Abstract
Use of combined oral contraceptives (COCs) by women increases the risk of venous thromboembolism (VTE), which can have a major impact on an individuals’ quality of life. VTE is also associated with an increase in healthcare costs. Our aim was to systematically review cost-effectiveness analyses (CEAs) considering any screening for risk of VTE in women using COCs. The quality of reporting in each study was assessed, a summary of results was prepared, and the key drivers of cost effectiveness in each of the eligible CEAs were identified. A search strategy using MeSH terms was performed in MEDLINE, Embase, the Centre for Review and Dissemination (CRD) database including the Economic Evaluation Database from the UK National Health Service, and Cochrane reviews. Two reviewers independently screened and determined the final articles, and a third reviewer resolved any discrepancies. Consolidated Health Economic Evaluation Reporting Standards was used to assess the quality of reporting in terms of perspective, effectiveness measures, model structure, cost, time-horizon and discounting. Four publications (three from Europe, one from the United States) were eligible for inclusion in the review. According to current criteria, relevant elements were sometimes not captured and the sources of epidemiological and effectiveness data used in the CEAs were of limited quality. The studies varied in terms of type of costs assessed, country settings, model assumptions and uncertainty around input parameters. Key drivers of CEAs were sensitivity and specificity of the test, incidence rate of VTE, relative risk of prophylaxis, and costs of the test. The reviewed studies were too dissimilar to draw a firm conclusion on cost-effectiveness analysis about universal and selective screening in high-risk groups. The new emerging diagnostic tools for identifying women at risk of developing VTE, that are more predictive and less costly, highlight the need for more studies that apply the latest evidence and utilize robust methods for cost-effectiveness analysis. This information is required to improve decision making for this pertinent issue within personalized medicine.
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Funding
The research underlying this publication has been primarily funded by the Swiss Commission for Technology and Innovation (CTI), the CTI Grant Number 18712.1 PFES-ES. According to CTI rules, an additional funding contribution of the involved company (Gene Predictis S.A.) is obligatory. Authors ZA, CSS, JVS and MS has received the obligatory research funding by Gene Predictis S.A. via employment institution, and JM and GT are employed by Gene Predictis S.A.
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Zanfina Ademi and C. Simone Sutherland shared first authorship.
Appendices
Appendix 1 Key word for search strategy
Clinical keywords | |
|---|---|
1 | exp Contraceptives, Oral/ |
2 | contraceptives, Oral.mp |
3 | oral contraceptives.mp |
4 | oral contraceptive.mp |
5 | exp Contraceptives, Oral, Combined/ |
6 | combined oral contraceptives.mp |
7 | combined oral contraceptive.mp |
8 | norethisterone.mp |
9 | norethisteron*.mp |
10 | norethindrone.mp |
11 | norethindron*.mp |
12 | ethynodiol diacetate.mp |
13 | lynestrenol.mp |
14 | lynestrenol*.mp |
15 | norethynodrel.mp |
16 | norethynodrel*.mp |
17 | dienogest.mp |
18 | dienogest*.mp |
19 | levonorgestrel.mp |
20 | levonorgestrel*.mp |
21 | norgestrel.mp |
22 | norgestrel*.mp |
