3. National Institute for Health andClinical Excellence.Measur-ing effectiveness and cost effectiveness: the QALY [online].Available from URL: http://www.nice.org.uk/newsroom/features/measuringeffectivenessandcosteffectivenesstheqaly.jsp[Accessed 2010 Jul 18]

4. American Academy of Orthopaedic Surgeons clinical guide-line on prevention of symptomatic pulmonary embolism inpatients undergoing total hip or knee arthroplasty. Rose-mont (IL): American Academy of Orthopaedic Surgeons,2007 May [online]. Available from URL: http://www.aaos.org/Research/guidelines/PE_guideline.pdf [Accessed 2007Jul 10]

5. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venousthromboembolism: the Eighth ACCP Conference on Anti-thrombotic and Thrombolytic Therapy. Chest 2008; 133(3 Suppl.): 381S-453S

6. McCullagh L, Tilson L, Walsh C, et al. A cost-effectivenessmodel comparing rivaroxaban and dabigatran etexilate withenoxaparin sodium as thromboprophylaxis after total hipand total knee replacement in the Irish healthcare setting.Pharmacoeconomics 2009; 27 (10): 829-46

7. Wolowacz SE, Roskell NS, Maciver F, et al. Economic eva-luation of dabigatran etexilate for the prevention of venousthromboembolism after total knee and hip replacementsurgery. Clin Ther 2009; 31 (1): 194-212

8. Wolowacz SE, Roskell NS, Plumb JM, et al. Economic eva-luation of dabigatran etexilate for the prevention of venousthromboembolism in patients aged over 75 years or withmoderate renal impairment undergoing total knee or hipreplacement. Thromb Haemost 2010; 103 (2): 360-71

The Authors’ Reply

We are grateful to the editors for the oppor-tunity to comment on the correspondence fromPlumb et al.[1] The authors indicate that healthtechnology assessment (HTA) agencies such asthe UK National Institute for Health and Clin-ical Excellence (NICE) and the Scottish Medi-cines Consortium (SMC) approved the use ofdabigatran for the prophylaxis of venous throm-boembolism (VTE) after total hip replacement(THR) and total knee replacement (TKR). Theywill be pleased to note that the National Centrefor Pharmacoeconomics in Ireland also issueda positive recommendation that resulted in re-imbursement of dabigatran for this indication.[2]

Plumb et al.[1] raise a number of methodolo-gical issues in our previous work.[3] In evaluatingnew technologies and pharmaceutical agents it isnecessary to make judgements and assumptionsduring the modelling process. Our work presentsone analysis, but other models with a longer time

horizon and with alternative methods of evidencesynthesis have also been presented by us else-where.[4,5] Reimbursement decisions can be sen-sitive to model choice and the way in which healthstates are valued.[6] For this reason, communica-tion of the outputs of multiple models/synthesesis useful so that those using the informationmay understand the impact of the modelling as-sumptions. We are therefore glad to have the op-portunity to communicate some of our findingshere.

Plumb et al.[1] note that the efficacy and safetydata used in the 180-day time horizon economicmodel were handled using an unadjusted indirectcomparison. These investigations have been re-peated[4] using the Buchermethod of adjusted indi-rect comparison.[7] In the THR base-case model,rivaroxaban continued to dominate both dabiga-tran and enoxaparin. The incremental cost-effec-tiveness ratios (ICERs) for dabigatran relative toenoxaparin were h37000 per life-year gained (LYG)and h24 667 per QALY. Probabilistic analysis in-dicated that, at a threshold of h45 000 per QALY,the probability that rivaroxabanwas themost cost-effective strategy after THR was 38%, followedby dabigatran (32.5%) and enoxaparin (29.5%).

In the TKR base-case model, rivaroxabancontinued to dominate both dabigatran and en-oxaparin. Dabigatran dominated enoxaparin. Ata threshold of h45 000 per QALY, the probabilitythat rivaroxaban was the most cost-effectivestrategy after TKR was 41%, followed by dabi-gatran etexilate (34%) and enoxaparin (25%).

These THR and TKR model results werecomparable to the unadjusted indirect compar-ison model results.

