Protecting against researcher bias in secondary data analysis: challenges and potential solutions

Analysis of secondary data sources (such as cohort studies, survey data, and administrative records) has the potential to provide answers to science and society’s most pressing questions. However, researcher biases can lead to questionable research practices in secondary data analysis, which can distort the evidence base. While pre-registration can help to protect against researcher biases, it presents challenges for secondary data analysis. In this article, we describe these challenges and propose novel solutions and alternative approaches. Proposed solutions include approaches to (1) address bias linked to prior knowledge of the data, (2) enable pre-registration of non-hypothesis-driven research, (3) help ensure that pre-registered analyses will be appropriate for the data, and (4) address difficulties arising from reduced analytic flexibility in pre-registration. For each solution, we provide guidance on implementation for researchers and data guardians. The adoption of these practices can help to protect against researcher bias in secondary data analysis, to improve the robustness of research based on existing data

Mental Health as a Mediator of the Association Between Educational Inequality and Cardiovascular Disease: A Mendelian Randomization Study.

Background Education is inversely associated with cardiovascular disease (CVD). Several mediators of this have been established; however, a proportion of the protective effect remains unaccounted for. Mental health is a proposed mediator, but current evidence is mixed and subject to bias from confounding factors and reverse causation. Mendelian randomization is an instrumental variable technique that uses genetic proxies for exposures and mediators to reduce such bias. Methods and Results We performed logistic regression and 2-step Mendelian randomization analyses using UK Biobank data and genetic summary statistics to investigate whether educational attainment affects risk of mental health disorders. We then performed mediation analyses to explore whether mental health disorders mediate the association between educational attainment and cardiovascular risk. Higher levels of educational attainment were associated with reduced depression, anxiety, and CVD in observational analyses (odds ratio [OR], 0.79 [95% CI, 0.77-0.81], 0.76 [95% CI, 0.73-0.79], and 0.75 [95% CI, 0.74-0.76], respectively), and Mendelian randomization analyses provided evidence of causality (OR, 0.72 [95% CI, 0.67-0.77], 0.50 [95% CI, 0.42-0.59], and 0.62 [95% CI, 0.58-0.66], respectively). Both anxiety and depression were associated with CVD in observational analyses (OR, 1.63 [95% CI, 1.49-1.79] and 1.70 [95% CI, 1.59-1.82], respectively) but only depression showed evidence of causality in the Mendelian randomization analyses (OR, 1.09; 95% CI, 1.03-1.15). An estimated 2% of the total protective effect of education on CVD was mediated by depression. Conclusions Higher levels of educational attainment protect against mental health disorders, and reduced depression accounts for a small proportion of the total protective effect of education on CVD

Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood?

Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother–child pairs, and 6,222 father–child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this sample, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining individual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale samples of genotyped families with information on childhood psychiatric outcomes

Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach.

BACKGROUND: Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene-environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, we aimed to delineate the sources of gene-environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health. METHODS: We did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank (n=143 473), Psychiatric Genomics Consortium (n=26 290), Avon Longitudinal Study of Parents and Children (n=8346), Adolescent Brain Cognitive Development Study (n=5400), and Generation R (n=1905). We included individuals who had phenotypic and genetic data available. We investigated single nucleotide polymorphism heritability and genetic correlations among different subtypes, operationalisations, and reports of childhood maltreatment. Family-based and population-based polygenic score analyses were done to elucidate gene-environment correlation mechanisms. We used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions. FINDINGS: Our meta-analysis of genome-wide association studies (N=185 414) identified 14 independent loci associated with childhood maltreatment (13 novel). We identified high genetic overlap (genetic correlations 0·24-1·00) among different maltreatment operationalisations, subtypes, and reporting methods. Within-family analyses provided some support for active and reactive gene-environment correlation but did not show the absence of passive gene-environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration). INTERPRETATION: Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment. Family-based analyses point to a role of active and reactive gene-environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. Our study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects. FUNDING: Wellcome Trust, UK Medical Research Council, Horizon 2020, National Institute of Mental Health, and National Institute for Health Research Biomedical Research Centre

Towards translation of environmental determinants of physical activity in children into multi-sector policy measures: study design of a Dutch project

Transport, and Safety) were screened for their content on physical activity in children. In addition, semi-structured interviews were conducted with policy makers of each of these sectors to identify critical success factors in the development and realization of multi-sector policy plans aimed at stimulating physical activity in children. The results of all these research activities will be discussed with local policy makers during interactive workshop sessions in order to identify clear cut multi-sector policy measures that stimulate physical activity in children. DISCUSSION: This paper describes the study design of a project that focuses on multi-sector policy measures that stimulate physical activity in children. Next to extensive research into the environmental determinants of physical activity in children, much emphasis is placed on the translation of the research outcomes into concrete and feasible policy plan

Understanding the Relationship between Activity and Neighbourhoods (URBAN) Study: research design and methodology

