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  • 1.
    Barros, Guilherme
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Estimation of hazard ratios from observational data with applications related to stroke2024Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The objective of this thesis is to examine some challenges that may emerge when conducting time-to-event studies based on observational data. Time-to-event (also called survival) is a setting that involves analyzing how different factors may influence the length of time until an individual experiences the event of interest. This type of analysis is commonly applied in fields such as medical research and epidemiology. In this thesis, which focuses on stroke, we are interested in the time to a recurrent stroke or the death of a patient who survived a first stroke.

    Hazard ratios are one of the main parameters estimated in time-to-event studies. Hazard ratios involve comparing the risk of experiencing the event between two groups, usually a treated group and an untreated group.  They can also involve other factors, such as different age groups. Hazard ratios can be estimated from the data by using the Cox regression model.

    Observational data, in contrast to experimental data, involves data collected without any intervention or random assignment of treatment to the individuals. Confounders, that is, variables that distort or obscure the true relationship between treatment and outcome, are always present and need to be controlled for in observational studies.

    National registers are an important source of observational data. A national registry is a centralized database or system that collects, stores, and maintains information about a specific population or group of individuals within a country. Sweden is known for its detailed and complete national registers. In this thesis, data from the Swedish Stroke Register (Riksstroke) is used to study factors related to stroke.

    In time-to-event studies involving observational data, several challenges may arise for the researcher during data analysis. Some individuals may not experience the event during the observation period and thus the information about their time until the event is incomplete. These individuals are considered as censored. Some individuals may experience another event rather than the one of interest, a competing risk. Additionally, models must be properly constructed, with researchers selecting variables and determining the suitable functional form.

    Four papers are included in the thesis. Paper I demonstrates how to handle competing risks in survival analysis. The study involves comparing individuals with and without standard modifiable risk factors and their risks of a recurrent stroke or death using data from the Swedish Stroke Register.

    The estimation of marginal hazard ratios is a common theme in the other three papers. All involve simulation studies in order to extend methods and explore best practices when estimating marginal hazard ratios.

    Paper II explores non-parametric methods that can be used as alternatives to more traditional parametric methods when balancing datasets in order to estimate a marginal hazard ratio. A case study was also conducted using data from the Swedish Stroke Register involving the prescription of anticoagulants at hospital discharge after a stroke.

    Paper III is about how censoring affects marginal hazard ratio estimation, even with perfect balancing of the dataset. We study this issue, taking into consideration varying effect sizes and censoring rates. A procedure to attenuate the problem is also studied.

    Paper IV concerns covariate selection in the case of high-dimensional data. High-dimensional data involves cases in which the number of covariates in the study is comparable to the number of individuals, and therefore covariate selection methods are needed. In the paper, we explore some of these methods and suggest a best-performing procedure. As Paper II, Paper IV involves a case study of anticoagulant prescription using data from the Swedish Stroke Register.

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  • 2.
    Barros, Guilherme
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Häggström, Jenny
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Covariate selection for the estimation of marginal hazard ratios in high-dimensional dataManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Hazard ratios are frequently reported in time-to-event and epidemiological studies to assess treatment effects. In observational studies, the combination of propensity score weights with the Cox proportional hazards model facilitates the estimation of the marginal hazard ratio (MHR). The methods for estimating MHR are analogous to those employed for estimating common causal parameters, such as the average treatment effect. However, MHR estimation in the context of high-dimensional data remain unexplored. This paper seeks to address this gap through a simulation study that consider variable selection methods from causal inference combined with a recently proposed multiply robust approach for MHR estimation. Additionally, a case study utilizing stroke register data is conducted to demonstrate the application of these methods. The results from the simulation study indicate that the double selection covariate selection method is preferable to several other strategies when estimating MHR. Nevertheless, the estimation can be further improved by employing the multiply robust approach to the set of propensity score models obtained during the double selection process.

