A Method to Redesign and Simplify Schedules of Assessment and Quantify the Impacts. Applications to Merck Protocols.

The growing complexity of biopharmaceutical sponsored trials has adverse impacts on increased burdens on participants, clinical sites, and sponsors, including greater difficulty recruiting and retaining participants, difficulty engaging sites to participate in trials, excessive cost of trials, and increased cycle times. The schedule of assessments (SoAs) is the origin of and blueprint for complexity that is often generated by copying and pasting from previous SoAs. We developed an approach, termed Lean Design, for redesigning the assessments in SoAs that generate data, the 'Data SoA.' It starts with a simple "ground zero" SoA. Any addition is challenged using several principles of trial design. We employed a system, the Faro Trial Designer Tool, to quantify the impacts of changes in an SoA to provide real-time feedback to the team and sponsor. We applied the approach in workshops with teams for six clinical trials in various stages of design and implementation. The approach resulted in recommendation for substantial potential savings in participant and site staff time, costs, and complexity of the trials. Application of this approach to very early stages of protocol design has the potential to reduce the complexity of biopharmaceutical sponsored trials and its consequences.

Participant characteristics and exclusion from phase 3/4 industry funded trials of chronic medical conditions: meta-analysis of individual participant level data.

Objectives: To assess whether age, sex, comorbidity count, and race and ethnic group are associated with the likelihood of trial participants not being enrolled in a trial for any reason (ie, screen failure). Design: Bayesian meta-analysis of individual participant level data. Setting: Industry funded phase 3/4 trials of chronic medical conditions. Participants: Participants were identified using individual participant level data to be in either the enrolled group or screen failure group. Data were available for 52 trials involving 72 178 screened individuals of whom 24 733 (34%) were excluded from the trial at the screening stage. Main outcome measures: For each trial, logistic regression models were constructed to assess likelihood of screen failure in people who had been invited to screening, and were regressed on age (per 10 year increment), sex (male v female), comorbidity count (per one additional comorbidity), and race or ethnic group. Trial level analyses were combined in Bayesian hierarchical models with pooling across condition. Results: In age and sex adjusted models across all trials, neither age nor sex was associated with increased odds of screen failure, although weak associations were detected after additionally adjusting for comorbidity (odds ratio of age, per 10 year increment was 1.02 (95% credibility interval 1.01 to 1.04) and male sex (0.95 (0.91 to 1.00)). Comorbidity count was weakly associated with screen failure, but in an unexpected direction (0.97 per additional comorbidity (0.94 to 1.00), adjusted for age and sex). People who self-reported as black seemed to be slightly more likely to fail screening than people reporting as white (1.04 (0.99 to 1.09)); a weak effect that seemed to persist after adjustment for age, sex, and comorbidity count (1.05 (0.98 to 1.12)). The between-trial heterogeneity was generally low, evidence of heterogeneity by sex was noted across conditions (variation in odds ratios on log scale of 0.01-0.13). Conclusions: Although the conclusions are limited by uncertainty about the completeness or accuracy of data collection among participants who were not randomised, we identified mostly weak associations with an increased likelihood of screen failure for age, sex, comorbidity count, and black race or ethnic group. Proportionate increases in screening these underserved populations may improve representation in trials. Trial registration number: PROSPERO CRD42018048202.

Systematic Review of Gender and Sex Terminology Use in Arthroplasty Research: There is Room for Improvement.

BACKGROUND: There is increasing appreciation of the distinction between gender and sex as well as the importance of accurately reporting these constructs. Given recent attention regarding transgender and gender nonconforming (TGNC) and intersex identities, it is more necessary than ever to understand how to describe these identities in research. This study sought to investigate the use of gender- and sex-based terminology in arthroplasty research. METHODS: The five leading orthopaedic journals publishing arthroplasty research were reviewed to identify the first twenty primary clinical research articles on an arthroplasty topic published after January 1, 2022. Use of gender- or sex-based terminology, whether use was discriminate, and whether stratification or adjustment based on gender or sex was performed, were recorded. RESULTS: There were 98 of 100 articles that measured a construct of gender or sex. Of these, 15 articles used gender-based terminology, 45 used sex-based terminology, and 38 used a combination of gender- and sex-based terminology. Of the 38 articles using a combination of terminology, none did so discriminately. All articles presented gender and sex as binary variables, and two attempted to explicitly define how gender or sex were defined. Of the 98 articles, 31 used these variables for statistical adjustments, though only six reported stratified results. CONCLUSIONS: Arthroplasty articles infrequently describe how gender or sex was measured, and frequently use this terminology interchangeably. Additionally, these articles rarely offer more than two options for capturing variation in sex and gender. Future research should be more precise in the treatment of these variables to improve the quality of results and ensure findings are patient-centered and inclusive.

