Table 1 Glossary: definitions of terms in this paper

Adverse drug reaction, ADR

Noxious and unintended responses to pharmacotherapy (or medicines)

A response to a medicinal product which is noxious and unintended. This includes adverse reactions which arise from:

• The use of a medicinal product within the terms of the marketing authorisation

• The use outside the terms of the marketing authorisation, including overdose, off-label use, misuse, abuse and errors

• Occupational exposure

European Medicines Agency (2017)p.6

A transgenerational ADR is across generations, affecting the child, not the parent taking the medicine.

[3] European Medicines Agency (EMA) Guideline on good pharmacovigilance (GVP). Module VI – Collection, management and submission of reports of suspected adverse reactions to medicinal products (Rev 2). 2017. Available: http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2017/08/WC500232767.pdf

‘Trans’ is the prefix used to denote ‘across / from one another’ (OED trans-, prefix: Oxford English Dictionary (oed.com))

Bias

‘Any process at any stage of inference which tends to produce results or conclusions that differ systematically from the truth’. (Adapted from Murphy. The Logic of Medicine. Baltimore: John Hopkins University Press. 1976)

[4] Sackett DL: Bias in analytic research. J Chronic Dis 1979, 32(1–2): 51–63

Collider bias

The distortion that occurs when two variables independently cause a third variable (the collider), and the analysis is conditioned on the third variable (the collider). The condition may be as a restriction (or condition) of study entry or as a covariate in a regression model. This is selection bias based on 2 or more variables.

[5] Munafò MR, Tilling K, Taylor AE, Evans DM, Davey Smith G: Collider scope: when selection bias can substantially influence observed associations. Int J Epidemiol 2018, 47(1): 226–235. P.227

Cole SR, Platt RW, Schisterman EF, Chu H, Westreich D, Richardson D, Poole C: Illustrating bias due to conditioning on a collider. International Journal of Epidemiology 2010, 39(2): 417–420, p.419

Confounding variable

A variable (measured or not) other than the predictor variables of interest that potentially affects the outcome variable. P.783

[6] Field A. Discovering statistics using spss. London: Sage; 2013 4^th edition

Confounder

A factor associated with both the exposure (predictor) and the outcome, and not part of the causal pathway from exposure to outcome. P.195

Other definitions exist, some specify that the confounder is present before the exposure [7] (VanderWeele TJ, Shpitser I. On the definition of a confounder. Ann Stat. 2013, 41(1):196–220. 10.1214/12-aos1058)

The Oxford English Dictionary definition is: ‘One who causes confusion or disorder, who confuses distinctions’.

[8] Kahlert J, Gribsholt SB, Gammelager H, Dekkers OM, Luta G: Control of confounding in the analysis phase – an overview for clinicians. Clin Epidemiol 2017, 9:195–204. 10.2147/CLEP.S129886

Covariate

Any variable that is measurable and considered to have a statistical relationship with the outcome variable is a potential covariate. A covariate is a possible predictive or explanatory variable of the outcome. P.2

[9] Salkind, NJ: Encyclopedia of Research Design (Vols. 1–0). Thousand Oaks, CA: SAGE Publications, Inc; 2010 https://doi.org/10.4135/9781412961288

Deprivation score

Deprivation scores, ranks and quintiles are based on small geographical areas of residence. The UK’s Townsend measure of material deprivation, one of the first of these to have been created, is calculated from rates of unemployment, vehicle ownership, home ownership, and overcrowding (Townsend, 1988). Such scores are unavailable in countries without area-based codes, increasing reliance on other measures, such as income and maternal time in education.

[10] Townsend P, Phillimore P, Beattie A: Health and Deprivation. London: Routledge; 1988

Determinant

A determining factor or agent; a ruling antecedent, a conditioning element; a defining word or element.

[11] Oxford English Dictionary (OED) Online

Marginal Structual Models

A class of causal models for the estimation, from observational data, of the causal effect of a time-dependent exposure (treatment) in the presence of time-dependent covariates that may be simultaneously confounders and intermediate variables (e.g. breastfeeding).

[12] Robins JM, Hernán MA, Brumback B. Marginal structural models and causal inference in epidemiology. Epidemiology. 2000 Sep;11(5):550–60. https://doi.org/10.1097/00001648-200009000-00011. PMID: 10,955,408

Mediator variable

An entity or process that intervenes between input and output. A variable functions as a mediator to the extent that it accounts for the relation between the predictor and the outcome. Whereas moderator variables specify when certain effects will hold, mediators speak to how or why such effects occur. This can be illustrated as a causal chain.

