<p>There are several traditions of conceptualizing and measuring harm from drinking. Two main approaches are considered in the introduction – the psychiatric epidemiology and the social survey research traditions. The present thesis adopts the latter, although, as discussed, on the empirical level there is no sharp borderline between the two perspectives, as there is not between personal (i.e. physical and psychological) and social harm from drinking as such. But while methods for studying personal harm are fairly well developed, social harm, i.e. adverse consequences of alcohol that involve social interaction, has received less attention. One of the aims of the thesis has been to explore different dimensions of harm from drinking, identify different harm areas and develop and apply area-specific measures using general population survey data.</p><p>Two papers examine psychometric properties of a widely used screening instrument, the AUDIT (Alcohol Use Disorder Identification Test). While the first paper is concerned with the validity of the AUDIT, testing it against different criteria, the second paper focuses on the test-retest reliability of the instrument. In the third paper, a number of summary measures of different areas of alcohol-related harm are constructed using factor analysis. These measures are then, in the last paper, applied to estimate prevalence and risk of alcohol-related harm in the Swedish general population. The analyses are based on data from a national survey on drinking problems in Sweden collected in 2001-2002.</p><p>It is concluded that the AUDIT screens well for both impaired self-control and social harm from drinking (as well as for high volume drinking), but performs less well when screening for health problems. The test-retest reliability of the AUDIT is relatively high. In the other two papers, constructing new summary measures and applying them to estimate prevalence of harm, it is concluded that, except for being young, no particular sociodemographic risk groups can be identified for different areas of harm from the same level and pattern of drinking. To what extent this reflects reality or is an effect of the methods we use and kind of population we reach in surveys is discussed.</p>

There are several traditions of conceptualizing and measuring harm from drinking. Two main approaches are considered in the introduction – the psychiatric epidemiology and the social survey research traditions. The present thesis adopts the latter, although, as discussed, on the empirical level there is no sharp borderline between the two perspectives, as there is not between personal (i.e. physical and psychological) and social harm from drinking as such. But while methods for studying personal harm are fairly well developed, social harm, i.e. adverse consequences of alcohol that involve social interaction, has received less attention. One of the aims of the thesis has been to explore different dimensions of harm from drinking, identify different harm areas and develop and apply area-specific measures using general population survey data. Two papers examine psychometric properties of a widely used screening instrument, the AUDIT (Alcohol Use Disorder Identification Test). While the first paper is concerned with the validity of the AUDIT, testing it against different criteria, the second paper focuses on the test-retest reliability of the instrument. In the third paper, a number of summary measures of different areas of alcohol-related harm are constructed using factor analysis. These measures are then, in the last paper, applied to estimate prevalence and risk of alcohol-related harm in the Swedish general population. The analyses are based on data from a national survey on drinking problems in Sweden collected in 2001-2002. It is concluded that the AUDIT screens well for both impaired self-control and social harm from drinking (as well as for high volume drinking), but performs less well when screening for health problems. The test-retest reliability of the AUDIT is relatively high. In the other two papers, constructing new summary measures and applying them to estimate prevalence of harm, it is concluded that, except for being young, no particular sociodemographic risk groups can be identified for different areas of harm from the same level and pattern of drinking. To what extent this reflects reality or is an effect of the methods we use and kind of population we reach in surveys is discussed.

Des données complexes sont fréquentes dans les essais cliniques récents et nécessitent des méthodes statistiques adaptées. La recherche vaccinale du VIH est un exemple d’un domaine avec des données complexes et une absence de critères de jugement validés dans les essais précoces. Cette thèse d’Université concerne des recherches méthodologiques sur la conception et les aspects statistiques des essais cliniques vaccinaux du VIH, en particulier sur les critères de jugement d’immunogénicité et les schémas d’essai de phase I-II. A l’aide des données cytokiniques multiplex, nous illustrons les aspects méthodologiques spécifiques à une technique de mesure. Nous proposons ensuite des définitions de critères de jugement et des méthodes statistiques adéquates pour l'analyse des données d'immunogénicité multidimensionnelles. En particulier, nous montrons l’intérêt des scores multivariés non-paramétriques, permettant de résumer l’information à travers différents marqueurs d’immunogénicité et de faire des comparaisons inter- et intra-groupe. Dans l’objectif de contribuer à la conception méthodologique des nouveaux essais vaccinaux, nous présentons la construction d’un schéma d’essai optimisé pour le développement clinique précoce. En imbriquant les phases I et II d’évaluation clinique, ce schéma permet d’accélerer le développement de plusieurs stratégies vaccinales en parallèle. L’intégration d’une règle d’arrêt est proposée dans des perspectives fréquentistes et Bayesiennes. Les méthodes mises en avant dans cette thèse sont transposables à d’autres domaines d’application avec des données complexes, telle que les données d’imagerie ou les essais d’autres immunothérapies. / Complex data are frequently recored in recent clinical trials and require the use of appropriate statistical methods. HIV vaccine research is an example of a domaine with complex data and a lack of validated endpoints for early-stage clinical trials. This thesis concerns methodological research with regards to the design and analysis aspects of HIV vaccine trials, in particular the definition of immunogenicity endpoints and phase I-II trial designs. Using cytokine multiplex data, we illustrate the methodological aspects specific to a given assay technique. We then propose endpoint definitions and statistical methods appropriate for the analysis of multidimensional immunogenicity data. We show in particular the value of non-parametric multivariate scores, which allow for summarizing information across different immunogenicity markers and for making statistical comparisons between and within groups. In the aim of contributing to the design of new vaccine trials, we present the construction of an optimized early-stage HIV vaccine design. Combining phase I and II assessments, the proposed design allows for accelerating the clinical development of several vaccine strategies in parallel. The integration of a stopping rule is proposed from both a frequentist and a Bayesian perspective. The methods advocated in this thesis are transposable to other research domains with complex data, such as imaging data or trials of other immune therapies.