Systematic analysis of approaches used in cardiac arrest trials to inform relatives about trial enrolment of non-surviving patients.

BACKGROUND: The recruitment of patients to emergency research studies without the requirement for prior informed consent has furthered the conduct of randomised studies in cardiac arrest. Frameworks enabling this vary around the world depending on local legal or ethical requirements. When an enrolled patient does not survive, researchers may take one of three approaches to inform relatives of their enrolment: a direct (active) approach, providing information indirectly (passively) and inviting relatives to seek further information if they choose, or providing no information about the trial (no attempt). Previous studies have described experiences of US researchers' active approach but there is little known about approaches elsewhere.We aimed to conduct a structured investigation of methods used in cardiac arrest trials to provide information about trial enrolment to relatives of non-surviving patients. METHODS: We systematically searched trial registries to identify randomised clinical trials that recruited cardiac arrest patients. Trials were eligible for inclusion if they recruited adults during cardiac arrest (or within 1 hour of return of spontaneous circulation) between 2010 and 2022 (in the decade prior to study conception). We extracted data from trial registries and, where relevant, published papers and protocols. Investigators were contacted and asked to describe the style, rationale and timing of approach to relatives of non-surviving patients. We present descriptive statistics. RESULTS: Our trial registry search identified 710 unique trials, of which 108 were eligible for inclusion. We obtained information from investigators for 64 (62%) trials. Approximately equal numbers of trials attempted to actively inform relatives of non-survivors (n=28 (44% (95% CI; 31% to 57%))), or made no attempt (n=25 (39% (95% CI; 27% to 52%))). The remaining studies provided general information about the trial to relatives but did not actively inform them (n=11 (17% (95% CI; 8% to 29%))). CONCLUSIONS: There is wide variability in the approach taken to informing relatives of non-surviving patients enrolled in cardiac arrest randomised clinical trials.

Leadership at work and risk of treatment for depressive and anxiety disorders in Denmark. A nationwide prospective study with register-based follow up.

Positive leadership behaviours at work are associated with worker well-being and performance. However there is less knowledge about whether exposure to low levels of positive leadership behaviours increase workers' risk of clinical mental disorders. We investigated whether low levels of positive leadership behaviours are prospectively associated with risk of treatment for depressive and anxiety disorders. In a cohort study, we linked survey data from 59,743 respondents from the Work Environment and Health in Denmark survey with national health register data. Leadership behaviours were measured with an eight-item scale. Treatment was defined as redeemed prescription for antidepressants or anxiolytics or hospital treatment for depression or anxiety. Using Cox proportional hazard regression, adjusting for demographic variables, job type and sector, adverse life events and childhood adversities, we estimated the association between leadership behaviours at baseline and risk of treatment during follow-up. We identified 999 cases of depression and anxiety treatment during follow-up. Compared to high levels of leadership behaviours, exposure to medium low and low levels were associated with an increased risk of treatment after adjustment for covariates. The results suggest that low levels of positive leadership behaviours are associated with an increased risk of treatment for depressive or anxiety disorders.

Developing an international consensus Reporting guideline for intervention Fidelity in Non-Drug, non-surgical trials: The ReFiND protocol.

BACKGROUND: Inadequate reporting of fidelity to interventions in trials limits the transparency and interpretation of trial findings. Despite this, most trials of non-drug, non-surgical interventions lack comprehensive reporting of fidelity. If fidelity is poorly reported, it is unclear which intervention components were tested or implemented within the trial, which also hinders research reproducibility. This protocol describes the development process of a reporting guideline for fidelity of non-drug, non-surgical interventions (ReFiND) in the context of trials. METHODS: The ReFiND guideline will be developed in six stages. Stage one: a guideline development group has been formed to oversee the guideline methodology. Stage two: a scoping review will be conducted to identify and summarize existing guidance documents on the fidelity of non-drug, non-surgical interventions. Stage three: a Delphi study will be conducted to reach consensus on reporting items. Stage four: a consensus meeting will be held to consolidate the reporting items and discuss the wording and structure of the guideline. Stage five: a guidance statement, an elaboration and explanation document, and a reporting checklist will be developed. Stage six: different strategies will be used to disseminate and implement the ReFiND guideline. DISCUSSION: The ReFiND guideline will provide a set of items developed through international consensus to improve the reporting of intervention fidelity in trials of non-drug, non-surgical interventions. This reporting guideline will enhance transparency and reproducibility in future non-drug, non-surgical intervention research.

