge on the effectiveness of integrating evidence-based maternal and newborn interventions and delivering them directly to pregnant women via existing community health infrastructure, for reducing neonatal mortality and morbidity, in a remote, mountainous area with a high NMR. Trial registration: NCT04798833, March 15, 2021. [ABSTRACT FROM AUTHOR]

Background: The Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin (LAKANA) trial in Mali aims to evaluate the efficacy and safety of azithromycin (AZI) mass drug administration (MDA) to 1–11-month-old infants as well as the impact of the intervention on antimicrobial resistance (AMR) and mechanisms of action of azithromycin. To improve the transparency and quality of this clinical trial, we prepared this statistical analysis plan (SAP). Methods/design: LAKANA is a cluster randomized trial that aims to address the mortality and health impacts of biannual and quarterly AZI MDA. AZI is given to 1–11-month-old infants in a high-mortality setting where a seasonal malaria chemoprevention (SMC) program is in place. The participating villages are randomly assigned to placebo (control), two-dose AZI (biannual azithromycin-MDA), and four-dose AZI (quarterly azithromycin-MDA) in a 3:4:2 ratio. The primary outcome of the study is mortality among the intention-to-treat population of 1–11-month-old infants. We will evaluate relative risk reduction between the study arms using a mixed-effects Poisson model with random intercepts for villages, using log link function with person-years as an offset variable. We will model outcomes related to secondary objectives of the study using generalized linear models with considerations on clustering. Conclusion: The SAP written prior to data collection completion will help avoid reporting bias and data-driven analysis for the primary and secondary aims of the trial. If there are deviations from the analysis methods described here, they will be described and justified in the publications of the trial results. Trial registration: ClinicalTrials.gov ID NCT04424511. Registered on 11 June 2020. [ABSTRACT FROM AUTHOR]

Background: Optimization of the clinical care process by integration of evidence-based knowledge is one of the active components in care pathways. When studying the impact of a care pathway by using a cluster-randomized design, standardization of the care pathway intervention is crucial. This methodology paper describes the development of the clinical content of an evidence-based care pathway for in-hospital management of chronic obstructive pulmonary disease (COPD) exacerbation in the context of a cluster-randomized controlled trial (cRCT) on care pathway effectiveness. Methods: The clinical content of a care pathway for COPD exacerbation was developed based on recognized process design and guideline development methods. Subsequently, based on the COPD case study, a generalized eight-step method was designed to support the development of the clinical content of an evidence-based care pathway. Results: A set of 38 evidence-based key interventions and a set of 24 process and 15 outcome indicators were developed in eight different steps. Nine Belgian multidisciplinary teams piloted both the set of key interventions and indicators. The key intervention set was judged by the teams as being valid and clinically applicable. In addition, the pilot study showed that the indicators were feasible for the involved clinicians and patients. Conclusions: The set of 38 key interventions and the set of process and outcome indicators were found to be appropriate for the development and standardization of the clinical content of the COPD care pathway in the context of a cRCT on pathway effectiveness. The developed eight-step method may facilitate multidisciplinary teams caring for other patient populations in designing the clinical content of their future care pathways. [ABSTRACT FROM AUTHOR]

