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Table 4 Cost-effectiveness results of included studies

From: Pharmacogenetic testing for adverse drug reaction prevention: systematic review of economic evaluations and the appraisal of quality matters for clinical practice and implementation

No Author, Year of published study setting Target populations Intervention vs comparator Cost effectiveness threshold Cost-effectiveness results
(ICER/ICUR)
Drug: warfarin, Biomarker: CYP2C9 and VKORC1
ADRs: bleeding events
1 Kim,DJ et al., 2017 [16] Korea mechanical heart valve replacement (MHVR) (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
$50,000 per QALY gained • ICER (b) vs (a): $13,562 per QALY gained
2 Verhoef et al., 2016 [17] UK and Sweden Atrial Fibrillation (AF) (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
UK £20,000 per QALY gained, Sweden500,000 SEK • In UK: ICER (b) vs (a): £6702 per QALY gained
• In Sweden: ICER (b) vs (a): 253,848 SEK per QALY gained
3 Mitropoulou et al., 2015 [18] Croatia ischemic stroke patients with AF (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
€40,000 to €50,000 per QALY gained • ICER (b) vs (a): €31,225 per QALY gained
4 Chong, HYet al, 2014 [21] Thailand newly initiated warfarin therapy (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
160,000 THB or $5333 per QALY gained • Healthcare system perspective:
ICER (b) vs (a):1,477,042 THB ($49,234) per QALY gained
• Societal perspective
ICER (b) vs (a): 1,473,852 THB ($49,128) per QALY gained
5 You, et al., 2014 [19] USA AF (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided treatment
$50,000 per QALY gained • ICER (b) vs (a): $ 2843 per QALY gained
6 Pink et al., 2014 [20] Sweden Non-valvular AF (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided treatment
(c) dabigatran
(d) rivaroxaban
(e) apixaban
£20,000–30,000 per QALY gained • ICER (b) vs (a): £ 13,226 per QALY gained
• ICER (e) vs (b): £20,671 per QALY gained
• (d) is dominated by (c) and (e), high cost and lower QALYs than (c) and (e)
• (c) is dominated by (e), high cost and lower QALYs than (e)
7 You et al., 2012 [22] USA newly diagnosed AF (a) warfarin
(b) CYP2C19and VKORC1genotyping-guided treatment
(c) dabigatran 110 mg twice daily
(d) dabigatran 150 mg twice daily
$50,000 per QALY gained • (a) is dominated by (b), high cost and lower QALYs than (b)
• ICER (d) vs (b): $13,810 per QALY gained
• (c) is dominated by (d), (d) lower cost and more effective than (c)
8 Meckley et al., 2010 [23] USA newly initiated warfarin therapy (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
$50,000 per QALY gained • ICER (b) vs (a): $ 60,725 per QALY gained
9 Eckman et al., 2009 [26] USA Non-valvular AF (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
$50,000 per QALY gained • ICER (b) vs (a): $171,750 per QALY gained
10 Patrick et al., 2009 [25] USA newly diagnosed AF (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
$50,000 per QALY gained • ICER (b) vs (a): ICER< 50,000 per QALY gained if it increased the time spent in the target INR range during the first 3 months of treatment by 5 to 9 percentage points
11 You et al., 2009 [24] USA newly initiated warfarin therapy (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
$50,000 per QALY gained • ICER (b) vs (a): $ 347,059 per QALY gained
12 McWilliam et al., 2008 [27] USA newly initiated warfarin therapy (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
N/A • Low baseline bleeding: ICER (b) vs (a): $82,890 per bleeding averted
• Medium baseline bleeding: ICER (b) vs (a): $13,589 per bleeding averted
• High baseline bleeding: (b) is dominated by (a) lower cost than (a)
13 Schalekamp et al., 2006 [28] The Netherlands newly initiated warfarin therapy (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
