BUSINESS CASE TEMPLATE
Commissioning Proposal For
Identification and Management of Familial
Hypercholesterolemia (FH) NICE CG 71
Provider(s)
Scheme Title
Responsible Officer including title
Contact Details – Tele
no. & Email
Submission
date
The Development of a Regional Cascade Family Testing Program and Register
[Database] for Familial Hypercholesterolaemia families in xxx
1 OUTLINE OF PROPSALS AND HOW IT SPECIFICALLY MEETS THE COMMISSIONER
OBJECTIVES AND BENEFITS
Background
Familial Hypercholesterolaemia [FH] is a genetically linked condition with a prevalence of 1 in 500
in the population and results in premature vascular disease with the risk of premature death.
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% of male
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) and this could be reduced to 3.7 (approximately a nine year
improvement in life expectancy) after statin therapy with existing medications. Statin potency has
improved since 1999. The prognosis can be improved further with more aggressive lipid
management if patients are accurately diagnosed.
The CVD Outcomes Strategy (2013) recognises the importance of familial hypercholesterolaemia:.
This builds on NICE Clinical Guideline 71(2008) and is supported by the NICE Quality Standard
41(2013)
Most people with FH have inherited a defective gene for FH from only one parent and are therefore
heterozygous. Rarely, a person will inherit a genetic defect from both parents and will have
homozygous FH or compound heterozygous FH, which will be collectively termed homozygous FH
for the purpose of this paper.Homozygous FH has an incidence of approximately one case per one
million population.
The NHS Operating Framework 2012/13 states;
"2.16 In addition to the outcomes strategies, NHS organisations should continue to support the
other clinical strategies aimed at reducing early mortality from cardiovascular disease, including
heart disease, stroke, kidney disease and diabetes.
2.17 There is strong evidence that early treatment supports better clinical outcomes. There are a
number of key areas where commissioners and providers can work together to ensure earlier
diagnosis and treatment."
This clearly supports the proposed model of care.
Table 1 below sets out the current local population, with estimates of their prevalence of FH.
The table includes data from local (num) CCGs. These figures are calculated using National
prevalence data and may therefore vary for each location, depending on various socio-economic
factors. The data is presented to show the numbers by region and to allow commissioners to have
information relevant to current regional NHS structures. These can readily be amended to reflect
updated population statistics or potential future realignment of primary care services across this
region.
2 NICE CLINICAL GUIDELINE 71 (CG71)
NICE issued Clinical Guideline 71 Familial Hypercholesterolemia; (1) identification and
management of familial hypercholesterolemia, in August 2008. Some of the key points are
identified below. Any proposed service model must take account of the specific issues identified.
Table 1: Predicted number of FH patients by CCG across xxxx
Xxx Area –
Name of CCG
Total PCT
Population
Expected
total
number of
FH patients
Of Which
Population
aged 0-15
years
Expected
number of
FH patients
under 16
years
To be completed locally
a) Patient-centred care
Treatment and care should take into account patients’ individual needs and preferences. Good
communication is essential, supported by evidence-based information, to allow patients to reach
informed decisions about their care. Follow Department of Health advice on seeking consent if
needed. If the patient agrees, families and carers should have the opportunity to be involved in
decisions about treatment and care. If caring for young people in transition between paediatric and
adult services refer to ‘Transition: getting it right for young people’ (available from www.dh.gov.uk).
Offer patients and their families’ written advice and information about patient support groups for
people with FH.
b) Key priorities for implementation
i)
Diagnosis
A family history of premature coronary heart disease should always be assessed in a person being
considered for a diagnosis of FH (see Simon Broome criteria, page 6). Clinicians make a diagnosis
of definite or probable FH by applying the Simon Broome1 criteria. These guidelines are only of
use in identifying index cases as this is what the criteria were developed to identify in the general
population (1 in 500 prevalence). Relatives of FH patients have 1 in 2 prevalence. There is also a
real issue in the diagnosis of tendon xanthoma which can be difficult even for experienced
clinicians. An index case is defined as the first patient from a family to be tested for FH. This
patient is then used to cross reference family members to help identify affected individuals.
