A pilot study for the establishment of large-scale bioresources by linking blood donor samples with electronic heal

Lead Research Organisation: University of Cambridge

Abstract

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Technical Summary

Reliable assessment of the interplay of genetic and major lifestyle factors in common diseases requires particularly large studies: for example, study of 0.5M healthy adults in the #60M UK Biobank study should yield 10,000 incident cases of myocardial infarction for analyses after several years of follow-up. The current proposal is for a pilot study to determine the feasibility and acceptability of establishing large bioresources by involving individuals accessing health services for other purposes. IN particular, it is proposed to explore linkage of: (i) millions of blood samples collected through the NHS blood and transplant (NHSBT, formerly the National Blood Service), and (ii) disease outcomes recorded in electronic records, notably the Myocardial Infarction National Audit Project. The proposed pilot study will focus on: (i) the potential impact of health questionnaires, genetic studies and data linkage on blood donation (i.e., assessment of acceptability to blood donors and to the NHSBT), (ii) feasibility of database linkage, and (iii) processing and storage of biological material. In addition to informing decisions about the potential conduct of a large study of blood donors, this pilot study should yield generalisable knowledge about the potential for embedding aspects of population health research into routine health services.
 
Description COMPARE study
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact Evidence from the COMPARE study has been key to reducing rates of anaemia among blood donors by convincing NHS Blood and Transplant (NHSBT) to introduce a new approach to pre-donation screening of donor haemoglobin across the entire national blood service in England in 2018. Following presentations and written submissions to the NHSBT Board, NHSBT acted swiftly on the study's two key recommendations. First, they replaced their previously used test with the finger-prick test that had been found in the study to be more accurate - capillary HemoCue®. Second, they fine-tuned ("re-calibrated") the copper sulphate test to enhance its accuracy. As a direct result of these changes, about 100 blood donors each day, or ~30,000 donors every year, are estimated to be saved from avoidable anaemia and potential iron deficiency. As iron deficiency can cause symptoms such as tiredness, shortness of breath, and palpitations, these are significant benefits for donors - who generously give blood to help others. A further related impact of this research has been to avoid potential reputational and financial damage to NHSBT. This could have arisen if NHSBT had gone ahead, without evaluation, with adopting non-invasive light-shining methods to screen haemoglobin levels of donors. Though these methods were used in blood services in Bavaria, Ireland and Spain, they were later found to perform poorly, leading donors to develop avoidable anaemia by being bled when their iron stores were low. The Irish Blood Transfusion Service had to suspend blood donations for a period and face legal action from, and provide financial compensation to, donors. By contrast, the reliable evidence from COMPARE evidence guided NHSBT to avoid spectrometry methods. COMPARE showed that these methods were insufficiently accurate, especially among people of different ethnicities and skin colour types, and were unsuitable for blood services in countries with a large and ethnically diverse pool of donors such as the UK.
URL https://onlinelibrary.wiley.com/doi/10.1111/tme.12750
 
Description INTERVAL study
Geographic Reach National 
Policy Influence Type Influenced training of practitioners or researchers
Impact The INTERVAL study provided NHS Blood and Transplant with the first data from a randomised trial of the effects of different blood donation intervals. The quantitative data produced from INTERVAL (and published in The Lancet) include data on the amount of blood collected from donors and the health and well being of blood donors and will inform NHSBT policy on blood donation strategies and policy.
 
Title COMPARE 
Description COMPARE is a study of 30,000 English blood donors set up to determine for NHS Blood and Transplant the most effective way of measuring haemaglobin levels in blood donors. Additionally, participants in the study have consented to have the blood samples used in research and data from genetic and biomarker assays and through linkage with electronic health records will be used across a range of research projects. 
Type Of Material Biological samples 
Year Produced 2017 
Provided To Others? Yes  
Impact No impact yet. 
URL http://www.comparestudy.org.uk/about-the-study/
 