Background: Deimplementing overused health interventions is essential to maximizing quality and value while minimizing harm, waste, and inefficiencies. Three national guidelines discourage continuous pulse oximetry (SpO2) monitoring in children who are not receiving supplemental oxygen, but the guideline-discordant practice remains prevalent, making it a prime target for deimplementation. This paper details the statistical analysis plan for the Eliminating Monitor Overuse (EMO) SpO2 trial, which compares the effect of two competing deimplementation strategies (unlearning only vs. unlearning plus substitution) on the sustainment of deimplementation of SpO2 monitoring in children with bronchiolitis who are in room air. Methods: The EMO Trial is a hybrid type 3 effectiveness-deimplementation trial with a longitudinal cluster-randomized design, conducted in Pediatric Research in Inpatient Settings Network hospitals. The primary outcome is deimplementation sustainment, analyzed as a longitudinal difference-in-differences comparison between study arms. This analysis will use generalized hierarchical mixed-effects models for longitudinal clustering outcomes. Secondary outcomes include the length of hospital stay and oxygen supplementation duration, modeled using linear mixed-effects regressions. Using the well-established counterfactual approach, we will also perform a mediation analysis of hospital-level mechanistic measures on the association between the deimplementation strategy and the sustainment outcome. Discussion: We anticipate that the EMO Trial will advance the science of deimplementation by providing new insights into the processes, mechanisms, and likelihood of sustained practice change using rigorously designed deimplementation strategies. This pre-specified statistical analysis plan will mitigate reporting bias and support data-driven approaches. Trial registration: ClinicalTrials.gov NCT05132322. Registered on 24 November 2021.

Influenza is a major cause of morbidity and mortality. The protective effect of a trivalent influenza vaccine (TIV) is undetermined in military personnel. We conducted an open-label, cluster randomized trial on active-duty servicemen of Beijing, Tianjin, and Shijiazhuang, who were randomly assigned to receive either a single dose of TIV or no treatment, according to cluster randomized sampling. The subjects were then followed for a maximum of six months to assess the incidence of laboratory-confirmed influenza. A total of 5445 subjects in 114 clusters received one dose of TIV before the 2015/2016 influenza season. Laboratory-confirmed influenza was identified in 18 in the vaccine group compared with 87 in the control group (6031 subjects in 114 clusters), resulting in a vaccine effectiveness (VE) of 76.4% (95%CI: 60.7 to 85.8) against laboratory-confirmed influenza. Influenza-like illness was diagnosed in 132 in the vaccine group compared with 420 in the control group, resulting in a VE of 64.1% (95%CI: 56.2 to 70.6). The estimated VE against influenza B viruses was 80.5% (95%CI: 65.6 to 88.9) and 8.6% (95%CI: −241 to 75.5) against influenza A viruses. In conclusion, the trivalent influenza vaccine is moderately effective, highly immunogenic, and generally safe to use in healthy male military servicemen. [ABSTRACT FROM AUTHOR]

Background: Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research.Methods: MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias.Results: Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%).Conclusions: De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design.Registration: OSF Open Science Framework hk4b2. [ABSTRACT FROM AUTHOR]

In this work, we propose nonparametric two-sample tests for population-averaged transition and state occupation probabilities for continuous-time and finite state space processes with clustered, right-censored, and/or left-truncated data. We consider settings where the two groups under comparison are independent or dependent, with or without complete cluster structure. The proposed tests do not impose assumptions regarding the structure of the within-cluster dependence and are applicable to settings with informative cluster size and/or non-Markov processes. The asymptotic properties of the tests are rigorously established using empirical process theory. Simulation studies show that the proposed tests work well even with a small number of clusters, and that they can be substantially more powerful compared to the only, to the best of our knowledge, previously proposed nonparametric test for this problem. The tests are illustrated using data from a multicenter randomized controlled trial on metastatic squamous-cell carcinoma of the head and neck. [ABSTRACT FROM AUTHOR]

