Study of Child-Parent Screening for Familial Hypercholesterolaemia

Lead Research Organisation: Queen Mary, University of London
Department Name: Wolfson Institute

Abstract

Familial hypercholesterolaemia (FH) is an inherited condition that causes high blood cholesterol levels from birth and an extremely high risk of heart attack at a young age ? about one hundred times the usual risk before age 40. There are about 115,000 people with FH in the UK, but only about 15,000 have been identified, leaving about 100,000 children and adults undiagnosed and without life-saving cholesterol lowering treatment. This project aims to test a new screening strategy (child-parent screening), which for the first time, has the potential to systematically identify and treat nearly all cases of FH in the population.
Research published in 2007 showed that a cholesterol test undertaken between the age of 1 and 9 would identify about 90% of all FH cases, with only about 1 per 1000 unaffected children falsely classified as positive. Screening children when they attend for immunization at 1 to 2 years of age by combining a blood test and immunization in a single procedure has been shown to be a feasible and acceptable method of implementing this screening method.
Each identified child has at least one affected parent (FH is inherited from parent to child) so screening children provides a means of identifying (and consequently treating) affected adults and children who have a high risk of a heart attack, before the onset of disease. There is now a need to test the accuracy and cost-effectiveness of child-parent screening in practice.
This award, if granted, would fund the screening, blood collection and data analysis in 10,000 children from 76 UK General Practices over a 3 year period. The immediate value of the results would be the formal scientific evaluation of this screening approach and the quantitative assessment of the measurements needed in screening. The longer term goal is the provision of a universal screening policy capable of identifying nearly all families with FH in the population and providing the opportunity to start treatment that could prevent about 800 deaths in young people each year.

Technical Summary

A common cause of ischaemic cardiovascular disease in young adult life is the autosomal dominant inherited disorder Familial Hypercholesterolaemia (FH). There are about 100,000 undiagnosed people with FH in the UK population. Identifying affected individuals before the onset of disease is important because statin therapy, which lowers blood cholesterol levels, substantially reduces the risk of heart disease and stroke.
A recent meta-analysis of observational studies has shown that a cholesterol measurement in children aged 1 to 9 identified about 90% of affected individuals with only about one per thousand unaffecteds falsely classified as positive. Screening newborns or adults was much less effective. The acceptability of screening children when they attend for routine immunization at 1 to 2 years of age has been demonstrated in a General Practice feasibility study. Each affected child will have one affected parent, identifiable as the one with the higher cholesterol, so screening children provides a means of identifying and treating both child and parent in a systematic manner. This has been called child-parent screening. There is now a need to test the predicted accuracy of child-parent screening in practice with a view to specifying an effective primary care based population screening policy.
We propose a study of child-parent screening in 76 UK General Practices, administered through the MRC General Practice Research Framework using DNA analysis on all the children screened (10,000) as the confirmatory test. The results of the study will determine the screen positive rate based on total cholesterol, the detection rate and false positive rate based on DNA analysis and the cost-effectiveness and acceptability of a national screening programme in Britain. This will provide independent scientific evidence on the accuracy of child-parent screening and determine what modifications, if any, to the screening protocol are needed. The study will last three years and cost approximately #833,000.

Publications

10 25 50
 
Description Chair of NHS England FH Expert Advisory Group
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description FH Steering Committee - NHS England
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact Too early to provide these estimates of impact.
 
Description HEART UK - Child Parent Screening Implementation Strategy Group
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact Too early to provide these estimates of impact.
 
Description HEART UK - Statement of Care for Young People with FH Committee.
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact Too early to provide these estimates of impact.
 
