Elucigene FH20 and LIPOchip for the diagnosis of familial hypercholesterolemia The National Institute for health and Clinical Excellence (NICE): Diagnostic Assessment Review (DAR) Sharma P, Boyers D, Boachie C, Stewart F, Miedzybrodzka Z, Simpson W, Kilonzo M, McNamee P, Mowatt G Elucigene and LIPOchip for the diagnosis of familial hypercholesterolemia. Sharma P 1 , Boyers D 1,2 , Boachie C 1,2 , Stewart F 2 , Miedzybrodzka Z, Simpson W, Kilonzo M, McNamee P, Mowatt G. Presented by: Dwayne Boyers 1 Health Services Research Unit (HSRU); 2 Health Economics Research Unit (HERU), University of Aberdeen, Aberdeen, Scotland, U.K. 9 th HTAi Annual Meeting 26th June, 2012, Bilbao
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Economic evaluation. Elucigene and LIPOchip for the diagnosis of familial hypercholesterolemia.
Elucigene and LIPOchip for the diagnosis of familial hypercholesterolemia.Sharma P1, Boyers D1,2, Boachie C1,2, Stewart F2, Miedzybrodzka Z, Simpson W, Kilonzo M, McNamee P, Mowatt G.
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Elucigene FH20 and LIPOchip for the diagnosis of familial
hypercholesterolemia
The National Institute for health and Clinical Excellence (NICE): Diagnostic Assessment Review
(DAR)
Sharma P, Boyers D, Boachie C, Stewart F, Miedzybrodzka Z, Simpson W, Kilonzo M, McNamee P, Mowatt G
Elucigene and LIPOchip for the diagnosis of familial hypercholesterolemia.
Sharma P1, Boyers D1,2, Boachie C1,2, Stewart F2, Miedzybrodzka Z, Simpson W, Kilonzo M,
McNamee P, Mowatt G.
Presented by: Dwayne Boyers
1 Health Services Research Unit (HSRU); 2 Health Economics Research Unit (HERU),University of Aberdeen, Aberdeen, Scotland, U.K.
9th HTAi Annual Meeting26th June, 2012, Bilbao
Familial Hypercholesterolemia (FH)
• an autosomal dominant genetic condition– Heterozygous / Homozygous
– 3 Culprit genes (LDLR / PSCK9 / APOB)
• Increased risk of coronary heart disease
• Prevalence estimated at 1/500 in the UK– approx 100,000 people in the UK have FH
– Approx 85% of these remain undiagnosed
Tests considered
• Elucigene FH20 (Tepnel Diagnostics)
• LIPOchip v.10 (Progenika)– (i) Test processed at UK genetics lab
– (ii) Test conducted by manufacturer in Spain – if negative on LIPOchip, full LDLR sequencing
• Comprehensive Genetic Analysis (CGA)
– Indirectly recommended by NICE CG71
• LDL_C testing
– Current standard of care
Strategies modelledTest for Index case Test for Relative
Elucigene Targeted genetic test
LIPOchip (UK lab based test) Targeted genetic test
LIPOchip (sample sent to Spain) Targeted genetic test
Elucigene - MLPA Targeted genetic test
Elucigene - LIPOchip Targeted genetic test
Elucigene – LIPOchip - MLPA Targeted genetic test
Elucigene – LIPOchip - CGA Targeted genetic test
Elucigene - CGA Targeted genetic test
LIPOchip - MLPA Targeted genetic test
LIPOchip - CGA Targeted genetic test
CGA Targeted genetic test
LDL-C only LDL-C
Diagnostic accuracy: Elucigene FH20
Study Country Diagnosis Criteria Total, n Sensitivity
%
Specificity
%
Hooper 2009 Australia DFH Dutch 63 28.6 NC
Taylor 2010 England DFH Simon Broome 190 48.6 NC
Taylor 2010 England PFH Simon Broome 394 40.2 NC
Taylor 2010 England UFH Simon Broome 51 38.5 NC
Taylor 2010 England DFH/PFH/UFH Simon Broome 635 44.0 NC
Yarram 2010 England DFH/PFH/UFH Simon Broome 104 52.0 NC
Diagnostic accuracy: LIPOchip v.10
Study id LIPOchip version
Diagnosis Criteria Totaln
Sensitivity%
Specificity %
Palacios V 10 UK mutations
NR Simon Broome 126 78.5 NC
Callaway 2010 V 8 (251 mutations)
DFH or possible Simon Broome 22 33.3 93.8
Palacios 2010 V 8 (251 mutations)
NR Simon Broome 120 56.9 NC
Stef 2009 247 mutations NR Dutch MedPed 2,462 94.5 NC
Alonso 2009 195 mutations DFH, probable FH
Dutch criteria 808 78.0 NC
Diagnostic accuracy: LDL-C for index cases
Study ID Criteria Diagnosis Total, n Sensitivity % Specificity %
Damgaard 2005 Simon Broome Overall 408 90 29
Dutch 408 99 6
MedPed 408 54 83
Civeira 2008 Simon Broome Overall 825 93 28
Dutch Overall 825 88 18
MedPed Overall 825 91 53
Widhalm 2003 MedPed Adults 147 66 NC
Children 116 81 NC
Mabuchi 2005 LDLC> 4mmol/L 281 98 NC
Diagnostic accuracy: LDL-C for relatives
Study ID Country Participants Total, n Sensitivity
• Results and conclusions were robust a range of sensitivity analyses
Conclusions• Uncertainty surrounding true sensitivity of tests
• Elucigene and LIPOchip are not cost-effective as standalone tests for the detection of FH among index cases or for the identification of at risk relatives for cascade testing
• A strategy of CGA for index cases and targeted sequencing for relatives was deemed the approach with greatest diagnostic accuracy and was therefore the most cost-effective strategy
– Only at very high sensitivity (>70%) would Elucigene be a cost-effective pre-screen to CGA
• LIPOchip is unlikely to be cost-effective given concerns over the detection of deletions and duplications compared with MLPA
This project was funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme and commissioned on behalf of NICE. It will be published in full in the Health Technology Assessment journal series. Visit the HTA programme website for more details www.hta.ac.uk/project/2450. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NICE, NIHR, NHS or the Department of Health.’