The development and acceptability of an educational and training intervention for recruiters to neonatal trials: the TRAIN project

BMC medical research methodology

Published On 2023/11/11

BackgroundSuboptimal or slow recruitment affects 30–50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN.MethodsTRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3 …

Journal

BMC medical research methodology

Published On

2023/11/11

Volume

23

Issue

1

Page

265

Authors

Carrol Gamble

Carrol Gamble

University of Liverpool

Position

Professor of Medical Statistics

H-Index(all)

69

H-Index(since 2020)

53

I-10 Index(all)

0

I-10 Index(since 2020)

0

Citation(all)

0

Citation(since 2020)

0

Cited By

0

Research Interests

clinical trials

University Profile Page

Valerie J Smith

Valerie J Smith

University of St Andrews

Position

H-Index(all)

67

H-Index(since 2020)

39

I-10 Index(all)

0

I-10 Index(since 2020)

0

Citation(all)

0

Citation(since 2020)

0

Cited By

0

Research Interests

comparative immunology

fish immunology

marine microbiology

marine biotechnology

SOI-USTAN

University Profile Page

John Lowe

John Lowe

Royal Holloway, University of London

Position

H-Index(all)

62

H-Index(since 2020)

26

I-10 Index(all)

0

I-10 Index(since 2020)

0

Citation(all)

0

Citation(since 2020)

0

Cited By

0

Research Interests

Quaternary science

Palaeoclimates

Tephrochronology

Dating methods

Shaun Treweek

Shaun Treweek

University of Aberdeen

Position

H-Index(all)

60

H-Index(since 2020)

46

I-10 Index(all)

0

I-10 Index(since 2020)

0

Citation(all)

0

Citation(since 2020)

0

Cited By

0

Research Interests

Randomised trials

Trial Methodology

Recruitment & retention

Representation

University Profile Page

Nicola Mills

Nicola Mills

University of Bristol

Position

Senior Research Fellow

H-Index(all)

33

H-Index(since 2020)

23

I-10 Index(all)

0

I-10 Index(since 2020)

0

Citation(all)

0

Citation(since 2020)

0

Cited By

0

Research Interests

Optimising recruitment to randomised controlled trials

University Profile Page

Other Articles from authors

Shaun Treweek

Shaun Treweek

University of Aberdeen

Journal of Clinical Epidemiology

Using the GRADE evidence to decision framework to reach recommendations together with ethnic minority community organizations: the example of COVID-19 vaccine uptake in the …

ObjectivesTo make recommendations regarding factors that affect COVID-19 vaccine uptake by ethnic minority individuals in the United Kingdom, together with strategies that could be used to increase uptake.Study Design and SettingThe results of two rapid systematic reviews—one identifying factors that affect respiratory vaccine uptake in ethnic minority adults and the other identifying experimental evaluations of strategies to increase vaccine uptake in ethnic minority adults—were put into Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Evidence to Decision frameworks to support discussion with a panel of ethnic minority community organizations, community-focused small companies, and academics of the relevance of the review findings to the UK COVID context. Aided by the frameworks, the panel made recommendations for factors that need to be addressed to increase …

Shaun Treweek

Shaun Treweek

University of Aberdeen

Discussion of the PROMETHEUS programme

The PROMETHEUS programme successfully embedded 42 SWATs within 31 host RCTs, exceeding the original target of 25 SWATs. This is the biggest single effort to generate SWAT evidence in the world, representing a substantial increase in the global methodological evidence base. The PROMETHEUS-funded SWATs represent an increase of 18%(12/68) more SWATs to the Cochrane systematic review of recruitment strategies, 23 and 79%(30/38) more SWATs to the Cochrane systematic review of retention strategies. 24The main findings from the PROMETHEUS SWATs reported to date show that for recruitment, there was no evidence of a significant difference in recruitment rates in any of the strategies tested. For retention, we found that pre-notification of trial participants by sending a card may result in a slight increase in attendance at a face-to-face primary outcome measurement visit; and that sending a pre …

Shaun Treweek

Shaun Treweek

University of Aberdeen

Trials

Improving the inclusion of an under-served group in trials: development and implementation of the INCLUDE Impaired Capacity to Consent Framework

