Verteporfin photodynamic therapy for neovascular age-related ...

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xExecutive summaryretreat on criteria used in the TAP trial. The protocol also specified key data which should becollected [BCVA, fundus colour photography and fundus fluorescein angiography (FA)] ateach visit during a treatment episode and at least annually thereafter. CS, HRQoL and resourceuse data were collected at 6-monthly intervals but only in a subset of hospitals chosen toprovide a representative sample of patients. The treatment costs of VPDT were obtained fromreference sources.Grading of neovascular age-related macular degeneration lesionsColour photographs and FAs were graded by independent, externally accredited personnelwithin a network of reading centres established for the study. The proportion of classic and occultchoroidal neovascularisation (CNV) was measured and lesions were classified into mutuallyexclusive categories namely predominantly classic, minimally classic or occult no classic. Treatedeyes were then classified into one of three categories based on whether or not the treated eye metfour key eligibility criteria for the TAP trials (presenting BCVA > 33 and < 74 letters, presence ofsome classic CNV, total CNV area ≥ 50% of the lesion and CNV under the geometric centre ofthe foveal avascular zone). Thus, each treated eye was classified as (a) meeting these eligibilitycriteria (‘eligible for TAP’; EFT); (b) not meeting the criteria (‘ineligible for TAP’; IFT); or (c) notclassifiable owing to the absence of a gradable baseline FA (‘unclassifiable’; UNC).AnalysesObjectives (a)–(d) are descriptive and were addressed by relevant statistical summaries of thedata set. Objective (e) required comparisons to be made with untreated patients similar to thosetreated in the study. We proposed three methods to do this, although only one was possible,namely quantifying the associations between BCVA and HRQoL, and between BCVA and healthand social service costs, and combining these associations with information about BCVA benefitfrom the TAP trials and from the cohort study. Except for objective (d), for which all treatedpatients were included, the main analyses included only one treated eye per patient for patientswith CNV from nAMD who had > 1 year of follow-up or who had completed their treatment.ResultsData were submitted by 47 participating hospitals for a total of 8323 treated eyes in 7748 patients.Key missing data (e.g. baseline BCVA, no follow-up data) reduced these numbers to 6647 eyesin 6223 patients. Only eyes which were treated > 350 days (1 year) before the most recent datasubmission, or which had completed treatment, were analysed; 4919 eyes in 4566 patients metthis criterion. The number of eyes classified against eligibility for the TAP trial were 1227 EFT,1187 IFT and 1629 UNC. Responses to at least one HRQoL and resource use questionnaire weresubmitted for about 2000 patients (the number varied by questionnaire).(a) Is verteporfin photodynamic therapy in the NHS provided as inrandomised trials?The percentages of treated eyes receiving one, two, three or more than three treatments in year 1was 25%, 34%, 25% and 16%, falling to 18%, 7%, 2% and 1%, respectively in year 2. The meannumber of treatments in years 1 and 2 was 2.3 and 0.4 much lower than in the ‘TAP’ phase 3trial on which NICE guidance was mainly based. About 50% of patients had completed theirtreatment by the end of year 1. Follow-up was incomplete because hospitals discharged patientsowing to the introduction of local policies that limited the number of outpatient reviews.Therefore, analyses of outcomes at 1 year (for comparison with 1-year outcomes in the TAP trial)required complex statistical modelling to take into account the missing follow-up data and toallow comparison with 1-year outcomes in the TAP trial.
