The HEART Study and version 1.0
Research type
Research Study
Full title
The Healthcare Evaluation of Absolute Risk Testing Study: A multi-centre, single arm, pragmatic study in primary care setting
IRAS ID
285420
Contact name
Ahmet Fuat
Contact email
Sponsor organisation
Genomics Plc
Clinicaltrials.gov Identifier
46497, CPMS
Duration of Study in the UK
0 years, 6 months, 20 days
Research summary
Research Summary
Early detection of risk in order to prevent disease is a fundamental challenge for public health. In line with the “Predictive Prevention“ strategy, supported by the Government and public health bodies, there is an opportunity to embed genetics into healthcare. Genetics can be tested at any age and is constant for life. The combination of a large number of disease-associated common genetic variants into a predictive score is referred to as a Polygenic Risk Score (PRS). PRSs are clinically useful predictors for multiple diseases, such as cardiovascular disease (CVD), where they generate similar or greater effect sizes than smoking or high blood pressure. An Integrated Risk Tool (IRT) is an algorithm which combines an individual’s PRS (genetic risk score) with validated clinical risk factors (eg. BMI or smoking). The output for an individual synthesises their genetic and lifestyle factors to give them an overall understanding of their risk of developing disease. We have shown that this tool has superior predictive power in the UK Biobank cohort compared to other PRSs.
This 1000 patient study at circa 10 GP practices will evaluate the operational use of the IRT for CVD in GP practices and the perceived value for patients and healthcare professionals.
Eligible participants are aged 45-64 years old, either biological sex
Exclusion Patients using statins or not eligible for NHS health check are excluded.
Visit 1 (Baseline) includes consent, demographics, blood collection for all participants of whom 100 will have additional saliva samples, QRISK2 score and a short questionnaire (4 questions).
Visit 2 (Results)will inform participants of their results and collect adverse events.
Visit 3 (Questionnaire) participants will receive an online questionnaire.
Visit 4 (Interview)only 30 participants will be selected for interview.
Healthcare professionals conducting the study are asked to complete a questionnaire and some will be invited for qualitative follow-up sessions.Summary of Results
Early detection of risk in order to prevent disease is a fundamental challenge for public health. In line with the “Predictive Prevention“ strategy, supported by the Government and public health bodies, there is an opportunity to embed genetics into healthcare.
Genetics can be tested at any age and is constant for life. The combination of a large number of disease-associated common genetic variants into a predictive score is referred to as a Polygenic Risk Score (PRS). PRSs are clinically useful predictors for multiple diseases, such as cardiovascular disease (CVD), where they generate similar or greater effect sizes than smoking or high blood pressure. An Integrated Risk Tool CVD-(IRT) is an algorithm which combines an individual’s PRS (genetic risk score) with validated clinical risk factors (eg. BMI or smoking). The output for an individual synthesises their genetic and lifestyle factors to give them an overall understanding of their risk of developing disease.
We have shown that this tool has superior predictive power in the UK Biobank cohort compared to other PRSs.This study planned to recruit up to 1000 in approx 10 GP practices to evaluate the operational use of the CVD-IRT in GP practices and the perceived value for patients and healthcare professionals. Eligible participants are aged 45-64 years old, either biological sex. Patients using statins or not eligible for NHS health check are excluded.
Visit 1 (Baseline) includes consent, demographics, blood collection for all participants of whom 100 will have additional saliva samples, QRISK2 score and a short questionnaire (4 questions).
Visit 2 (Results)will inform participants of their results and collect adverse events.
Visit 3 (Questionnaire) participants will receive an online questionnaire.
Visit 4 (Interview)only 30 participants will be selected for interview.
Healthcare professionals conducting the study are asked to complete a questionnaire and some will be invited for qualitative follow-up sessions.Results Summary
The HEART Study recruited 836 participants from 12 GP surgeries across the North East and Cumbria. 832 participants took part in the study by providing a small blood sample during their routine NHS Health Check appointment. All participants answered a questionnaire before they received their test results, and 520 answered a second online questionnaire after they received their test results. 100 participants from one GP surgery were also asked to provide a saliva sample, to compare whether saliva was comparable to their blood sample in the DNA extracted.
