FAMCAT2: Identifying patients at risk of familial hypercholesterolaemia

The issue:

Identification of people at high risk of Familial Hypercholesterolaemia (FH) is a key priority of the NHS England national cardiovascular disease (CVD) programme and the NHS Long Term Plan, which sets the ambition to help prevent over 150,000 heart attacks, strokes and dementia cases by 2029.

Key findings:

• This was a system collaborative piece of work and only possible due to the joint working and ambition from the Medicines Optimisation Team at Hampshire and Isle of Wight Integrated Care Board, the Wessex FH Service, Health Innovation Wessex and PRIMIS.
• This was well received by GP Practices and led to the identification of over 260 patients with a confirmed diagnosis of FH.
• Integral to the success of this project was an established Wessex FH Service that has the clinical expertise to offer advice and guidance to GPs, and coordinate and deliver genetic testing with a systematic approach. This is not available in all systems.
• This FAMCAT2 initiative in combination with the subsequent PCN directed enhanced service (DES) Impact and Investment fund (IIF) CVD-04 led to not only an increase in diagnosis of FH, but also raised awareness of FH amongst primary care health care professionals. This is evidenced in a sustained increase in referrals following the end of this initiative.

What impact did it have?

• 55 practices ran the FAMCAT2 tool.
• Almost one million registered patients’ clinical records were searched.
• 1,702 patients were found to have a probable diagnosis of FH.
• 911 of those patients were identified as having a high probability of having FH.
• 784 referrals for genetic testing were made which increased referrals 5-fold between April 2022 and March 2023.
• A total of 262 patients were diagnosed with FH and can therefore be treated to prevent future cardiac related events.
• Cascade testing of family members has been initiated for those 262 patients and is ongoing.

Background

This project was a successful collaboration between Health Innovation Wessex, PRIMIS (University of Nottingham), the Medicines Optimisation team at Hampshire and Isle of Wight Integrated Care Board (ICB) and Wessex Familial Hypercholesterolaemia Service (hosted by Wessex clinical Genetics Service).

FAMCAT2 is an algorithm developed by University of Nottingham academics (PRISM) to identify patients at greatest probability of having familial hypercholesterolaemia (FH). The algorithm has been shown to predict FH more accurately than other case finding methods.

In collaboration with the academic research team, PRIMIS developed a FAMCAT2 tool for implementation in GP practices using the EMIS patient record system. The tool comprises a set of EMIS web searches, which are run on the GP clinical system and imported into the FAMCAT2 display tool. The tool generates a probability score for all patients aged 16 years and over with a cholesterol result. Once a score has been established, patients can be ranked in order of their probability of having FH, helping health care systems to prioritise referrals for testing at regional genomic testing hubs.

The FAMCAT2 tool helps GP practices to proactively find patients with the highest probability of having FH but who do not have a coded diagnosis in their electronic record.

FAMCAT2 has the added benefit of highlighting patients with an existing coded diagnosis where lipid lowering treatment can be started and optimised.

The project built upon a previous medication safety collaboration, PINCER; the Pharmacist-led Information technology-based iNtervention for the reduction of Clinically important ERrors in medicines management, which had demonstrated a reduction of 18,935 clinically significant medication errors in 2,800 GP practices in England.

What we did

The Hampshire Healthy Hearts Project was funded by Public Health in Wessex, and initially deployed the FAMCAT2 tool in Gosport and Andover to identify patients who were likely to have FH, or who needed appropriate medication for high cholesterol.

Patient lists, generated by the FAMCAT2 tool, were interrogated by a pharmacy technician. Patients who met the referral criteria were referred for genetic testing. Patients identified as needing primary prevention were contacted by a senior pharmacist and an appropriate statin (a cholesterol-lowering medication) prescribed alongside lifestyle and other advice. As a result of this project, the FAMCAT2 tool was revised by the PRIMIS team at the University of Nottingham to enhance its accuracy and useability.

Following this proof-of-concept phase, the Health Innovation Wessex and PRIMIS FAMCAT2 pilot was launched in December 2021. Health Innovation Wessex funded the use of the tool for a period of 12 months to enable free access for PCNs in Hampshire. The project was subsequently extended to the end of June 2023.

The FAMCAT2 tool was deployed in 55 GP practices that used the EMIS clinical system across Hampshire and Isle of Wight. Practices in this area had used this and other PRIMIS tools and therefore had existing experience and knowledge.

The initial project plan aimed to work with three PCNs covering around 20 practices in the pilot phase. However, at the end of the project, 55 GP practices had implemented the tool in almost one million patient records.

An FH webinar was held to support practice staff and PCN pharmacy teams in both the clinical and practical aspects of delivering this CVD project.

What the Wessex Familial Hypercholesterolaemia (FH) Service did

The Wessex FH Service was commissioned in 2016 by a consortium of Hampshire & Isle of Wight Clinical Commissioning Groups. In preparation for this initiative and referrals for genetic testing, we worked in collaboration with the Medicines Optimisation team at HIoW ICB to develop a core brief to provide specific guidance regarding: the identification of FH; clinical criteria; and top tips on how to refer (please see attached core brief).

We also:

• Developed an example discussion with patients to be held prior to referral.
• Developed a standardised referral form available on the electronic referral system.
• On receipt of referral, this was triaged and specific advice and guidance was given when referrals did not meet the criteria for genetic testing. Approximately 20% of referrals were ejected at this point for not meeting clinical criteria for genetic testing.

The Wessex FH Service provided clinical assessment for these referrals including:

• Initial assessment to determine whether referrals reached the clinical criteria for genetic testing.
• Clinic appointments with patients to discuss:
  • Condition of FH and implications for the individual patient and their family
  • Drawing of family tree (pedigree)
  • Strengths and limitations of genetic testing
  • Record of discussion for genetic testing (consent)
  • Entry of patient and family details on to PASS database to facilitate a systematic approach to genetic testing and family cascade testing.
  • Result appointments to explain possible outcomes of genetic testing that can include:
    1. Pathogenic variant (molecular confirmation of diagnosis) and initiation of cascade testing in family.
    2. Variant of uncertain significance and its implications.
    3. A monogenic cause for the individual’s hypercholesterolaemia has not been identified(negative results) and its implications.
• Referral back to primary care and secondary care when clinically indicated.

The outcomes of genetic testing

Between April 2022 & April 2023, 430 samples (including 119 cascades) were referred on to the laboratory from Wessex FH service for genetic testing. Of these, 120 were identified to have a pathogenic variant and therefore were molecularly confirmed to have a clinical diagnosis of FH.

Between April 2023 & April 2024, 515 samples (including 136 cascades) were referred on the laboratory from Wessex FH Service for genetic testing. Of these, 142 were identified to have a pathogenic variant and therefore were molecularly confirmed to have a diagnosis of FH.

Practice Feedback

• The instructional videos and resources were very useful.
• It was a clear and simple process to import and run the tool in EMIS.
• Users provided feedback and suggestions to the PRIMIS team to further automate the process and reduce manual workload.
• The inability to develop a SystmOne version of the FAMCAT2 tool was a significant barrier to wider rollout by the ICB at the time. However the PRIMIS team have now developed new ways of implementing the FAMCAT2 algorithm to identify patients at increased probability of having FH and further information can be found on their website: https://www.nottingham.ac.uk/primis/projects/projects.aspx.
• The colour-coded summary sheet was very well received but the data sheet was described by some as ‘overwhelming’. Users suggested hiding more of the columns.
• Whilst many GP practices/PCNs have run the searches, they said that greater support was needed to optimise the results. Worked examples would be useful and could relate to different levels of practice capacity available.