Plumb et al.[1] also note the 180-day time hor-izon of the model. In contrast to the extensivedocumentation available on the short-term out-come of patients with acute deep vein thrombo-sis (DVT), less information is available on thelong-term clinical course of the disease.[8] From adecision-maker’s perspective, it was consideredpragmatic to include the well documented acuteevents only. However, the impact of taking intoaccount the long-term events associated withthromboprophylaxis-induced major bleeding havealso been investigated and the results presented

784 Letter to the Editor

ª 2010 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2010; 28 (9)

elsewhere.[4] A hybrid model (combining a 180-daydecision-tree module and a lifetime Markov pro-cess module) was used.

In the THR lifetime model, rivaroxabandominated both dabigitran and enoxaparin. TheICERs for dabigatran relative to enoxaparin de-creased to h1868 per LYG and h1868 per QALY.At a threshold of h45 000 per QALY, the proba-bility that rivaroxaban was the most cost-effectivestrategy increased to 67%, followed by dabiga-tran (21.5%) and enoxaparin (11.5%).

In the TKR lifetime model, rivaroxaban do-minated both dabigatran and enoxaparin. Dabi-gatran dominated enoxaparin. At a thresholdof h45 000 per QALY, the probability that riv-aroxaban was the most cost-effective strategy in-creased to 83%, followed by enoxaparin (13%)and dabigatran (4%).

Following the publication of the RE-LY(Randomized Evaluation of Long-Term Antico-agulation Therapy) study,[9] indicating the benefitof dabigatran in patients with atrial fibrillation,national HTA agencies such as ours look for-ward to the assessment of the cost effectiveness ofdabigatran for this therapeutic indication withwarfarin as the comparator.

Laura McCullagh,1 Lesley Tilson,1 Cathal Walsh1,2

and Michael Barry1

1 National Centre for Pharmacoeconomics,St James’s Hospital, Dublin, Ireland

2 Department of Statistics, Trinity College Dublin,Dublin, Ireland

References1. Plumb JM, Clemens A, Monz BU. Cost effectiveness of ve-

nous thromboembolism pharmacological prophylaxis intotal hip and knee replacement: a systematic review [letter].Pharmacoeconomics 2010; 28 (9): 781-2

2. The National Centre for Pharmacoeconomics (NCPE) inIreland. Economic evaluation on the cost effectiveness ofdabigatran etexilate (Pradaxa�) for the primary preventionof venous thromboembolic events in adult patients who haveundergone total hip replacement or total knee surgery. Du-blin: NCPE, 2008 Sep [online]. Available from URL: http://www.ncpe.ie/u_docs/doc_159.pdf [Accessed 2010 Jul 23]

3. McCullagh L, Tilson L, Walsh C, et al. A cost-effectivenessanalysis model comparing rivaroxaban and dabigatran etex-ilate with enoxaparin sodium as thromboprophylaxis aftertotal hip and total knee replacement in the Irish healthcaresetting. Pharmacoeconomics 2009; 27 (10): 829-46

4. McCullagh L, Tilson L, Walsh C, et al. Cost effectiveness ofrivaroxaban and dabigatran etexilate for the prophylaxis ofvenous thromboembolism and associated long term com-plications post total hip replacement in Ireland [poster pre-sentation]. ISPOR 12th Annual European Congress; 2009Oct 24-27; Paris

5. McCullagh L, Walsh C, Barry M. An application of valueof information analysis to decrease uncertainty [posterpresentation]. HTAi 7th Annual Meeting; 2010 Jun 6-9;Dublin

6. Adams R, Walsh C, Veale D, et al. Understanding the re-lationship between the EQ-5D, SF-6D, HAQ and diseaseactivity in inflammatory arthritis. Pharmacoeconomics2010; 28 (6): 477-87

7. Bucher HC, Guyatt GH, Griffith LE, et al. The results of di-rect and indirect treatment comparisons in meta-analysisof randomized controlled trials. J Clin Epidemiol 1997; 50:683-91

8. Prandoni P, Villata S, Bagatella P, et al. The clinical course ofdeep vein thrombosis, prospective long term follow up of528 symptomatic patients. Haematologica 1997; 82: 423-8

9. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatranversus warfarin in patients with atrial fibrillation. N EnglJ Med 2009; 361: 1139-51

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ª 2010 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2010; 28 (9)