Of the participants who completed the post-results questionnaire, 21 were invited to complete a telephone interview about their experiences of taking part in the study. Additionally, 48 healthcare providers (HCPs) took part in the study (14 GPS, 13 Practice nurses, 9 Research nurses and 2 pharmacists). Of these HCPs 23 completed an online questionnaire about their experiences of the study, 7 took part in focus groups and 2 took part in an interview. Two Primary Care Commissioners (PCCs) took part in a focus group and 1 took part in an interview, to give their opinions on the feasibility of the CVD IRT in routine care.
Blood and saliva samples were collected, and DNA was extracted and analysed to generate a polygenic risk score (PRS), which was combined with other health information collected at the NHS Health Check appointment (QRISK) to produce the Cardiovascular Disease Integrated Risk Test (CVD IRT) score - a 10 year risk of developing cardiovascular disease.
This CVD IRT score was returned to the GP surgery and the GP or other HCP (such as a practice nurse or pharmacist) then discussed the CVD IRT score with the participant, either in person or via a telephone or video call. The HCP then completed a questionnaire on their experience of discussing the results with the participant, and the healthcare management that they would recommend based on the CVD IRT, and based on the QRISK alone.
At the end of the visit, the participant was sent a link via email to a SurveyMonkey online questionnaire. This questionnaire included questions on their experience of the test, whether they would recommend the test to friends and family, and whether the test was useful to them personally.
Some participants were then invited to take part in a telephone interview with a researcher. This interview included questions about:
their experience of taking part in predictive genetic testing, how the information about the test was presented to them the procedure itself any concerns they might have had how the results were given to them what they thought about the results whether they would make any lifestyle changes after having the testAll of the healthcare professionals involved in the study were also invited to take part in an interview or focus group. These HCPs were asked questions about:
Receiving the test results and communicating them to the participants Integrating the test into their normal practice Feedback from the participants Their views on how the test might affect patient careA group of Primary Care Commissioners (PCCs – the people who decide whether the NHS will use a test) were also invited to an interview or focus group. They were asked about:
What they thought about the test and how it compered to other tests for cardiovascular disease risk How the test could be used in general practice If they thought there were any issues or risks with the testThroughout the study we also collected information relating to participant safety – no participant safety concerns were identified.
Study participants:
Adults between the ages of 45 and 64 took part in the study. Of the 836 people who participated from 12 GP surgeries in the North west of the UK, 518 were female (62%) and 318 (38%) were male. This proportion of females to males was expected as women are more likely to attend Health Check screenings than men, even though men are at great risk of heart disease. The average age of participants was 55 years, and 97% described themselves as being white. When asked about their level of education, 33% said they had completed early education (up to GCSE or EBacc level), 31% had completed further education (up to A-level/apprenticeship or vocational training) and 36% had completed higher education (Undergraduate or postgraduate degree).
Key results:
A CVD-IRT test result was produced from every blood sample provided and returned to the GP surgeries (832/832). A test result was produced from all 91 saliva samples that were tested; the test results from blood and saliva were the same, showing that in the future, saliva samples could be used for the test instead of blood.
Of the 832 participants, 824 received their test results from the GP or another healthcare professional. It was not possible to contact six participants and two results had to be corrected after the appointment.
89.9% of participants said that they were “likely” or “very likely” to recommend use of this test to their family or friends. 98.8% of participants found the test was personally useful and 94.6% said the results were easy to understand.
In 90.7% of reports disseminated by healthcare providers, they agreed that the genetic test can be incorporated into their practice in a straightforward manner. Individually, 17/23 HCPs (73.9%) would be “very likely” or “likely” to recommend the test to colleagues in other practices.
When the CVD-IRT result was higher than the standard QRISK score for disease risk, the healthcare provider in 27.8% of cases would plan to make changes to the care of that patient.
Limitations of the study
Planned rather than conducted changes in management practices were evaluated as HCPs delivered standard of care in the first instance.. This study did not include an independent control group, so references to association only, rather than causation, regarding clinical decision making may be stated here.
Conclusion
Including a genetic test alongside a routine cardiovascular risk assessment in a GP setting is feasible and safe. HCPs thought the test was useful in discussions with patients and would recommend the use of this genetic test in their practice. Patients thought the addition of the genetic information was personally useful and of value in helping them make decisions on the options available to them in improving their cardiovascular health.REC name
North of Scotland Research Ethics Committee 1
REC reference
21/NS/0097
Date of REC Opinion
17 Aug 2021
REC opinion
Further Information Favourable Opinion