Periodic Reporting for period 2 - FundaMentalHM (FundaMentalHM: Innovative methods for better estimation of Fundamental Health Metrics associated with Mental disorders and other general medical conditions) Reporting period: 2021-01-01 to 2021-12-31 Summary of the context and overall objectives of the project The contribution of mental disorders to the Global Burden of Diseases (GBD) Study is now well recognized – mental disorders account for 6.8% of the total burden worldwide. Because the GBD’s health metric Disability-Adjusted Life Year (DALY) combines the impact of both morbidity (Years Lived with Disability; YLDs) and mortality (Years of Life Lost; YLLs), it has foregrounded the previously neglected contribution of mental disorders to the global disease burden. However, this health metric does not account for comorbidity adequately, which leads to an underestimation of excess morbidity and mortality associated with mental disorders. This bias has serious implications for service planning and resource allocation. The focus of FundaMentalHM is to use aggregated data from the GBD Study and register-based individual-level data from the whole Danish population to fill the existing methodological gaps, by developing and applying new methodologies in order to better estimate the burden of mental disorders. FundaMentalHM aims to (i) provide the most comprehensive detailed analysis of comorbidity between mental disorders and other general medical conditions, (ii) advance the area of science related to health metrics by incorporating dependent (instead of independent) comorbidity to the estimates, and (iii) use innovative methods to better estimate the excess mortality associated with mental disorders. In accomplishing FundaMentalHM’s objectives, I will provide a more accurate, unbiased view of the true burden – including true number of deaths – associated with mental disorders. FundaMentalHM has provided the most comprehensive register-based studies on mental health mortality to date with a landmark paper published in The Lancet and cited more than 200 times since it was published in 2019. This study has contributed greatly to the field of psychiatric epidemiology by providing an ‘atlas’ of mortality estimates for a comprehensive range of mental disorders. This paper reports (for the first time) an innovative measure that is better able to capture the impact of mental disorders on life expectancy (compared to relative risks such as Mortality Rate Ratios). Policy makers and politicians can readily understand this type of health measure. In order to facilitate the use of this new metric by other researchers, FundaMentalHM has developed an R package that is freely available online, and which has been downloaded more than 16,500 times and used in several scientific publications since it was released in early 2020. As part of this MSCA project, we have recently led a study published in PLOS Medicine applying this method to 1,800 different health conditions: the ‘Danish Atlas of Disease Mortality’ (http://nbepi.com/atlas). In addition to mortality, FundaMentalHM has also explored other types of outcomes, such as comorbidity. FundaMentalHM's studies on comorbidity (Momen et al. New England Journal of Medicine 2020; Plana-Ripoll et al. World Psychiatry 2020; Momen et al JAMA Psychiatry 2022) have used advanced designs, and have laid the foundations for other projects, not only in mental health, but also in other fields of medicine. Because comorbidity is common across the entire spectrum of health, FundaMentalHM has developed an informative metric (Weye et al. Lancet Psychiatry 2021) that estimates the contribution of (i) an index disorder (e.g. depression), and (ii) comorbid mental and other medical conditions (e.g. alcohol use disorders, diabetes). This measure shows never-before-seen details of the impact of comorbidity on disability. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far All three aims of FundaMentalHM have already been fulfilled. For aim 1, we carried out a comprehensive study investigating the association between all mental disorders and a broad range of medical conditions. This study has been performed in collaboration with my colleague Dr Natalie Momen and has been published in the New England Journal of Medicine. We used data from 5.9 million Danish residents who were followed from 2000 to 2016. Using national registers, we observed that most mental disorders were associated with an increased risk of a subsequent medical condition, and risks varied according to the time since the diagnosis of the mental disorders. Additionally, together with PhD student Nanna Weye, we have estimated register-based years lived with disability associated with mental disorders for the entire Danish population, in a paper that is published in Lancet Psychiatry. For aim 2, we carried out a study investigating the association between all mental disorders and excess mortality. I have been the main author of the paper, which was published in The Lancet. We used data from 7.2 million Danish residents from 1995 to 2015, and we observed that all mental disorders were associated with a reduction in life expectancy, for both men and women (on average 10 years in men and 7 years in women). Additionally, we wrote a research letter to JAMA Psychiatry investigating time trends in life expectancy gap for those with mental disorders. Combining aims 1 and 2, we have performed several studies (that were not originally planned in my grant proposal) looking at the association between comorbid conditions and later mortality (Plana-Ripoll et al. World Psychiatry 2020; Momen et al JAMA Psychiatry 2022. For aim 3, we have created two new health metrics that can be applied for a better understanding of disease burden. For the mortality papers, we used a new metric to estimate life expectancy that overcomes some of the limitations of the metrics used in the past (for example we were able to use the observed age of onset, instead of a fixed age of onset). In order to make this new methodology available to a broader range of researchers, I developed a statistical package that is freely available. Additionally, we wrote a tutorial that was published open access in Plos One. We have now applied this metric to 1,800 different health conditions (Plana-Ripoll et al. PLOS Medicine 2022). For comorbidity, we have developed an informative metric (Weye et al. Lancet Psychiatry 2021) that estimates the contribution of (i) an index disorder (e.g. depression), and (ii) comorbid mental and other medical conditions (e.g. alcohol use disorders, diabetes). This measure shows never-before-seen details of the impact of comorbidity on disability. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) My work has demonstrated that the burden of mental disorders has been systematically underestimated. And more importantly, the relevance of comorbidity on the course of health conditions has been largely ignored. All three aims have gone well beyond the state of the art, providing comprehensive results that have had an impact on research. For example, other researchers are now using the same innovative design and statistical analyses that we developed to investigate other types of comorbidity and mortality associated with health conditions. Finally, my research has an impact on policy and practice – the Danish Health Authority has presented a 10-year plan for psychiatry, and evidence behind this work comes directly from our recent studies. I am also a collaborator of the GBD Study, which is one of the most important resources for informed policymaking worldwide. Life years lost in individuals with schizophrenia