€20,000 • ICER (b) vs (a): € 4233 per bleeding averted
14 You et al., 2004 [29] USA newly initiated warfarin therapy (a) warfarin
(b) CYP2C19 and VKORC1 genotyping-guided dosing of warfarin
N/A • ICER (b) vs (a): $5778 per bleeding averted
Drug: clopidogrel, Biomarker: CYP2C19 ADRs: major cardiac/adverse cardiovascular events
1 Wang Y et al., 2018 [30] Hong Kong ACS undergoing PCI (a) clopidogrel
(b) ticagrelor
(c) CYP2C19 testing guided therapy
Test: positive: ticagrelor;
Test negative: clopidogrel
$42,423 per QALY gained • ICER (c) vs (a): $2560 per QALY gained
• (b) is dominated by (c), high cost and lower QALYs than (c)
2 Jiang, M et al., 2017 [31] USA ACS undergoing PCI (a) clopidogrel
(b) prasugrel or ticagrelor
(c) CYP2C19 testing guided therapy
Test: positive: prasugrel or ticagrelor;
Test negative: clopidogrel
$50,000 per QALY gained • (a) is dominated by (c), high cost and lower QALYs than (c)
• (b) is dominated by (c), high cost and lower QALYs than (c)
3 Deiman BA et al., 2016 [32] the Netherlands ACS undergoing PCI (a) clopidogrel
(b) prasugrel
(c) ticagrelor
(d) CYP2C19 testing guided therapy
Test: positive: prasugrel or ticagrelor;
Test negative: clopidogrel
€65,000 per QALY gained • ICER (d) vs (a): €81,500 per QALY gained
• ICER (d) vs (b): €9111 per QALY gained
• ICER (d) vs (c): €5972 per QALY gained
4 Kazi DS et al., 2014 [34] USA ACS undergoing PCI (a) clopidogrel
(b) prasugrel
(c) ticagrelor
(d) CYP2C19 testing guided therapy
Test: positive: prasugrel or ticagrelor;
Test negative: clopidogrel
$50,000 per QALY gained • Genotyping with prasugrel vs (a): $35,800 per QALY gained
• Genotyping with ticagrelor vs (a): $30,200 per QALY gained
5 Patel et al., 2014 [33] USA ACS undergoing PCI (a) clopidogrel+asprin
(b) prasugrel+aspirin
(c) CYP2C19 testing guided therapy
Test: positive: prasugrel+asprin;
Test negative: clopidogrel+asprin
$50,000 per QALY gained • ICER (c) vs (a): $4200 per QALY gained
• (b) is dominated by (c), high cost and lower QALYs than (c)
6 LALA A et al., 2013 [36] USA ACS undergoing PCI (a) clopidogrel
(b) prasugrel
(c) CYP2C19 testing guided therapy
Test: positive: prasugrel;
Test negative: clopidogrel
$50,000 per QALY gained • (a) is dominated by (c), (c) lower cost and more effective than (a)
• (b) is dominated by (c), (c) lower cost and more effective than (b)
7 Sorich et al., 2013 [35] Australia ACS undergoing PCI (a) clopidogrel
(b) ticagrelor
(c) CYP2C19 testing guided therapy
Test: positive: ticagrelor;
Test negative: clopidogrel
AUS$
50,000 per QALY gained
• ICER (c) vs (a): $AUS 6346 per QALY gained
• ICER (b) vs (c): $AUS 22,821 per QALY gained
8 Panattoni L et al., 2012 [38] New Zealand ACS (included the four largest ethnic groups) (a) clopidogrel
(b) prasugrel
(c) CYP2C19 testing guided therapy
Test: positive: prasugrel;
Test negative: clopidogrel
$NZ50000 per QALY gained • (b) is dominated by (a), high cost and lower QALYs than (a)
• ICER (c) vs (a): $NZ 24,617 per QALY gained
• (b) is dominated by (c), (c) lower cost and more effective than (b)
9 Reese E S et al., 2012 [37] USA ACS, recent MI or stroke undergoing PCI (a) clopidogrel
(b) prasugrel
(c) CYP2C19 testing guided therapy
Test: positive prasugrel;
Test negative clopidogrel
N/A • (a) is dominated by (c), (c) lower cost and more effective than (a)
• (b) is dominated by (c), (c) lower cost and more effective than (b)
Drug: statin, Biomarker: pharmacogenetics test ADR: myopathy, rhabdomyolysis
1 Mitchel et al., 2017 [39] Canada cardiovascular patients (a) statin
(b) genotyping-guided treatment with statin (only patients experiencing musculoskeletal pain are being tested)
CAN
$6150 per QALY gained
