Harmonising electronic health records for reproducible research: challenges, solutions and recommendations from a UK-wide COVID-19 research collaboration.

BACKGROUND: The CVD-COVID-UK consortium was formed to understand the relationship between COVID-19 and cardiovascular diseases through analyses of harmonised electronic health records (EHRs) across the four UK nations. Beyond COVID-19, data harmonisation and common approaches enable analysis within and across independent Trusted Research Environments. Here we describe the reproducible harmonisation method developed using large-scale EHRs in Wales to accommodate the fast and efficient implementation of cross-nation analysis in England and Wales as part of the CVD-COVID-UK programme. We characterise current challenges and share lessons learnt. METHODS: Serving the scope and scalability of multiple study protocols, we used linked, anonymised individual-level EHR, demographic and administrative data held within the SAIL Databank for the population of Wales. The harmonisation method was implemented as a four-layer reproducible process, starting from raw data in the first layer. Then each of the layers two to four is framed by, but not limited to, the characterised challenges and lessons learnt. We achieved curated data as part of our second layer, followed by extracting phenotyped data in the third layer. We captured any project-specific requirements in the fourth layer. RESULTS: Using the implemented four-layer harmonisation method, we retrieved approximately 100 health-related variables for the 3.2 million individuals in Wales, which are harmonised with corresponding variables for > 56 million individuals in England. We processed 13 data sources into the first layer of our harmonisation method: five of these are updated daily or weekly, and the rest at various frequencies providing sufficient data flow updates for frequent capturing of up-to-date demographic, administrative and clinical information. CONCLUSIONS: We implemented an efficient, transparent, scalable, and reproducible harmonisation method that enables multi-nation collaborative research. With a current focus on COVID-19 and its relationship with cardiovascular outcomes, the harmonised data has supported a wide range of research activities across the UK.

Validating the QCOVID risk prediction algorithm for risk of mortality from COVID-19 in the adult population in Wales, UK.

Introduction: COVID-19 risk prediction algorithms can be used to identify at-risk individuals from short-term serious adverse COVID-19 outcomes such as hospitalisation and death. It is important to validate these algorithms in different and diverse populations to help guide risk management decisions and target vaccination and treatment programs to the most vulnerable individuals in society. Objectives: To validate externally the QCOVID risk prediction algorithm that predicts mortality outcomes from COVID-19 in the adult population of Wales, UK. Methods: We conducted a retrospective cohort study using routinely collected individual-level data held in the Secure Anonymised Information Linkage (SAIL) Databank. The cohort included individuals aged between 19 and 100 years, living in Wales on 24th January 2020, registered with a SAIL-providing general practice, and followed-up to death or study end (28th July 2020). Demographic, primary and secondary healthcare, and dispensing data were used to derive all the predictor variables used to develop the published QCOVID algorithm. Mortality data were used to define time to confirmed or suspected COVID-19 death. Performance metrics, including R2 values (explained variation), Brier scores, and measures of discrimination and calibration were calculated for two periods (24th January-30th April 2020 and 1st May-28th July 2020) to assess algorithm performance. Results: 1,956,760 individuals were included. 1,192 (0.06%) and 610 (0.03%) COVID-19 deaths occurred in the first and second time periods, respectively. The algorithms fitted the Welsh data and population well, explaining 68.8% (95% CI: 66.9-70.4) of the variation in time to death, Harrell's C statistic: 0.929 (95% CI: 0.921-0.937) and D statistic: 3.036 (95% CI: 2.913-3.159) for males in the first period. Similar results were found for females and in the second time period for both sexes. Conclusions: The QCOVID algorithm developed in England can be used for public health risk management for the adult Welsh population.