By COVID-19 LH&W National Core Study, on 14 March 2022
By Robin Flaig
The UK Longitudinal Linkage Collaboration (UK LLC) is a national resource for COVID-19 research. It’s a new and globally unique Trusted Research Environment (TRE) that offers predictable and efficient access to longitudinal data for researchers and analysts across the UK. Through a single application the UK LLC TRE offers pre-pandemic and pandemic data from more than 20 longitudinal population studies linked with health data.
These data are provided by over 200,000 participants who volunteer to be part of their studies. This work wouldn’t be possible without their participation and willingness to offer insights into many aspects of their lives for the benefit of others. The studies retain control of who can access their participants’ linked data and all permissions set by participants remain in place.
Robin Flaig, Deputy Director of the UK LLC, talks us through how the idea for this new resource has been bubbling for many years and how the coronavirus pandemic accelerated its development.
The idea for what would eventually become the UK Longitudinal Linkage Collaboration (UK LLC) that we have today was something that has been talked about for over a decade across the longitudinal research community.
“There must be a simpler way to link data”
“There must be a quicker way to link data”
“There must be a more efficient way to link data”
I worked for UK Biobank for 7 years running their linkage programme. What became clear is that linking data is hard but is absolutely crucial for participant follow up in longitudinal studies and helping ensure those harder-to-reach can be included. It was clear to me that this was a problem that needed solving. At the same time, Andy Boyd – now UK LLC Director, who was then leading the Data Linkage Team at ALSPAC (Avon Longitudinal Study of Parents and Children) and leading on data linkage at CLOSER – was facing the same sorts of challenges. He led work with Garry Coleman (then Service Director of Data Dissemination at NHS Digital) on how to create a solution for studies in relation to onward sharing of linked data. I attended a meeting where this was discussed and Andy and I had many more discussions around the challenges of data linkage, in particular the challenges of linking to GP data.
The longitudinal research community had often talked about the complexities involved in being able to link study participants data so while the pandemic certainly resulted in this infrastructure being put in place urgently, the need for a more efficient and effective way was identified much earlier.
As a result of these ongoing discussions there was a theoretical plan for how this new, efficient, effective and innovative piece of infrastructure could be created.
At the start of the pandemic, the longitudinal research community realised they had an important role to play by asking their study participants how the pandemic was affecting them. At this point in time, I had moved to work as Chief Operations Officer of Generation Scotland. Mary De Silva (then Head of the Longitudinal Research Strategy at Wellcome Trust) asked Generation Scotland and ALSPAC to lead the development of a COVID-19 questionnaire and as part of this funding she asked Andy and I to develop a substantive proposal to create the concept for the UK LLC. This was done in collaboration with the studies, with whom we were already collaborating on the work around the questionnaire development. This funding provided us with a part-time researcher, Jazz Croft to help us get our plan off the ground.
Mary had been working with MRC/ESRC on an initiative called ‘Population Research UK’ which is being designed to develop more effective and joined up ways of working across the longitudinal research community.
We undertook discussions with many key individuals across the UK longitudinal population community. We named this group the ‘Vanguard’, leading the way on bringing all the necessary expertise together to build this new piece of infrastructure and lay out our vision for the road ahead. In a very short space of time, this group co-designed the protocol, agreed our name and put the building blocks in place to create the UK Longitudinal Linkage Collaboration. The first Vanguard members included Andy and myself representing ALSPAC and Generation Scotland and representatives from 1970 BCS, Born in Bradford, ELSA, EXCEED, GLAD, Millennium Cohort Study, NCDS58, Next Steps, NSHD46, SABRE, TwinsUK and Understanding Society. We all reached out to key individuals to consult on what considerations were critical to successfully build a safe and secure Trusted Research Environment housing study data that linked to other types of data. This brought in expertise from those developing systems for sharing NHS data, such as David Ford from the SAIL Databank, Garry Coleman from NHS Digital and both Cathie Sudlow and David Seymour from HDR UK.
Their input, guidance and support was critical for this collaboration to have any chance of success. I’m delighted to say that the desire and motivation from studies was strong, and we believed we had a strong and viable proposition to build the UK LLC.
As the pandemic continued to take hold and its severity became evident. The country looked to science for answers. One of the many calls that our country’s scientists answered was to set up the National Core Studies – at the request of Sir Patrick Vallance, the government’s Chief Scientific Adviser. Six National Core Studies (NCS) were established in response to the coronavirus pandemic including the COVID-19 Longitudinal Health and Wellbeing NCS – where the UK LLC now is embedded.