Title INTERVAL Bioresource 
Description INTERVAL is a randomised controlled trial in up to 50,000 whole-blood donors recruited at 25 locations across England. Participants are involved in a two-year intervention during which they are invited to give blood either at usual donation intervals or more often. The primary aim of the intervention is to establish whether donors can safely and acceptably give blood more often than is now collected by NHS Blood and Transplant. A further aim of INTERVAL is to create a national epidemiological bioresource, including a recall-by-genotype (phenotype) resource, which will enable detailed study of the health of blood donors and broader public health and biomedical issues. Participant recruitment commenced in June 2012. Our target of 50,000 study participants was reached two years later, in June 2014. Participants have consented to: use of their data and biological samples for a wide range of analyses, invitation to further biomedical studies, and long-term linkage to e-health records. Funding that has been awarded from NHSBT and NIHR will allow the study of the following factors in 50,000 participants i) extended haematological profile (>200 parameters) ii) lifestyle profiling, including assessment of smoking, alcohol consumption, dietary intake, and, in large subsets, monitoring of physical activity through the use of worn accelerometry devices; (iii) cognitive function traits related to different domains of mental function and well-being; and (iv) linkage with e-health records, eg, various morbidity registers, hospital discharge records (v) a novel gene array containing 850,000 single nucleotide variants (SNVs), which includes many functional SNVs and a GWAS scaffold to deliver imputation of ~20 million variants; (vi) ~200 candidate biomarkers related to haematological traits and other pathways for a wide range of disease processes (eg, liver and renal function; autoimmunity; hormonal status). 
Type Of Material Biological samples 
Year Produced 2014 
Provided To Others? Yes  
Impact Serum samples collected during the study have been used to measure the levels of ferritin in participants. DNA has been used in a genome-wide association study of haemoglobin concentration and related parameters, and genotyping of the HFE gene. 
 
Title COMPARE 
Description COMPARE is a study of 30,000 English blood donors set up to determine for NHS Blood and Transplant the most effective way of measuring haemaglobin levels in blood donors. Additionally, participants in the study have consented to have the blood samples used in research and data from genetic and biomarker assays and through linkage with electronic health records will be used across a range of research projects. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact In the largest study reporting head-to-head comparisons of four methods to measure haemoglobin prior to blood donation, our results support replacement of NHS Blood and Transplant's (NHSBT) customary method with portable haemoglobinometry. The results from this study directly changed NHSBT practice. https://onlinelibrary.wiley.com/doi/10.1111/tme.12750 
URL http://www.comparestudy.org.uk
 
Title Database 
Description A database has been built using: demographic data, physical measurements' data (e.g. height, weight, blood pressure), health and lifestyle questionnaire data (e.g. smoking, physical activity, diet, alcohol, family history), attitudinal questionnaire data in relation to acceptability of the research, physical activity data 
Type Of Material Database/Collection of data 
Year Produced 2011 
Provided To Others? Yes  
Impact None at present 
URL http://www.phpc.cam.ac.uk/ceu/research/cardioresource/
 
Title INTERVAL Bioresource 
Description INTERVAL is a randomised controlled trial in up to 50,000 whole-blood donors recruited at 25 locations across England. Participants are involved in a two-year intervention during which they are invited to give blood either at usual donation intervals or more often. The primary aim of the intervention is to establish whether donors can safely and acceptably give blood more often than is now collected by NHS Blood and Transplant. A further aim of INTERVAL is to create a national epidemiological bioresource, including a recall-by-genotype (phenotype) resource, which will enable detailed study of the health of blood donors and broader public health and biomedical issues. Participant recruitment commenced in June 2012. Our target of 50,000 study participants was reached two years later, in June 2014. Participants have consented to: use of their data and biological samples for a wide range of analyses, invitation to further biomedical studies, and long-term linkage to e-health records. Funding that has been awarded from NHSBT and NIHR will allow the study of the following factors in 50,000 participants i) extended haematological profile (>200 parameters) ii) lifestyle profiling, including assessment of smoking, alcohol consumption, dietary intake, and, in large subsets, monitoring of physical activity through the use of worn accelerometry devices; (iii) cognitive function traits related to different domains of mental function and well-being; and (iv) linkage with e-health records, eg, various morbidity registers, hospital discharge records (v) a novel gene array containing 850,000 single nucleotide variants (SNVs), which includes many functional SNVs and a GWAS scaffold to deliver imputation of ~20 million variants; (vi) ~200 candidate biomarkers related to haematological traits and other pathways for a wide range of disease processes (eg, liver and renal function; autoimmunity; hormonal status). 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? Yes  
Impact Further collaboration, most notably with the Wellcome Trust Sanger Institute 
URL http://www.intervalstudy.org.uk/
 
