Multidisciplinary Ecosystem to study Lifecourse Determinants and Prevention of Early-onset Burdensome Multimorbidity (MELD-B)

Background Multimorbidity occurs earlier in the lifecourse among people from more disadvantaged backgrounds.

Wider determinants such as education and work influence development of long-term physical and mental health conditions (LTCs) across the lifecourse. Sequence of accrual of conditions varies considerably and influences outcomes. Sentinel conditions (the first LTC to occur in the lifecourse) may play an important role.

Understanding how wider determinants, sentinel conditions and LTC accrual sequence affect risk of early-onset burdensome/complex multiple LTC multimorbidity (MLTC-M) is vital to inform when and how to deploy prevention interventions.

Data at sufficient scale linking whole lifecourse events, including wider determinants, with clinical information is lacking.Through our Development Award ( MELD ) we established the necessary environment, principles, systems, methods and team to use artificial intelligence (AI) techniques to study lifecourse causes of early-onset MLTC-M.

The aim for our Research Collaboration is to safely deliver an Artificial Intelligence (AI)-enhanced epidemiological analytic system in which optimal lifecourse time points and targets for prevention of early-onset, burdensome MLTC-M are identified through multidisciplinary synthesis and analysis of birth cohorts and electronic health records, and disseminated to key stakeholders.

Methods - five Work-Packages (WP): Through qualitative evidence synthesis and a consensus study we will develop deeper understanding of what burdensomeness and complexity mean to people living with early-onset (by age 65) MLTC-M, carers and healthcare professionals, and produce a suite of burdensomeness/complexity indicators for use as clustering domains in routine healthcare data.(WP1–lead Fraser) We will provide the safe data environment and readiness for AI analyses across large, representative routine healthcare datasets (Secure Anonymised Information Linkage (SAIL) and Clinical Practice Research Datalink (CPRD)) and birth cohorts (National Child Development Study (NCDS), Aberdeen Children of the 1950s (ACONF), 1970 British Cohort Study (BCS70)), then harmonise specified LTCs across birth cohorts and routine data.(WP2–lead Boniface) Using the WP1 burdensomeness/complexity indicators, we will apply AI methods to identify novel early-onset, burdensome MLTC-M clusters and sentinel conditions in routine data, develop and apply semi-supervised learning to match individuals in birth cohorts into routine data MLTC-M clusters, identify determinants of burdensome clusters using matched datasets, and model trajectories of LTC and burden accrual.(WP3–lead Hoyle) We will characterise clusters of early-life (pre-birth to 18-years) risk factors for early-onset, burdensome MLTC-M and sentinel conditions, define population groups in early life at risk of future MLTC-M, identify critical time points and targets for prevention, and model counterfactual prevention scenarios of interventions acting on combined risk factors at key timepoints.(WP4–lead Alwan).

We will investigate the influence of sentinel conditions and sequence of determinant and condition accrual on development of early-onset, burdensome MLTC-M clusters and compare AI and causal inference modelling for potential preventable moments across the lifecourse (WP3/4). Patient and public involvement is embedded throughout.

Timeline: 30 months from April 2022 Impact and Dissemination We will identify and engage key stakeholders to explore timepoints and targets to prevent/delay specified sentinel conditions and early-onset, burdensome MLTC-M.

Partnering with our PPI Advisory Board, and maintaining stakeholder engagement, we will co-produce public health implementation recommendations based on our findings.(WP5(cross-cutting)–lead Wilkinson).