A variable functions as a mediator when: a) variations in levels of the predictor variable significantly account for variations in the presumed mediator, b) variations in the mediator significantly account for variations in the outcome variable, and c) when these are both controlled, a previously significant relation between the predictor and outcome variables is no longer significant. P.1176

[13] Baron RM, Kenny DA: The moderator–mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. Journal of Personality and Social Psychology 1986, 51(6):1173–1182. 10.1037/0022-3514.51.6.1173

Moderator variable / effect modifier

A qualitative (e.g., sex, race, class) or quantitative variable that affects the direction and/or strength of the relation between a predictor variable and an outcome variable. Specifically, within a correlational analysis framework, a moderator is a third variable that affects the zero-order correlation between two other variables. P.1174

[13] Baron RM, Kenny DA: The moderator–mediator variable distinction in social psychological research: Conceptual, strategic, and statistical considerations. Journal of Personality and Social Psychology 1986, 51(6):1173–1182. 10.1037/0022-3514.51.6.1173

Multi-level modelling

A strategy to account for clustering of participants e.g. by primary care provider or school. Where participants are clustered, exposures and outcomes may not be independent. This hierarchical analysis is used in educational effectiveness studies to explore the influence of individual schools and classes.

[14] Miles J. & Shelvin M. 2001 Applying Regression and Correlation. Sage, London. P.192

Parameter

A term with extended and technical uses in many disciplines, including statistics, music, geometry.

In general usage: any distinguishing or defining characteristic or feature, esp. one that may be measured or quantified; an element or aspect of something; (more widely) a boundary or limit.

[11] Oxford English Dictionary (OED) Online https://www.oed.com/view/Entry/137519?redirectedFrom=parameter#eid

Pharmaco-epidemiology

Pharmacoepidemiology is the study of the use and effects of drugs in large numbers of people (WHO 2002 p.42); by applying epidemiological methods to pharmacology questions it bridges two disciplines.

[15] World Health Organization (2002). The importance of pharmacovigilance, safety monitoring of medicinal products. Geneva. https://apps.who.int/iris/bitstream/handle/10665/42493/a75646.pdf?sequence=1&isAllowed=y

Pharmaco-vigilance

Pharmacovigilance, a branch of pharmacoepidemiology, is the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problems (WHO 2002 p.7).

[15] World Health Organization (2002). The importance of pharmacovigilance, safety monitoring of medicinal products. Geneva. https://apps.who.int/iris/bitstream/handle/10665/42493/a75646.pdf?sequence=1&isAllowed=y

Regression / multiple regression

An equation (or model) where the outcome is predicted by a combination of ≥ 2 predictor (or exposure or input) variables. The model assigns a regression coefficient to each predictor variable, whose statistical significance can then be calculated.

[6] Field A. Discovering statistics using spss. London: Sage; 2013 4^th edition

Risk factor

A risk factor a) precedes the outcome, and b) when used it divides a population into high risk and low risk subgroups. Risk factors may be population specific. They may be fixed markers, variable markers or causal risk factors.

[16] Offord DR, Kraemer HC

Risk factors and prevention

Evidence-Based Mental Health 2000;3:70–71

Selection bias

The introduction of error due to systematic differences in the characteristics between those selected and those not selected for a given study.

[17] PubMed MeSH database (1990) Selection bias: http://www.ncbi.nlm.nih.gov/mesh?term=selection%20bias. Accessed 14 December 2012

Socio-economic status, SES

Social class, social stratification, social or SES or position, are often used interchangeably. Socioeconomic status (SES) is a combination of economic and social factors (income, education, housing tenure, occupation) that influence the positions individuals or groups hold within the structure of a society (Krieger, 1997). It encompasses concepts with different theoretical, historical and disciplinary origins (Galobardes, 2006).

SES is a relative, not absolute, measure. The most disadvantaged of some countries may be better situated than the most advantaged of others

[18] Krieger N, Williams DR, Moss NE: Measuring social class in US public health research: concepts, methodologies, and guidelines. Annu Rev Public Health 1997, 18:341–378

[19] Galobardes B, Shaw M, Lawlor DA, Lynch JW, Davey Smith G: Indicators of socioeconomic position (part 1). J Epidemiol Community Health 2006, 60(1):7–12. 10.1136/jech.2004.023531

Structural equation modelling

A general analytic technique for testing complex hypotheses that cannot be adequately described in regression models.

[14] Miles J. & Shelvin M. 2001 Applying Regression and Correlation. Sage, London. P.199

Variable

Anything that varies within a set of data. P.17

[20] Altman DG: Practical Statistics for Medical Research. London: Chapman & Hall; 1991

Variance

In statistics, a measure of dispersion, the square of the standard deviation or the sum of the distances between the observations and the mean divided by (n-1). P.34

[20] Altman DG: Practical Statistics for Medical Research. London: Chapman & Hall; 1991

Volunteer bias

Any process which tends to produce results or conclusions that differ systematically from the truth, arising where volunteers from a specified sample may exhibit exposures or outcomes which differ from those of non-volunteers. P.2

[21] Jordan S, Watkins A, Storey M, Allen SJ, Brooks CJ, Garaiova I, Heaven ML, Jones R, Plummer SF, Russell IT, Thornton CA, Morgan G. (2013) Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis. PLoS ONE 8(7): e67912. 10.1371/journal.pone.0067912