This idea that we’d talked about for more than a decade could now be a critical part of building a new research resource to help scientists and policy makers respond to the pandemic. And to make sure our preparedness for future pandemics, was as robust, flexible and responsive as possible. And to create a resource that can be used for other purposes too, including climate change, impacts of financial uncertainty and a myriad of other potential uses.
Our application to be part of the Longitudinal Health and Wellbeing NCS was funded in October 2020 for an initial period of 6 months to see if we could put the infrastructure in place. This study has six other research themes in addition to the UK LLC. These are healthcare disruption; mental health; society and health; vaccination; serology and long-Covid and you can read more about the impact of this work on their website: National Core Study | COVID-19 Longitudinal Health and Wellbeing National Core Study – UCL – University College London
So this really was happening! After an incredibly intense period of time getting to this point we now had the green light to set up a brand new way of working. Challenging at the best of times but like the rest of the country, delivering this work in the midst of a pandemic was truly daunting. However, Andy and I had a clear plan and set about building a team who could help us achieve our goals. Time for a deep breath.
We have a series of blogs written by our team on their own experiences of joining the UK LLC and using their expertise to build our infrastructure. Look out for these on the UK LLC website to hear more about our story.
Andy and I would like to thank the following people for their contributions to the creation of the UK LLC:
UK LLC Vanguard Group, David Seymour, David Ford, Cathie Sudlow, Martin Tobin, Mary De Silva, John McLeod, Jonathan Sterne, Nish Chaturvedi, Nic Timpson, David Porteous, Garry Coleman.
About the UK Longitudinal Linkage Collaboration:
A new way of working for record linkage in longitudinal research.
A four-nations and interdisciplinary infrastructure for secure cross-cohort analysis – with regularly refreshed linkages of COVID-19-relevant health records (geo-spatial linkages underway, administrative data linkages planned for the future)
Aligning complex and divergent governance frameworks into a streamlined and predictable linkage/access route for researchers studying COVID-19 as a disease and the impacts of the pandemic.
Developing a sustainable data science infrastructure that is inclusive of the wider UK LPS community, is responsive to emerging demands, and can inform crisis management and policy maker requirements.
By COVID-19 LH&W National Core Study, on 9 December 2021
Update from the Convalescence team.
Over 100 participants have been enrolled to take part in the Convalescence Deep Phenotyping Clinic!
What is the Convalescence Study? The NIHR/UKRI funded Convalescence study (Characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19: providing the evidence base for health care services) aims to help define, diagnose, and describe long COVID, to better understand the mechanisms of long COVID, and ultimately inform recovery methods and healthcare.
This is being achieved by using national anonymised linked primary care electronic health records, and longitudinal population studies (LPS) that include people of all ages across the UK. A wealth of data including health and socioeconomic information has been collected on LPS participants for many years before the pandemic. During the pandemic we have asked about physical health, long COVID, mental health and wellbeing, social and economic circumstances and lifestyle; via questionnaires.
From these LPS, we are asking people reporting long COVID, and comparator groups, to wear a wrist band measuring exercise ability, breathing, and heart rate, and to complete online questionnaires on mental health and cognitive function. They are also being invited to our deep phenotyping clinic at UCL for non-invasive imaging to look at potential damage to vital organs, such as the brain, lungs and heart. The clinic is aiming to recruit 800 participants over two years.
What sets this study apart from other long COVID studies? Recruiting from existing LPS, that span the UK, is a major strength of this work. Firstly, these cohorts include people who have not consulted with health care services for their long COVID symptoms, enhancing generalisability of findings. Secondly, as detailed, pre-pandemic data has been captured on all individuals, this will help to identify the true effects of infection on disease, as opposed to progression of underlying ill-health, or indeed the general impact of government policies to contain the virus, such as lockdown and furlough which have also impacted long term health.
Deep Phenotyping Clinic The study has begun recruitment from the TwinsUK study, and is aiming to begin recruitment from other cohort studies including Children of the 90s (ALSPAC), Born in Bradford, and Generation Scotland in the coming months. 50 participants have already attended a clinic appointment at UCL’s Bloomsbury Centre for Clinical Phenotyping.
During the visit, participants undertake the following tests:
- Lung function using spirometry
- Resting heart rate variability and electrocardiogram (ECG), lying, seated, standing brachial and central blood pressure (BP)
- Cardiopulmonary exercise testing, including assessment of peak VO2, 12 lead ECG, blood pressure, muscle perfusion using near infrared spectroscopy, echocardiographic cardiac output and pre- post exercise lactate
- Retinal Optical Coherence Tomography angiography
- Strength and physical performance
- Blood and urine samples for storage
Watch the participant clinic visit video here:
Feedback from the participants have been very positive, with one participant commenting: “To be involved in cutting edge research is a privilege. Also, useful to find out more about my health and fitness”
A huge thank you to everyone who has participated so far in this very important research.
