Cardiovascular Rare Disease Node
Lead Research Organisation:
Imperial College London
Department Name: National Heart and Lung Institute
Abstract
Cardiovascular Rare Diseases (CVRD) and Inherited Cardiac Conditions (ICCs) represent a challenging health burden, with a combined prevalence of at least 1/200, including the commonest causes of sudden death in young adults and the leading causes of heart transplantation. In addition to their impact on affected individuals, they create a substantial burden for family members who may be at risk, and for health systems that provide long-term surveillance to both affected and unaffected relatives.
Opportunities for research using healthcare data generated as part of routine patient care could transform the diagnosis and treatment of people with these medically important conditions. However, innovative solutions are needed to overcome existing challenges around data access and linkage - and the MRC CRVD node will develop these. Importantly, these solutions will also benefit people with other rare diseases, since many of the challenges faced in ICCs are shared with other conditions.
Patients with ICCs report research participation as rewarding and empowering, yet many do not access research opportunities. The MRC CVRD node will remove barriers to research participation, streamlining consent processes to make routine health care data available for research, to enable recontact of potential research participants, and to build ongoing relationships with ICC patients as research partners.
The NHS Genomic Medicine Service provides remarkable opportunities for scalable research. For example, a national network of ICC centres converge on just four laboratories that provide genetic testing services to England and Wales, providing an opportunity to obtain consent and capture data at national scale through very focused investment. Many of the most pressing challenges in ICCs could be addressed using the rich repositories of data that already exist but are currently siloed. National data science infrastructure could hold and process these data and present new clinical and research opportunities. The MRC CVRD node will provide the final connections to unlock these opportunities - developing robust dynamic consent procedures for data use, and linking key national data science infrastructure including the British Heart Foundation Data Science Centre (at Health Data Research UK), the National Genome Research Library (at Genomics England), and National Disease Registration Service (at NHS Digital). Governance challenges will be addressed centrally, freeing individual research groups from the challenges of linking diverse health data sources, and a new Trusted Research Environment for rare heart diseases will provide secure access to rich data for approved bona fide researchers.
Opportunities for research using healthcare data generated as part of routine patient care could transform the diagnosis and treatment of people with these medically important conditions. However, innovative solutions are needed to overcome existing challenges around data access and linkage - and the MRC CRVD node will develop these. Importantly, these solutions will also benefit people with other rare diseases, since many of the challenges faced in ICCs are shared with other conditions.
Patients with ICCs report research participation as rewarding and empowering, yet many do not access research opportunities. The MRC CVRD node will remove barriers to research participation, streamlining consent processes to make routine health care data available for research, to enable recontact of potential research participants, and to build ongoing relationships with ICC patients as research partners.
The NHS Genomic Medicine Service provides remarkable opportunities for scalable research. For example, a national network of ICC centres converge on just four laboratories that provide genetic testing services to England and Wales, providing an opportunity to obtain consent and capture data at national scale through very focused investment. Many of the most pressing challenges in ICCs could be addressed using the rich repositories of data that already exist but are currently siloed. National data science infrastructure could hold and process these data and present new clinical and research opportunities. The MRC CVRD node will provide the final connections to unlock these opportunities - developing robust dynamic consent procedures for data use, and linking key national data science infrastructure including the British Heart Foundation Data Science Centre (at Health Data Research UK), the National Genome Research Library (at Genomics England), and National Disease Registration Service (at NHS Digital). Governance challenges will be addressed centrally, freeing individual research groups from the challenges of linking diverse health data sources, and a new Trusted Research Environment for rare heart diseases will provide secure access to rich data for approved bona fide researchers.
Technical Summary
Cardiovascular Rare Diseases (CVRD) and inherited cardiovascular conditions (ICC) present an important national and global health burden. Care encompasses probands and relatives, with substantial burden on individuals and healthcare systems.
Challenges: most ICCs are unexplained on current genetic testing. There are no disease-modifying therapies for most ICCs. Some available treatments have high cost and morbidity, and since clinical course is unpredictable therapies are poorly targeted to those who will benefit, leading to unnecessary treatment harm.
ICCs display incomplete penetrance, and we cannot identify which individuals carrying a "disease-causing" variant will manifest disease, leading to burdensome long-term surveillance. Variants in ICC genes are commonly identified as secondary findings, and guidelines recommend screening for these, but the relative benefits and harms of screening are unknown.
Large scale natural history studies are needed, but ICCs are relatively rare, with individual centres following hundreds, not thousands, of patients. It is very costly to obtain consent and longitudinal phenotype data using conventional approaches. Healthcare data are siloed in individual centres, not available for impactful research.
Targeted investment to improve access to routine healthcare data, with data linkage in a secure environment, will address these challenges and more.
The CVRD will (i) aggregate all diagnostic genetic test results across England and provide summary data for genome interpretation (via National Rare Disease Service), (ii) provide streamlined consent processes to enable scalable national recruitment to a longitudinal cohort study, (iii) establish a Trusted Research Environment with secure access to data for accredited researchers (with HDRUK BHF Data Science Centre), (iv) establish data linkages with structured (e.g. HES) and unstructured (e.g. imaging/ECG) data from routine healthcare, and (v) enrich this with genomic data.
Challenges: most ICCs are unexplained on current genetic testing. There are no disease-modifying therapies for most ICCs. Some available treatments have high cost and morbidity, and since clinical course is unpredictable therapies are poorly targeted to those who will benefit, leading to unnecessary treatment harm.
ICCs display incomplete penetrance, and we cannot identify which individuals carrying a "disease-causing" variant will manifest disease, leading to burdensome long-term surveillance. Variants in ICC genes are commonly identified as secondary findings, and guidelines recommend screening for these, but the relative benefits and harms of screening are unknown.
Large scale natural history studies are needed, but ICCs are relatively rare, with individual centres following hundreds, not thousands, of patients. It is very costly to obtain consent and longitudinal phenotype data using conventional approaches. Healthcare data are siloed in individual centres, not available for impactful research.
Targeted investment to improve access to routine healthcare data, with data linkage in a secure environment, will address these challenges and more.
The CVRD will (i) aggregate all diagnostic genetic test results across England and provide summary data for genome interpretation (via National Rare Disease Service), (ii) provide streamlined consent processes to enable scalable national recruitment to a longitudinal cohort study, (iii) establish a Trusted Research Environment with secure access to data for accredited researchers (with HDRUK BHF Data Science Centre), (iv) establish data linkages with structured (e.g. HES) and unstructured (e.g. imaging/ECG) data from routine healthcare, and (v) enrich this with genomic data.