  • 3.
    Barros, Guilherme
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Häggström, Jenny
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Impact of non-informative censoring on propensity score based estimation of marginal hazard ratiosManuskript (preprint) (Övrigt vetenskapligt)
  • 4.
    Barros, Guilherme W. F.
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Häggström, Jenny
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Performance of modeling and balancing approach methods when using weights to estimate treatment effects in observational time-to-event settings2023Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 18, nr 12, artikel-id e0289316Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In observational studies weighting techniques are often used to overcome bias due to confounding. Modeling approaches, such as inverse propensity score weighting, are popular, but often rely on the correct specification of a parametric model wherein neither balance nor stability are targeted. More recently, balancing approach methods that directly target covariate imbalances have been proposed, and these allow the researcher to explicitly set the desired balance constraints. In this study, we evaluate the finite sample properties of different modeling and balancing approach methods, when estimating the marginal hazard ratio, through Monte Carlo simulations. The use of the different methods is also illustrated by analyzing data from the Swedish stroke register to estimate the effect of prescribing oral anticoagulants on time to recurrent stroke or death in stroke patients with atrial fibrillation. In simulated scenarios with good overlap and low or no model misspecification the balancing approach methods performed similarly to the modeling approach methods. In scenarios with bad overlap and model misspecification, the modeling approach method incorporating variable selection performed better than the other methods. The results indicate that it is valuable to use methods that target covariate balance when estimating marginal hazard ratios, but this does not in itself guarantee good performance in situations with, e.g., poor overlap, high censoring, or misspecified models/balance constraints.

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  • 5.
    Beharry, James
    et al.
    Department of Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, University of Melbourne, Victoria, Australia; Department of Neurology, Christchurch Hospital, Christchurch, New Zealand.
    Yogendrakumar, Vignan
    Department of Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
    Barros, Guilherme W. F.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Davis, Stephen
    Department of Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
    Norrving, Bo
    Lund University Department of Clinical Sciences Lund, Neurology, Skåne University Hospital, Sweden.
    Figtree, Gemma
    Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Cardiovascular Discovery Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia; Department of Cardiology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
    Donnan, Geoffrey
    Department of Neurology, Melbourne Brain Centre at Royal Melbourne Hospital, University of Melbourne, Victoria, Australia.
    von Euler, Mia
    Department of Neurology and Rehabilitation, School of Medicine, Örebro University, Örebro, Sweden.
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Recurrent ischemic stroke and mortality in stroke patients without standard modifiable risk factors: an analysis of the riksstroke registryManuskript (preprint) (Övrigt vetenskapligt)
  • 6.
    Franco, Vithor Rosa
    et al.
    Department of Psychology, São Francisco University, Campinas, Brazil.
    Barros, Guilherme
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Wiberg, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Laros, Jacob Arie
    Institute of Psychology, University of Brasília, Brasília, Brazil.
    Chain graph reduction into power chain graphs2022Ingår i: Quantitative and Computational Methods in Behavioral Sciences, E-ISSN 2699-8432, Vol. 2, nr 1, artikel-id e8383Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Reduction of graphs is a class of procedures used to decrease the dimensionality of a given graphin which the properties of the reduced graph are to be induced from the properties of the largeroriginal graph. This paper introduces both a new method for reducing chain graphs to simplerdirected acyclic graphs (DAGs), that we call power chain graphs (PCG), as well as a procedure forstructure learning of this new type of graph from correlational data of a Gaussian graphical model.Adefinitionfor PCGs is given, directly followed by the reduction method. The structure learningprocedure is a two-step approach:first,the correlation matrix is used to cluster the variables; andthen, the averaged correlation matrix is used to discover the DAGs using the PC-stable algorithm.The results of simulations are provided to illustrate the theoretical proposal, which demonstrateinitial evidence for the validity of our procedure to recover the structure of power chain graphs.The paper ends with a discussion regarding suggestions for future studies as well as some practicalimplications

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