Multicentric validation of a Multimorbidity Adjusted Disability Score to stratify depression-related risks using temporal disease maps

In the EU project TRAJECTOME, we used a novel methodology to identify temporal disease maps of depression and highly prevalent co-occurring disease conditions. This information was combined with disability weights established by the Global Burden of Disease Study 2019 to create a depression-related health risk assessment tool, the Multimorbidity Adjusted Disability Score (MADS). MADS was used to stratify over one million cases from three different cohorts and evaluate the impact on utilisation of healthcare resources, mortality, pharmacological burden, healthcare expenditure and multimorbidity progression. Results indicate statistically significant associations between MADS and increased mortality rate (P <.001), heightened healthcare utilization (i.e. emergency room visits P <.001; hospitalizations P <.001; pharmaceutical prescriptions P <.001; total healthcare expenditure P <.001), and a higher risk of disease progression and incidence of new depression-related comorbidities. MADS seems to be a promising approach to predict depression-related health risk and depression’s impact on individuals and healthcare systems, which can be tested in other diseases; nevertheless, clinical validation is still necessary. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The initiative was supported by ERA PerMed program (TRAJECTOME project, ERAPERMED2019-108). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: As a multicentric study, TRAJECTOME accessed multiple cohorts data, all subject to the legal regulations of their respective regions of origin and obtained the necessary approvals from the corresponding ethics committees. For CHSS cohort, the Ethical Committee for Human Research at Hospital Clinic de Barcelona approved the core study of TRAJECTOME on the 24th of March of 2021 (HCB/2020/1051) and subsequently approved the analysis for the generation and validation of MADS on the 25th of July of 2022 (HCB/2022/0720). UK Biobank received ethical approval from the National Research Ethics Service Committee Northwest Haydock (ref. 11/NW/0382). The THL cohort integrates information from the Finrisk databases: 1997 (Ethical committee of National Public Health Institute. Statement 38/96. 30.10.1996), 2002 (Helsinki University Hospital, Ethical committee of epidemiology and public health, Statement 87/2001. Reference 558/E3/2001. 19.12.2001), 2007 (Helsinki University Hospital, Coordinating ethics committee, Dnro HUS 229/EO/2006, 20.6.2006) and 2012 (Helsinki University Hospital, Coordinating ethics committee, Dnro HUS 162/13/03/11, 1.12.2011), the FinHealth 2017 (Helsinki University Hospital, Coordinating ethics committee, 37/13/03/00/2016 22.3.2016) and the Health 2000/2011 databases (Ethical committee of National Public Health Institute, 8/99/12. Helsinki University Hospital, Ethical committee of epidemiology and public health, 407/E3/2000. 31.05.2000 and 17.06.2011). The ethics committees exempted the requirement to obtain informed consent for the analysis, and publication of retrospectively acquired and fully anonymized data in the context of this noninterventional study. All the data was handled in compliance with the General Data Protection Regulation 2016/679, which safeguards data protection and privacy for all individuals in the European Union. The study was conducted in conformity with the Helsinki Declaration (Stronghold Version, Brazil, October 2013) and in accordance with the protocol and the relevant legal requirements (Biomedical Research Act 14/2007 of 3 July). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data for this study are not publicly available due to patient privacy concerns. The scripts used to compute MADS are available from the corresponding author upon reasonable request. * AISBE : Health District of Barcelona-Esquerra AMG : Adjusted Morbidity Groups BDMM : Bayesian Direct Morbidity Maps CHSS : Catalan Health Surveillance System DW : Disability Weights GBD : Global Burden of Disease MADS : Multimorbidity Adjusted Disability Score MCPM : Multisource Clinical Predictive Modelling MDD : Major Depressive Disorder PR : Probability of Relevance THL : Finnish National Institute for Health and Welfare Biobank UKB : United Kingdom Biobank