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Sharma P, Boyers D, Boachie C, et al. Elucigene FH20 and LIPOchip for the Diagnosis of Familial Hypercholesterolaemia: A Systematic Review and Economic Evaluation. Southampton (UK): NIHR Journals Library; 2012 Mar. (Health Technology Assessment, No. 16.17.)

4Assessment of factors relevant to the NHS and other parties

Factors relevant to the NHS

Funding of the DNA testing

The current NICE clinical guideline (CG71)1 identifies DNA testing as the recommended method for confirming a clinical diagnosis of FH among Simon Broome definite FH and possible FH probands and also (and perhaps most importantly) the identification of first-, second- and possibly third-degree relatives of the index case for testing using a targeted sequencing test. However, findings from the 2010 audit of FH services18 suggest that the current NICE guideline is not being widely implemented, primarily because of shortages in funding at a local level. The 2010 audit found that, although 97% of sites have access to an accredited laboratory for lipid measurement, only15% had access to funded DNA testing.

Our results confirm that CGA is the most sensitive testing strategy for identifying at-risk relatives and, based on the results from probabilistic sensitivity analysis, is likely to be the most cost-effective testing strategy. This is in line with recommendations from CG71.1 CGA is, however, the most costly diagnostic test (although the cost implications can be partially offset against cost savings emanating from reduced cardiovascular events treated and more appropriate targeted treatments for these people). With concerns about access to funding for DNA testing being raised in the FH audit18 there may be perceived barriers to the widespread adoption of CGA as the strategy of choice.

The adoption of less costly approaches than CGA is possible. Other non-dominated strategies also appear cost-effective at points below conventional willingness to pay for a QALY values. However, strategies such as Elucigene FH20 and LIPOchip are imperfect methods for detecting gene deletions and duplications, such that a MLPA test would be required with Elucigene FH20 and may well be pragmatically required in addition to LIPOchip to confirm the diagnosis for these cases. On the plus side, however, such strategies may be simpler and cheaper than CGA.

It is probable, however, that the cost of implementing testing with CGA will reduce in future years. It is estimated from previous guidance that the cost of cascade testing of all at-risk individuals would be approximately £12.913M per year80 over 5–10 years, after which time costs would fall further as more and more of the current 100,000 or so patients with FH would be detected. After this 5- to 10-year period, cascade testing would be on a case-by-case basis of those who had not previously been tested. With reductions in costs associated with next-generation gene sequencing, these cost estimates have fallen over recent years and are likely to fall further in coming years. Additionally, atorvastatin therapy is coming off patent in 2011, which will also ease the financial burden of implementing the guidance. It may therefore be a more efficient use of NHS resources to adopt a comprehensive testing programme now to avoid the additional costs of delaying and retesting patients currently cascaded using LDL-C with genetic tests in the future. There may therefore be some savings to the NHS that have not as yet been identified. It is difficult to quantify such potential savings as this would depend on future NICE guidance and whether or not primary care trusts implement the current guidelines as per CG711 to use at least some form of DNA testing strategy.

Financial burden to NHS of (as yet) undiagnosed patients

The NHS needs to be aware of the financial burden of the significant number of individuals (estimated to be around 100,000) who have FH and are as yet undiagnosed (but who would subsequently be diagnosed through cascade testing). The management and treatment of these cases, once identified, will generate a significant resource burden to already tight NHS budgets. Also, it is unclear whether or not the capacity currently exists in lipid clinics to identify cases, trace family history and refer all those requiring testing. Clinical expert opinion suggests that capacity is available within the genetics laboratories in the UK to conduct all relevant tests.

Factors relevant to other parties

Benefits to individuals of a definitive diagnosis

Should the widespread implementation of cascade testing be achieved in the UK, there are a number of benefits that individuals identified with FH through that process can expect to incur. For example, appropriate treatment can be started quickly, cholesterol levels can be monitored and managed, the risk of getting CHD and having a heart attack is reduced and close family members can be screened and treatment started if necessary. It is also known that, if treatment can be started early, before CHD is established, this reduces the risk of dying prematurely.2

Possible adverse sequelae of a definitive diagnosis

Despite the benefits that a definitive diagnosis can bring, it is also well known that psychological sequelae can arise for individuals and their family following the formal diagnosis of a clinical condition. There are issues of anxiety associated with being diagnosed with a genetic disease; however, equally there may be a sense of closure for the patient, who will be able to proceed with an action plan to manage his or her FH using appropriate treatment methods. Although no evidence exists linking psychological impact to QALY gain for FH patients, as FH is very treatable once identified, it is likely that the psychological impact of the genetic testing would be positive for the patient. Individuals, especially parents, may also gain positive views from the knowledge that a relative, especially their children, will be treated correctly should they be diagnosed with FH.

Insurance for those diagnosed with familial hypercholesterolaemia

If you are being treated for a medical condition you usually have to declare it to your insurance company, otherwise it could invalidate your insurance. Having a diagnosis of FH may affect how a person is treated when they apply for life assurance or travel insurance and could also have an impact on mortgage applications. Some insurance companies may decide that a person with FH has a higher risk of getting CHD and may charge higher premiums. Also some insurance companies may not differentiate between high cholesterol as a result of poor diet and other lifestyle factors and high cholesterol caused by an inherited condition such as FH.2

Other issues

The use of strategies involving Elucigene FH20 and/or LIPOchip could provide advantages to patients in terms of early detection of disease and provision of an unequivocal diagnosis, allowing cascade testing for the early identification and treatment of relatives. Although the benefits of such tests in achieving a definitive diagnosis are clearly evident, there are some ethical and equity issues arising from the recommendation of a less than fully sensitive and specific genetic test. As reported in Chapter 3 (compared with LDL-C), although strategies such as Elucigene FH20 or LIPOchip (platform processed in Spain) appear to offer a cost-effective use of NHS resources at less than usual threshold values of willingness to pay, their recommendation as a single test may raise ethical concerns. Elucigene FH20 and LIPOchip both detect a limited set of FH-causing mutations. Owing to concerns over LIPOchip's ability to detect copy number changes as accurately as MLPA, some relatives of index cases with less commonly occurring mutations may go undetected. Such individuals would be disadvantaged owing to the documented inadequacies of the use of LDL-C to give a definitive diagnosis of FH.

© 2012, Crown Copyright.

Included under terms of UK Non-commercial Government License.

Cover of Elucigene FH20 and LIPOchip for the Diagnosis of Familial Hypercholesterolaemia: A Systematic Review and Economic Evaluation
Elucigene FH20 and LIPOchip for the Diagnosis of Familial Hypercholesterolaemia: A Systematic Review and Economic Evaluation.
Health Technology Assessment, No. 16.17.
Sharma P, Boyers D, Boachie C, et al.
Southampton (UK): NIHR Journals Library; 2012 Mar.

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