Verteporfin photodynamic therapy for neovascular age-related ...

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32 Key changes to the protocolIn addition to estimating the overall associations between BCVA and HRQoL, we also soughtto test two pre-specified subhypotheses. One concerned the shape of the association. Wehypothesised that the associations would be sigmoid, with a relatively shallow gradient at theextremes of the visual function continuum. We reasoned that HRQoL would vary a relativelysmall amount (shallow gradient) among people above and below visual function thresholds forbeing easily able, and completely unable, to carry out tasks that depend on vision; conversely, wereasoned that HRQoL would drop sharply over the range of visual function when people’s abilityto do such tasks also deteriorated markedly. The second subhypothesis concerned adaptation overtime to poorer visual function. We hypothesised that the gradients of the relationships woulddecrease with increasing time from first treatment, as patients adapted to their residual vision.We used BCVA and CS measurements from the better-seeing eye and HRQoL data forcorresponding visits. Visits were classified using the following time intervals: 0 months (firsttreatment date), 3 months (> 77 to ≤ 168 days), 6 months (> 168 to ≤ 259 days), 9 months (> 259to ≤ 350 days), 12 months (> 350 to ≤ 442 days), 15 months (> 441 to ≤ 533 days), 18 months(> 533 to ≤ 624 days), 21 months (> 624 to ≤ 715 days) or 24 months (> 715 to ≤ 807 days) after thedate of first treatment. Intervals were not symmetrical around the 3-monthly schedule becausefollow-up visits tended to shift towards longer rather than shorter intervals.Mixed regression models were used to allow all available visits to contribute to the analysis,taking into account multiple visits by the same patients and visits without HRQoL data. To allowfor the correlation of the data, an unstructured covariance matrix was used where possible,otherwise random intercepts and slopes were fitted.To address our second objective, that relationships are sigmoid, we fitted a range of putativemodels; these included linear, quadratic, cubic and spline functions. We addressed our thirdobjective, that gradients decrease with time since first treatment, by modelling time in 3-monthintervals (see above). The analyses investigated both time interval and the interaction betweenBCVA and time, allowing the gradient of the relationship to vary with time.We also fitted a range of covariates (including age, gender, participating centre, smoking statusand whether or not the fellow eye was the better-seeing eye). Covariates did not materially alterthe shape or gradient of the relationships between visual function and HRQoL, and their effectsare not described.We judged that the cause of CNV was very unlikely to influence the association between BCVAand HRQoL. There was also no reason why the association would be influenced by whether ornot a patient had completed treatment. By virtue of modelling BCVA in the better-seeing eye, theissue of treatment in both eyes did not arise. Therefore, the cohort for this analysis included allpatient visits for which visual function data (BCVA or CS) and HRQoL data (NEIVFQ or SF-36)were reported.How cost-effective is verteporfin photodynamic therapy?The CEA element of objective E consisted of three parts: (a) estimation of the costs of deliveringVPDT in routine clinical practice; (b) development of a regression model to quantify changes inHSS for a given change in visual function (i.e. BCVA); and (c) assessment of the cost-effectivenessof VPDT versus best supportive care (BSC) using the findings from (a) and (b).Overview of the cost-effectiveness analysisThe VPDT cohort study was designed to assess the costs and HRQoL of VPDT and to report thecost-effectiveness of VPDT versus BSC. The CEA was undertaken in accordance with currentmethodological standards. It took a health and personal social services perspective and so
DOI: 10.3310/hta16060Health Technology Assessment 2012; Vol. 16: No. 633included all relevant costs to HSS. 28 The main assumptions underlying this CEA are reportedin Box 2.The study used the BCVA measures reported in the TAP trial to assess the cost-effectiveness ofVPDT versus BSC. 3 The effect of VPDT on BCVA was taken from the subgroup of eyes withpredominantly classic lesions in the TAP trials; the effectiveness of VPDT was largest in thissubgroup of eyes (mean difference in BCVA letters lost from baseline of 11 letters at 2 years),which was the basis for the previous NICE recommendations. 3,6,30 This report combines thesedata from the TAP trials with estimates from the VPDT cohort study of (a) the relationshipbetween BCVA and HRQoL (see How effective is verteporfin photodynamic therapy?), (b)treatment frequency in routine practice (see A: Is verteporfin photodynamic therapy in the NHSprovided as in randomised trials?) and (c) the relationship between BCVA and HSS cost (usingthe same methods as when estimating the relationship between BCVA and HRQoL, described inHow effective is verteporfin photodynamic therapy?). This report also estimates the costs of VPDTin routine practice and the cost-effectiveness of PDT versus BSC over 2 years.Costs of verteporfin photodynamic therapy and best supportive careThe VPDT cohort study recorded the number of outpatient visits, tests performed (colourphotography or FA) and VPDT treatments administered. For each patient, the treatment costswere measured from the date on which the first eligible eye was treated for up to 2 years. Costswere categorised as falling in year 1 or year 2 (Definition of year 1 and year 2). Because theprobability of receiving one FA for each visit (whether a treatment or follow-up visit) exceeded0.95 for > 90% of study centres, it was assumed that there was one FA for each visit.We assumed that one vial of verteporfin was used per treated eye as stipulated in the licence.Verteporfin costs were taken from the British National Formulary (£860 per treatment) andexcluded value added tax. 53 The numbers of treatment and follow-up visits were combined withnational unit costs (£113 and £67 for treatment and follow-up visits respectively). 54The costs of BSC were estimated by assuming plausible costs for follow-up without VPDT.In the base-case analysis, it was assumed that there would be on average 1 and 1.5 low-visionassessments scheduled in years 1 and 2 respectively.Health and social sciences use and costs related to vision lossThe cost of HSS for patients affected by nAMD was estimated from the HSS use questionnaireswhich were administered every 6 months to patients attending a subset of 18 of the participatingBOX 2 Assumptions made in the CEAThe target population was patients treated with VPDT in routine NHS practiceVPDT treatment was given to the better-seeing eyenAMD costs and HRQoL only varied according to BCVA which, in turn, depends on whether treatment is or isnot given and changes over time as described in the TAP trialsTreatment frequency was as observed in VPDT studyFor patients having both eyes treated, the treatment costs were assumed to be the twice the costs for patientshaving a single eye treatedTo calculate QALYs from HRQoL, it was assumed that there was no mortalityCosts and QALYs in year 2 were discounted at 3.5%© Queen’s Printer and Controller of HMSO 2012. This work was produced by Reeves et al. under the terms of a commissioning contract issued by theSecretary of State for Health.
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84 References16. Stelmack J. Qualit
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86 References49. Guymer RH, Chiu AW
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88 References83. Margrain TH. Minim
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90 Appendix 1THE VERTEPORFIN PHOTOD
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92 Appendix 11. Overview of Manual
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94 Appendix 1And, if also collectin
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102 Appendix 14. Study population4.
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110 Appendix 1The Verteporfin Photo
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FeedbackThe HTA programme and the a
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