BackgroundFor the potential benefits of trials to reach all that they should, trials must be designed to ensure that those taking part reflect the population who will receive the intervention. However, adults with impaired capacity to consent are frequently excluded from trials — partly because researchers are unfamiliar with the legal and ethical frameworks and lack the necessary methodological expertise. Researchers identified a need for guidance on designing more inclusive trials. Building on the NIHR INCLUDE initiative, we developed the INCLUDE Impaired Capacity to Consent Framework to help researchers design inclusive trials.MethodsThe framework was developed over five phases: (1) establishing the scope and content of the framework and adapting the INCLUDE Ethnicity Framework for this population; (2) scoping the relevance of the framework to different populations and piloting in a range of trials; (3 …

Carrol Gamble

Carrol Gamble

University of Liverpool

Journal of the Intensive Care Society

Guidance to inform research recruitment processes for studies involving critically ill patients

Clinical research in intensive care units (ICUs) is essential for improving treatments for critically ill patients. However, invitations to participate in clinical research in this situation pose numerous challenges. Studies are frequently initiated within a narrow time window when patients are often unconscious and unable to consent. Consultations or consent discussions must therefore be held with consultees or representatives, usually the patient’s relatives. Conversations about research participation in this setting may be difficult, as relatives are often overwhelmed and may feel uneasy about making decisions on behalf of their relatives. In some circumstances, legislation allows doctors to act as consultees or representatives to enrol patients in research. However, there is little good quality evidence on UK stakeholders’ perspectives to inform how recruitment is carried out in ICU studies. The Perspectives Study collected …

Shaun Treweek

Shaun Treweek

University of Aberdeen

Health Promotion Journal of Australia

Evidencing the impacts of health research: Insights from trials reported in the 2018 Australian Engagement and Impact Assessment

Issue Addressed While definitions of impact may vary, they often refer to the wider benefits of research evidenced beyond academia. We evaluated case studies featuring randomised trials from the 2018 Engagement and Impact Assessment to better understand how the impacts of health research are evidenced and assessed within Australia. Methods We collated and evaluated ‘high’ scoring case studies submitted by higher education institutions with a focus on randomised trials across all areas of health research. A qualitative coding system was used for manual content analysis to assess the key characteristics of trials reported, subsequent impacts and the methods used to evidence impacts. Results A total of 14 case studies were identified citing 35 clinical trials. The majority of interventions were behavioural with a focus on mental, behavioural or neurodevelopmental disorders. Most trials were phase III …

Nicola Mills

Nicola Mills

University of Bristol

European Journal of Pediatrics

Graded exercise therapy compared to activity management for paediatric chronic fatigue syndrome/myalgic encephalomyelitis: pragmatic randomized controlled trial

The MAGENTA pragmatic parallel groups randomized controlled trial compared graded exercise therapy (GET) with activity management (AM) in treating paediatric myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). Children aged 8-17 years with mild/moderate ME/CFS and presenting to NHS specialist paediatric services were allocated at random to either individualised flexible treatment focussing on physical activity (GET, 123 participants) or on managing cognitive, school and social activity (AM, 118 participants) delivered by NHS therapists. The primary outcome was the self-reported short-form 36 physical function subscale (SF-36-PFS) after 6 months, with higher scores indicating better functioning. After 6 months, data were available for 201 (83%) participants who received a mean of 3.9 (GET) or 4.6 (AM) treatment sessions. Comparing participants with measured outcomes in their allocated …

Valerie J Smith

Valerie J Smith

University of St Andrews

Women’s experiences of maternity care in the United Kingdom during the COVID-19 pandemic: A follow-up systematic review and qualitative evidence synthesis

BackgroundMaternity care services in the United Kingdom have undergone drastic changes due to pandemic-related restrictions. Prior research has shown maternity care during the pandemic was negatively experienced by women and led to poor physical and mental health outcomes in pregnancy. A synthesis is required of published research on women’s experiences of maternity care during the latter half of the COVID-19 pandemic.AimTo update a previous systematic review of maternity care experiences during the pandemic to June 2021, exploring experiences of maternity care specifically within the United Kingdom and how they may have changed, in order to inform future maternity services.MethodsA systematic review of qualitative literature was conducted using comprehensive searches of five electronic databases and the Cochrane COVID Study Register, published between 1 June 2021 and 13 October …

Shaun Treweek

Shaun Treweek

University of Aberdeen

Lessons learnt for implementing SWATs

In this chapter, we describe our experience of implementing SWATs, and present case studies of different approaches to implementing SWATs using a case study of individual, standalone SWATs testing the effectiveness of pens for retention; and case studies of co-ordinated SWATs undertaken–one testing a training course for staff recruiting trial participants, and the other testing the effectiveness of sending Christmas cards to participants on retention rates. This chapter also highlights the pros and cons of standalone and co-ordinated SWATs.