Background: Among rural Chinese patients with non-communicable diseases (NCDs), low socioeconomic status increases the risk of developing NCDs and associated financial burdens in paying for medicines and treatments. Despite the chronic disease medicine reimbursement policy of the local government in Nantong City, China, various barriers prevent patients from registering for and benefitting from the policy. This study aims to develop a behavior science-based intervention program for promoting the adoption of the policy and to evaluate the effectiveness of the program compared with usual practices.Methods: Barriers and opportunities affecting stakeholders in adopting the policy were identified through contextual research and summarized through behavior mapping. The intervention is designed to target these barriers and opportunities through behavior science theories and will be evaluated through a 6-month cluster randomized controlled trial in Tongzhou District, Nantong, China. A total of 30 villages from two townships are randomized in a 1:1 ratio to either the intervention or the control arm (usual practices). Village doctors in the intervention arm (1) receive systematic training on policy details, registration procedures, and intervention protocol, (2) promote the policy and encourage registration, (3) follow up with patients in the first, third, and sixth months after the intervention, and (4) receive financial incentives based on performance. The primary outcome is policy registration rate and the secondary outcomes include the number of patients registering for the policy, medical costs saved, frequency of village doctor visits, and health measures such as blood pressure and glucose levels.Discussion: This study is one of very few that aims to promote adoption of NCDs outpatient medication reimbursement policies, and the first study to evaluate the impact of these policies on patients' financial and physical wellbeing in China. The simple, feasible, and scalable intervention is designed based on the theories of behavior science and is applicable to similar low-income regions nationwide where outpatient medical costs remain a financial burden for patients.Trial Registration: ClinicalTrials.gov NCT04731194 , registered on 29 January 2021; Chinese Clinical Trial Registry ChiCTR2100042152 , registered on 14 January 14 2021. [ABSTRACT FROM AUTHOR]

Simple Summary: The risk of melanoma is higher in first-degree relatives (FDRs, i.e., brother, sister, father, mother, or children) of a patient with melanoma than in the general population. FDRs are advised to undergo annual screening to detect any melanoma earlier and to adopt sun-protective behavior by seeking shade, wearing a hat and long-sleeved clothing, staying indoors between 12 noon and 4 p.m., and applying sunscreen with SPF > 50. We know that these general instructions, usually given orally to the patients, are inconsistently followed by FDRs. Our goal was to determine whether written support intended for FDRs of patients would improve early detection and photoprotection as compared with usual oral advice. We developed and evaluated the use of a tip sheet given by patients to their FDRs. The adherence of FDRs to early detection by medical examination and to sun protection was not improved by delivery of the tip sheet as compared with the usual oral advice. Background: First-degree relatives (FDRs, defined as parents, children, and siblings) of melanoma patients are at a two-to-fivefold increased risk of developing melanoma themselves. FDRs are advised to perform self-skin examination (SSE) and annual medical total cutaneous examination (TCE) performed either by a dermatologist or a general practitioner, and to change their sun-related behavior. This advice is given orally to melanoma patients who are asked to relay the information to their FDRs. Objective: Our aim was to determine the impact of providing a tip sheet to melanoma patients intended to their first-degree relatives (FDRs) on early detection and sun-related behaviors in this group at increased risk of melanoma. Methods: A superiority, cluster-randomized trial was conducted at nine hospital centers. In the intervention group, dermatologists were asked to deliver to melanoma patients (index cases) the tip sheet and oral advice intended to their FDRs. The control group were asked to deliver the usual oral advice alone. The primary outcome was early detection of melanoma in FDRs with a medical TCE performed within one year after the first visit of the index case. Secondary outcomes were SSE and sun-related behaviors in FDRs. Results: A total of 48 index cases and 114 FDRS in the control group, 60 index cases and 166 FDRS in the intervention group were recruited. In the intervention group, 36.1% of FDRs performed a medical TCE as compared to 39.5% of FDRs in the control group (OR 0.9 [95% CI 0.5 to 1.5], p = 0.63). We did not find a between-group difference in SSE and sun-related behaviors. Conclusion: A tip sheet added to the usual oral advice did not increase medical TCE among FDRs of melanoma patients. Overall, the rate of TCE among FDRs was low. Research on other strategies is needed to increase melanoma detection in this population. [ABSTRACT FROM AUTHOR]