Kids SIPsmartER reduces sugar-sweetened beverages among Appalachian middle-school students and their caregivers: a cluster randomized controlled trial.

BACKGROUND: High consumption of sugar-sweetened beverages (SSB) is a global health concern. Additionally, sugar-sweetened beverage (SSB) consumption is disproportionately high among adolescents and adults in rural Appalachia. The primary study objective is to determine the intervention effects of Kids SIPsmartER on students' SSB consumption. Secondary objectives focus on caregivers' SSB consumption and secondary student and caregiver outcomes [e.g, body mass index (BMI), quality of life (QOL)]. METHODS: This Type 1 hybrid, cluster randomized controlled trial includes 12 Appalachian middle schools (6 randomized to Kids SIPsmartER and 6 to control). Kids SIPsmartER is a 6-month, 12 lesson, multi-level, school-based, behavior and health literacy program aimed at reducing SSB among 7th grade middle school students. The program also incorporates a two-way text message strategy for caregivers. In this primary prevention intervention, all 7th grade students and their caregivers from participating schools were eligible to participate, regardless of baseline SSB consumption. Validated instruments were used to assess SSB behaviors and QOL. Height and weight were objectively measured in students and self-reported by caregivers. Analyses included modified two-part models with time fixed effects that controlled for relevant demographics and included school cluster robust standard errors. RESULTS: Of the 526 students and 220 caregivers, mean (SD) ages were 12.7 (0.5) and 40.6 (6.7) years, respectively. Students were 55% female. Caregivers were mostly female (95%) and White (93%); 25% had a high school education or less and 33% had an annual household income less than $50,000. Regardless of SSB intake at baseline and relative to control participants, SSB significantly decreased among students [-7.2 ounces/day (95% CI = -10.7, -3.7); p < 0.001, effect size (ES) = 0.35] and caregivers [-6.3 ounces/day (95% CI = -11.3, -1.3); p = 0.014, ES = 0.33]. Among students (42%) and caregivers (28%) who consumed > 24 SSB ounces/day at baseline (i.e., high consumers), the ES increased to 0.45 and 0.95, respectively. There were no significant effects for student or caregiver QOL indicators or objectively measured student BMI; however, caregiver self-reported BMI significantly decreased in the intervention versus control schools (p = 0.001). CONCLUSIONS: Kids SIPsmartER was effective at reducing SSB consumption among students and their caregivers in the rural, medically underserved Appalachian region. Importantly, SSB effects were even stronger among students and caregivers who were high consumers at baseline. TRIAL REGISTRATION: Clincialtrials.gov: NCT03740113. Registered 14 November 2018- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03740113 .

Effectiveness and Cost-Effectiveness of Survivorship Care for Survivors of Hodgkin Lymphoma (INSIGHT Study): Protocol for a Multicenter Retrospective Cohort Study With a Quasi-Experimental Design.

BACKGROUND: Hodgkin lymphoma (HL) occurs at young ages, with the highest incidence between 20 and 40 years. While cure rates have improved to 80%-90% over the past decades, survivors of HL are at substantial risk of late treatment-related complications, such as cardiovascular diseases, breast cancer, severe infections, and hypothyroidism. To reduce morbidity and mortality from late treatment effects, the Dutch Better care after lymphoma, Evaluation of long-term Treatment Effects and screening Recommendations (BETER) consortium developed a survivorship care program for 5-year survivors of HL that includes risk-based screening for and treatment of (risk factors for) late adverse events. Even though several cancer survivorship care programs have been established worldwide, there is a lack of knowledge about their effectiveness in clinical practice. OBJECTIVE: The Improving Nationwide Survivorship care Infrastructure and Guidelines after Hodgkin lymphoma Treatment (INSIGHT) study evaluates whether Dutch BETER survivorship care for survivors of HL decreases survivors' burden of disease from late adverse events after HL treatment and associated health care costs and improves their quality of life. METHODS: The INSIGHT study is a multicenter retrospective cohort study with a quasi-experimental design and prospective follow-up, embedded in the national BETER survivorship care infrastructure. The first BETER clinics started in 2013-2016 and several other centers started or will start BETER clinics in 2019-2024. This allows us to compare survivors who did and those who did not receive BETER survivorship care in the last decade. Survivors in the intervention group are matched to controls (n=450 per group) based on sex, age at diagnosis (±5 years), age in 2013 (±5 years), and treatment characteristics. The primary outcome is the burden of disease in disability-adjusted life years from cardiovascular disease, breast cancer, severe infections, and hypothyroidism. In a cost-effectiveness analysis, we will assess the cost of BETER survivorship care per averted or gained disability-adjusted life year and quality-adjusted life year. Secondary outcomes are BETER clinic attendance, adherence to screening guidelines, and knowledge and distress about late effects among survivors of HL. Study data are collected from a survivor survey, a general practitioner survey, medical records, and through linkages with national disease registries. RESULTS: The study was funded in November 2020 and approved by the institutional review board of the Netherlands Cancer Institute in July 2021. We expect to finalize recruitment by October 2024, data collection by early 2025, and data analysis by May 2025. CONCLUSIONS: INSIGHT is the first evaluation of a comprehensive survivorship program using real-world data; it will result in new information on the (cost-)effectiveness of survivorship care in survivors of HL in clinical practice. The results of this study will be used to improve the BETER program where necessary and contribute to more effective evidence-based long-term survivorship care for lymphoma survivors. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55601.

