Periodic Reporting for period 1 - SCOUT (Supporting Causal Conclusions from Observational Survival Studies)
Periodo di rendicontazione: 2018-10-01 al 2020-09-30
This Marie Skłodowska Curie Action (MSCA) titled ‘Supporting Causal Conclusions from Observational Survival Studies” (SCOUT) falls within the field of biostatistics. Broadly speaking, the challenges of a biostatistician either concern (1)prediction: quantifying how likely it is for an individual with certain characteristics (age, sex, blood lipids) to develop a certain disease (coronary heart disease) in, say, 10 years or (2) explanation: quantifying how much a certain intervention (e.g. lowering cholesterol levels with a defined statin prescription) would change the risk of developing the disease or (3) description: describing empirical associations in a dataset. As hinted in the title of this MSAC a major focus lay on explanation, also often denoted as ‘causal inference’. Particularly, we were not just interested in quantifying the effect of an intervention, but rather in decomposing the total effect into direct and indirect components (e.g. how much of the effect of the statin use is explained through a reduction in cholesterol and, are there other, perhaps more direct, effects of the intervention). In clinical studies such analyses can help to elucidate an underlying mechanism, to alter and further improve its components, or even to shift its target. Another key interest lay in the comparison of different models for time-to-event data. Such data occur in clinical or epidemiological research when one is interested in the time from an intervention to the occurrence of a particular event, but due to several constrains cannot observe the event in every individual. The most popular model to analyse such data is Cox’s proportional hazards model, mainly due its seemingly easy-to-report outcome measure. However, for causal inference an alternative model, Aalen’s additive hazards model, gained relevance, while the literature on its performance in prediction tasks is sparse. Therefore, we investigated gains and difficulties of these models in clinical case studies, archetypical for prediction and causal inference tasks. The work was carried out at the Section for Clinical Biometrics at the Medical University of Vienna (MUW) under the supervision of Assoc. Prof. Georg Heinze and led to a vibrant two-way transfer of knowledge between myself, my supervisor and the entire Prognosis Research Group.
The objectives of this MSCA were to (a) to utilize penalised likelihood techniques in an innovative way to improve mediation analysis with sparse data, e.g rare side effects of interventions and (b) to compare the Aalen additive hazards model to the more widely used Cox proportional hazards model in a series of case studies regarding the interpretability of effect estimates, ease of application and applicability of assumptions. Another milestone goal was to foster my career development.
The objectives and goals were addressed via 6 work packages (WPs) with specific tasks: (1) WP1 concerned mediation analysis techniques for sparse data. The WP resulted in 1 published paper and another manuscript is already submitted. Two further manuscripts are underway. Presentations of preliminary results were accepted for poster presentations at 2 conferences, however these events are postponed due to the COVID19 pandemic. (2) WP2 focused on the comparison of the Cox and Aalen models in practice. We published 1 paper, 2 manuscripts are underway. The results were presented in 2 poster presentations and 1 oral presentation at international conferences. (3) WP3 was reserved for a secondment period; Working on WP2 it became clear that stay at the Oslo Center of Biostatistics and Epidemiology would be beneficial. The stay was cut short due to the pandemic. Further travel restriction led to plan adaptions so that I would gain experience in the private sector at the Austrian branch of SAS (Statistical Analysis Systems), a multinational software company dealing with data warehousing, statistical analysis pipelines and statistical consulting. I took part in several company activities, such as the newcomer session and the regular meetings of the SAS DACH (Germany-Austria-Switzerland) community, where I also presented my research activities. This led to a joint project with the manufacturing branch on minimizing the vibrations in a cement mill. We summarized our experience in a presentation to the community. (4) WP 4 involved participation in courses offered by the MUW’s Human Resources Development department. I chose courses on English writing skills, intellectual property rights and project management, ethics in medicine and good scientific practice and will participate in pandemic-postponed course next spring. (5) The focus of WP5 was my future career development. To gain more experience in the full range of academic job tasks, I taught 4 different courses, 3 compulsory courses for the medical program and 1 course for the public health doctoral program. Further, I contributed 15 review reports for high level methodological journals as well as applied journals within neurobiology, nephrology, atherosclerosis or cancer research. Within a collaboration with the Department of Epidemiology at the MUW I could gain supervision experience and also contribute my methodological expertise in 5 published manuscripts. Ultimately, this fruitful collaboration led to my new job post. (6) WP 6 was about networking, communication and dissemination. I presented my work in 2 oral presentations, and 4 poster presentations were accepted at international conferences. In 4 presentations I reached audiences working in public health, statisticians working in pharmaceutical industry and regulatory institutions and members from SAS business analytics or marketing departments. I was appointed ‘secretary’ of the Viennese Biometric Section of the Austro-Swiss Region of the International Biometric Society. Together with the organisation’s president, we coordinated 24 colloquium talks and 3 workshops and organized an interdisciplinary seminar on ‘Update in Evidence Synthesis Methods – Current Topics in Meta-analysis’ with eight national and international speakers. Overall, the goals of the MSCA IF proposal were met, despite secondment adjustments due to the COVID19 pandemic.