DOI: 10.3310/hta16060Health Technology Assessment 2012; Vol. 16: No. 6xi(b) Is ‘outcome’ the same in the NHS as in randomised trials?Analyses of BCVA outcome at 1 year found no difference in the rate at which vision waslost in patients in the different eligibility groups. Patients in the EFT group lost 11.6 letters(95% confidence interval 10.1 to 13.0 letters) by 1 year compared with 9.9 letters in the TAPtrial subgroup.(c) Is ‘outcome’ the same for patients who would have been ineligible forthe TAP trial?Given that there was no difference in the rate at which vision was lost in the different eligibilitygroups, patients in the IFT and UNC groups also lost 11.6 letters by 1 year. Note that this doesnot mean that VPDT is equally effective in these other groups, as the study had no data for therate of deterioration in BCVA over time without VPDT, which may differ by eligibility group.After adjusting for covariates, patients in the EFT group had, on average, poorer BCVA atbaseline (a difference of just over two letters) than patients in the IFT and UNC groups.(d) Is VPDT safe when provided in the NHS?Frequencies of ARs (immediately following treatment) and AEs (recorded at the subsequent visit,covering the interval between visits) decreased dramatically after the first treatment visit, eitherbecause local investigators did not record adverse effects of the same kind on repeat visits orbecause adverse effects deterred patients or their ophthalmologists from continuing treatment.ARs were reported on 1.4% of first visits and AEs following 1.9% of first visits; these frequencieswere lower than those reported for patients treated with VPDT in the TAP trial.(e) How effective and cost-effective is verteporfin photodynamic therapy?Associations between the best BCVA in either eye with (i) HRQoL and (ii) health and social careresource use in the community were estimated from data for visits for which BCVA and HRQoLdata were available. These associations allowed the 11-letter difference in BCVA between VPDTand sham treatment in the TAP trial to be ‘translated’ into a utility difference of 0.012 and intoa health and social service resource use difference equivalent to £60 in year 1 and £92 in year 2.The cost-effectiveness of VPDT was estimated on the basis of these quality-adjusted life-years(QALYs) and community cost differences derived for the TAP trial and the costs of the lowerfrequency of treatment observed in the cohort study, giving an incremental cost per QALY over2 years’ treatment of £170,000.Comment and conclusionsThe main findings were that (i) VPDT was administered much less frequently in routine clinicalpractice than in the TAP trial; (ii) in routine clinical practice, patients were followed much lessfrequently than in the research setting of the TAP trial, with attendance tending to stop onceBCVA had dropped; (iii) for the EFT group, deterioration in BCVA over time was similar to thatin the TAP trial; (iv) there was no evidence that safety was worse than in the TAP trial; and (v)the estimated cost per QALY was similar to the highest previous estimate.The main limitation was the exclusion and early loss to follow-up of some patients, who arelikely to have been those with a worse than average outcome; this limitation would have ledtreatment frequency to be overestimated and deterioration in BCVA and cost per QALY tobe underestimated.A number of observations on the introduction of this technology into routine clinical practicecan be made: (i) there was wide variation in the readiness of centres to follow a proscribedprotocol including follow-up; (ii) there was variable engagement by centres with the collection© 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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68 Discussion of resultsThe VPDT st
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74 Discussion of resultsVPDT. It is
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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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96 Appendix 1more patients in the v
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98 Appendix 12.4 Limitations of the
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100 Appendix 1Box 2 Key advantages
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102 Appendix 14. Study population4.
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104 Appendix 15. Recruitment to the
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106 Appendix 16. Background data co
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108 Appendix 1Table 1: Schedule of
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110 Appendix 1The Verteporfin Photo
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112 Appendix 1• Additional clinic
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114 Appendix 18. Recording adverse
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116 Appendix 1level of benefit from
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122 Appendix 112. Data issues12.1 D
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124 Appendix 113. Organisation13.1
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126 Appendix 114. References[1] Ref
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128 Appendix 1Barnes RM, Gee L, Tay
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130 Appendix 1Appendix 1: Classifyi
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132 Appendix 1Liverpool re-treatmen
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134 Appendix 1Service StructurePlea
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136 Appendix 1Has your photographer
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138 Appendix 1There are many differ
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140 Appendix 1testing on vision tes
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144 Appendix 1College of Ophthalmol
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146 Appendix 1Appendix 5:Protocol f
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148 Appendix 16.2 Subjective Refrac
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152 Appendix 1Appendix 6:Protocol f
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174 Appendix 1Appendix 11: Recommen
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176 Appendix 1ADVERSE REACTION AND
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FeedbackThe HTA programme and the a
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