Shaun Treweek

Shaun Treweek

University of Aberdeen

Lessons learnt for governance approvals for SWATs

Lessons learnt for governance approvals for SWATs-Undertaking Studies Within A Trial to evaluate recruitment and retention strategies for randomised controlled trials: lessons learnt from the PROMETHEUS research programme-NCBI Bookshelf

Carrol Gamble

Carrol Gamble

University of Liverpool

Trials

Good Statistical Practice—development of tailored Good Clinical Practice training for statisticians

Statisticians are fundamental in ensuring clinical research, including clinical trials, are conducted with quality, transparency, reproducibility and integrity. Good Clinical Practice (GCP) is an international quality standard for the conduct of clinical trials research. Statisticians are required to undertake training on GCP but existing training is generic and, crucially, does not cover statistical activities. This results in statisticians undertaking training mostly unrelated to their role and variation in awareness and implementation of relevant regulatory requirements with regards to statistical conduct. The need for role-relevant training is recognised by the UK NHS Health Research Authority and the Medicines and Healthcare products Regulatory Agency (MHRA). The Good Statistical Practice (GCP for Statisticians) project was instigated by the UK Clinical Research Collaboration (UKCRC) Registered Clinical Trials Unit (CTU …

Carrol Gamble

Carrol Gamble

University of Liverpool

Trials

The use of healthcare systems data for RCTs

BackgroundHealthcare systems data (HSD) has the potential to optimise the efficiency of randomised controlled trials (RCTs), by decreasing trial-specific data demands. Therefore, the use of HSD in trials is expected to increase. In 2019, it was estimated that 47% of NIHR-funded trials were planning to use HSD. We aim to understand the extent and nature of its current use and its evolution over time.MethodsWe identified a cohort of RCTs within the NIHR Journals Library that commenced after 2019 and were described as being in progress on 6 June 2022. Details on the source and use of HSD were extracted from eligible RCTs. The use of HSD was categorised according to whether it was used as the sole data source for outcomes and whether the outcomes were primary or secondary. HSD is often insufficient for patient-reported outcomes (PROs). We aimed to determine methods used by trialists for collecting …

Shaun Treweek

Shaun Treweek

University of Aberdeen

What factors influence the uptake of bowel, breast, and cervical cancer screening?: An overview of international research

What factors influence the uptake of bowel, breast, and cervical cancer screening? An overview of international research — The University of Aberdeen Research Portal Skip to main navigation Skip to search Skip to main content The University of Aberdeen Research Portal Home The University of Aberdeen Research Portal Logo Help & FAQ Home Profiles Disciplines Research output Research Facilities Datasets Impacts Activities Press/Media Prizes Projects Search by expertise, name or affiliation What factors influence the uptake of bowel, breast, and cervical cancer screening? An overview of international research Miriam Brazzelli, Shaun Treweek Health Services Research Unit (HSRU) Institute of Applied Health Sciences Research output: Contribution to journal › Article › peer-review Overview Original language English Journal European Journal of Public Health Publication status Accepted/In press - 26 Mar …

Nicola Mills

Nicola Mills

University of Bristol

Trials

Needle fasciotomy versus limited fasciectomy for the treatment of Dupuytren’s contractures of the fingers (Hand-2):: study protocol for a randomised controlled trial

Background: Dupuytren’s contractures (DC) are fibrous cords under the skin of the hand that cause one or more fingers to curl gradually and irreversibly towards the palm. These contractures are usually painless but can cause a loss of hand function. Two treatments for Dupuytren’s contractures are widely used within the National Health Service (NHS) in the United Kingdom: removal of the contractures via surgery (limited fasciectomy), and division of the contractures via a needle inserted through the skin (needle fasciotomy).

