Multidisciplinary ecosystem to study lifecourse determinants and prevention of early-onset burdensome multimorbidity (MELD-B) - protocol for a research collaboration

Simon Ds Fraser^{1

2}, Sebastian Stannard¹, Emilia Holland¹, Michael Boniface³, Rebecca B Hoyle⁴, Rebecca Wilkinson⁵, Ashley Akbari⁶, Mark Ashworth⁷, Ann Berrington⁸, Roberta Chiovoloni⁶, Jessica Enright⁹, Nick A Francis¹, Gareth Giles¹⁰, Martin Gulliford⁷, Sara Macdonald¹¹, Frances S Mair¹¹, Rhiannon K Owen⁶, Shantini Paranjothy^{12

13}, Heather Parsons¹⁴, Ruben J Sanchez-Garcia^{4

15}, Mozhdeh Shiranirad⁴, Zlatko Zlatev³, Nisreen Alwan^{1

14

16

2}

Affiliations

¹ School of Primary Care, Population Sciences and Medical Education, Faculty of Medicine, Southampton General Hospital, Southampton, UK.
² NIHR Applied Research Collaboration Wessex, Southampton, UK.
³ School of Electronics and Computer Science, University of Southampton, Southampton, UK.
⁴ School of Mathematical Sciences, University of Southampton, Southampton, UK.
⁵ Southampton City Council, Southampton, UK.
⁶ Population Data Science, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, UK.
⁷ School of Life Course and Population Sciences, King's College London, London, UK.
⁸ Department of Social Statistics and Demography, University of Southampton, Southampton, UK.
⁹ Computing Science, University of Glasgow, Glasgow, UK.
¹⁰ Public Policy Southampton, University of Southampton, Southampton, UK.
¹¹ School of Health and Wellbeing, General Practice and Primary Care, University of Glasgow, Glasgow, UK.
¹² School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
¹³ NHS Grampian Health Board, Aberdeen, UK.
¹⁴ Patient and Public Involvement and Engagement, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
¹⁵ The Alan Turing Institute, London, UK.
¹⁶ NIHR Southampton Biomedical Research Centre, Southampton, UK.

PMID: 37766757
PMCID: PMC10521301
DOI: 10.1177/26335565231204544

Multidisciplinary ecosystem to study lifecourse determinants and prevention of early-onset burdensome multimorbidity (MELD-B) - protocol for a research collaboration

Simon Ds Fraser et al. J Multimorb Comorb. 2023.

. 2023 Sep 25:13:26335565231204544.

doi: 10.1177/26335565231204544. eCollection 2023 Jan-Dec.

Authors

Affiliations

¹ School of Primary Care, Population Sciences and Medical Education, Faculty of Medicine, Southampton General Hospital, Southampton, UK.
² NIHR Applied Research Collaboration Wessex, Southampton, UK.
³ School of Electronics and Computer Science, University of Southampton, Southampton, UK.
⁴ School of Mathematical Sciences, University of Southampton, Southampton, UK.
⁵ Southampton City Council, Southampton, UK.
⁶ Population Data Science, Swansea University Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea, UK.
⁷ School of Life Course and Population Sciences, King's College London, London, UK.
⁸ Department of Social Statistics and Demography, University of Southampton, Southampton, UK.
⁹ Computing Science, University of Glasgow, Glasgow, UK.
¹⁰ Public Policy Southampton, University of Southampton, Southampton, UK.
¹¹ School of Health and Wellbeing, General Practice and Primary Care, University of Glasgow, Glasgow, UK.
¹² School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.
¹³ NHS Grampian Health Board, Aberdeen, UK.
¹⁴ Patient and Public Involvement and Engagement, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
¹⁵ The Alan Turing Institute, London, UK.
¹⁶ NIHR Southampton Biomedical Research Centre, Southampton, UK.

PMID: 37766757
PMCID: PMC10521301
DOI: 10.1177/26335565231204544

Abstract

Background: Most people living with multiple long-term condition multimorbidity (MLTC-M) are under 65 (defined as 'early onset'). Earlier and greater accrual of long-term conditions (LTCs) may be influenced by the timing and nature of exposure to key risk factors, wider determinants or other LTCs at different life stages. We have established a research collaboration titled 'MELD-B' to understand how wider determinants, sentinel conditions (the first LTC in the lifecourse) and LTC accrual sequence affect risk of early-onset, burdensome MLTC-M, and to inform prevention interventions.

Aim: Our aim is to identify critical periods in the lifecourse for prevention of early-onset, burdensome MLTC-M, identified through the analysis of birth cohorts and electronic health records, including artificial intelligence (AI)-enhanced analyses.

