Options Appraisal

Familial Hypercholesterolaemia – Providing equity of service across the West Midlands

Planning: Project Initiation Document (PID)

Issue Date: 4th February 2014

Document Number: 0.4

Prepared by: Marilyn McKoy

Amendment History:

Version / Date / Amendment History
0.1 / First draft for comment
0.2 / 26/11/13 / Second draft for comment to Liz Bagley
0.3 / 29/11/13 / Third draft for comments by Ben Knight
0.4 / 04/02/14 / Fourth draft with updates

Reviewers

This document must be reviewed by the following:

Name / Signature / Title / Responsibility / Date / Version
Ben Knight / Programme Lead
Marilyn McKoy / Quality Improvement Lead
Liz Bagley / Quality Improvement Lead

Network and Clinical Approvals

This document must be approved by the following:

Name / Signature / Title / Responsibility / Date / Version
Rob Wilson / Network Manager
Dr Tony Kenton / Network Clinical Director
Dr Indira Natarajan / Network Clinical Director

Related Documents

This document should be read and approved in conjunction with the following:

Name / Owner / Location
PID / Project Team

Contents

1. Executive Summary

2. Background

3. Prevalence of FH the West Midlands.

4.Current position

5. Outline of Options

Pathway Elements

6. DNA and Cascade testing

7. Drug Treatment

8. Specialist Referrals

9. Nursing and Administration

10. Patient Database

11. Recommendations

12. References

13. Appendices

  1. FH Cascade Testing Strategy.
  2. Option 1 Do Nothing
  3. Option 2 Develop an local service model
  4. Option 3 Develop a regional service model

1Executive Summary

In some people, a high cholesterol concentration in the blood is caused by an inherited genetic defect known as familial hypercholesterolemia (FH).The prevalence of heterozygous FH (from one parent) in the UK is 1:500. Homozygous FH (inherited from both parents) is rare, and has an incidence of approximately one case per one million populations. Symptoms appear in childhood and are associated with early death before reaching adult age from CHD. Patients with FH are at 300 times greater risk of developing CHD than the general population.

In the UK, it is estimated that 110,000 people are affeceted. In the West Midlands geographical area it is believed that there are around 10,725 people with FH of which 25% have been identified. The vast majority of the remaining 75% will die prematurely if left untreated.

This document forms part of a large programme of work by the West Midlands Cardivacular Strategic Clincal Network to support commissioners and providers to implemt new FH servics across the West Midlands to ensure the regional population have equitable acess to disgnosis, information anf testing. This document provides an options appraisal of three models of care for FH. Following its development in 2012, Option 3 has been reviewed by both providers and commissioners in Janauary 2014.In summary, Option 3potentially provoides way forward to improve FH service provision on a regional basis.

2Background

In some people, a high cholesterol concentration in the blood is caused by an inherited genetic defect known as familial hypercholesterolemia. A raised cholesterol concentration in the blood is present from birth and may lead to early development of atherosclerosis and Coronary Heart Disease (CHD). The disease generally shows an autosomal dominant pattern of inheritance (passed from one parent only), being transmitted from generation to generation in such a way that siblings and children of a person with FH have a 50% risk of inheriting the condition. The prevalence of heterozygous FH (from one parent) in the UK is 1:500. Homozygous FH (inherited from both parents) is rare, and has an incidence of approximately one case per one million populations. Symptoms appear in childhood and are associated with early death before reaching adult age from CHD.

Patients with FH are at 300 times greater risk of developing CHD than the general population. This is significant when risk assessing CHD in primary care. Statistics suggest that male FH patients will develop significant CHD before the age of forty years if untreated (approximately 45% will bemale patients). In 1999 the UK FH register reported that the standardised mortality ratio (SMR) for untreated FH patients between 20 and 59 years of age was 8.1 (roughly equivalent to a 23 year reduction in life expectancy) This could be reduced to 3.7 (approximately a nine year improvement in life expectancy) after statin therapy where potency has improved greatly and can reduce cholesterol levels by up to 50% in the individual.

The prognosis for this cohort of patients could be improved further if individuals were identified; of which only approximately 15% of FH patients in England currently are. In the West Midlands geographical area it is believed that there are around 10,725 people with FH of which 25% have been identified. The vast majority of the remaining 75% will die prematurely if left untreated.

If 50% of FH patients were identified and given optimal treatment, the following number of events could be avoided and produce cost savings to the NHS per 1,000 patients during their lifetime.