Valerie J Smith

Valerie J Smith

University of St Andrews

Journal of Clinical Epidemiology

Using behavioral science to increase core outcome set use in trials

ObjectivesCore outcome sets are agreed sets of outcomes for use in clinical trials, which can increase standardization and reduce heterogeneity of outcomes in research. Using a core outcome set, or not, is a behavior that can potentially be increased using behavioral strategies. The aim of this study was to identify behavioral intervention components to potentially increase use of core outcome sets in trials.MethodsThis project was informed by the Behavior Change Wheel framework. Two reviewers extracted barriers and facilitators to core outcome set use from four recently published studies examining core outcome set use in trials. Barriers and facilitators were coded to the Capability, Opportunity, Motivation-Behavior (COM-B) model, which forms part of the Behavior Change Wheel. COM-B findings were mapped to intervention functions by two reviewers, and then mapped to behavior change techniques. Full-team …

Shaun Treweek

Shaun Treweek

University of Aberdeen

PROMETHEUS results

5. study design.Our classification resulted in all the funded retention strategies being classified under domains A ‘Data collection’or domain B ‘Participants’. There was only one SWAT classified under domain A, and this SWAT fell under the subdomain of ‘A1. Questionnaire design’. The remaining SWATs in domain B (Participants) were classified under the subdomains of ‘B1. Reminders and prompts’(13 SWATs);‘B2. Monetary incentives’(1 SWAT);‘B3. Non-monetary incentives’(3 SWATs) and ‘B4. Maintaining participant engagement’(12 SWATs).

Shaun Treweek

Shaun Treweek

University of Aberdeen

Lessons learnt for statistical considerations

Randomised SWATs are like any other trial and as such, the statistical considerations for SWATs are similar to those for a typical trial. Although constrained within the context of the host trial, a SWAT should still follow principles for rigorous analysis, to ensure that the findings are considered reliable. Within this chapter, sample size, analyses and costing considerations when undertaking a SWAT will be detailed, alongside examples of our learnings from the PROMETHEUS programme.

Carrol Gamble

Carrol Gamble

University of Liverpool

The overlap between randomised evaluations of recruitment and retention interventions: An updated review of recruitment (Online Resource for Recruitment in Clinical triAls) and …

BackgroundThe Online Resource for Recruitment in Clinical triAls (ORRCA) and the Online Resource for Retention in Clinical triAls (ORRCA2) were established to organise and map the literature addressing participant recruitment and retention within clinical research. The two databases are updated on an ongoing basis using separate but parallel systematic reviews. However, recruitment and retention of research participants is widely acknowledged to be interconnected. While interventions aimed at addressing recruitment challenges can impact retention and vice versa, it is not clear how well they are simultaneously considered within methodological research. This study aims to report the recent update of ORRCA and ORRCA2 with a special emphasis on assessing crossover of the databases and how frequently randomised studies of methodological interventions measure the impact on both recruitment and …

Carrol Gamble

Carrol Gamble

University of Liverpool

Trials

Using healthcare systems data for outcomes in clinical trials: issues to consider at the design stage

BackgroundHealthcare system data (HSD) are increasingly used in clinical trials, augmenting or replacing traditional methods of collecting outcome data. This study, PRIMORANT, set out to identify, in the UK context, issues to be considered before the decision to use HSD for outcome data in a clinical trial is finalised, a methodological question prioritised by the clinical trials community.MethodsThe PRIMORANT study had three phases. First, an initial workshop was held to scope the issues faced by trialists when considering whether to use HSDs for trial outcomes. Second, a consultation exercise was undertaken with clinical trials unit (CTU) staff, trialists, methodologists, clinicians, funding panels and data providers. Third, a final discussion workshop was held, at which the results of the consultation were fed back, case studies presented, and issues considered in small breakout groups.ResultsKey topics included in …

Shaun Treweek

Shaun Treweek

University of Aberdeen

Effective interventions to increase representation of under-served groups in randomised trials in UK and Ireland: a scoping literature review

Background Participants in clinical trials often do not reflect the populations that could benefit from the treatments being investigated. There are known barriers to trial participation for under-served groups, but limited evidence on strategies to alleviate these barriers to improve representation. This scoping review aimed to identify effective interventions and design features that improve the representation `of under-served groups in trials, focusing on the UK and Ireland. Methods We included methodological research studies that reported interventions to improve representation of ethnic minority groups, socioeconomically disadvantaged groups, older people, or those with impaired capacity to consent to randomised controlled trials, conducted in the UK and Ireland, published between 2000–2021. Systematic searches were conducted in November 2021 and data were independently extracted by two authors and narratively synthesised. Results Seven studies were included: one randomised controlled study embedded in five trials, one mixed-methods study, and five studies reporting ‘lessons learnt’ from one trial. We categorised the 47 reported interventions or strategies into nine broad themes: Recruitment sites, recruitment settings, community engagement, and communication with participants, incentives, inclusion criteria, flexibility, patient documentation, and the consent process. Only 28/47 interventions were evaluated, 23 of which were comparison of recruitment pathways. The randomised study found that a £100 incentive mentioned in the invitation letter increased positive responses overall across drug trials in cardiovascular disease and …