Abstract Background Reducing sugar-sweetened beverage (SSB) consumption is a promising dietary target for childhood obesity prevention. This paper describes the design and methods of a cluster randomized trial of H2GO!, a youth empowerment intervention to prevent childhood obesity through reducing SSB consumption among a low-income, ethnically diverse sample of youth. Methods This cluster randomized controlled trial is an academic-community partnership with the Massachusetts Alliance of Boys and Girls Clubs (BGC). Ten BGC sites will be randomly assigned to the H2GO! intervention or a wait-list, usual care control. Eligible study participants will be N = 450 parent-child pairs (youth ages 9–12 years and their parents/caregivers) recruited from participating BGCs. The 6-week in-person H2GO! intervention consists of 12 group-based sessions delivered by BGC staff and youth-led activities. An innovative feature of the intervention is the development of youth-produced narratives as a strategy to facilitate youth empowerment and parental engagement. Child outcomes include measured body mass index z scores (zBMI), beverage intake, and youth empowerment. Parent outcomes include beverage intake and availability of SSBs at home. Outcomes will be measured at baseline and at 2, 6, and 12 months. With a 75% retention rate, the study is powered to detect a minimum group difference of 0.1 zBMI units over 12 months. Discussion Empowering youth may be a promising intervention approach to prevent childhood obesity through reducing SSB consumption. This intervention was designed to be delivered through BGCs and is hypothesized to be efficacious, relevant, and acceptable for the target population of low-income and ethnically diverse youth. Trial registration ClinicalTrials.gov NCT04265794 . Registered 11 February 2020.

Introduction: To investigate the association between individual and community‐level measures of HIV stigma and HIV incidence within the 21 communities participating in the HPTN (071) PopART trial in Zambia and South Africa. Methods: Secondary analysis of data from a population‐based cohort followed‐up over 36 months between 2013 and 2018. The outcome was rate of incident HIV infection among individuals who were HIV negative at cohort entry. Individual‐level exposures, measured in a random sample of all participants, were: (1) perception of stigma in the community, (2) perception of stigma in health settings and (3) fear and judgement towards people living with HIV. Individual‐level analyses were conducted with adjusted, individual‐level Poisson regression. Community‐level HIV stigma exposures drew on data reported by people living with HIV, health workers and community members. We used linear regression to explore the association between HIV stigma and community‐level HIV incidence. Results: Among 8172 individuals who were HIV negative and answered individual‐level stigma questions at enrolment to the cohort, there was no evidence of a statistically significant association between any domain of HIV stigma and risk of incident HIV infection. Among the full cohort of 26,110 individuals among whom HIV incidence was measured, there was no evidence that community‐level HIV incidence was associated with any domain of HIV stigma. Conclusions: HIV stigma is often cited as a barrier to the effectiveness of HIV prevention programming. However, in the setting for the HPTN 071 "PopART trial," measured stigma alone was not associated with the risk of HIV infection. [ABSTRACT FROM AUTHOR]

Background: Stepped wedge trials are an appealing and potentially powerful cluster randomized trial design. However, they are frequently implemented with a small number of clusters. Standard analysis methods for these trials such as a linear mixed model with estimation via maximum likelihood or restricted maximum likelihood (REML) rely on asymptotic properties and have been shown to yield inflated type I error when applied to studies with a small number of clusters. Small-sample methods such as the Kenward-Roger approximation in combination with REML can potentially improve estimation of the fixed effects such as the treatment effect. A Bayesian approach may also be promising for such multilevel models but has not yet seen much application in cluster randomized trials.Methods: We conducted a simulation study comparing the performance of REML with and without a Kenward-Roger approximation to a Bayesian approach using weakly informative prior distributions on the intracluster correlation parameters. We considered a continuous outcome and a range of stepped wedge trial configurations with between 4 and 40 clusters. To assess method performance we calculated bias and mean squared error for the treatment effect and correlation parameters and the coverage of 95% confidence/credible intervals and relative percent error in model-based standard error for the treatment effect.Results: Both REML with a Kenward-Roger standard error and degrees of freedom correction and the Bayesian method performed similarly well for the estimation of the treatment effect, while intracluster correlation parameter estimates obtained via the Bayesian method were less variable than REML estimates with different relative levels of bias.Conclusions: The use of REML with a Kenward-Roger approximation may be sufficient for the analysis of stepped wedge cluster randomized trials with a small number of clusters. However, a Bayesian approach with weakly informative prior distributions on the intracluster correlation parameters offers a viable alternative, particularly when there is interest in the probability-based inferences permitted within this paradigm. [ABSTRACT FROM AUTHOR]