Few patients are appropriately referred to a specialist lipid clinic (ie many are referred based upon
a high serum cholesterol level) and many others are referred to inappropriate secondary care
services, notably cardiology.
In children at risk of FH because of one affected parent, the following diagnostic tests should be
carried out by the age of 10, or at the earliest opportunity thereafter:
1
Simon Broome diagnostic criteria for index individuals
Diagnose a person with definite FH if they have: cholesterol concentrations as defined in table 2 below and tendon
xanthoma, or evidence of these signs in first- or second-degree relative or
DNA-based evidence of an LDL-receptor mutation, familial defective apolipoprotein B-100, or a PCSK9 mutation.
Diagnose a person with possible FH if they have cholesterol concentrations as defined in table 2 and at least one of the
following:
* Family history of myocardial infarction: aged younger than 50 years in second-degree relative or aged younger than
60 years in first-degree relative.
* Family history of raised total cholesterol: greater than 7.5 mmol/l in adult first- or second-degree relative or greater
than 6.7 mmol/l in child, brother or sister aged younger than 16 years.
3
Table 2: Cholesterol Levels as Diagnostic Criteria:
Cholesterol levels to be used as diagnostic criteria for the index individual *
Total cholesterol
LDL-C
Child/young person
> 6.7 mmol/l
> 4.0 mmol/l
Adult
> 7.5 mmol/l
> 4.9 mmol/l
* Levels either pre-treatment or highest on treatment. LDL-C = low-density lipoprotein cholesterol.
A DNA test if the family mutation is known should be undertaken;
LDL-C concentration measurement can be used if the family mutation is not known. When
excluding a diagnosis of FH a further LDL-C measurement should be repeated after puberty
because LDL-C concentrations change during puberty.
Coronary heart disease risk estimation tools such as those based on the Framingham algorithm
should not be used because people with FH are already at a high risk of premature coronary heart
disease.
ii)
Identifying people with FH using cascade testing
Healthcare professionals should offer all people with FH a referral to a specialist with expertise in
FH for confirmation of diagnosis and initiation of cascade testing.
Cascade testing using a combination of DNA testing and LDL-C concentration measurement is
recommended to identify affected relatives of those index individuals with a clinical diagnosis of
FH. This should include at least the first- and second- and, when possible, third-degree biological
relatives. The use of a nationwide, family-based, follow-up system is recommended to enable
comprehensive identification of people affected by FH.
c) Management
i)
Adults
Healthcare professionals should consider prescribing a high-intensity statin to achieve a
recommended reduction in LDL-C concentration of greater than 50% from baseline (that is, LDL-C
concentration before treatment).
ii)
Children and young people
Healthcare professionals should offer all children and young people diagnosed with, or being
investigated for a diagnosis of, FH a referral to a specialist with expertise in FH in children and
young people. This should be in an appropriate child/young person-focused setting that meets the
standards within the ‘National service framework for children, young people and maternity services’
(available from www.dh.gov.uk).
d) Familial Hypercholesterolemia: Key Priorities for Implementation
i)
Information needs and support
Information and counselling on contraception for women and girls with FH. When lipid-modifying
drug therapy is first considered for women and girls, the risks for future pregnancy and to the
foetus while taking lipid-modifying drug therapy should be discussed. This discussion should be
revisited at least annually.
ii)
Ongoing assessment and monitoring
4
All people with FH should be offered a regular structured review that is carried out at least
annually.
3 QUALITY AND PRODUCTIVITY BENEFITS OF IMPLEMENTING CG71 IN Y&H
Table 3 applies the principles of Quality, Innovation, Productivity and Prevention (QIPP) to the
development of FH services, to comply with NICE Clinical Guideline 71.
