Dabigatran etexilate for the prevention of venous thromboembolism ...

Dabigatran etexilate for the prevention of venous thromboembolismThe submitted two-phase economic modelcompares DBG with enoxaparin and fondaparinuxin total hip and knee replacement. The modelstructure is appropriate and the model assumptionsare reasonable. The health states, costs, utilitiesand recurrence rates used are considered to beappropriate for the required analysis. The modelestimated that at the licensed dose of 220 mg oncedaily DBG dominates enoxaparin in both totalhip replacement and total knee replacement andthat at the lower dose of 150 mg once daily DBGdominates enoxaparin in total hip replacementand enoxaparin dominates DBG in total kneereplacement. DBG is less cost-effective thanfondaparinux in total hip replacement at bothdoses; the cost per quality-adjusted life-year offondaparinux versus DBG is £11,111 and £6857for the higher and lower doses of DBG respectively.In total knee replacement, both DBG doses aredominated by fondaparinux. For DBG versus allcomparators in all cases the cost-effectivenessresults are based on small incremental cost andhealth benefits. Weaknesses of the submittedevidence include that methods used for screeningstudies, data extraction and applying qualityassessment criteria to included studies, as well askey details of trials included in the MTC, werenot adequately described. In addition, someinput parameters into the modelling process areincorrect. The ERG was unable to correct all ofthese mistakes and the impact on the model resultsis therefore unknown. The National Institute forHealth and Clinical Excellence guidance issued as aresult of the STA states that DBG is recommendedas an option for the primary prevention of VTEevents in adults who have undergone elective totalhip or knee replacement surgery.IntroductionThe National Institute for Health and ClinicalExcellence (NICE) is an independent organisationwithin the NHS that is responsible for providingnational guidance on the treatment and care ofpeople using the NHS in England and Wales.One of the responsibilities of NICE is to provideguidance to the NHS on the use of selected newand established health technologies, based on anappraisal of those technologies.NICE’s single technology appraisal (STA) processis specifically designed for the appraisal of a singleproduct, device or other technology, with a singleindication, for which most of the relevant evidencelies with one manufacturer or sponsor. 1 Typically,it is used for new pharmaceutical products closeto launch. The principal evidence for an STA isderived from a submission by the manufacturer/sponsor of the technology. In addition, a reportreviewing the evidence submission is submittedby the evidence review group (ERG), an externalorganisation independent of NICE. This paperpresents a summary of the ERG report for the STAof dabigatran etexilate for the prevention of venousthromboembolism in patients undergoing electivehip and knee surgery. 2Description of theunderlying health problemVenous thromboembolism (VTE) is the formationof a blood clot (thrombus) in a vein, whichmay dislodge from its site of origin to cause anembolism. Most thrombi occur in the deep veins ofthe legs; this is called deep vein thrombosis (DVT).Dislodged thrombi may travel to the lungs; thisis called a pulmonary embolism (PE) and can befatal. Thrombi can also cause long-term morbiditydue to venous insufficiency and post-thromboticsyndrome, potentially leading to venous ulceration.Recurrence of DVT is common. Studies have shownthat up to 30% of patients who have experiencedan acute DVT will experience one or morerecurrences over the following 10–15 years. 3–5Total hip or knee replacement surgery is astrong risk factor for VTE. In the absence ofthromboprophylaxis the risk of developing a DVTafter a primary total hip replacement and after aprimary total knee replacement is 50% and 60%respectively. 6Mortality due to VTE is significant. Long-termfollow-up of patients who have experienced anepisode of VTE (usually acute DVT) has shown thatthere is a high mortality rate over the subsequent10–15 years. 3,5,7,8PE has a high mortality rate with 13% proving fatalin elderly patients 1 month after onset 9 and 17.5%within 3 months. 10The National Joint Registry for England and Walesrecorded 61,456 hip replacement procedures, ofwhich 10% were revisions or reoperations, and60,986 knee replacement procedures, of which 8%were revisions or reoperations, undertaken between1 January and 31 December 2006. 1156