<p>Abstract</p> <p>Background</p> <p>Built environment attributes are recognized as being important contributors to physical activity (PA) engagement and body size in adults and children. However, much of the existing research in this emergent public health field is hindered by methodological limitations, including: population and site homogeneity, reliance on self-report measures, aggregated measures of PA, and inadequate statistical modeling. As an integral component of multi-country collaborative research, the Understanding the Relationship between Activity and Neighbourhoods (URBAN) Study seeks to overcome these limitations by determining the strengths of association between detailed measures of the neighborhood built environment with PA levels across multiple domains and body size measures in adults and children. This article outlines the research protocol developed for the URBAN Study.</p> <p>Methods and design</p> <p>The URBAN Study is a multi-centered, stratified, cross-sectional research design, collecting data across four New Zealand cities. Within each city, 12 neighborhoods were identified and selected for investigation based on higher or lower walkability and Māori demographic attributes. Neighborhoods were selected to ensure equal representation of these characteristics. Within each selected neighborhood, 42 households are being randomly selected and an adult and child (where possible) recruited into the study. Data collection includes: objective and self-reported PA engagement, neighborhood perceptions, demographics, and body size measures. The study was designed to recruit approximately 2,000 adults and 250 children into the project. Other aspects of the study include photovoice, which is a qualitative assessment of built environment features associated with PA engagement, an audit of the neighborhood streetscape environment, and an individualized neighborhood walkability profile centered on each participant's residential address. Multilevel modeling will be used to examine the individual-level and neighborhood-level relationships with PA engagement and body size.</p> <p>Discussion</p> <p>The URBAN Study is applying a novel scientifically robust research design to provide urgently needed epidemiological information regarding the associations between the built environment and health outcomes. The findings will contribute to a larger, international initiative in which similar neighborhood selection and PA measurement procedures are utilized across eight countries. Accordingly, this study directly addresses the international priority issues of increasing PA engagement and decreasing obesity levels.</p

Maternal postnatal depressive symptoms and offspring emotional and behavioral development at age 7 years in a U.K. birth cohort: The role of paternal involvement

There is considerable variability in developmental outcomes of children whose mothers experience depression. Few longitudinal studies have examined contributions of paternal involvement in the association between maternal postnatal depression (PND) and offspring development. We examined pathways from maternal PND at 8 weeks (Edinburgh Postnatal Depression Scale; total score) to offspring emotional and behavioral development at 7 years (Strengths and Difficulties Questionnaire; total score) through behavioral, affective, and cognitive dimensions of paternal involvement in a U.K.-based birth cohort (Avon Longitudinal Study of Parents and Children; n = 3,434). Analyses were adjusted for baseline confounders and paternal PND (Edinburgh Postnatal Depression Scale; total score) as an intermediate confounder. Maternal PND was strongly associated with offspring development, but this association was not mediated by the combination of all indirect pathways through various dimensions of paternal involvement. Only father–child conflict emerged as a risk factor for adverse offspring development and as a mediator in the association between maternal PND and offspring development (albeit the effect size was small). If found causal, interventions that reduce father–child conflict may reduce the risk of adverse development in offspring of mothers with PND

The infant feeding activity and nutrition trial (INFANT) an early intervention to prevent childhood obesity : cluster-randomised controlled trial

Background : Multiple factors combine to support a compelling case for interventions that target the development of obesity-promoting behaviours (poor diet, low physical activity and high sedentary behaviour) from their inception. These factors include the rapidly increasing prevalence of fatness throughout childhood, the instigation of obesity-promoting behaviours in infancy, and the tracking of these behaviours from childhood through to adolescence and adulthood. The Infant Feeding Activity and Nutrition Trial (INFANT) aims to determine the effectiveness of an early childhood obesity prevention intervention delivered to first-time parents. The intervention, conducted with parents over the infant\u27s first 18 months of life, will use existing social networks (first-time parent\u27s groups) and an anticipatory guidance framework focusing on parenting skills which support the development of positive diet and physical activity behaviours, and reduced sedentary behaviours in infancy.Methods/Design : This cluster-randomised controlled trial, with first-time parent groups as the unit of randomisation, will be conducted with a sample of 600 first-time parents and their newborn children who attend the first-time parents\u27 group at Maternal and Child Health Centres. Using a two-stage sampling process, local government areas in Victoria, Australia will be randomly selected at the first stage. At the second stage, a proportional sample of first-time parent groups within selected local government areas will be randomly selected and invited to participate. Informed consent will be obtained and groups will then be randomly allocated to the intervention or control group.Discussion : The early years hold promise as a time in which obesity prevention may be most effective. To our knowledge this will be the first randomised trial internationally to demonstrate whether an early health promotion program delivered to first-time parents in their existing social groups promotes healthy eating, physical activity and reduced sedentary behaviours. If proven to be effective, INFANT may protect children from the development of obesity and its associated social and economic costs.<br /

Health Indicators of Native Hawaiian and Pacific Islanders in the United States

This study aimed to describe health indicators and behaviors of Native Hawaiian and Pacific Islander (NHPI) adults and to compare findings to previous reports on US NHPI and the US population. A sample of N = 100 (56 M, 44 F) NHPI adults aged 40–59 years completed an anonymous questionnaire addressing education and household income, tobacco use, physical activity, fruit and vegetable (F&V) consumption, cancer screening and health status. Objective measures of height and weight were taken to calculate body mass index (BMI). The study sample consisted of 49% current smokers and the majority was not meeting guidelines for physical activity (80%) or F&V consumption (99%). Cancer screening rates ranged from 0 to 57% and were higher among females. Mean BMI was 33.9 ± 7.5 kg/m2 and 95% were overweight or obese. While 36.7% were hypertensive, only 11.1% were taking prescribed medication. Compared to both the general US population and available data for US NHPI, study participants reported higher prevalence of obesity and chronic conditions (hypertension, high cholesterol, diabetes, and angina/CHD) and lower levels of physical activity, F&V consumption and cancer screening rates. Study findings contribute to the limited knowledge regarding health behaviors of US NHPI. Comparisons to US data increase evidence of NHPI health disparities, while comparisons to previous NHPI studies emphasize the magnitude of unhealthy lifestyle behaviors and subsequent adverse health conditions for this particular sample. Further improvements to community outreach and recruitment strategies could successfully encourage high-risk individuals to participate in health promotion and behavior intervention studies to improve NHPI health behaviors