Background: Musculoskeletal and mental health complaints are the dominant diagnostic categories in long-term sick leave and disability pensions in Norway. Continuing to work despite health complaints is often beneficial, and a good work environment can improve work inclusion for people affected. In 2001, the Norwegian Labour and Welfare Administration began to offer inclusive work measures to improve the psychosocial work environment and work inclusion of people with health complaints. In 2018, the Norwegian Labour and Welfare Administration and specialist health services started offering the new collaborative Health in work program. Its workplace intervention presents health and welfare information that may improve employees' coping ability regarding common health complaints. It encourages understanding of coworkers' health complaints and appropriate work adjustments to increase work participation. Objective: This protocol presents an ongoing, 2-arm, pragmatic cluster-randomized trial. Its aim is to compare the effect of monodisciplinary inclusive work measures (treatment as usual) and interdisciplinary Health in work in terms of changes in overall sickness absence, health care use, health-related quality of life, and costs. The secondary objectives are to compare changes in individual sickness absence, psychosocial work environment, job and life satisfaction, health, and health anxiety at both the individual and group levels. Methods: Data will be collected from national registers, trial-specific registrations, and questionnaires. Effects will be explored using difference-in-difference analysis and regression modeling. Multilevel analysis will visualize any cluster effects using intraclass correlation coefficients. Results: Inclusion was completed in July 2021 with 97 workplaces and 1383 individual consents. Data collection will be completed with the last questionnaires to be sent out in July 2023. Conclusions: This trial will contribute to filling knowledge gaps regarding the effectiveness and costs of workplace interventions, thereby benefiting health and welfare services, political decision makers, and the public and business sectors. The findings will be disseminated in reports, peer-reviewed journals, and conferences. Trial Registration: ClinicalTrials.gov NCT04000035; https://clinicaltrials.gov/ct2/show/NCT04000035 International Registered Report Identifier (IRRID): DERR1-10.2196/36166 [ABSTRACT FROM AUTHOR]

Background: The shortage of available organs for life-saving transplants persists worldwide. While a majority support donating their organs or tissue when they die, many have not registered their wish to do so. When registered, next of kin are much more likely to follow-through with the decision to donate. In many countries, most people visit their family physician office each year and this setting is a promising, yet underused, site where more people could register for deceased organ donation. Our primary aim was to evaluate the effectiveness of an intervention to promote organ donation registration in family physician's offices.Methods: We developed an intervention to address barriers and enablers to organ donation registration that involved physician office reception staff inviting patients to register on a tablet in the waiting room while they waited for their appointment. We conducted a cross-sectional stepped-wedge cluster randomized controlled registry trial to evaluate the intervention. We recruited six family physician offices in Canada. All offices began with usual care and then every two weeks, one office (randomly assigned) started the intervention until all offices delivered the intervention. The primary outcome was registration for deceased organ donation in the provincial organ registration registry, assessed within the 7 days of the physician visit. At the end of the trial, we also conducted interviews with clinic staff to assess any barriers and enablers to delivering the intervention.Results: The trial involved 24,616 patient visits by 13,562 unique patients: 12,484 visits in the intervention period and 12,132 in the control period. There was no statistically significant difference in the percentage of patients registered for deceased organ donation in the intervention versus control period (48.0% vs 46.2%; absolute difference after accounting for the secular trend: 0.12%; 95% CI: - 2.30, 2.54; p=0.92). Interviews with clinic staff indicated location of the tablet within a waiting room, patient rapport, existing registration, confidence and motivation to deliver the intervention and competing priorities as barriers and enablers to delivery.Conclusions: Our intervention did not increase donor registration. Nonetheless, family physician offices may still remain a promising setting to develop and evaluate better interventions to increase organ donation registration.Trial Registration: NCT03213171. [ABSTRACT FROM AUTHOR]