PRINCIPLE
Quality
Innovation
Productivity
Prevention
RESULTS



















Patient centred services
Specialist services in local DGHs
Compliance with NICE CG71
Delivering Outcome 5 of The CVD Outcomes Stragegy
Delivering NICE Quality Standard 41
Treatment appropriate to patient’s relative CHD risk (FH = very high risk)
Single visit for the whole family
Development of an Integrated Pathway of Care
Introduction of multidisciplinary Family Clinics
Regional service developed in collaboration with other regions – national
system potential
Reduced cost of wasted out patient 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
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
4 PROPOSED DETAIL OF THE RECOMMENDED MODEL
a)
The FH Service Specification template document has been drafted and is shown in Appendix
A. CCG Specific versions will need to drafted for contracting discussions.
b)
The locally agreed algorithm/care pathway is shown in Figure 1
Figure 1: DRAFT FH Pathway Model
Insert algorithm/pathway diagram
c)
Primary care clinicians and lipidologists agree that the aim of any service should be the early
discharge of patients back to primary care. There are some minor points that require
clarification but which will be incorporated into any implementation plan:
 Patients diagnosed in clinic as FH positive will initially be treated to target lipid levels in
clinic.
5
 Patients will be provided with individual information about their condition and treatment
regime.
 Discharge information will be clear and concise.
 Primary care must ensure appropriate follow up (at least yearly).
 Primary care will have direct access to specialist support should a patient’s condition alter.
 Provision must be made to inform and support patients contemplating pregnancy (or
already pregnant).
 Where patients present in primary care with a “To whom it may concern” letter they will be
referred immediately to the nearest/chosen clinic for genetic counselling or offered this
service within primary care (including DNA diagnostic testing).
 Primary care will be expected to follow the referral pathways for individuals who present
with possible/probable FH. The initial diagnostic tests must have been undertaken for a
referral to be accepted. These patients can then be cross referenced by the genetic
counselling service to known families and appropriate testing requested.
5 PROJECTED OUTCOMES OF THE RECOMMENDED SERVICE
Supporting the proposed service additional funding will be expected to deliver the following
outcomes;
1. Patients with suspected FH will follow a clear pathway of care.
2. Relatives will be identified and contacted through a cascade programme coordinated at
regional level.
3. The service will include patients under the age of 16years.
4. Molecular genetics testing will be targeted using the cascade programme to minimise cost
risk of inappropriate testing.
5. Commissioners will ensure providers continue to meet the requirements set out in the
service specification.
6. The additional cost may reduce the overall mortality in treated male patients by up to 48%.
7. The service will reduce the number of heart attacks by approximately 15 per year (a
reduction will occur from year 1)
8. The service will reduce the number of CABG procedures by 2-3 per year and the number of
primary PCI’s by up to 15 per year. It may also reduce the number of elective PCI’s.
9. The number of inappropriate referrals to cardiology out patient clinics (and other
specialities) will be reduced from year 1.
10. If patients are diagnosed at an early age (under 30 years) their CVD risk can be reduced to
that expected for their age group in the general population.
6 FINANCIAL AND SERVICE IMPLICATIONS
FH Activity Projection
Total population = to insert
Predicted Number of FH Patients = to insert
Table 4: Projected Activity – based upon using DNA analysis
Year 1
Year 2
Year 3
Number of Suspected Index Cases tested
Minus 17% FH negative2
Number Consenting to Cascade Testing3
Number of Relatives to be tested4
2 NICE
CG71 Costing tool
80% uptake – see 3 above
3 Assuming
6
Of which 20% will be paediatric
Total predicted new Adult referrals5
Total predicted new Paediatric referrals
Predicted number of Adult follow up
appointments6
Predicted number of Paediatric follow up
appointments7
% of total expected regional FH patients
identified
These projected activity figures are based on the proposed model of using DNA analysis as the
definitive diagnosis of FH. It is to be expected that adult activity would remain static post Year 3,
with an eventual reduction from Year 5 as patients are identified, treated and discharged back to
primary care. Paediatric activity is likely to grow, with the increase being in follow up activity, as
children may require more intensive long term follow up and monitoring.
Projected FH Activity Costs
The following costs are based upon the information provided in the NICE Clinical Guideline 71
costing tool.
