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Sweden has numerous linkable registers which are a goldmine for research in the ̽»¨¾«Ñ¡ and social sciences. However, as increasingly more complex research questions are being addressed, there are challenges to correctly and efficiently analyse such data, and further methods development is needed. We aim to develop and apply methods for register-based research that are relevant for a wide range of settings. We also aim to transfer new methodology to subject-matter scientists and train the next generation of biostatistical scientists. The long-term goal is to leverage the rich information within the registers for the benefit of patients, policy-makers and society. Specifically, we will develop, evaluate and apply methods for:1. Missing data in registers2. Causal mediation analysis3. Policy-relevant complex disease models and lifetime outcomes in health economics 4. Federated analyses and synthetic data to share information.Our proposal focuses on the development of statistical methods, but each aim is motivated by real problems in medicine and social science, e.g. improving cancer screening, understanding causal mechanisms for social inequalities in cancer survival, time trends in disease incidence trends and situations when individual-level data cannot cross borders. Our team of biostatistical scientists will work in close collaboration with an extended network of Swedish and Nordic register holders, epidemiologists, clinical and social scientists, and relevant stakeholders.

Our general aim is to use modelling to reduce the burden due to prostate and cervical cancer through cost-effective screening. For prostate cancer, new tests, magnetic resonance imaging (MRI) and artificial intelligence (AI) assisted pathology are expected to reduce harms while maintaining the mortality benefits from early detection. For cervical cancer, human papillomavirus (HPV) vaccinations are expected to substantially reduce HPV incidence and eventually lead to the eradication of cervical cancer. With changes to HPV transmission, cervical cancer screening may require extended genotyping, self-sampling and renewed guidelines to be cost-effective.We will evaluate the cost-effectiveness of: (i) organised prostate cancer testing (OPT) in Sweden, including MRI and the Stockholm3 test

(ii) prostate cancer testing using a genetic risk score

(iii) prostate cancer diagnostics using AI-assisted pathology

and (iv) primary HPV testing with extended genotyping in vaccinated cohorts with clinic-based testing or self-sampling. These results will inform policy for (a) the development and planning of a national OPT program, (b) the use of AI-assisted histopathology, and (c) the development of national cervical cancer screening guidelines for vaccinated cohorts.