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Draft guidance from NICE's Diagnostics Assessment Programme on two genetic tests used to diagnose familial hypercholesterolaemia (FH) is issued today for consultation. The provisional recommendations do not support the use of the Elucigene and LIPOchip tests in the NHS in England for the confirmation of a clinical diagnosis of FH or for the screening of relatives of people with confirmed FH.

FH is a type of high cholesterol that is caused by an inherited genetic mutation which reduces the rate of cholesterol clearance from the blood. To date approximately 1400 unique genetic mutations that are known to cause FH have been identified worldwide, of which 200 have been reported in the UK population. The condition is estimated to affect some 100,000 people in the UK and, if left untreated, often results in unnecessary illness and early death from coronary heart disease (CHD). The risk of CHD can be greatly reduced by early diagnosis of FH and appropriate treatment with lipid-modifying drugs (statins) in combination with lifestyle changes.

Identification of FH is achieved through a combination of clinical signs and symptoms, including measurement of low-density lipoprotein cholesterol (LDL-C), and DNA testing. Elucigene and LIPOchip can detect 20 and 189 genetic mutations associated with FH in the UK population respectively. Because Elucigene and LIPOchip can only detect a subset of people with FH, the Diagnostics Advisory Committee considered using other genetic tests, including CGA (comprehensive genetic analysis) after these tests to increase the sensitivity of the overall testing process. However, no strategy that included either Elucigene or LIPOchip proved to be as clinically and cost-effective as simply using CGA (in the index individual) and targeted DNA testing (in the relatives of the index individual).

Professor Adrian Newland, Chair of the independent Diagnostics Advisory Committee, said: "NICE's clinical guideline on the identification and management of FH published in 2008 found that the use of DNA testing (using CGA) for unequivocal confirmation of a diagnosis of FH was, because it detects almost all mutations known to cause FH, extremely cost-effective. In addition, knowing the specific family mutation means that, as part of cascade testing, the individual's relatives can be offered a simple targeted DNA test where the laboratory tests just for the family mutation. The evidence and analysis considered by the Diagnostics Advisory Committee confirmed that compared to Elucigene or LIPOchip, CGA testing was clearly the most clinically effective, while cost-effective, strategy for confirming a diagnosis of FH in index individuals and targeted DNA testing was the most clinically and cost-effective for cascade screening of their relatives."

He continued: "Despite the recommendations in the NICE clinical guideline, uptake of DNA testing for FH has remained low, primarily because clinical capacity for identifying and managing the condition in index individuals and their relatives is not currently adequate in the NHS. The Diagnostics Advisory Committee considered that, even though Elucigene and LIPOchip are less costly tests than CGA, because they are less sensitive the cost savings would be more than offset by the lower health outcomes associated by false negative tests and the inability to undertake cascade testing using a targeted DNA test. Therefore, the Diagnostics Advisory Committee concluded that it could not recommend Elucigene and LIPOchip for the confirmation of a clinical diagnosis of FH, or for cascade testing of relatives. It remains the case, however, that only a fraction of people in England are identified as having FH, often with tragic consequences for the majority who are not. The NICE clinical guideline provides a pragmatic blueprint for reducing tens of thousands of unnecessary deaths and the vital role played by CGA and targeted DNA testing in achieving that."

More information on the diagnostics draft guidance consultation for Elucigene and LIPOchip is available at http://guidance.nice.org.uk/DT/2. The consultation closes on 23 August 2011 and final guidance is expected to be published in December 2011.

Notes to Editors

About the NICE Diagnostics Assessment Programme

1. Further information about the NICE diagnostics assessment programme can be found at: www.nice.org.uk/diagnostics

2. Topics to be considered by the Programme are routed through the related Medical Technologies Assessment Programme. Further information about this can be found at: www.nice.org.uk/mt

3. The NICE clinical guideline: Identification and management of familial hypercholesterolaemia (CG71) is available on the NICE website at http://guidance.nice.org.uk/CG71

About NICE

4. The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance and standards on the promotion of good health and the prevention and treatment of ill health.

5. NICE produces guidance in three areas of health:

• public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
• health technologies - guidance on the use of new and existing medicines, treatments, medical technologies (including devices and diagnostics) and procedures within the NHS
• clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

6. NICE produces standards for patient care:

• quality standards - these reflect the very best in high quality patient care, to help healthcare practitioners and commissioners of care deliver excellent services
• Quality and Outcomes Framework - NICE develops the clinical and health improvement indicators in the QOF, the Department of Health scheme which rewards GPs for how well they care for patients

7. NICE provides advice and support on putting NICE guidance and standards into practice through its implementation programme, and it collates and accredits high quality health guidance, research and information to help health professionals deliver the best patient care through NHS Evidence.