The Wellcome Longitudinal Population Studies COVID-19 Questionnaire Secretariat – one year on and what’s next.
By COVID-19 LH&W National Core Study, on 19 July 2021
By David Porteous*, Robin Flaig*, Lynn Molloy** and Nic Timpson**
Generation Scotland, University of Edinburgh* and ALSPAC, University of Bristol**
Is it really (just) a year since Wellcome kick-started the Longitudinal Population Studies (LPS) Secretariat with crucial start-up funding? In that time, have we really been able to engage with 13 diverse cohorts to assemble COVID-19 relevant questionnaires? And make these readily and freely available? Have they been picked up and used in whole or part by more than 100 studies? With more than 31,000 responses from our volunteers? The answer is a remarkable ‘yes’ to all of the above.
Since May 2020, the Steering Group has grown to 32 active members. We have met online 6 times. We have assembled questionnaires to query each of the following topics relevant to the pandemic: Physical health; Long COVID; Mental health and wellbeing; Social Circumstances; Lifestyle; Parents concerning children and young people; Personal response to the pandemic; Impact of Brexit; COVID-19 knowledge and policy; Domestic violence; Healthcare; Environmental attitudes; and coming soon, measures for Children and young people. You can access them here.
Whenever you post or publish your findings, do please reference the resource. Every bit of evidence counts when measuring the added value from the Wellcome Trust investment.
The LPS Secretariat has demonstrated like never before how agile are the UK’s broad portfolio of longitudinal population cohorts. The willingness under COVID-19 to collaborate has paid dividends, widening diversity and increasing statistical power. Anchored by pre-pandemic assessments of health and wellbeing, sociodemographic information – and biological markers in most – one key feature is our ability to measure change under COVID-19. This vital feature has enhanced interpretation and reliability of LPS over the plethora of de novo cross-sectional studies conducted over the past year.
The LPS Secretariat has underpinned several important research publications, with many more in the pipeline. You can find them here. It has also fed into policy, through reports to Wellcome and other funder representatives on the Steering Group, and to SAGE via HDR UK.
For early stage career scientists, it has catalysed previously unimaginable levels of networking, skills, knowledge and best-practice sharing. It has provided a lifeline and lifetime opportunity for several whose research plans were stalled abruptly by the pandemic.
Alongside parallel efforts to collect valuable new COVID-19 relevant data such as serial antibody testing results, it has laid the platform for the successful and substantial bids to the National Core Studies (NCS) programme and MRC/NIMHR open call for Long COVID research proposals for Longitudinal Health and Wellbeing and Longitudinal Linkage Collaboration. Together, these efforts are not only looking to contribute meaningfully to the analysis of COVID-19 and the impact of the pandemic now, but also to leave an important legacy data set able to chart the long-term impact of this simultaneously global yet personal event. Importantly, several of the NCS analysts were themselves important contributors to the success of the LCS Secretariat.
So what next? The added value already demonstrated in such a short time surely means that as a community, we must continue and build on what has been started. The relevance of what has already been achieved directly supports other major infrastructure platforms such as CLOSER and HDR UK. It is highly relevant to the nascent Population Research UK initiative. There are other ambitious plans brewing in UKRI which would benefit.
Wellcome made it very clear at the outset that their support was a ‘one off’ and time limited. ALSPAC and Generation Scotland will keep things going for now. We would however love to hear from others who might want to lend a hand, share some administrative assistance or help maintain, update or co-host the resource.
By COVID-19 LH&W National Core Study, on 8 July 2021
By Professor Nish Chaturvedi and Professor Jonathan Sterne
Like many of our colleagues, each of us adapted our research from March 2020 onwards, to prioritise information that would help mitigate the impacts of the pandemic. This included asking our established population-based cohorts additional questions about COVID-19, and planning how best to harness the unique strengths of whole population anonymised health records to address key questions. Using these and other approaches, our knowledge of COVID-19 has evolved rapidly. Yet further research is required to understand the long-term health, social, and economic impacts of this disease.
The COVID-19 Longitudinal Health and Wellbeing National Core Study
In October 2020, Sir Patrick Vallance, UK Government Chief Scientific Adviser, established the National Core Studies (NCS) as part of the UK’s response to the COVID-19 pandemic. Six NCS were created focussing on key areas in which the UK needed to rapidly increase research scale to respond to the near term strategic, policy, and operational needs. These included Epidemiology and Surveillance, Clinical Trials Infrastructure, Transmission and Environment, Immunity, Data Connectivity, and Longitudinal Health and Wellbeing.