• (a) is dominated by (b), high cost and lower QALYs than (b)
• (b) would be cost-effective as long as the test costs less than CAN$906
Drug: allopurinol, Biomarker: HLAB-5801
ADR: SJS/TEN, DRESS
1 Cheng H et al., 2018 [41] China (Han population) Hyperuricemia and gout (a) allopurinol 100 mg and 600 mg per day
(b) febuxostat 40mgand 80 mg per day
(c) HLA-B5801 testing prior to treatment
Test positive: febuxostat
Test negative: allopurinol
N/A • In all 253 patients
• (c) saved 1,384,040 yuan for allopurinol and febuxostat at the lowest dosages
• (c) saved 2,807,770 yuan for allopurinol and febuxostat at the highest dosages
2 Chong et al., 2018 [40] Malaysia gout (a) allopurinol starting dose 300 mg, target dose 600 mg per day (current practice)
(b) probenecid target dose 2 g per day
(c) HLA-B5801 testing prior to treatment
Test positive: probenecid
Test negative: allopurinol
MYR 39,000 or $8695 per QALY gained • (b) is dominated by (a), high cost and lower QALYs than (a)
• (c) is dominated by (a), high cost and lower QALYs than (a)
3 Jutkowitz et al., 2017 [44] USA gout (a) allopurinol-febuxostat sequential therapy: allopurinol:target dose 300 mg/day and febuxostat: 80 mg/day, (current practice)
(b) HLA-B5801 testing prior to treatment
Test positive: febuxostat
Test negative:allopurinol
$109,000 per QALY gained • ICER (b) vs (a): for
-Asians $64,190,
-African Americans $83,450,
-Caucasians or Hispanics $183,720 per QALY gained
4 Ke CH et al., 2017 [43] Taiwan gout with chronic kidney disease (a) benzbromarone 100 mg/day (current practice)
(b) allopurinol target dose 100 mg/ day
(c) febuxostat 80 mg/day
(d) HLA-B5801 testing prior to treatment
Test positive: febuxostat or benzbromarone
Test negative: allopurinol
NT
$800,000 or US
$25,600 per QALY gainedin 2015
• (b) is dominated by (a), high cost and lower QALYs than (a) current practice)
• (c) is dominated by (d), high cost and lower QALYs than (d) current practice)
• ICER (d) vs (a): NT$ 234,610 per QALY gained in the base-case and NT$ 230,925 per QALY gained in patients with chronic kidney disease
5 Plumpton CO et al., 2017 [42] UK gout (a) allopurinol target dose 300 mg per day add prophylactic treatment with colchicine
(b) HLA-B5801 testing prior to treatment
Test positive: febuxostat: target dose 80 mg per day
Test negative: allopurinol
£30,000 per QALY gained • ICER (d) vs (a): £44,954 in the base case and £38,478 per QALY in patients with chronic renal insufficiency
6 Dong D et al., 2015 [46] Singapore gout (a) allopurinol starting dose 300 mg, target dose 600 mg per day
(b) allopurinol +safety program (SP)
(c) HLA-B5801 testing prior to treatment + SP
(d) HLA-B5801 testing prior to treatment + SP
Test positive: probenecid target dose 2 g per day
Test negative: allopurinol
(e) HLA-B5801 testing prior to treatment
Test positive: probenecid target dose 2 g per day
Test negative: allopurinol
(f) no allopurinol (treatment of acute flares only)
$50,000 per QALY gained • -ICER (b) vs (a): $79,140 per QALY
• (c) is dominated by (b), high cost and lower QALYs than (b) current practice)
• ICER (d) vs (b): $85,630 per QALY
• (e) is dominated by (d), high cost and lower QALYs than (d) current practice)
• (f) is dominated by (d), high cost and lower QALYs than (d) current practice)
7 Park DJ et al., 2015 [45] Korea gout with chronic renal insufficiency (a) allopurinol starting dose 100 mg, target dose 300 mg per day
(b) HLA-B5801 testing prior to treatment
Test positive: febuxostat starting dose 40 mg, target dose 80 mg) per day
Test negative: allopurinol
N/A • Costs of (a) $1193 and (b) $1055
(b) is less costly and more effective than (a)
8 Saokaew et al., 2014 [47] Thailand gout (a) allopurinol starting dose 300 mg per day
(b) HLA-B5801 testing prior to treatment