Table 1: Event and Cost Avoidance for Treating 50% of FH patients

Event / No. of events avoided (per 1,000 FH patients diagnosed) / Cost saving to NHS (per 1,000 FH patients diagnosed)
MI / 141 / £239, 937
Stroke / 262 / £2, 828, 559
Heart Failure / 142 / £255, 083
Re-vascularisation / 34 / £368, 933
Unstable angina / 41 / £46, 910
CV death / 101 / £475, 255

3Prevalence of FH the West Midlands.

Using ONS 2011 population data it is estimated within the West Midlands, that there are 11,217 people with Heterozygous FH and 5 to 6 people with Homozygous FH, (see table 2).

Table 2: Estimated FH prevalence calculated using ONS Mid 2011 Population estimates data

Area Team / Population / Heterozygous / Homozygous
Arden, Hereford and Worcestershire / 1,613,645 / 3,227 / 1.6
Birmingham and the Black Country / 2,422,818 / 4,846 / 2.4
Shropshire and Staffordshire / 1,572,204 / 3,144 / 1.6
West Midlands Total / 5,608,667 / 11,217 / 5.6

NICE guidance estimates that only 10-15% of people with FH have been diagnosed. In relation to the West Midlands, this should equate to 1,683 people. However, without a shared registry of diagnosed FH patients it is not possible to verify the accuracy of this number, (see table 3). Additionally, a significant proportion will have been clinically diagnosed as potentially FH without confirmation using genetic testing which is considered to be the definitive test for this cohort of patients.

Table 3: Number of diagnosed FH patients calculated using ONS Mid 2011 Population estimates data

England / West Midlands
Estimated FH Prevalence / 100,000 / 11,217
Predicted number of FH diagnosed (15%) / 15,000 / 1,683
Predicted number of Undiagnosed (85%) / 85,000 / 9,534
Predicted Number of Diagnosed FH cases each year / - / 827

4Current position

There are 15 Lipid clinics servicing FH patients within the West Midlands. Regionally, FH service provision varies from no FH service progressing to a consultant led adult and paediatric service, supported by a dedicated team which includes a FH nurse. Some FH clinics are led by a range of specialists including FH nurses, Chemical Pathologists, Cardiologists and Lipidologists. FH clinics may operate within Pathology, Cardiology or Endocrine directorate dependent on individual trust arrangements. FH specialists report that a code for FH does not exist, therefore coding FH clinics and accurately capturing activity is problematic.

Table 4: Baseline position of FH clinics within the West Midlands

Lipid Clinic Location / FH Clinic / FH Nurse / Adult / Paeds service / Funded DNA
& cascade testing / Nationwide
data system
Worcesrter Royal Hospital / Yes / No / Adult / No / No
Hereford County Hospital / No / No / Neither / No / No
Coventry and Warwick Hospitals - UHCW / Yes / Yes / Both / No / No
Russells Hall Hospital - DGOH / Yes / Yes / Yes / No / No
New Cross Hospital -Wolverhampton / Yes / No / Adult / No / No
Manor Hopsital- Walsall Healthcare Trust / Yes / No / Adult / No / No
Good Hope and Heartlands Hosptials- (HEFT) / Yes / Yes / Adult / No / No
Birmingham Childrens Hospital / Yes / No / Paeds / No / No
Queen Elizabeth Hospital Birmingham-(UHBFT) / Yes / No / Adult / No / No
City and Sandwell Hospital
(SWBH) / Yes / No / Adult / No / No
Queens Hospital-BHFT / Yes / No / Adult / No / No
Royal Shrewsbury and Princess Royal Hospital / Yes / No / Adult / No / No
Staffordshire General Hospital (UHNS) / Yes / No / Adult / No / No

*Hereford patients are sent to Worcester Royal Hospital

Despite, a legacy of concerted efforts to improve service provision, the West Midlands remains non-compliant with numerous recommendations highlighted within NICE Clinical Guidance 71 (NICE CG 71) or Quality Standard 41 (QS 41).

NICE recommends a combination of DNA testing and LDL-C concentration measurement to identify affected relatives of index individuals with a clinical diagnosis of FH and the testing of at least first- and second-degree relatives and the inclusion of third-degree relatives if possible. NICE guidance also recommends the use of a nationwide, family-based, follow-up system to enable comprehensive identification of affected people. At present the West Midlands is non-compliant with NICE guidance (See table 4). In order to achieve NICE compliance within these areas a regional approach is required.

Quality, Innovation, Production and Prevention(QIPP)

Table 5below, provides associated QIPP benefits that could be realised through the development of FH services that comply with NICE CG71.