Leads for each of the NCS were approached some weeks before their launch, to articulate research gaps within their domains and devise plans to address these. We agreed that the overarching aim of the COVID-19 Longitudinal Health and Wellbeing (LH&W) NCS is to understand the health, social and economic impacts of the COVID-19 pandemic. Funding to support this major initiative was provided by UK Research and Innovation (UKRI).
The pandemic has resulted in collaborative, multidisciplinary research on an unprecedented scale and the LH&W NCS is no exception. Our team unites experts from leading institutions across the UK whose domains include epidemiology, biomedicine, social sciences, statistics, engineering and computer science. We are working to enhance and interrogate national, anonymised, integrated health records and, in parallel, longitudinal population cohorts for COVID-19 research. Participating institutions are mostly universities, but also include NHS trusts and representation from The National Institute for Health and Care Excellence (NICE). This multi-institutional collaborative team adapted to rapidly changing circumstances during the first phase of the LH&W NCS. Entering the second phase, we have 7 research themes:
UK Longitudinal Linkage Collaboration
Society and Health
Characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19: providing the evidence base for health care services (CONVALESCENCE Study)
Although the existence of Long COVID is recognised, much remains unknown. In March 2021, we were given the go ahead to start the NIHR-UKRI funded CONVALESCENCE study. This will help to define Long COVID, its determinants and health, social and economic consequences to improve diagnosis, management and support using a combination of quantitative, qualitative and deep phenotyping approaches. Working with NICE, we will ensure that the latest evidence is passed on immediately, supporting NICE’s goal of providing ‘living guidance’ for the diagnosis and management of Long COVID.
The value of uniting established longitudinal population cohorts and national anonymised electronic health records
The team are addressing each research question by using data from established longitudinal population cohorts (led by NC) and national pseudonymised whole-population linked electronic health records (EHR ( led by JS)). These include the SAIL Databank (Wales), EAVE II (Scotland), and OpenSAFELY and the NHS Digital Trusted Research Environment Service for England, which both cover the whole of England and were established in direct response to the pandemic to enable secure, rapid analysis on primary care data linked to secondary care and COVID datasets.
Longitudinal cohorts, though smaller, have detailed pre-pandemic health and socioeconomic data, collected on all participants, where possible using objective measurement methods. This enables greater granularity of enquiry than that allowed by EHR analysis, and importantly allows us to understand how pre-pandemic factors modify disease risk and its outcomes. The UK is proudly and uniquely placed globally in the richness of its population cohorts spanning the country, covering many age and socioeconomic groups, and including hard-to-reach groups such as ethnic minorities. Renowned cohorts collaborating within the LH&W NCS include ALSPAC, BCS70, Born In Bradford , ELSA, Generation Scotland , Millennium Cohort Study , NCDS, Next Steps , NSHD , SABRE Study TwinsUK and Understanding Society . They have been at the forefront of the UK’s response to COVID-19, and importantly include people who have not consulted with health care services.
Parallel analysis of whole-population linked EHR, which provide breadth of coverage, and in-depth data from population cohorts will provide complementary insights that enhance the robustness of our findings. By linking EHR and cohorts, we can relate the detailed, universal pre-pandemic information from cohorts to disease endpoints captured in EHR.
Although some cohorts have linked their data with EHR before the pandemic there was no unified or comprehensive approach. We have therefore established the UK Longitudinal Linkage Collaboration (UK LLC), which will unite cohort and EHR data within a single Trusted Research Environment. This key LH&W NCS initiative unites processes, minimises duplication of effort, ensures data security, and provides secure access to accredited researchers.
Impact of results
The result of this work will inform policies to help mitigate the impacts of the pandemic on health and society. To date we have provided policy makers and NICE with vital information on:
• Long COVID risk factors https://www.medrxiv.org/content/10.1101/2021.06.24.21259277v1
• Long COVID GP coding differences https://bjgp.org/content/early/2021/06/28/BJGP.2021.0301
• The effect of the pandemic on mental health https://www.medrxiv.org/content/10.1101/2021.03.26.21254424v2
• The significance of pre-pandemic mental health on health care disruptions https://www.medrxiv.org/content/10.1101/2021.04.01.21254765v1
• How government initiatives such as the furlough scheme have affected health and wellbeing https://www.medrxiv.org/content/10.1101/2021.06.08.21258531v1
• Inequalities in healthcare disruption https://www.medrxiv.org/content/10.1101/2021.06.08.21258546v1
These outputs provide early evidence of the value and impact of this kind of multi-disciplinary, inter-institutional, cross platform approach to answering a broad range of key questions.