Description Population and Systems Medicine Board (PSMB)
Amount £43,628 (GBP)
Funding ID G1002158/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2014 
End 06/2015
 
Description Great Ormond Street Hospital Department of Molecular Genetics 
Organisation Great Ormond Street Hospital (GOSH)
Department Department of Molecular Genetics
Country United Kingdom 
Sector Hospitals 
PI Contribution DNA analysis
Collaborator Contribution DNA analyses
Impact Awaited (recruitment complete)
Start Year 2011
 
Description London School of Hygiene and tropical Medicine, Department of Health Economics 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Faculty of Public Health and Policy
Country United Kingdom 
Sector Academic/University 
PI Contribution Health economics
Collaborator Contribution Health economics
Impact Awaited
Start Year 2011
 
Description Primary Care Research Network 
Organisation National Institute for Health Research
Department School for Primary Care Research
Country United Kingdom 
Sector Academic/University 
PI Contribution Overall study design, coordination, implementation
Collaborator Contribution Primary care research infrastructure
Impact Awaited (recruitment currently at 3000)
Start Year 2011
 
Description 2. Paediatric Familial Hypercholesterolemia 2017 Update: 85th EAS Congress - Prague - 27 April 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a talk on 'Child-parent FH screening'.
Year(s) Of Engagement Activity 2017
 
Description Engagement focussed website - www.fhscreen.website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact To encourage international public engagement in FH identification and the prevention of premature ischaemic heart disease but providing a free service to model FH identification according to detection strategy using real-world public data and user input data. Audience is global.
Year(s) Of Engagement Activity 2019,2020
URL http://www.fhscreen.website
 
Description FH Europe Network Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Keynote speaker about Child-Parent Screening for Familial Hypercholesterolemia
Year(s) Of Engagement Activity 2016
 
Description FH Foundation Global Summit - Miami - 24-25 September 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a talk on 'Earlier Detection and Diagnosis' of Familial Hypercholesterolemia
Year(s) Of Engagement Activity 2017
 
Description FH Foundation key note lecture in Los Angeles 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited lecture to disseminate research and provide framework for adoption /implementation in different countries
Year(s) Of Engagement Activity 2018
 
Description FH Summit key note lecture in Melbourne 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited lecture to disseminate research and provide framework for adoption /implementation in different countries
Year(s) Of Engagement Activity 2019
 
Description Great Ormond Street Hospital 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other audiences
Results and Impact Keynote presentation on the Child-Parent Screening Study
Year(s) Of Engagement Activity 2017
 
Description Heart UK Annual Meeting & Science Conference - London - 5-7 July 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a talk on the Child-Parent Screening Study
Year(s) Of Engagement Activity 2017
 
Description Keynote lecture - Heart UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Heart UK annual conference
Year(s) Of Engagement Activity 2014
 
Description Monthly recruitment reports 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Newsletters have been sent to 80 research nurses in about 80 general Practices across England, providing information of recruitment, the top 10 recruiters and useful clinical information regarding FH screening that is relevant to the conduct of the Child Parent Screening Study

This has created a high level of Nurse Engagement with the project.
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015
 
Description NOCLOR Research Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact 50 delegates attended and asked questions about how to get involved in research in primary care

Engaged people in rsearch
Year(s) Of Engagement Activity 2013
 
Description National Institute for Preventive Cardiology National Prevention Conference - Ireland - 18 November 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a talk on 'Child Screening and Prevention Matters in FH'
Year(s) Of Engagement Activity 2017
URL https://www.eventbrite.ie/e/nipc-national-prevention-conference-2017-invited-delegates-registration-...
 
Description National monthly Child-Parent Screening study (CPSS) newsletter 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Health professionals
Results and Impact Provide update on recruitment
Share clinical and research experiences across practices
Year(s) Of Engagement Activity 2014
 
Description Nurse Practitioner Training 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact 20 delegates who will take on FH screening in East of England

Training well received by nurse practitioners and PCRN staff
Year(s) Of Engagement Activity 2013
 
Description Specialist nurse training 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact Lead to enrollment of new research practices in east of England
Year(s) Of Engagement Activity 2014
 
Description Westminster FH Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact 200 participants attended from experts to politicians followed by a dinner and talk in the House of Lords

Increased awareness and priority for FH screening in England
Year(s) Of Engagement Activity 2012