Life Course Digital Twins–Intelligent Monitoring for Early and Continuous Intervention and Prevention (LifeTIME): Proposal for a Retrospective Cohort Study

\ua9 Madison Milne-Ives, Lorna K Fraser, Asiya Khan, David Walker, Michelle Helena van Velthoven, Jon May, Ingrid Wolfe, Tracey Harding, Edward Meinert. Originally published in JMIR Research Protocols (https://www.researchprotocols.org),26.05.2022. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Research Protocols, is properly cited. The complete bibliographic information, a link to the original publication on https://www.researchprotocols.org, as well as this copyright and license information must be included. Background: Multimorbidity, which is associated with significant negative outcomes for individuals and health care systems, is increasing in the United Kingdom. However, there is a lack of knowledge about the risk factors (including health, behavior, and environment) for multimorbidity over time. An interdisciplinary approach is essential, as data science, artificial intelligence, and engineering concepts (digital twins) can identify key risk factors throughout the life course, potentially enabling personalized simulation of life-course risk for the development of multimorbidity. Predicting the risk of developing clusters of health conditions before they occur would add clinical value by enabling targeted early preventive interventions, advancing personalized care to improve outcomes, and reducing the burden on health care systems. Objective: This study aims to identify key risk factors that predict multimorbidity throughout the life course by developing an intelligent agent using digital twins so that early interventions can be delivered to improve health outcomes. The objectives of this study are to identify key predictors of lifetime risk of multimorbidity, create a series of simulated computational digital twins that predict risk levels for specific clusters of factors, and test the feasibility of the system. Methods: This study will use machine learning to develop digital twins by identifying key risk factors throughout the life course that predict the risk of later multimorbidity. The first stage of the development will be the training of a base predictive model. Data from the National Child Development Study, the North West London Integrated Care Record, the Clinical Practice Research Datalink, and Cerner’s Real World Data will be split into subsets for training and validation, which will be done following the k-fold cross-validation procedure and assessed with the Prediction Model Risk of Bias Assessment Tool (PROBAST). In addition, 2 data sets—the Early-Life Data Cross-linkage in Research study and the Children and Young People’s Health Partnership randomized controlled trial—will be used to develop a series of digital twin personas that simulate clusters of factors to predict different risk levels of developing multimorbidity. Results: The expected results are a validated model, a series of digital twin personas, and a proof-of-concept assessment. Conclusions: Digital twins could provide an individualized early warning system that predicts the risk of future health conditions and recommends the most effective intervention to minimize that risk. These insights could significantly improve an individual’s quality of life and healthy life expectancy and reduce population-level health burdens

Long term extension of a randomised controlled trial of probiotics using electronic health records

Most randomised controlled trials (RCTs) are relatively short term and, due to costs and available resources, have limited opportunity to be re-visited or extended. There is no guarantee that effects of treatments remain unchanged beyond the study. Here, we illustrate the feasibility, benefits and cost-effectiveness of enriching standard trial design with electronic follow up. We completed a 5-year electronic follow up of a RCT investigating the impact of probiotics on asthma and eczema in children born 2005-2007, with traditional fieldwork follow up to two years. Participants and trial outcomes were identified and analysed after five years using secure, routine, anonymised, person-based electronic health service databanks. At two years, we identified 93% of participants and compared fieldwork with electronic health records, highlighting areas of agreement and disagreement. Retention of children from lower socio-economic groups was improved, reducing volunteer bias. At 5 years we identified a reduced 82% of participants. These data allowed the trial's first robust analysis of asthma endpoints. We found no indication that probiotic supplementation to pregnant mothers and infants protected against asthma or eczema at 5 years. Continued longer-term follow up is technically straightforward