Description INTERVAL 
Organisation NHS Blood and Transplant (NHSBT)
Country United Kingdom 
Sector Public 
PI Contribution We provide scientific leadership and operational support. We are the academic coordinating centre, running the administration and data management of the trial (including the helpline).
Collaborator Contribution NHSBT provide funding and operational support. The University of Oxford provide scientific leadership and operational support.
Impact INTERVAL is a randomised controlled trial in up to 50,000 whole-blood donors recruited at 25 locations across England. Participants are involved in a two-year intervention during which they are invited to give blood either at usual donation intervals or more often. The primary aim of the intervention is to establish whether donors can safely and acceptably give blood more often than is now collected by NHS Blood and Transplant. A further aim of INTERVAL is to create a national epidemiological bioresource, including a recall-by-genotype (phenotype) resource, which will enable detailed study of the health of blood donors and broader public health and biomedical issues. Participant recruitment commenced in June 2012. Our target of 50,000 study participants was reached two years later, in June 2014. Participants have consented to: use of their data and biological samples for a wide range of analyses, invitation to further biomedical studies, and long-term linkage to e-health records. Funding that has been awarded from NHSBT and NIHR will allow the study of the following factors in 50,000 participants i) extended haematological profile (>200 parameters) ii) lifestyle profiling, including assessment of smoking, alcohol consumption, dietary intake, and, in large subsets, monitoring of physical activity through the use of worn accelerometry devices; (iii) cognitive function traits related to different domains of mental function and well-being; and (iv) linkage with e-health records, eg, various morbidity registers, hospital discharge records (v) a novel gene array containing 850,000 single nucleotide variants (SNVs), which includes many functional SNVs and a GWAS scaffold to deliver imputation of ~20 million variants; (vi) ~200 candidate biomarkers related to haematological traits and other pathways for a wide range of disease processes (eg, liver and renal function; autoimmunity; hormonal status).
Start Year 2012
 
Description INTERVAL 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution We provide scientific leadership and operational support. We are the academic coordinating centre, running the administration and data management of the trial (including the helpline).
Collaborator Contribution NHSBT provide funding and operational support. The University of Oxford provide scientific leadership and operational support.
Impact INTERVAL is a randomised controlled trial in up to 50,000 whole-blood donors recruited at 25 locations across England. Participants are involved in a two-year intervention during which they are invited to give blood either at usual donation intervals or more often. The primary aim of the intervention is to establish whether donors can safely and acceptably give blood more often than is now collected by NHS Blood and Transplant. A further aim of INTERVAL is to create a national epidemiological bioresource, including a recall-by-genotype (phenotype) resource, which will enable detailed study of the health of blood donors and broader public health and biomedical issues. Participant recruitment commenced in June 2012. Our target of 50,000 study participants was reached two years later, in June 2014. Participants have consented to: use of their data and biological samples for a wide range of analyses, invitation to further biomedical studies, and long-term linkage to e-health records. Funding that has been awarded from NHSBT and NIHR will allow the study of the following factors in 50,000 participants i) extended haematological profile (>200 parameters) ii) lifestyle profiling, including assessment of smoking, alcohol consumption, dietary intake, and, in large subsets, monitoring of physical activity through the use of worn accelerometry devices; (iii) cognitive function traits related to different domains of mental function and well-being; and (iv) linkage with e-health records, eg, various morbidity registers, hospital discharge records (v) a novel gene array containing 850,000 single nucleotide variants (SNVs), which includes many functional SNVs and a GWAS scaffold to deliver imputation of ~20 million variants; (vi) ~200 candidate biomarkers related to haematological traits and other pathways for a wide range of disease processes (eg, liver and renal function; autoimmunity; hormonal status).
Start Year 2012
 
Description NHSBT R&D conference, Oxford 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact 150 people attended the conference including senior NHSBT management

Initiated discussions, with senior NHSBT management, on the potential for future research studies in blood donors
Year(s) Of Engagement Activity 2010