Table 5: Out Patient Lipid Clinic Referral
2013/14 National Tariff - Endocrinology
First Out Patient
Appointment
Follow Up
Appointment
Adult
£190
£90
Paediatric
£379
£179
These tariffs are provided by The Department of Health.
Genetics.
There are two elements of Genetic services required to support an FH service:
1.
2.
Molecular Genetics – this is the actual DNA analysis to support diagnosis;
Index Case/Cascade Testing – this provides specialist genetic counselling to all patients
before undergoing any DNA analysis; it will also produce family pedigrees and run all
aspects of cascade testing.
Molecular genetics
DNA testing should be contracted through an NHS Accredited laboratory. It recommended
decisions on provider should be based upon quality assurance and cost effectiveness.
4.It
is assumed each index case will generate on average 4 first degree relatives. Of these 50% will be positive. This will
result in 4 second degree relatives and 4 third degree relatives requiring testing as a negative DNA/clinical diagnosis will
prevent unnecessary testing
5 Number of relatives + number of index cases – number of paediatrics
6Assuming 52% discharge rate – NICE CG71 costing tool
7
Assuming 50% prevalence and all FH positive children needing follow up.
7
Subject to any national recommendations on preferred providers
Cascade Testing
Cascade testing should be undertaken by a suitably experienced NB: wording from NICE. This
function is a core requirement of any service provision and should be funded through the agreed
contract.
Database
To be inserted
Table 6: Projected Yearly Molecular Genetics Costs
Expected
Activity
Projected Cost
Option 1
Option 2
Index Cases
Relatives where family mutation is
identified8
Total
These costs would reduce after Year 5 as more cases are identified. There are a finite number of
adults in the population with FH.
Table 7: Projected Yearly Cost of New Referrals Years 1 – 3 Including Out patient costs and
Genetics costs
Patient
Number
Unit Cost
9Total
NHS Service
Index
Cascade DNA
Cascade No
DNA
BAND 7
NURSE
Based upon a 70% detection rate for mutation – 30% of FH cases will not have an identified mutation so relatives will
require no DNA testing
8
8
TOTAL COST
We need to then include the projected cost of follow-up appointments from year 2 onward. These
are required to meet NICE CG71. Table 8 gives costs for years 1 – 3 including these additional
costs.
Table 8: Projected Total Cost of Referrals Years 1 – 3
Year 1
Year 2
Year 3
New Referrals
Adult Follow up
Paediatric Follow up
Total Cost
Table 9: Potential Additional Cost Savings from Current System
Saving Expected
Number of prevented CABG Procedures
Number of MIs Prevented
Number of Inappropriate Out Patient
Appointments saved
Existing DNA testing spend
Total Expected Annual Savings
See assumptions below
These can then be added to the overall cost analysis as set out in table 10.
*Current costs estimated, based upon 342 new and 1140 follow up patients seen currently (this
equates to 40% of all current lipid clinic referrals, not all of which are appropriate
Current Spend Estimate = £188,265
[1] Yearly total – (current spend estimate £188,265 + £92,196 additional Regional cost
savings from current system)
Table 10 Projected Additional Cost and Number of FH Cases by CCG(summarises tables 7,
8 and 9)
CCG
Population
Expected FH
Cases
Year 1
Cost
Year 2
Cost
Year 3
Cost
9
Table 11 10 Year Cost Projection for a West Yorkshire FH Service
Year
1
2
3
4
Projected Additional
Cost
Projected Potential
Additional Cost
Savings10
Year
6
7
8
9
Projected Additional
Cost
Projected Additional
Cost Savings
5
10
*Genetics cost years 4 -5 based on 60% years 1-3, years 6-10 based on 20% years 1 - 3
*New referral costs 4-5 based on 60% years 1-3, years 6-10 based on 20% years 1 – 3
*Costs based on no fall in follow up patients in lipid clinics – there will be difficult patients identified
who require more intense follow up so no fall is anticipated.
This model predicts achieving a 62% detection over 10 years = 3,714 FH positive patients
identified.
