The impact of epidemiologic methods on findings in studies of causal effects and prediction modelling

Luijken, K. (2022)

Doctoral Thesis

Over the last decades, increasingly so in the last years, epidemiological methods have been refined, making it challenging to keep abreast of all methodological developments. The choice of the data analytical method directly influences the interpretation and clinical meaning of results of an analysis, yet it is undesirable that technical considerations define the subject of the investigation. Having a deeper understanding of the impact that data analytical decisions can have on the interpretation of numerical results of a study would help to apply analytical tools that are both suitable and appropriate to answer clinical questions. The aim of this thesis was to investigate the impact of choices regarding the design and statistical analysis of a study on the meaning of its numerical results in two sets of case studies in research into causal effects (Part I) and prediction research (Part II). The thesis concludes with a discussion on the role and importance of clinical research questions and estimands. Clearly defining a clinically relevant estimand ensures that data analytical decisions yield meaningful results. Making targeted research questions central to quantitative clinical research can reduce fallacious confidence in (complex) methods and can add to intelligibility of findings.

• Epidemiology
• Observational research
• Statistics
• Immortal time bias
• Exploratory analyses
• Confounder selection
• Risk of bias
• Predictor measurement heterogeneity
• External validation
• Estimand

• All authors: Luijken, K.
• Supervisor: Groenwold, R.H.H.
• Committee: Dekkers, O.M.; Fiocco, M.; Steyerberg, E.W.; Klugkist, I.G.; Hooft, L.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2022-05-19
• ISBN (print): 9789464168426