Methodological quality of systematic reviews on atopic dermatitis treatments: a cross-sectional study.

BACKGROUND: Systematic reviews (SRs) could offer the best evidence supporting interventions, but methodological flaws limit their trustworthiness in decision-making. This cross-sectional study appraised the methodological quality of SRs on atopic dermatitis (AD) treatments. METHODS: We searched MEDLINE, EMBASE, PsycINFO, and Cochrane Database for SRs on AD treatments published in 2019-2022. We extracted SRs' bibliographical data and appraised SRs' methodological quality with AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. We explored associations between methodological quality and bibliographical characteristics. RESULTS: Among the 52 appraised SRs, only one (1.9%) had high methodological quality, while 45 (86.5%) critically low. For critical domains, only five (9.6%) employed comprehensive search strategy, seven (13.5%) provided list of excluded studies, 17 (32.7%) considered risk of bias in primary studies, 21 (40.4%) contained registered protocol, and 24 (46.2%) investigated publication bias. Cochrane reviews, SR updates, SRs with European corresponding authors, and SRs funded by European institutions had better overall quality. Impact factor and author number positively associated with overall quality. CONCLUSIONS: Methodological quality of SRs on AD treatments is unsatisfactory. Future reviewers should improve the above critical methodological aspects. Resources should be devolved into upscaling evidence synthesis infrastructure and improving critical appraisal skills of evidence users.

Shining a light on the road towards conducting principle-based co-production research in rehabilitation.

Moving from participatory approaches incorporating co-design to co-production in health research involves a commitment to full engagement and partnership with people with lived experience through all stages of the research process-start to finish. However, despite the increased enthusiasm and proliferation of research that involves co-production, practice remains challenging, due in part to the lack of consensus on what constitutes co-production, a lack of guidance about the practical steps of applying this approach in respect to diverse research methods from multiple paradigms, and structural barriers within academia research landscape. To navigate the challenges in conducting co-produced research, it has been recommended that attention be paid to focusing and operationalising the underpinning principles and aspirations of co-production research, to aid translation into practice. In this article, we describe some fundamental principles essential to conducting co-production research (sharing power, relational resilience, and adopting a learning mindset) and provide tangible, practical strategies, and processes to engage these values. In doing so, we hope to support rehabilitation researchers who wish to engage in co-production to foster a more equitable, ethical, and impactful collaboration with people with lived experience and those involved in their circle of care.

Purposeful Sampling: Advantages and Pitfalls.

This editorial monograph explores the advances and pitfalls of the common forms of purposeful sampling. Purposeful sampling is a common research design in qualitative research.

A case study to engage students in the research design and ethics of high-throughput metagenomics.

Case studies present students with an opportunity to learn and apply course content through problem solving and critical thinking. Supported by the High-throughput Discovery Science & Inquiry-based Case Studies for Today's Students (HITS) Research Coordination Network, our interdisciplinary team designed, implemented, and assessed two case study modules entitled "You Are What You Eat." Collectively, the case study modules present students with an opportunity to engage in experimental research design and the ethical considerations regarding microbiome research and society. In this manuscript, we provide instructors with tools for adopting or adapting the research design and/or the ethics modules. To date, the case has been implemented using two modalities (remote and in-person) in three courses (Microbiology, Physiology, and Neuroscience), engaging over 200 undergraduate students. Our assessment data demonstrate gains in content knowledge and students' perception of learning following case study implementation. Furthermore, when reflecting on our experiences and student feedback, we identified ways in which the case study could be modified for different settings. In this way, we hope that the "You Are What You Eat" case study modules can be implemented widely by instructors to promote problem solving and critical thinking in the traditional classroom or laboratory setting when discussing next-generation sequencing and/or metagenomics research.

A practical guide to cross-cultural and multi-sited data collection in the biological and behavioural sciences.