Nicola Mills

Nicola Mills

University of Bristol

Trials

Sertraline for anxiety in adults with a diagnosis of autism (STRATA): study protocol for a pragmatic, multicentre, double-blind, placebo-controlled randomised controlled trial

BackgroundSelective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects.MethodsSTRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to …

Other articles from BMC medical research methodology journal

faith yego

faith yego

Moi University

BMC Medical Research Methodology

Gaussian process emulation to improve efficiency of computationally intensive multidisease models: a practical tutorial with adaptable R code

BackgroundThe rapidly growing burden of non-communicable diseases (NCDs) among people living with HIV in sub-Saharan Africa (SSA) has expanded the number of multidisease models predicting future care needs and health system priorities. Usefulness of these models depends on their ability to replicate real-life data and be readily understood and applied by public health decision-makers; yet existing simulation models of HIV comorbidities are computationally expensive and require large numbers of parameters and long run times, which hinders their utility in resource-constrained settings.MethodsWe present a novel, user-friendly emulator that can efficiently approximate complex simulators of long-term HIV and NCD outcomes in Africa. We describe how to implement the emulator via a tutorial based on publicly available data from Kenya. Emulator parameters relating to incidence and prevalence of HIV …

Darren Brenner

Darren Brenner

University of Calgary

BMC Medical Research Methodology

Text analysis framework for identifying mutations among non-small cell lung cancer patients from laboratory data

BackgroundLaboratory data can provide great value to support research aimed at reducing the incidence, prolonging survival and enhancing outcomes of cancer. Data is characterized by the information it carries and the format it holds. Data captured in Alberta’s biomarker laboratory repository is free text, cluttered and rouge. Such data format limits its utility and prohibits broader adoption and research development. Text analysis for information extraction of unstructured data can change this and lead to more complete analyses. Previous work on extracting relevant information from free text, unstructured data employed Natural Language Processing (NLP), Machine Learning (ML), rule-based Information Extraction (IE) methods, or a hybrid combination between them.MethodsIn our study, text analysis was performed on Alberta Precision Laboratories data which consisted of 95,854 entries from the Southern Alberta …

Jennifer Pierce

Jennifer Pierce

University of Michigan

BMC Medical Research Methodology

Understanding facilitators of research participation among adults with self-reported chronic pain–a survey examining hypothetical research participation

BackgroundAn inability to successfully recruit participants into clinical research has consequences that negatively affect the conduct and reliability of research studies. Understanding facilitators of research participation, namely motives for participation and preferred research outcomes, may improve recruitment and retention of clinical trials related to chronic pain. The present study explored research participation facilitators among individuals with chronic pain and their association with demographic characteristics, pain-related characteristics, and factors related to future research engagement.MethodsIndividuals from Michigan who were 18 years or older and self-reported having chronic pain completed an online survey assessing motives for research participation and desired research outcomes. Analyses were conducted in three stages. First, we evaluated underlying factors of motives for participation and …

Björn Bokelmann

Björn Bokelmann

Humboldt-Universität zu Berlin

BMC Medical Research Methodology

Extension of a conditional performance score for sample size recalculation rules to the setting of binary endpoints

BackgroundSample size calculation is a central aspect in planning of clinical trials. The sample size is calculated based on parameter assumptions, like the treatment effect and the endpoint’s variance. A fundamental problem of this approach is that the true distribution parameters are not known before the trial. Hence, sample size calculation always contains a certain degree of uncertainty, leading to the risk of underpowering or oversizing a trial. One way to cope with this uncertainty are adaptive designs. Adaptive designs allow to adjust the sample size during an interim analysis. There is a large number of such recalculation rules to choose from. To guide the choice of a suitable adaptive design with sample size recalculation, previous literature suggests a conditional performance score for studies with a normally distributed endpoint. However, binary endpoints are also frequently applied in clinical trials and the application …

Annika Hoyer

Annika Hoyer

Ludwig-Maximilians-Universität München

BMC Medical Research Methodology

Estimation of mortality rate ratios for chronic conditions with misclassification of disease status at death