Test positive: probenecid target dose 1 mg target to 2 g per day
Test negative: allopurinol
160,000 THB per QALY gained • ICER (b) vs (a): 156,937 THB per QALY
Drug: abacavir, Biomarker: HLA B*57:01
ADR: hypersensitivity
1 Kubaeva et al., 2018 [48] Russia HIV (a) abacavir regimen
(b) HLA-B* 5701 testing prior to treatment
Test positive: alternative regimens without abacavir
Test negative: abacavir regimen
N/A • (b) vs (a): was cost-saving 54,1646 rubles
2 Kapoor R et al., 2015 [49] 3 ethnic groups in Singapore HIV (a) abacavir-based ART
(b) tenofovir-based ART
(c) HLA-B:5701 testing prior to treatment
Test positive: tenofovir-based ART
Test negative: abacavir-based ART
$50,000 per QALY gained Early stage: ICER (c) vs (a):
Chinese $415,845 per QALY gained,
Malay $318,029 per QALY gained,
Indian $208,231 per QALY gained
Late stage: ICER (c) vs (a):
Chinese $926,938 per QALY gained, Malay $624,297 per QALY gained, Indian $284,598 per QALY gained
HIV who are contraindicated to tenofovir
ICER (b) vs (a): all ethnicity was not cost-effective, except for Indian patients with early-stage ICER (c) vs (a): $44,649 per QALY gained
3 Nieves Calatrava et al., 2010 [51] Spain HIV (a) abacavir regimen
(b) HLA-B:5701 testing prior to treatment
Test positive: alternative HAART regimen without ABC
Test negative: abacavir regimen
N/A • cost per HSR avoided of €630
4 Kauf TL et al., 2010 [52] USA HIV (a) short-term: abacavir+ lamivudine+efavirenz
(b) long-term: tenofovir+emtricitabine+efavirenz
(c) HLA-B:5701 testing prior to treatment
Test positive: tenofovir+emtricitabine+efavirenz
Test negative: abacavir+lamivudine+efavirenz;
$50,000 per QALY gained • Short-term: (c) is dominated by (a), high cost and lower QALYs than (a)
• Long-term: (b) is dominated by (c), high cost and lower QALYs than (c)
5 Wolf et al., 2010 [50] Germany HIV (a) combination of abacavir+ lamivudine
(b) HLA-B:5701 testing prior to treatment
Test positive combination of tenofovir, emtricitabine
Test negative combination of abacavir+ lamivudine
N/A • (b) vs (a): (b) cost-saving €44 and 127 per screened patient from healthcare payer and societal perspective
6 Schackman BR et al., 2008 [53] USA HIV (a) abacavir-based regimen
(b) tenofovir-based regimen
(c) HLA-B:5701 testing prior to treatment
Test positive: tenofovir or AZT-based regimen
Test negative: abacavir-based regimen
$50,000 per QALY gained • ICER (c) vs (a): $36,700 per QALY gained
• (b) is dominated by (a),high cost and lower QALYs than (a)
7 Hughes DA et al., 2004 [54] UK HIV (a) Trizivir (AZT/3TC/ABC)
(b) HLA-B:5701 testing prior to treatment
Test positive: HAART regimen without abacavir
Test negative: Trizivir (AZT/3TC/ABC)
(HAART: highly active antiretroviral therapy)
N/A • (a) is dominated by (b), high cost and lower benefit than (b), except for Trizivir is substituted with ritonavir+indinavir+combivir
• ICER (b) vs (a): € 22,811 per hypersensitivity reaction avoided
Drug: efavirenz, Biomarker: CYP2B6, ADRs: sub- or supratherapeutically dosed
1 Schackman et al., 2015 [55] USA HIV (a) efavirenz 600 mg + tenofovir+ emtricitabine
(b) CYP 2B6 testing prior to treatment
Test positive: decrease dose to 200,400 mg
Test negative: efavirenz 600 mg
(c) Universal low dose efavirenz 400 mg + tenofovir+ emtricitabine
$ < 100,000 per QALY gained • (a) is dominated by (b), high cost and lower benefit than (b)
Drug: azathioprine, Biomarker: TPMT ADR: neutropenia or severe neutropenia
1 Thompson AJ et al., 2014 [56] UK autoimmune diseases (a) azathioprine therapy
(b) TPMT testing prior to treatment
Test positive: alternative treatment
Test negative: azathioprine
£20,000 per QALY gained • (b) is dominated by (a) lower cost and lower QALYs than (a)
2 Priest VLet al, 2006 [58] New Zealand inflammatory bowel disease (IBD) (a) azathioprine