Researchers in the biological and behavioural sciences are increasingly conducting collaborative, multi-sited projects to address how phenomena vary across ecologies. These types of projects, however, pose additional workflow challenges beyond those typically encountered in single-sited projects. Through specific attention to cross-cultural research projects, we highlight four key aspects of multi-sited projects that must be considered during the design phase to ensure success: (1) project and team management; (2) protocol and instrument development; (3) data management and documentation; and (4) equitable and collaborative practices. Our recommendations are supported by examples from our experiences collaborating on the Evolutionary Demography of Religion project, a mixed-methods project collecting data across five countries in collaboration with research partners in each host country. To existing discourse, we contribute new recommendations around team and project management, introduce practical recommendations for exploring the validity of instruments through qualitative techniques during piloting, highlight the importance of good documentation at all steps of the project, and demonstrate how data management workflows can be strengthened through open science practices. While this project was rooted in cross-cultural human behavioural ecology and evolutionary anthropology, lessons learned from this project are applicable to multi-sited research across the biological and behavioural sciences.

Trends in authorship in the Journal of Cutaneous Pathology, 1981-2020.

BACKGROUND: The increase in authors per scientific article in many different medical and scientific disciplines has raised concerns over ethical authorship. Trends in authorship in dermatopathology are unknown. METHODS: Cross-sectional study of a random sample of 200 articles from the Journal of Cutaneous Pathology (1981-2020). RESULTS: The number of authors per article increased by an estimated 96% between 1981 and 2020 (2.7-5.3), while the relative citation ratio decreased by an estimated 56% during the same period (1.19-0.52). Higher author counts were not associated with higher relative citation ratios (p = 0.2349) or analytic study designs (p = 0.2987). Higher relative citation ratios were associated with analytic study designs (p = 0.0374). CONCLUSIONS: There has been significant growth in authorship credit at the journal without a corresponding increase in research impact or study rigor. Remedial measures to stem authorship inflation and promote more impactful studies may be necessary.

Beyond Men's Experiences: Scale Development and Psychometric Testing of the Fitness in Nursing Scale-Men (FiNS-M).

Background and Purpose: Men believe they are perceived as unfit for nursing. No scales exist to measure perceptions of men's fitness for nursing. Additionally, women have been largely excluded from this area of inquiry. This study's purpose was to develop and test the psychometric properties of the Fitness in Nursing Scale for Men. Methods: Six hundred thirty-five nurses participated. Scale development entailed concept clarification, item development, and scale testing. Results: Confirmatory factor analysis suggested a two-factor structure (F1: nursing fitness and F2: strengths of men in nursing) which demonstrated good model fit, root mean square error of approximation = .059, 90% CI (.056, .063), standardized root mean square residual = .055, comparative fit index = .932, Tucker-Lewis index = .927, and ωt = .98. Invariance held. Latent means were not significantly different for women (M = 5.90) compared with men (M = 5.92). Conclusions: Findings suggest men are perceived as fit for nursing, but results are inconsistent with men's qualitative experiences. Future research should attempt to reconcile the disagreement. Findings can inform cultural awareness strategies in the workplace and classroom.

Patient engagement in research: lessons learned from CAPTURE ALS, a longitudinal observational ALS study.

Objective: There are compelling ethical and practical reasons for patient engagement in research (PEIR), however, evidence for best practices remains limited. We investigated PEIR as implemented in CAPTURE ALS, a longitudinal observational study, from study inception through the first 2.5 years of operations. Methods: Data were drawn from three engagement initiatives: a community-led letter-writing campaign; consultation with patient and caregiver focus groups; and a study-embedded 'participant partner advisory council' (PPAC). Data were derived retrospectively from study documentation. We used the International Association of Public Participation (IAP2) participation spectrum as a framework for investigation. Results: 2401 letters from community members to the Canadian government affirmed study objectives and advocated for funding. Feedback from focus group consultation influenced study design and supported the study's data-sharing plan. PPAC collaboration shaped all aspects of the study. Contributions included: co-creation of governance documents, input on study protocols and public-facing communication, and development of engagement webinars for study participants and feedback surveys. Effective communication practices fostered collaboration and helped avoid tokenistic engagement. CAPTURE ALS encompassed all IAP2 participation levels. Conclusions: CAPTURE ALS was shaped by meaningful engagement initiatives over the course of the study. Lessons learned included: begin early and embed PEIR within research; build relationships and foster mutual learning; be flexible, open to adaptation, and seek diversity. Primary challenges included funding for early implementation, time needed to maintain relationships, and attrition due to disease progression. All IAP2 participation levels contributed to meaningful PEIR. 'Empowerment' was demonstrated through advocacy.