The objectives and goals were addressed via 6 work packages (WPs) with specific tasks: (1) WP1 concerned mediation analysis techniques for sparse data. The WP resulted in 1 published paper and another manuscript is already submitted. Two further manuscripts are underway. Presentations of preliminary results were accepted for poster presentations at 2 conferences, however these events are postponed due to the COVID19 pandemic. (2) WP2 focused on the comparison of the Cox and Aalen models in practice. We published 1 paper, 2 manuscripts are underway. The results were presented in 2 poster presentations and 1 oral presentation at international conferences. (3) WP3 was reserved for a secondment period; Working on WP2 it became clear that stay at the Oslo Center of Biostatistics and Epidemiology would be beneficial. The stay was cut short due to the pandemic. Further travel restriction led to plan adaptions so that I would gain experience in the private sector at the Austrian branch of SAS (Statistical Analysis Systems), a multinational software company dealing with data warehousing, statistical analysis pipelines and statistical consulting. I took part in several company activities, such as the newcomer session and the regular meetings of the SAS DACH (Germany-Austria-Switzerland) community, where I also presented my research activities. This led to a joint project with the manufacturing branch on minimizing the vibrations in a cement mill. We summarized our experience in a presentation to the community. (4) WP 4 involved participation in courses offered by the MUW’s Human Resources Development department. I chose courses on English writing skills, intellectual property rights and project management, ethics in medicine and good scientific practice and will participate in pandemic-postponed course next spring. (5) The focus of WP5 was my future career development. To gain more experience in the full range of academic job tasks, I taught 4 different courses, 3 compulsory courses for the medical program and 1 course for the public health doctoral program. Further, I contributed 15 review reports for high level methodological journals as well as applied journals within neurobiology, nephrology, atherosclerosis or cancer research. Within a collaboration with the Department of Epidemiology at the MUW I could gain supervision experience and also contribute my methodological expertise in 5 published manuscripts. Ultimately, this fruitful collaboration led to my new job post. (6) WP 6 was about networking, communication and dissemination. I presented my work in 2 oral presentations, and 4 poster presentations were accepted at international conferences. In 4 presentations I reached audiences working in public health, statisticians working in pharmaceutical industry and regulatory institutions and members from SAS business analytics or marketing departments. I was appointed ‘secretary’ of the Viennese Biometric Section of the Austro-Swiss Region of the International Biometric Society. Together with the organisation’s president, we coordinated 24 colloquium talks and 3 workshops and organized an interdisciplinary seminar on ‘Update in Evidence Synthesis Methods – Current Topics in Meta-analysis’ with eight national and international speakers. Overall, the goals of the MSCA IF proposal were met, despite secondment adjustments due to the COVID19 pandemic.
The anticipated impacts of the MSCA concerned, enhancement of my future career prospects, high quality measures to exploit and disseminate the results and communication of the action’s activities to different target audiences, which were all achieved. During the fellowship I broadened my academic network to include researchers from the Departments of Epidemiology, Nephrology, General Gynecology/Gynecologic Oncology and the Clinical Division of Hematology at the MUW. These interdisciplinary activities allowed to promote causal inference concepts in various clinical disciplines. Ultimately, we hope this will improve study designs and analysis strategies of future research projects as well as critical appraisal of previous and published work in the reached communities. Further, I worked together with colleagues from the Leiden University Medical Center and the University of Utrecht as well as other members of Prof. Heinze`s international network, while I maintained my professional ties with previous colleagues in Norway, Denmark and Boston. Currently we are working towards establishing a joint research group to strengthen the Austrian research environment with our combined knowledge in epidemiological methods.