23 | dl-norgestrel.mp |
24 | dl-norgestrel*.mp |
25 | desogestrel.mp |
26 | desogestrel*.mp |
27 | norgestimate.mp |
28 | norgestimat*.mp |
29 | gestodene.mp |
30 | gestoden*.mp |
31 | medroxyprogesterone acetate.mp |
32 | chlormadinone acetate.mp |
33 | nomegestrol.mp |
34 | nomegestrol*.mp |
35 | nestorone.mp |
36 | cyproterone acetate.mp |
37 | drospirenone.mp |
38 | drospirenon*.mp |
39 | oestrogen*.m_titl |
40 | estrogen.m_titl |
41 | exp Ethinyl Estradiol/ |
42 | ethinyl Estradiol.mp |
43 | ethinylestradiol.mp |
44 | ethinylestradiol*.mp |
45 | mestranol.mp |
46 | mestranol*.mp |
47 | estradiol valerate.mp |
48 | progestogen*.m_titl |
49 | OR/1–48 |
50 | deep vein thrombosis.m_titl |
51 | deep venous thrombosis.m_titl |
52 | venous Thrombosis.m_titl |
53 | vein thrombosis.m_titl |
54 | exp venous thrombosis/ |
55 | exp thrombophlebitis/ |
56 | exp upper extremity deep vein thrombosis/ |
57 | thrombophlebitis.m_titl |
58 | pulmonary embolism.m_titl |
59 | exp pulmonary embolism/ |
60 | venous thromboembolism.m_titl |
61 | exp venous thromboembolism/ |
62 | venous thromboembolic disorders.m_titl |
63 | venous.m_titl |
64 | thromboembolic.m_titl |
65 | disorder.m_titl |
66 | 63 AND 64 AND 65 |
67 | venous thromboembolic diseases.m_titl |
68 | venous thromboembolic disease.m_titl |
69 | venous thrombotic.m_titl |
70 | exp thromboembolism/ |
71 | venous.mp |
72 | vein.mp |
73 | veins.mp |
74 | 71 OR 72 OR 73 |
75 | 70 AND 74 |
76 | OR/50–62 OR/66–69 OR 75 |
77 | risk.mp |
78 | risks.mp |
79 | risk factor.mp |
80 | risk factors.mp |
81 | OR/77–80 |
82 | women.mp |
83 | woman*.mp |
84 | women*.mp |
85 | girl.mp |
86 | girls.mp |
87 | female/ |
88 | OR/82–87 |
89 | 49 AND 76 AND 81 AND 88 |
90 | animal/ not humans/ |
91 | 89 not 90 |
Health economic keywords | |
|---|---|
92 | afford$.mp |
93 | capital expenditures.mp |
94 | cost$.mp |
95 | cost-benefit analyses.mp |
96 | cost-benefit analysis.mp |
97 | cost consequences analysis.mp |
98 | cost-consequences analysis.mp |
99 | cost-effectiveness analyses.mp |
100 | cost-effectiveness analysis.mp |
101 | cost-minimization analyses.mp |
102 | cost-minimization analysis.mp |
103 | cost-utility .mp |
104 | cost-utility analyses.mp |
105 | cost-utility analysis.mp |
106 | economic$ .mp |
107 | economic-evaluation .mp |
108 | expenditure$ .mp |
109 | Fee$ .mp |
110 | finance$ .mp |
111 | financial.mp |
112 | financing.mp |
113 | health expenditures.mp |
114 | health resource allocation .mp |
115 | health resource utilization.mp |
116 | health-economic$.mp |
117 | medical savings accounts.mp |
118 | monetary.mp |
119 | pharmaco-economic analyses.mp |
120 | pharmaco-economic analysis .mp |
121 | pharmacoeconomic$ .mp |
122 | pharmacoeconomic-analyses .mp |
123 | pharmacoeconomic-analysis .mp |
124 | price$ .mp |
125 | socioeconomic$.mp |
126 | OR/92–124 |
127 | 91 and 126 |
Appendix 2 Characteristics of excluded economic evaluations (NOTE: excluded at second level screening, full text)
Author | Year | Reason excluded |
|---|---|---|
CADTH | 2015 | Genetic testing for VTE, and not specific for women |
RubioTerres | 2015 | Genetic testing for VTE, and not specific for women |
Auerbach(7) | 2004 | No oral contraception population |
Eckman(8) | 2002 | no differentiation, combined OC and pregnancy |
Clark(9) | 2002 | Population of interest was only pregnant women |
Marchetti | 2001 | Male population |
Crenin | 2002 | Not a cost effectiveness analyses |
Palaretti | 1999 | Not a cost effectiveness analyses |
