Verteporfin photodynamic therapy for neovascular age-related ...

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xiiExecutive summaryof data, with improvement in data quality occurring over time only at centres with highlycommitted research-focused staff; (iii) provider organisations had varying degrees of difficultyin establishing and maintaining consistent provision to the service specification required by thenational commissioning and professional bodies.Implications for practiceImplications for practice do not relate to the use of VPDT to treat nAMD because VPDT has nowbeen superseded by the introduction of new treatments.■■■■■■■■■■The small number of treatments administered suggests that treatment regimens receivingmarketing authorisation may overestimate the intensity of treatment required. This ispotentially an important consideration in relation to other new health technologies.This limitation of loss to follow-up should be carefully considered in the design of similarstudies for interventions requiring treatment or follow-up over many months, especially ifthe effectiveness of an intervention is not dramatic.Use of VPDT should be limited to (a) circumstances in which newer technologies arecontraindicated or refused by patients or (b) categories of age-related macular degenerationsuch as polypoidal choroidopathy or other diseases with neovascularisation arising fromthe choroid.Appraisal of a technology that benefits one eye should evaluate the benefit at the level of aperson, not an eye.The consequences of the shallow gradients of relationships (a) between BCVA and EuropeanQuality of Life-5 Dimensions utility and (b) between BCVA and health and social servicesresource use/cost need to be considered carefully when appraising other technologies to treateye diseases that impair vision.Research recommendationsSimilarly, our research recommendations are outside the context of nAMD:■■■■■■Further studies are required to investigate the effectiveness and cost-effectiveness of VPDTfor neovascularisation due to myopia, inflammation and other choroidal diseases includingcentral serous chorioretinopathy.Modification of the effectiveness of new interventions for nAMD by covariates found toinfluence effectiveness in this study should be studied.The relationships between BCVA and HRQoL/health and social services resource use areimportant for modelling cost-effectiveness. Further research should investigate how widelythese relationships can be applied, for example to other diseases that reduce BCVA.ConclusionsThe VPDT cohort study model was successful in establishing a network of research expertise,expanding research capacity, engaging professional bodies and developing purchaser–providerrelationships around research and development. It formed a structure for the managedintroduction of the technology including the necessary training and service specificationdevelopment. The success of the model was limited by the freedom of providers to divertinvestment into other services and to revise care pathways. Improvements in models of theintroduction of costly new technology into the NHS are recommended.
DOI: 10.3310/hta16060Health Technology Assessment 2012; Vol. 16: No. 61Chapter 1IntroductionBackground and rationaleMacular degeneration (MD) is the commonest cause of visual impairment in the developedworld. 1,2 It mainly affects central vision, which underpins the ability to do tasks that requirefine detail to be resolved, for example reading, watching television and recognising faces.The commonest cause of MD is ageing, although there are many other less frequent causes.Age-related MD (AMD) causes visual loss principally through the development of newvessels, which form in the choroid under the retina and leak fluid, bleed and eventually fibrose(choroidal neovascularisation, CNV). A less frequent site for the development of new vessels isin the retina itself, and this is termed retinal angiomatous proliferation (RAP). The process ofneovascularisation is often referred to as ‘wet’ or neovascular AMD (nAMD) to distinguish itfrom a less aggressive or ‘dry’ form. CNV is identified and categorised using fundus fluoresceinangiography (FA) into ‘classic’ and ‘occult’ forms based on patterns of fluorescence and locationunder the retina. RAP is identifiable using FA but more readily using indocyanine greenangiography. At the onset of nAMD, a progressive fall in vision in the affected eye generallyoccurs over weeks and months and is more rapid with classic than occult CNV.Verteporfin is a light-sensitive drug which is used in combination with an infrared laser to treatabnormal blood vessels proliferating under or within the macular retina in patients with nAMDand, less frequently, in some other eye conditions. The drug is injected intravenously and bindsselectively to endothelial cells in the abnormal retinal vessels. The drug is activated by low-energylaser radiation, causing the abnormal vessels to regress. These two steps, that is initial infusion ofverteporfin followed by laser exposure, are known as verteporfin photodynamic therapy (VPDT).Over time the vessels frequently reopen and so treatment usually needs to be repeated 3-monthly.Verteporfin photodynamic therapy has been shown in randomised clinical trials to be betterthan sham treatment in maintaining sight in patients with nAMD. In the clinical trials of VPDTcarried out for licensing, the Treatment of Age-related macular degeneration with Photodynamictherapy (TAP) trials and the Verteporfin in Photodynamic therapy (VIP) trials, 3–5 the overalldifference between treatment and placebo groups was small except in a subgroup of patientsin whom ≥ 50% of the area of CNV was classified as classic by FA; in this subgroup, the benefitwas larger. 4There are no established criteria for stopping a course of treatment. The treatment protocol usedin the TAP trials required 3-monthly reviews of FA for 2 years with retreatment if active CNVwas observed. 3The cost of a course of therapy has been estimated to be between £6000 and £8000. This relativelyhigh cost arises largely because of the frequency of retreatment episodes in research cohorts.Cost-effectiveness was not estimated alongside the clinical trials used for licensing. In 2003,the National Institute for Clinical Excellence (NICE; now the National Institute for Health andClinical Excellence) recommended treatment in the UK NHS for patients with nAMD ‘who havea confirmed diagnosis of classic with no occult subfoveal choroidal neovascularisation’. 6 However,NICE did not recommend VPDT for people with predominantly classic CNV ‘except as part of© 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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