Estimation of mortality rates and mortality rate ratios (MRR) of diseased and non-diseased individuals is a core metric of disease impact used in chronic disease epidemiology. Estimation of mortality rates is often conducted through retrospective linkage of information from nationwide surveys such as the National Health Interview Survey (NHIS) and death registries. These surveys usually collect information on disease status during only one study visit. This infrequency leads to missing disease information (with right censored survival times) for deceased individuals who were disease-free at study participation, and a possibly biased estimation of the MRR because of possible undetected disease onset after study participation. This occurrence is called “misclassification of disease status at death (MicDaD)” and it is a potentially common source of bias in epidemiologic studies. In this study, we conducted a simulation …

Sue VandeWoude

Sue VandeWoude

Colorado State University

BMC Medical Research Methodology

Estimating cutoff values for diagnostic tests to achieve target specificity using extreme value theory

BackgroundRapidly developing tests for emerging diseases is critical for early disease monitoring. In the early stages of an epidemic, when low prevalences are expected, high specificity tests are desired to avoid numerous false positives. Selecting a cutoff to classify positive and negative test results that has the desired operating characteristics, such as specificity, is challenging for new tests because of limited validation data with known disease status. While there is ample statistical literature on estimating quantiles of a distribution, there is limited evidence on estimating extreme quantiles from limited validation data and the resulting test characteristics in the disease testing context.MethodsWe propose using extreme value theory to select a cutoff with predetermined specificity by fitting a Pareto distribution to the upper tail of the negative controls. We compared this method to five previously proposed cutoff selection …

Fred H. Geisler, M.D., Ph.D.

Fred H. Geisler, M.D., Ph.D.

University of Saskatchewan

BMC medical research methodology

Studying missingness in spinal cord injury data: challenges and impact of data imputation

BackgroundIn the last decades, medical research fields studying rare conditions such as spinal cord injury (SCI) have made extensive efforts to collect large-scale data. However, most analysis methods rely on complete data. This is particularly troublesome when studying clinical data as they are prone to missingness. Often, researchers mitigate this problem by removing patients with missing data from the analyses. Less commonly, imputation methods to infer likely values are applied.ObjectiveOur objective was to study how handling missing data influences the results reported, taking the example of SCI registries. We aimed to raise awareness on the effects of missing data and provide guidelines to be applied for future research projects, in SCI research and beyond.MethodsUsing the Sygen clinical trial data (n = 797), we analyzed the impact of the type of variable in which data is missing, the pattern according to …

Lesley Inker

Lesley Inker

Tufts University

BMC Medical Research Methodology

Comparing Bayesian hierarchical meta-regression methods and evaluating the influence of priors for evaluations of surrogate endpoints on heterogeneous collections of clinical …

BackgroundSurrogate endpoints, such as those of interest in chronic kidney disease (CKD), are often evaluated using Bayesian meta-regression. Trials used for the analysis can evaluate a variety of interventions for different sub-classifications of disease, which can introduce two additional goals in the analysis. The first is to infer the quality of the surrogate within specific trial subgroups defined by disease or intervention classes. The second is to generate more targeted subgroup-specific predictions of treatment effects on the clinical endpoint.MethodsUsing real data from a collection of CKD trials and a simulation study, we contrasted surrogate endpoint evaluations under different hierarchical Bayesian approaches. Each approach we considered induces different assumptions regarding the relatedness (exchangeability) of trials within and between subgroups. These include partial-pooling approaches, which allow …

Stephen Burgess

Stephen Burgess

University of Cambridge

BMC Medical Research Methodology

A data-adaptive method for investigating effect heterogeneity with high-dimensional covariates in Mendelian randomization

BackgroundMendelian randomization is a popular method for causal inference with observational data that uses genetic variants as instrumental variables. Similarly to a randomized trial, a standard Mendelian randomization analysis estimates the population-averaged effect of an exposure on an outcome. Dividing the population into subgroups can reveal effect heterogeneity to inform who would most benefit from intervention on the exposure. However, as covariates are measured post-“randomization”, naive stratification typically induces collider bias in stratum-specific estimates.MethodWe extend a previously proposed stratification method (the “doubly-ranked method”) to form strata based on a single covariate, and introduce a data-adaptive random forest method to calculate stratum-specific estimates that are robust to collider bias based on a high-dimensional covariate set. We also propose measures based on …

Hisham Mehanna

Hisham Mehanna

University of Birmingham

BMC Medical Research Methodology

Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial

BackgroundIn this article we describe the methodology of the time-to-event continual reassessment method in the presence of partial orders (PO-TITE-CRM) and the process of implementing this trial design into a phase I trial in head and neck cancer called ADePT-DDR. The ADePT-DDR trial aims to find the maximum tolerated dose of an ATR inhibitor given in conjunction with radiotherapy in patients with head and neck squamous cell carcinoma.MethodsThe PO-TITE-CRM is a phase I trial design that builds upon the time-to-event continual reassessment method (TITE-CRM) to allow for the presence of partial ordering of doses. Partial orders occur in the case where the monotonicity assumption does not hold and the ordering of doses in terms of toxicity is not fully known.ResultsWe arrived at a parameterisation of the design which performed well over a range of scenarios. Results from simulations were used …