(b) TPMT testing prior to treatment (Phenotype and genotype)
N/A • Phenotype and genotype testing dominated by (a), high cost and lower QALYs than (a) There are cost-savings (vs no testing) of $NZ120,000 and 71 neutropenias avoided;-034QALYs and $NZ11,000 and 40 neutropenias avoided, −058QALYs)
Drug: azathioprine, Biomarker: TPMT ADR: leukopenia
3 Hagaman JTet al, 2010 [57] USA Idiopathic Pulmonary Fibrosis (IPF) (a) conservative therapy which no specific therapy
(b) azathioprine+N-acetylcysteine and steroids (no testing)
(c) TPMT testing prior to treatment
Test positive: conservative therapy
Test negative: azathioprine+N-acetylcysteine and steroid
$50,000 per QALY gained • ICER (b) vs (a): $49,245 per QALY
*ICER (c) vs (b): $29,663 per QALY gained
4 Dubinsky MC et al., 2005 [60] USA Crohn’s disease (a) TPMT testing prior to treatment
Test positive: metrotrexate
Test negative: azathioprine
(b) metabolite monitoring (MM) prior to treatment with azathioprin
(c) TPMT testing +MM prior to treatment with azathioprine
(d) community care (CC)
N/A • (d) is dominated by (a), (b),and (c), (d) less costs and faster time to response or sustained response
5 Winter J et al., 2004 [61] Scotland IBD (a) azathioprine
(b) TPMT testing prior to treatment
N/A • for a 30 year old: ICER (b) vs (a): £347 per life-year saved and
• for a 60 year old: ICER (b) vs (a): £817 per life-year saved
Drug: azathioprine, Biomarker: TPMT ADR: all adverse events
6 Sayani FA et al., 2005 [59] Canada Crohn’s disease and IBD (a) azathioprine
(b) TPMT testing prior to treatment
N/A • The direct health care costs for (a) $30,011 per patient and (b) $34,887 per patient
Drug: azathioprine, Biomarker: TPMT ADR: severe bone marrow toxicity
7 Oh KT et al., 2004 [62] Korea rheumatoid arthritis and systemic lupus erythematosus (a) azathioprine
(b) TPMT testing prior to treatment
N/A • (a) is dominated by (b), (b) lower cost and more effective than (a)
Drug: azathioprine, Biomarker: TPMT ADR: hematological cytopenias
8 Marra CA et al., 2002 [63] Canada rheumatoid arthritis and systemic lupus erythematosus (a) azathioprine
(b) TPMT testing prior to treatment
N/A • (a) cost $677 Cdn per patient, (b) cost $663 Cdn per patient
Drug: carbamazepine, Biomarker: HLAA*15:02, ADRs: SJS, TENs, hypersensitivity
1 Chong et al., 2017 [64] Malaysia Epilepsy (a) carbamazepine (current practice)
(b) sodium valproate (VPA)
(c) HLA-B*15:02 testing prior to treatment
Test positive: VPA
Test negative: carbamazepine
MYR 37,000 ($ 8982) per QALY gained • (b) is dominated by (a), high cost and lower QALYs than (a) current practice)
• (c) is dominated by (a), high cost and lower QALYs than (a) current practice)
2 Chen et al., 2016 [65] Hong Kong Epilepsy (a) current situation, using antiepileptic drug (pre-policy period)
(b) current situation, using antiepileptic drug (post-policy period)
(c) HLA-B*15:02 testing prior to treatment (the ideal situation) (ideal situation)
Test positive: alternative anti-epileptic drug
Test negative: carbamazepine or phenytoin
(d) HLA-B*15:02 testing prior to either carbamazepine or phenytoin (extended situation)
$50,000 per QALY gained • ICER (b) vs (a): $85,697 per QALY gained
• ICER (c) vs (a): $11,090 per QALY gained
• ICER (d) vs (a): $197,158 per QALY gained
3 Rattanavipapong W et al., 2013 [67] Thailand Epilepsy or neuropathic pain (a) carbamazepine (no HLA-B*15:02 testing)
(b) HLA-B*15:02 testing prior to treatment
Test positive:
for epilepsy: valproate, for neuropathic pain: gabapentin;
Test negative: carbamazepine
(c) all prescribed alternative (no HLA-B*15:02 testing) (epilepsy: valproate, neuropathic pain: gabapentin)
120,000 THB per QALY gained • ICER (b) vs (a):