Kalev | 1999 | Not a cost effectiveness analyses |
Rousseau | 2013 | Only abstract |
Bryant | 1996 | Book chapter |
Appendix 3 Type of costs reported in the included economic evaluations
Publication | Type of costs | Sources |
|---|---|---|
Compagni et al. [17] | Direct costs Cost of testing Biochemical tests Genetic tests Hospitalization costs (DVT, PE, AMI, IS, PH, PTS, VTE, haemorrhagic stroke, unwanted pregnancies) Pharmacological treatment in hospital OCs | Hospital discharge records using micro-costing method (Galleria hospital discharge records) and drug prices for national formulary |
Smith et al. [15] | Direct costs Cost of screening and counseling Hospitalization costs (DVT, PE, major and minor bleed, death, post-phlebitic syndrome) Prophylactic treatment with low molecular weight heparin | Aujesky 2005. Oral anticoagulation strategies after first idiopathic Venus thrombosis event, Red book: pharmacy fundamental reference, Thomson health care 2006 |
Szucs et al. [14] | Direct costs (third party payer) Hospitalizations DVT PE OCs Cost of testing | Krankheitsartenstatistik 1995, Bonn |
Wu et al. [16] | Direct costs Screening for thrombophilia Management of DVT (including prophylactic treatment) Management of PE (including prophylactic treatment) OCs | British national formulary and national health services in Scotland |
Appendix 4 Critical appraisal: consolidated health economic evaluation report standards (CHEERS) checklist (10)
S | Author | Compagni et al. [17] | Smith et al. [15] | Szucs et al. [14] | Wu et al. [16] | Percentage |
|---|---|---|---|---|---|---|
Item# | Item/year | 2013 | 2008 | 1996 | 2005 | |
1 | Title | 1 | 0 | 1 | 1 | 0.75 |
2 | Abstract | 0.5 | 0.5 | 0.5 | 1 | 0.625 |
3 | Background & objectives | 1 | 1 | 1 | 1 | 1 |
4 | Target population & subgroups | 1 | 1 | 0.5 | 1 | 0.875 |
5 | Setting & location | 1 | 0 | 1 | 1 | 0.75 |
6 | Study perspective | 1 | 0 | 1 | 1 | 0.75 |
7 | Comparators | 1 | 1 | 1 | 1 | 1 |
8 | Time horizon | 0.5 | 1 | 0.5 | 1 | 0.75 |
9 | Discount rate | 1 | 1 | 0 | 0 | 0.5 |
10 | Choice of health outcomes | 0.5 | 1 | 1 | 1 | 0.875 |
11 | Measure of effectiveness | 1 | 1 | 1 | 1 | 1 |
12 | Evaluation of preference based outcomes | NA | NA | NA | NA | 0 |
13 | Estimating resources and costs | 1 | 1 | 1 | 1 | 1 |
14 | Currency, price, date and conversion | 0.5 | 0 | 0.5 | 1 | 0.5 |
15 | Choice of model | 0.5 | 1 | 0.5 | 1 | 0.75 |
16 | Assumptions | 1 | 1 | 0 | 1 | 0.75 |
17 | Analytical methods | 0 | 1 | 0 | 1 | 0.5 |
18 | Study parameters | 1 | 1 | 0.5 | 0 | 0.625 |
19 | Incremental costs and outcomes | 1 | 1 | 1 | 1 | 1 |
20 | Characterizing uncertainty | 1 | 1 | 0.5 | 1 | 0.875 |
21 | Characterizing heterogeneity | 1 | 1 | 0 | 1 | 0.75 |
22 | Study findings, limitations, generalizability, and current knowledge | 1 | 1 | 1 | 1 | 1 |
23 | Source of funding | 1 | 1 | 0 | 0 | 0.5 |
24 | Conflicts of interest | 0 | 1 | 0 | 0 | 0.25 |
Total scores | Average score = 0.76 | Average score = 0.83 | Average score = 0.61 | Average score = 0.83 | ||
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Ademi, Z., Sutherland, C.S., Van Stiphout, J. et al. A systematic review of cost-effectiveness analysis of screening interventions for assessing the risk of venous thromboembolism in women considering combined oral contraceptives. J Thromb Thrombolysis 44, 494–506 (2017). https://doi.org/10.1007/s11239-017-1554-5
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DOI: https://doi.org/10.1007/s11239-017-1554-5