Wei-Ting Hwang

Wei-Ting Hwang

University of Pennsylvania

BMC Medical Research Methodology

Survival analysis under imperfect record linkage using historic census data

BackgroundAdvancements in linking publicly available census records with vital and administrative records have enabled novel investigations in epidemiology and social history. However, in the absence of unique identifiers, the linkage of the records may be uncertain or only be successful for a subset of the census cohort, resulting in missing data. For survival analysis, differential ascertainment of event times can impact inference on risk associations and median survival.MethodsWe modify some existing approaches that are commonly used to handle missing survival times to accommodate this imperfect linkage situation including complete case analysis, censoring, weighting, and several multiple imputation methods. We then conduct simulation studies to compare the performance of the proposed approaches in estimating the associations of a risk factor or exposure in terms of hazard ratio (HR) and median …

Wiley D. Jenkins

Wiley D. Jenkins

Southern Illinois University Carbondale

BMC Medical Research Methodology

Evaluation of respondent-driven sampling in seven studies of people who use drugs from rural populations: findings from the Rural Opioid Initiative

BackgroundAccurate prevalence estimates of drug use and its harms are important to characterize burden and develop interventions to reduce negative health outcomes and disparities. Lack of a sampling frame for marginalized/stigmatized populations, including persons who use drugs (PWUD) in rural settings, makes this challenging. Respondent-driven sampling (RDS) is frequently used to recruit PWUD. However, the validity of RDS-generated population-level prevalence estimates relies on assumptions that should be evaluated.MethodsRDS was used to recruit PWUD across seven Rural Opioid Initiative studies between 2018-2020. To evaluate RDS assumptions, we computed recruitment homophily and design effects, generated convergence and bottleneck plots, and tested for recruitment and degree differences. We compared sample proportions with three RDS-adjusted estimators (two variations of RDS-I …

Angela Wood

Angela Wood

University of Cambridge

BMC Medical Research Methodology

Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort

BackgroundPatients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort.MethodsThe CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of …

Prof. Antonis C. Antoniou

Prof. Antonis C. Antoniou

University of Cambridge

BMC Medical Research Methodology

Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort

BackgroundPatients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort.MethodsThe CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of …

mohammad hamed hosseini

mohammad hamed hosseini

Birjand University of Medical Sciences

BMC Medical Research Methodology

Modeling heart rate of individual and team manual handling with one hand using generalized additive mixed models

ObjectivesDespite the fact that team manual handling is common in different working environments, the previous studies in this regard, particularly those with a physiological approach are quite limited. The present study is an attempt to model the heart rate (HR) of individual and team manual handling with one hand.MethodsTwenty-five young men (aged 21.24±1.42 year) volunteered for this study. The experiments included individual and two-person handling of the load with three different weights with and without height difference. The participants’ HR was registered at the end of the route by a chest-strap pulse monitor and a polar watch according to the manufacturer's recommendation. A multivariate Generalized Additive Mixed Model (MGAMM) was used for modeling heart rate based on explanatory variables of workload, carry method, HRrest, body weight, height, knee height, shoulder height, elbow height …

Omar Galarraga

Omar Galarraga

Brown University

BMC Medical Research Methodology

Gaussian process emulation to improve efficiency of computationally intensive multidisease models: a practical tutorial with adaptable R code

BackgroundThe rapidly growing burden of non-communicable diseases (NCDs) among people living with HIV in sub-Saharan Africa (SSA) has expanded the number of multidisease models predicting future care needs and health system priorities. Usefulness of these models depends on their ability to replicate real-life data and be readily understood and applied by public health decision-makers; yet existing simulation models of HIV comorbidities are computationally expensive and require large numbers of parameters and long run times, which hinders their utility in resource-constrained settings.MethodsWe present a novel, user-friendly emulator that can efficiently approximate complex simulators of long-term HIV and NCD outcomes in Africa. We describe how to implement the emulator via a tutorial based on publicly available data from Kenya. Emulator parameters relating to incidence and prevalence of HIV …