Abstract Background In order to correctly assess the effect of intervention from stratified cluster randomized trials (CRTs), it is necessary to adjust for both clustering and stratification, as failure to do so leads to misleading conclusions about the intervention effect. We have conducted a systematic survey to examine the current practices about analysis and reporting of stratified CRTs. Method We used the search terms to identify the stratified CRTs from MEDLINE since the inception to July 2019. In phase 1, we screened the title and abstract for English-only studies and selected, including the main results paper of the identified protocols, for the next phase. In phase 2, we screened the full text and selected studies for data abstraction. The data abstraction form was piloted and developed using the REDCap. We abstracted data on multiple design and methodological aspects of the study including whether the primary method adjusted for both clustering and stratification, reporting of sample size, randomization, and results. Results We screened 2686 studies in the phase 1 and selected 286 studies for phase 2—among them 185 studies were selected for data abstraction. Most of the selected studies were two-arm 140/185 (76%) and parallel-group 165/185 (89%) trials. Among these 185 studies, 27 (15%) of them did not provide any sample size or power calculation, while 105 (57%) studies did not mention any method used for randomization within each stratum. Further, 43 (23%) and 150 (81%) of 185 studies did not provide the definition of all the strata, while more than 60% of the studies did not include all the stratification variable(s) in the flow chart or baseline characteristics table. More than half 114/185 (62%) of the studies did not adjust the primary method for both clustering and stratification. Conclusion Stratification helps to achieve the balance among intervention groups. However, to correctly assess the intervention effect from stratified CRTs, it is important to adjust the primary analysis for both stratification and clustering. There are significant deficiencies in the reporting of methodological aspects of stratified CRTs, which require substantial improvements in several areas including definition of strata, inclusion of stratification variable(s) in the flow chart or baseline characteristics table, and reporting the stratum-specific number of clusters and individuals in the intervention groups.

Abstract Background Cluster randomized trials are common in health research in low- and middle-income countries raising issues that challenge interpretation of standard ethical guidelines. While the Ottawa Statement on the ethical design and conduct of cluster randomized trials provides guidance for researchers and research ethics committees, it does not explicitly focus on low- and middle-income settings. Main body In this paper, we use the lens of the Ottawa Statement to analyze two cluster randomized trials conducted in low- and middle-income settings in order to identify gaps or ethical issues requiring further analysis and guidance. The PolyIran trial was a parallel-arm, cluster trial examining the effectiveness of a polypill for prevention of cardiovascular disease in Golestan province, Iran. The PASTAL trial was an adaptive, multistage, parallel-arm, cluster trial evaluating the effect of incentives for human immunodeficiency virus self-testing and follow-up on male partners of pregnant women in Malawi. Through an in-depth case analysis of these two studies we highlight several issues in need of further exploration. First, standards for verbal consent and waivers of consent require methods for operationalization if they are to be employed consistently. Second, the appropriate choice of a control arm remains contentious. Particularly in the case of implementation interventions, locally available care is required as the comparator to address questions of comparative effectiveness. However, locally available care might be lower than standards set out in national guidelines. Third, while the need for access to effective interventions post-trial is widely recognized, it is often not possible to guarantee this upfront. Clarity on what is required of researchers and sponsors is needed. Fourth, there is a pressing need for ethics education and capacity building regarding cluster randomized trials in these settings. Conclusion We identify four issues in cluster randomized trials conducted in low- and middle-income countries for which further ethical analysis and guidance is required.