222,000 THB per QALY for epilepsy, 130,000 THB per QALY for neuropathic pain
• ICER (c) vs (a):
32,522,000 per QALY for epilepsy, (epilepsy), 35,877,000 per QALY for neuropathic pain
4 Tiamkao S et al., 2013 [66] Thailand Epilepsy or neuropathic pain and neurological diseases (a) carbamazepine
(b) HLA-B*15:02 testing prior to treatment
Test positive: non-specified
Test negative: carbamazepine
N/A • (b) vs (a): (b) was cost-saving 98,54,994 THB per 100 cases of carbamazepine users
5 Dong D et al., 2012 [68] Singapore Epilepsy (a) carbamazepine or phenytoin
(b) HLA-B*15:02 testing prior to treatment
Test positive: valproate;
Test negative carbamazepine or phenytoin
(c) valproate (no screening)
$50,000 per QALY gained ICER (b) vs (a):
Chinese patients $37,030 per QALY gained, Malay $7930 per QALY gained and Indians $136,630 per QALY gained
• (c) is dominated by (b), high cost and lower QALYs than (b)
Drug: carbamazepine, Biomarker: HLAA*31:01, ADRs: SJS, TENs, hypersensitivity
1 Plumpton et al., 2015 [69] UK Epilepsy (a) carbamazepine
(b) HLA-B*31:01 testing prior to treatment
Test positive: lamotrigine;
Test negative: carbamazepine
£20,000 per QALY gained • ICER (b) vs (a): £ 12,808 per QALY gained
Drug: Fluoropyrimidines, Biomarker: DPYD*2A genotype–guided dosing ADR: toxicity iehematologic, GI
1 Deenen MJ et al., 2016 [70] The Netherland cancer (a) fluoropyrimidines-based therapy
(b) DPYD*2A testing prior to treatment
Test positive: alternative regimen
Test negative: Fluoropyrimidines-based
N/A • (b) vs (a): (b) cost-savings of €45 ($61) per patient
Drug: irinotecan, Biomarker: UGT1A1 ADR: severe neutropenia
1 Pichereau S et al., 2010 [71] France metastatic colorectal cancer (a) FOLFIRI regimen (5-fluorouracil, leucovorin and irinotecan)
(b) UGT1A1 testing prior to treatment with FOLFIRI
Test positive: FOLFOX regimen (oxaliplatine + 5-FU + folinic acid)
Test negative: FOLFIRI
N/A • ICER (b) vs (a): to avoid one febrile neutropenia per 1000 patients treated was € 9428 to € 10,901
2 Gold HT et al., 2009 [72] USA metastatic colorectal cancer (a) FOLFIRI regimen (5-fluorouracil, leucovorin and irinotecan)
(b) UGT1A1 testing prior to treatment with FOLFIRI
Test positive: reduce dose to intermediate dose
Test negative: FOLFIRI
$100,000 per QALY gained • ICER (b) vs (a): was cost-effective if the treatment efficacy of irinotecan in homozygotes after dose reduction had to be ≥984% of full-dose efficacy for genetic testing to remain preferred
Drug: nortriptyline, Biomarker: CYP2D6 ADRs: sub- or supratherapeutic dose
1 Bern EJ et al., 2016 [73] The Netherland major depressive disorder (a) nortriptyline
(b) CYP2D6 genotyping-guided dosing of nortriptyline
€50,000 per QALY gained • ICER (b) vs (a): €1,333,000 per QALY gained
Drug: oral contraceptive, Biomarker: factor V Leiden ADR: Thromboembolism
1 Smith KJ, et al., 2008 [74] USA women who receiving oral contraceptives (OCPs) (a) usual care
(b) genotyping
(c) genotyping with OCP counseling
(d) genotyping with OCP counseling and AC for high-risk events
(e) genotyping with OCP counseling and AC for long-term
$20,000 per QALY gained • ICER (d) vs (c): $ 147 per QALY gained
• ICER (e) vs (d): $ 639,500 per QALY
• (a) is dominated by (d), high cost and lower QALYs than (d)
• (b) is dominated by (d), high cost and lower QALYs than (d))
  1. AC: anticoagulation, ACS: Acute Coronary Syndrome, CBA: Cost-benefit analysis, CEA: Cost-effectiveness analysis, CMA: Cost-minimization analysis, CUA: Cost-utility analysis, EE: Economic evaluation, ICER: Incremental Cost-Effectiveness Ratio
  2. OCP: oral contraceptive pill, PCI: Percutaneous Coronary Intervention, PSA: Probabilistic Sensitivity Analysis
  3. QALY: Quality adjusted life-year, N/A: Not Applicable, WTP: Willingness to pay