Mehrdad Mahdian

Mehrdad Mahdian

Kashan University of Medical Sciences

BMC medical research methodology

Extraction frequent patterns in trauma dataset based on automatic generation of minimum support and feature weighting

PurposeData mining has been used to help discover Frequent patterns in health data. it is widely used to diagnose and prevent various diseases and to obtain the causes and factors affecting diseases. Therefore, the aim of the present study is to discover frequent patterns in the data of the Kashan Trauma Registry based on a new method.MethodsWe utilized real data from the Kashan Trauma Registry. After pre-processing, frequent patterns and rules were extracted based on the classical Apriori algorithm and the new method. The new method based on the weight of variables and the harmonic mean was presented for the automatic calculation of minimum support with the Python.ResultsThe results showed that the minimum support generation based on the weighting features is done dynamically and level by level, while in the classic Apriori algorithm considering that only one value is considered for the minimum …

Gilberto Kac

Gilberto Kac

Universidade Federal do Rio de Janeiro

BMC Medical Research Methodology

Identifying biologically implausible values in big longitudinal data: an example applied to child growth data from the Brazilian food and nutrition surveillance system

BackgroundSeveral strategies for identifying biologically implausible values in longitudinal anthropometric data have recently been proposed, but the suitability of these strategies for large population datasets needs to be better understood. This study evaluated the impact of removing population outliers and the additional value of identifying and removing longitudinal outliers on the trajectories of length/height and weight and on the prevalence of child growth indicators in a large longitudinal dataset of child growth data.MethodsLength/height and weight measurements of children aged 0 to 59 months from the Brazilian Food and Nutrition Surveillance System were analyzed. Population outliers were identified using z-scores from the World Health Organization (WHO) growth charts. After identifying and removing population outliers, residuals from linear mixed-effects models were used to flag longitudinal outliers. The …

Stijn Vansteelandt

Stijn Vansteelandt

Universiteit Gent

BMC Medical Research Methodology

The potential impact fraction of population weight reduction scenarios on non-communicable diseases in Belgium: application of the g-computation approach

Overweight is a major risk factor for non-communicable diseases (NCDs) in Europe, affecting almost 60% of all adults. Tackling obesity is therefore a key long-term health challenge and is vital to reduce premature mortality from NCDs. Methodological challenges remain however, to provide actionable evidence on the potential health benefits of population weight reduction interventions. This study aims to use a g-computation approach to assess the impact of hypothetical weight reduction scenarios on NCDs in Belgium in a multi-exposure context. Belgian health interview survey data (2008/2013/2018, n = 27 536) were linked to environmental data at the residential address. A g-computation approach was used to evaluate the potential impact fraction (PIF) of population weight reduction scenarios on four NCDs: diabetes, hypertension, cardiovascular disease (CVD), and musculoskeletal (MSK) disease. Four scenarios were considered: 1) a distribution shift where, for each individual with overweight, a counterfactual weight was drawn from the distribution of individuals with a “normal” BMI 2) a one-unit reduction of the BMI of individuals with overweight, 3) a modification of the BMI of individuals with overweight based on a weight loss of 10%, 4) a reduction of the waist circumference (WC) to half of the height among all people with a WC:height ratio greater than 0.5. Regression models were adjusted for socio-demographic, lifestyle, and environmental factors. The first scenario resulted in preventing a proportion of cases ranging from 32.3% for diabetes to 6% for MSK diseases. The second scenario prevented a proportion of cases ranging from 4.5 …

PD Dr. rer.nat. Pablo Emilio Verde

PD Dr. rer.nat. Pablo Emilio Verde

Heinrich-Heine-Universität Düsseldorf

BMC Medical Research Methodology

An assessment of the informative value of data sharing statements in clinical trial registries

BackgroundThe provision of data sharing statements (DSS) for clinical trials has been made mandatory by different stakeholders. DSS are a device to clarify whether there is intention to share individual participant data (IPD). What is missing is a detailed assessment of whether DSS are providing clear and understandable information about the conditions for data sharing of IPD for secondary use.MethodsA random sample of 200 COVID-19 clinical trials with explicit DSS was drawn from the ECRIN clinical research metadata repository. The DSS were assessed and classified, by two experienced experts and one assessor with less experience in data sharing (DS), into different categories (unclear, no sharing, no plans, yes but vague, yes on request, yes with specified storage location, yes but with complex conditions).ResultsBetween the two experts the agreement was moderate to substantial (kappa=0.62, 95% CI [0 …