Elucigene FH20 and LIPOchip   for the diagnosis of for the    Elucigene and LIPOchip familial      hypercholesterolemia   ...
Familial   Hypercholesterolemia (FH)• an autosomal dominant genetic condition   – Heterozygous / Homozygous   – 3 Culprit ...
Tests considered• Elucigene FH20 (Tepnel Diagnostics)• LIPOchip v.10 (Progenika)  – (i) Test processed at UK genetics lab ...
Strategies modelledTest for Index case               Test for RelativeElucigene                         Targeted genetic t...
Diagnostic accuracy:                      Elucigene FH20Study         Country     Diagnosis   Criteria       Total, n Sens...
Diagnostic accuracy:                     LIPOchip v.10Study id        LIPOchip        Diagnosis       Criteria         Tot...
Diagnostic accuracy:                LDL-C for index casesStudy ID         Criteria        Diagnosis   Total, n   Sensitivi...
Diagnostic accuracy:               LDL-C for relativesStudy ID     Country      Participants             Total, n   Sensit...
Diagnostic accuracy:             Discussion• Specificity of genetic tests assumed equal to 1• Sensitivity of CGA assumed e...
Cost-effectiveness• Cost-utility analysis (cost per QALY)   – Cohort of 1000 index cases with suspected FH   – Cascade tes...
Methods• Model informed by sensitivity and prevalence rates• Costs   – Diagnostics (MOLUs)   – Clinical management   – Dru...
Cost-effectiveness                              results                                Total        Total   Incremental In...
Cost-effectivenessacceptability curves
Discussion:           Cost-effectiveness• Little high quality evidence of test accuracy• Rapidly evolving environment:   –...
Conclusions• Uncertainty surrounding true sensitivity of tests• Elucigene and LIPOchip are not cost-effective as  standalo...
Thank you very muchContact Details:d.boyers@abdn.ac.ukUseful links:http://www.abdn.ac.uk/heruhttp://www.abdn.ac.uk/hsruhtt...
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Economic evaluation. Elucigene and LIPOchip for the diagnosis of familial hypercholesterolemia.

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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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Economic evaluation. Elucigene and LIPOchip for the diagnosis of familial hypercholesterolemia.