Additional Information/Assumptions
1.
2.
3.
4.
5.
6.
7.
8.
Introducing an FH service will reduce inappropriate referrals to Cardiology
Total savings do not include the cost of follow up and drug therapy, post cardiac events.
Activity estimates are likely to be excessive as they are based on NICE calculations. These
are not supported by the evidence from Wales (where a national screening programme is
now in place) and Scotland (where DNA testing is funded but cascade testing is not).
Numbers tested are lower in both systems.
The potential variance in activity (and hence cost risk) will be minimised as the capacity of
the service will be limited. Limiting the number of sites offering the service and setting the
number of clinical sessions will ensure activity is capped. This is appropriate given the
nature of FH incidence as no new patients will develop FH – it can’t be “caught”.
It is expected activity will fall by 15% - 20% per year from Year 4. The number of patients
with FH in the region will only increase through new births or migration. The cost of the
service will fall accordingly. Cost savings will be also be generated as more cardiac events
are prevented, resulting in reduced numbers of acute episodes and all the associated long
term costs of care.
Paediatric activity is expected to rise until Year 5 and will then remain static from Year 6.
It is anticipated that the cost of an FH service will reduce from Year 4 as activity in index
case and cascade testing falls, as the percentage of identified patients increases beyond
60% of the expected cases.
Pressure on drugs budgets should be minimal, as any patient with elevated cholesterol
should already be being treated with lipid lowering medication. Atorvastatin is now “off
patent”. It is anticipated that a significant number of FH patients (50-70%) will already be on
medication. This can be costed using NICE tools but takes no account of the existing
expenditure and would result in highly over-inflated drug costs.
Service Implications
To be completed locally
Financial Implications
10
Provided we use the existing cohort to implement the service
10
a)
The NICE costing tool developed to supplement CG71 is designed to help identify potential
costs for specified populations. There are a number of assumptions used within the tool that
can be challenged:



Not all FH referrals will require expensive DNA analysis
Counselling and paediatric service availability need to be costed within tariff
Current patients with elevated cholesterol are currently treated – the number of FH
patients already treated can not be accurately assessed as they are not coded in
primary care systems.
b)
DNA testing is expensive, however the assumptions made in other service models need to be
challenged. In order to identify cost risk more accurately the number of tests required must be
estimated.
c)
Genetic counselling and paediatric support, although essential, may not prove costly if these
elements can be funded through tariff income.
d)
The NICE costing template uses endocrinology MDT tariff for adults and children. These are
payable in a setting where multidisciplinary teams are present in a single clinic. If the model is
designed to deliver this it also meets one of the key recommendations in the NICE guidance
around developing “family clinics”. Unlike other outpatient services, the cost of diagnostics in
an FH service will in effect only be molecular genetics, as much of the necessary chemical
pathology results (lipid profiles, liver function and thyroid function tests) are required for
acceptance of the referral and so should have been undertaken in primary care. The question
arises: would tariff income fund the proposed regional elements of a service (genetic
counselling, DNA analysis and paediatric support)? The expected number of patients would
not require such clinics to be run on a very regular basis. It may be possible for such elements
to be provided using an outreach model to DGH based, specialist clinics on a monthly/bimonthly basis. Developing such resources regionally may provide cost benefits as well as
helping with developing a regionally/nationally coordinated FH screening programme.
e)
The cost of prescribing identified in the costing tool may be excessive and takes no account of
patients already diagnosed with FH/hypercholesterolemia who are already being treated with
lipid lowering medication. FH patients need to be managed more aggressively and this may
require more costly drug regimes, including combination therapies. There is also an issue for
any service to identify these patients to clarify their FH status and initiate cascade testing. The
benefits must be assessed in relation to the probable mid to long term cost savings associated
with early diagnosis and treatment.
f)
Developing a robust cascade programme and using index cases already in the service should
help reduce potential costs. The national pilot study identified the level of relatedness in
patients already known to the lipid services and the geographical separation of families.