Table 5 : Application of QIPP to the development of FH services, to comply with NICE CG71

PRINCIPLE / RESULTS
Quality /
  • Patient centred services
  • Specialist services in local DGH or outreach clinic
  • Compliance with NICE CG71 AND QS 41
  • Treatment appropriate to patient’s relative CHD risk (FH = very high risk)
  • Some localities able to provide a single visit option for families

Innovation /
  • Development of an Integrated Pathway of Care
  • Introduction of multidisciplinary Family Clinics
  • Regional service developed in collaboration with other regions – national system potential

Productivity /
  • Reduced cost of wasted outpatient capacity in other specialities
  • Commissioners fund using HRG tariffs
  • Reduced number of patient visits
  • Telephone/electronic support for primary care to reduce inappropriate clinic referral
  • Reduced resources on expensive interventions through early treatment

Prevention /
  • Early diagnosis of high risk CHD patients
  • Identification of family members’ FH status through cascade testing
  • Targeted lifestyle advice from an early age
  • Appropriate treatment plan co-ordinated between Secondary and Primary Care

Service Developments: Coroner’s office

Alongside actions such as Stakeholder engagement, Programme management, and leading the first national Strategic Clinical Network FH event, the West Midlands Cardiovascular Strategic Clinical Network has successfully engaged the Coroner’s office to commence retrospective case finding if death from FH is suspected. This innovation will not only enable proactive and targeted case finding of patients who are at high risk of Cardiovascular disease and death, but it will involve partnership working with non-healthcare focussed organisations.

5Outline of Options

It is accepted that there is no one service model for FH. The option or options adopted within the West Midlands will depend on local circumstances and shared care agreements. The options put forward are as follows:

  1. Do Nothing
  2. Develop an local service model
  3. Develop a regional service model

Option 1: Do nothing. (See appendix 2)

This option will result in the continuation of the current position i.e fragmented, inequitable and inefficient service. Patients within the West Midlands would continue to receive care that is not in line with NICE CG71 and QS 41).Undiagnosed and untreated patients would continue to be at risk of avoidable CVD events and death. Variation in service provision would continue to remain across localities within the West Midlands. Resources would be wasted through inappropriate referrals. Cascade testing would continue to remain unfunded and sporadic. There would be no opportunity to develop targeted diagnosis using cascade testing and the rates of gene mutation detection would plateau. Data collection on FH cases, treatment and management would not be completed or shared on a regional or national basis. The level of knowledge held by Primary and Secondary care professionals regarding the diagnosis, treatment and management of FH, would not improve and may reduce as the workforce changes.

Option 2: Develop a local service model (see appendix 3)

This option requires agreement between local commissioners and local service providers across the West Midlands. Service specifications would need to be developed in order to cover as many aspects of NICE as possible, however if commissioned this service would not be fully compliant. Whilst individual development of a local service model would aim to meet NICE CG71 and QS 41 as a minimum, gaps and inequalities would remain, for example, undiagnosed and untreated patients in neighbouring localities would continue to be at risk of avoidable CardiovascularDisease or death. Variation in service provision would continue to remain across localities within the West Midlands.DNA and cascade testing, funded by local CCG’s, may result in testing being available in some localities and not available in others. Without data sharing agreements, data collection, treatment and management would be limited to being completed and shared on a local basis. The outcome of this model would be that locally, there would be improved service delivery, however, variation would remain, inequalities in patient outcomes may widen across the localities within the West Midlands.In addition, there would be reduced opportunity to look at efficiencies through economy of scale and a local service model would not support regional/national information collation.

Option 3: Develop a regional common service model (see appendix 4)

Building on the gaps highlighted within option 2 (Develop a local service model), Option 3 has two main elements. Firstly, that it is links all localities across the West Midlands and secondly that it allows for links with other bordering regions. Whilst there may be variation in the model used by each locality, this model links all localities together, through the commonalties of service provision. This model would include individual service specifications which include primary and secondary care agreements on patient referrals, patient data sharing, information collection and DNA/ cascade testing arrangements. This model would have the capacity to deliver seamless, efficient, equitable and high quality FH service provision. This would allow the associated with benefits of cascade screening, treatment, management and data sharing to be realised. Associated benefits of cascade screening are reductions in avoidable CVD events, reductions in premature deaths, improved targeted treatment, improved knowledge and identification of FH gene mutations.

Potentially this model would be a single service commissioned locally, with agreement on the identification, treatment, management and follow up of FH patients within the West Midlands. The model would also include information sharing agreements and a system which would allow the seamless communication of information.