  1. 1. Elucigene FH20 and LIPOchip for the diagnosis of for the Elucigene and LIPOchip familial hypercholesterolemia diagnosis of familial hypercholesterolemia.1,2, Sharma P1, Boyers D1,2, Boachie C Stewart F2, Miedzybrodzka Z, Simpson W, The National Institute for health and Clinical Kilonzo M, McNamee P, Mowatt G.Excellence (NICE): Diagnostic Assessment Review Presented (DAR) by: Dwayne Boyers 9th HTAi Annual Meeting 26th June, 2012, Bilbao Sharma P, Boyers D, Boachie C, Stewart F, Miedzybrodzka Z, Simpson W, Kilonzo M, McNamee P, Mowatt G 1 Health Services Research Unit (HSRU); 2 Health Economics Research Unit (HERU), University of Aberdeen, Aberdeen, Scotland, U.K.
  2. 2. 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
  3. 3. 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
  4. 4. Strategies modelledTest for Index case Test for RelativeElucigene Targeted genetic testLIPOchip (UK lab based test) Targeted genetic testLIPOchip (sample sent to Spain) Targeted genetic testElucigene - MLPA Targeted genetic testElucigene - LIPOchip Targeted genetic testElucigene – LIPOchip - MLPA Targeted genetic testElucigene – LIPOchip - CGA Targeted genetic testElucigene - CGA Targeted genetic testLIPOchip - MLPA Targeted genetic testLIPOchip - CGA Targeted genetic testCGA Targeted genetic testLDL-C only LDL-C
  5. 5. Diagnostic accuracy: Elucigene FH20Study Country Diagnosis Criteria Total, n Sensitivity Specificity % %Hooper 2009 Australia DFH Dutch 63 28.6 NCTaylor 2010 England DFH Simon Broome 190 48.6 NCTaylor 2010 England PFH Simon Broome 394 40.2 NCTaylor 2010 England UFH Simon Broome 51 38.5 NCTaylor 2010 England DFH/PFH/UFH Simon Broome 635 44.0 NCYarram 2010 England DFH/PFH/UFH Simon Broome 104 52.0 NC
  6. 6. Diagnostic accuracy: LIPOchip v.10Study id LIPOchip Diagnosis Criteria Total Sensitivity Specificity version n % %Palacios V 10 NR Simon Broome 126 78.5 NC UK mutationsCallaway 2010 V 8 DFH or possible Simon Broome 22 33.3 93.8 (251 mutations)Palacios 2010 V8 NR Simon Broome 120 56.9 NC (251 mutations)Stef 2009 247 mutations NR Dutch MedPed 2,462 94.5 NCAlonso 2009 195 mutations DFH, probable Dutch criteria 808 78.0 NC FH
  7. 7. Diagnostic accuracy: LDL-C for index casesStudy ID Criteria Diagnosis Total, n Sensitivity % Specificity %Damgaard 2005 Simon Broome Overall 408 90 29 Dutch 408 99 6 MedPed 408 54 83Civeira 2008 Simon Broome Overall 825 93 28 Dutch Overall 825 88 18 MedPed Overall 825 91 53Widhalm 2003 MedPed Adults 147 66 NC Children 116 81 NCMabuchi 2005 LDLC> 4mmol/L 281 98 NC
  8. 8. Diagnostic accuracy: LDL-C for relativesStudy ID Country Participants Total, n Sensitivity Specificity % %Lee 2010 UK Relatives 90 91.5 93.0 45-54years old group 80.0 70.0Starr 2008 Netherlands First-degree relatives 3294 68.0 85.2 Denmark First-degree relatives 321 79.4 85.1 Norway First-degree relatives 1116 83.7 83.8Wiegman Netherlands Children of definite FH 611 96.0 NC2003 parents
  9. 9. Diagnostic accuracy: Discussion• Specificity of genetic tests assumed equal to 1• Sensitivity of CGA assumed equal to 1 (Caveat?) – All cases will also receive LDL-C testing• Uncertainty in estimates of sensitivity across studies – Limited evidence on most recent versions of tests – Fast changing environment - analysis at a snapshot in time – LIPOchip – is MLPA required aswell?
  10. 10. Cost-effectiveness• Cost-utility analysis (cost per QALY) – Cohort of 1000 index cases with suspected FH – Cascade testing of at risk 1st, 2nd and 3rd degree relatives• Time horizon: Patient life time• Discounting: Costs and QALYs (3.5%)• Perspective: UK NHS
  11. 11. Methods• Model informed by sensitivity and prevalence rates• Costs – Diagnostics (MOLUs) – Clinical management – Drug treatment – Reduced cardiovascular events• QALYs – QALY gains from reduced mortality, reduced cardiovascular events
  12. 12. Cost-effectiveness results Total Total Incremental Incremental ICERTest strategy Costs QALYs costs (£) QALYS (£/QALY)Elucigene £43,371,985 36,653LDL-C £43,880,789 34,744 Dominated Dominated DominatedElucigene_MLPA £44,470,770 37,216 Ext. Dom Ext. Dom Ext. DomLIPOchip £46,506,304 38,240 Ext. Dom Ext. Dom Ext. DomElucigene_Lipochip £46,578,004 38,240 Dominated Dominated DominatedLIPOchip processed in Spain £47,298,810 38,668 £3,926,825 2,015 £1,949LIPOchip_MLPA £47,597,529 38,803 Ext. Dom Ext. Dom Ext. DomElucigene_LIPOchip_MLPA £47,669,229 38,803 Dominated Dominated DominatedCGA £48,501,362 39,231 £1,202,552 563 £2,135Elucigene_CGA £48,548,912 39,231 Dominated Dominated DominatedLIPOchip_CGA £48,672,212 39,231 Dominated Dominated DominatedElucigene_Lipochip_CGA £48,743,912 39,231 Dominated Dominated Dominated
  13. 13. Cost-effectivenessacceptability curves
  14. 14. Discussion: Cost-effectiveness• Little high quality evidence of test accuracy• Rapidly evolving environment: – Tests constantly improving – New versions of tests being developed – Next generation sequencing• Results and conclusions were robust a range of sensitivity analyses
  15. 15. 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
  16. 16. Thank you very muchContact Details:d.boyers@abdn.ac.ukUseful links:http://www.abdn.ac.uk/heruhttp://www.abdn.ac.uk/hsruhttp://www.nice.org.ukhttp://www.hta.co.ukThis project was funded by the National Institute for Health Research Health TechnologyAssessment (NIHR HTA) programme and commissioned on behalf of NICE. It will be publishedin full in the Health Technology Assessment journal series. Visit the HTA programme website formore details www.hta.ac.uk/project/2450. The views and opinions expressed therein are thoseof the authors and do not necessarily reflect those of the HTA programme, NICE, NIHR, NHS orthe Department of Health.’

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