Establishing family pedigrees should reduce the need for costly DNA analysis in patients
where relationships can be identified, provided this is co-ordinated on a regional/national
basis.
10 SUMMARY AND OVERALL RECOMMENDATIONS:
This paper sets out the case for a regional model of service to implement CG71.
Insert local summary and recommendations
11 REFERENCES
1. NICE Clinical Guideline 71; August 2008 – The Identification and Management of Familial
Hypercholesterolemia.
11
2. Recommendations to the DoH from the Steering Group of the DH FH Cascade Testing Audit
Project July 2007.
12
Appendix A - Impact Assessment
Familial Hypercholesterolaemia
Impact Analysis
Introduction
The following impact analysis provides an estimation of the potential impact of delivery of
implementing NICE CG71 - Identification and Management of Familial Hypercholesterolaemia (FH)
to the population of xxx
The calculations are based on the information provided by NICE in the costing analysis
accompanying CG71 August 2008. As such they are only estimates of the impact on
implementation.
Service Model Options
There are three potential service models for the future commissioning of an FH service:
o
o
o
No change or improvement to current lipid service delivery, ie no changes commissioned;
Delivery of services at a sub regional level, ie services commissioned by individual Primary
Care organisations;
Development of a co-ordinated service for the xxx region.
HRG Tariff
In 2013/14, lipid referral is covered by the Adult and Paediatric first out patient and follow up tariffs.
2012/13 National Tariff - Endocrinology
First Out Patient
Appointment
Follow Up
Appointment
Adult
£190
£90
Paediatric
£379
£179
13
Impact of Commissioning Options x to complete locally
Additional Cost in
2013/14
Commissioning
Options for Familial
Hypercholesterolaemia
Cost
£0
Assuming payment
of the conventional
tariff
£0
Benefits
Additional
number of
cardiac
interventions
prevented
0
The estimated
QALY gain per
annum
NICE CG71
Implemented
NA
No
No FH service
commissioned
Sub Regional services
developed for FH
Issues


£variable
depending on
area
£variable depending
on area
Variable
depending on
area
£2,700 in
areas where
service
introduced
Partially





x
x
x
£2,700
A co-ordinated
common FH service
developed
x



Page 14 of 16
No increase in lives saved and no
cardiac events prevented
Future cost savings from reduced
coronary heart disease not realised
NICE CG71 not implemented
Inequity of patient care
Some future cost savings not realised
through economies of scale
Some preventable cardiac events not
prevented
Difficult to measure and compare
productivity outcomes
Requires adequate infrastructure
Needs co-ordinating across traditional
boundaries
Would benefit from a wider National
service to maximise quality and cost
benefits
Conclusions
The level of investment in lipid services should impact on the benefits to patients at significant risk
of premature cardiovascular events.
Investment would provide direct mid to long term savings through reducing the numbers of
expensive invasive procedures, coronary artery bypass graft (CABG) percutaneous coronary
interventions (PCI) and the associated long term patient follow up costs.
Fully implementing NICE CG71 would provide significant improvement in both life expectancy and
quality of life for patients diagnosed and treated early for FH. The estimated cost per QALY is
approximately £270011.
The net additional cost of implementing the recommended model would be xxx in 201x/1x.
Genetic spend would increase but this will be offset by managing primary care referrals and access
to DNA testing more appropriately.
Significant benefits will be realised in the first year of a new service through early diagnosis and
treatment of potentially very high risk patients.
Overall the analysis indicates that:




11
Benefits of investment are a combination of QALY gained, appropriate referral/treatment
and savings to the NHS.
Benefits increase significantly by delivering a fully co-ordinated and audited regional
service.
Investment will deliver significant benefits to the younger population.
Required investment will decrease from Year 5 as more patients are registered.
Marks D, Wonderling D, Thorogood M et al. Cost effectiveness of different approaches of screening for familial
hypercholesterolaemia. BMJ 2002; 324:1-6.
Page 15 of 16
Appendix B – Service Specification
-
Service Specification –
Page 16 of 16