Design: We will develop deeper understanding of 'burdensomeness' and 'complexity' through a qualitative evidence synthesis and a consensus study. Using safe data environments for analyses across large, representative routine healthcare datasets and birth cohorts, we will apply AI methods to identify early-onset, burdensome MLTC-M clusters and sentinel conditions, develop semi-supervised learning to match individuals across datasets, identify determinants of burdensome clusters, and model trajectories of LTC and burden accrual. We will characterise early-life (under 18 years) risk factors for early-onset, burdensome MLTC-M and sentinel conditions. Finally, using AI and causal inference modelling, we will model potential 'preventable moments', defined as time periods in the life course where there is an opportunity for intervention on risk factors and early determinants to prevent the development of MLTC-M. Patient and public involvement is integrated throughout.

Keywords: Life course; artificial intelligence; birth cohorts; burdensome; complex; health; long-term conditions; multimorbidity; prevention; routine healthcare datasets.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RKO is a member of the National Institute for Health and Care Excellence (NICE) Technology Appraisal Committee, member of the NICE Decision Support Unit (DSU), and associate member of the NICE Technical Support Unit (TSU). She has served as a paid consultant to the pharmaceutical industry, providing unrelated methodological advice. She reports teaching fees from the Association of British Pharmaceutical Industry (ABPI) and the University of Bristol.

Figures

**Figure 1.**
Study work package structure.

**Figure 2.**
MELD-B research collaboration outputs by work package.

See this image and copyright information in PMC

Cited by

Capturing the human impact of living with multiple long-term conditions in routine electronic health records - lost in translation?
Fraser SDS, Holland E, Laidlaw L, Francis NA, Macdonald S, Mair FS, Alwan NA, Boniface M, Hoyle RB, Fair N, Dylag JJ, Shiranirad M, Chiovoloni R, Stannard S, Poole R, Akbari A, Ashworth M, Dregan A. Fraser SDS, et al. J Multimorb Comorb. 2025 Apr 1;15:26335565251329869. doi: 10.1177/26335565251329869. eCollection 2025 Jan-Dec. J Multimorb Comorb. 2025. PMID: 40176980 Free PMC article.
A conceptual framework for characterising lifecourse determinants of multiple long-term condition multimorbidity.
Stannard S, Berrington A, Paranjothy S, Owen R, Fraser S, Hoyle R, Boniface M, Wilkinson B, Akbari A, Batchelor S, Jones W, Ashworth M, Welch J, Mair FS, Alwan NA. Stannard S, et al. J Multimorb Comorb. 2023 Sep 3;13:26335565231193951. doi: 10.1177/26335565231193951. eCollection 2023 Jan-Dec. J Multimorb Comorb. 2023. PMID: 37674536 Free PMC article.
Mapping domains of early life determinants of future multimorbidity across three UK longitudinal cohort studies.
Stannard S, Berrington A, Fraser SDS, Paranjothy S, Hoyle RB, Owen RK, Akbari A, Shiranirad M, Chiovoloni R, Alwan NA. Stannard S, et al. Sci Rep. 2024 Sep 13;14(1):21454. doi: 10.1038/s41598-024-72275-5. Sci Rep. 2024. PMID: 39271760 Free PMC article.
The impact of living with multiple long-term conditions (multimorbidity) on everyday life - a qualitative evidence synthesis.
Holland E, Matthews K, Macdonald S, Ashworth M, Laidlaw L, Cheung KSY, Stannard S, Francis NA, Mair FS, Gooding C, Alwan NA, Fraser SDS. Holland E, et al. BMC Public Health. 2024 Dec 18;24(1):3446. doi: 10.1186/s12889-024-20763-8. BMC Public Health. 2024. PMID: 39696210 Free PMC article.
Cohort profile: creation of the SAIL MELD-B e-cohort (SMC) and SAIL MELD-B children and young adult e-cohort (SMYC) to investigate the lived experience of the 'burdensomeness' of multimorbidity.
Chiovoloni R, Dylag JJ, Alwan NA, Berrington A, Boniface M, Fair N, Holland E, Hoyle R, Shiranirad M, Stannard S, Zlatev Z, Owen RK, Fraser S, Akbari A. Chiovoloni R, et al. BMJ Open. 2025 Jan 7;15(1):e087946. doi: 10.1136/bmjopen-2024-087946. BMJ Open. 2025. PMID: 39773797 Free PMC article.

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Multidisciplinary ecosystem to study lifecourse determinants and prevention of early-onset burdensome multimorbidity (MELD-B) - protocol for a research collaboration

Affiliations

Multidisciplinary ecosystem to study lifecourse determinants and prevention of early-onset burdensome multimorbidity (MELD-B) - protocol for a research collaboration

Authors

Affiliations

Abstract

Conflict of interest statement

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