It is therefore recommended that option 3 (in addition to the completion of local service level improvements) would enable NICE compliance, ultimately resulting in delivering the best outcomes for FH patients within the West Midlands.

Options: Risks and Benefits

Whilst the information contained in the options tables below are not exhaustive, it does provide indications as to the risks and benefits associated with each option. Each option is assessed against its alignment with strategy, NICE key priorities for implementation and finally the potential impact on Patients and public.

Option 3: West Midlands Regional FH Care Pathway

Taken from 2011 Business Case

Option 3: West Midlands Regional FH Genetic Testing Pathway

Taken from 2011 Business Case

Whilst calculations have been completed based on numbers of cases expected to be identified, it (see appendix1), should be recognised the costs below do not fully reflect the complete cost of implementing option 3. In addition to costs being based on assumptions there are notable gaps in information surrounding service activity, backlogs and capacity. The forecasted costs saved by implementing option 3 are also not included. Whilst further cost analysis is required, this information provides a potential baseline figure.

Option 3: Pathway elements considerations

  1. DNA and Cascade testing
  2. Drug Treatment: Statins
  3. Specialist Referrals
  4. Admin, Nursing and Biochemistry /lipid profile tests
  5. Patient Database
  6. Number of coronary events avoided

Table 8 Pathway Cost Summary

Year / Total
Number / Cost
1 / 2 / 3 / Min / Max
DNA and Cascade testing / 2094 / 2094 / 2094 / 6282 / 478,782 / 1,088,820
Drug Treatment: Statins / 662 / 662 / 662 / 1986 / 110,032
Number of FH cases commencing:
Ezetimibe, Bile acid sequestrate, Fibrates and Nicotine Acid / More information required
Specialist Referrals: Number of Adult referrals to lipid specialists (30%) / 179 / 179 / 179 / 537 / 180,432.00
Number of Paediatric referrals to lipid specialists (28%) / 232 / 232 / 232 / 696 / 331,992.00
Number of Adult referrals to cardiology / 60 / 60 / 60 / 180 / 37,800.00
Number of Adult annual reviews / n/a / 595 / 595 / 1190 / 399,840.00
Number of Paediatric annual reviews / n/a / 232 / 232 / 464 / 79,808.00
Nursing and Admin:
Admin cost for Index and Relatives / 6282 / 166,362
Nurse cost for Index and Relatives / 6282 / 241,306
Cost Invitation and results letters / 19,008
Biochemistry /lipid profile tests / 2094 / 2094 / 2094 / 6282 / 10,925
Patient Database : i.e. PASS / £ 1100 per licence.
Cost of implementing Option 3 Pathway / 2,764,645

Source: NICE CG71 Costing report and Astra Zeneca

6Pathway Element : DNA and Cascade testing

FH is caused by mutations in three different genes LDL Receptor (LDLR), for the apolipoprotein B (APOB), and for an enzyme involved in the degradation of the receptor as it recycles (PCSK9). Evidence suggests that mutations can be found in 70–80% of people with definite FHand 20–30% of people with possible FH, as defined by strict clinical criteria. The availability of DNA diagnosis at an asymptomatic stage and effective lipid-lowering therapy saves NHS costs and improves quality of life for patients and their families. Cascade testing using cholesterol or genetic only testing is not recommended by NICE. Using either method exclusively for cascade testing for FH, would leave relatives of index cases at risk of inappropriate screening or missing appropriate treatment. The most cost effective cascade strategy combines the strengths of both.

DNA and Cascade testing: Risks and Benefits

Risks

  • Despite advances in technology, DNA testing may not find a mutation- however this does not mean that the person does not have FH

Benefits

  • Nationally, if 50% of predicted relatives of people with FH were diagnosed and received treatment this could save £1.7 million per year on healthcare for heart disease
  • Nationally implementing cascade testing could save £1.4 million per year
  • Even without the genetic confirmation the person is identified as being at high risk and will be offered the necessary lipid-lowering treatment
  • Can provide a near definitive diagnosis of FH (some gene mutations are not yet identified as FH causing)
  • Knowing the specific family mutation means that relatives can be offered a simple single DNA test, in which the laboratory tests only for the family mutation. In addition to reducing costs, this is useful because cholesterol measurement alone may not offer a clear diagnosis.
  • Able to identify, treat and reduce the risk of coronary heart disease in relatives who have FH, many of whom may be asymptomatic
  • Lipid-lowering treatment therapy saves NHS costs and improves quality of life for patients and their families.

DNA and Cascade testing: Costs