Verteporfin photodynamic therapy for neovascular age-related ...

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10 MethodsTABLE 2 Example of flow chart for making retreatment decisions – Liverpool retreatment criteriaParameter Retreat Do not retreatFA Leakage No leakage/no leakage at centreVisual acuity Dropping Stable or < 20 lettersSubretinal fluid Persistent ClearedHaemorrhage New ClearedCNV Extension InactiveNext visit 3 months ≥ 9 months aa This visit interval was recommended at Liverpool prior to the start of the VPDT cohort study. The schedule of data collection (see Table 3) tookprecedence in the study; this required 3-monthly visits when a patient was being actively treated or received.be representative of the events observed in usual practice. The manual of operations specified thatall ARs (during or just after treatment) or AEs (between treatment visits) should be recorded inthe database. Any AR or AE considered to be serious and possibly, probably or definitely associatedwith treatment had to be reported to the Data Management Centre within 24 hours in accordancewith good clinical practice in clinical research.Other predictors of visual functionData were collected at baseline to characterise study participants. The data included variables thatwere considered important for describing the study population and potential predictors of BCVAthat might confound associations investigated in the analyses:■■■■■■■■agegenderbaseline BCVA and CSCNV composition, that is lesion area and proportion of the lesion graded as classic andoccult CNV.The collection of additional potential predictors of visual function was instituted after the studystarted to recruit (see Chapter 4, Collection of additional predictors of visual function).Network of Ophthalmic Reading Centres in the UKThe baseline morphological characteristics of CNV lesions were defined in the protocol aspotentially important covariates/confounding factors (see Other predictors of visual function) withrespect to the primary outcome of visual acuity (see Outcomes). For example, classic comparedwith occult CNV is associated with more rapid loss of vision but greater responsiveness totreatment. 4 Changes in the morphological characteristics of CNV lesions over time, with orwithout treatment, were also defined as secondary outcomes (see Outcomes).Considerable training is required to distinguish the various components of CNV lesions reliably,and, although the training put in place by the Royal College of Ophthalmologists and theresearch team included a session on lesion composition, this was not considered sufficient forresearch purposes. When designing the study, the research team was concerned that judgementsabout CNV composition made by the ophthalmologists treating patients might be unreliable andpotentially biased. Unreliable judgements about CNV composition would have biased observed
DOI: 10.3310/hta16060Health Technology Assessment 2012; Vol. 16: No. 611associations to the null. More importantly, given that the study was to some degree the meansby which patients with predominantly classic CNV lesions could access treatment, there wasa possibility that ophthalmologists might tend to overdiagnose the presence of classic CNV inorder to classify patients as eligible.The research context was also important. The TAP trials that were reporting at the time thestudy was being designed had taken great care to assure the quality of photographic images andthe grading of these images. All photographers were accredited at the outset and reaccreditedannually. All photographic images (colour fundus and FA) were submitted to a central readingcentre for independent grading. 3 The VPDT cohort study research team wanted to establish thesame standards to ensure that the results of the study were credible.Therefore, NetwORC UK was established with the capacity to carry out independent gradingof, potentially, > 5000 angiograms per year. Three geographically distinct centres, in Belfast,London and Liverpool, with facilities to grade stereoscopic fundus colour images and FAs werecombined into a single network with a management facility in Belfast (Central AngiographicResource Facility; CARF) to co-ordinate the administrative and technical issues. CARF managedthe collection and archiving of images from designated VPDT treatment centres, performedconsistency checks, certification and training of photographers, and transmitted imageselectronically to the three reading centres using a customised software platform. Regular trainingand concordance exercises were organised to ensure consistency between the reading centregrading staff and minimise grading protocol discordance.The large volume of FAs to be graded precluded a double grading. Therefore, quality assurancewas built in as an integral feature of the grading process. One in every eight FAs was randomlyselected for regrading by the same reading centre, and 1 in 80 FAs was randomly selected forregrading by one of the other reading centres. All graders were masked to whether a particulargrading was the original grading or a regrading.Stereoscopic colour images and FAs were graded by the three reading centres that made upNetwORC UK using previously published definitions and protocols. 35,36 Grading involved thedelineation and measurement of the area of classic and occult CNV and other lesion componentscontiguous to CNV, for example fibrosis and haemorrhage.Data collection and managementTable 3 shows the schedule of data collection at follow-up visits. A decision was taken to collectHRQoL and HSS data in a subset of centres because of the workload involved and because notall primary care trusts (PCTs) paid the full tariff covering the costs of data collection. There wasa strong desire to ensure that these data were collected in a representative population. Therefore,the research team reviewed fully funded sites and their geographic disposition and recommendedto the Steering Committee that 18 centres collect these data. The geographic distribution of allsites is shown in Figure 2, distinguishing between the sites which collected only the clinical dataset and the sites which also collected HRQoL and HSS data.To meet its objectives, the VPDT study had to collect data from all of the hospitals designated forproviding VPDT identified at the outset. These hospitals had been selected to form a network ofspecialist retinal practitioners. When planning the study, we estimated that these hospitals wouldenrol about 7000 patients each year and that each patient would make, on average, three clinicvisits per year. The study was planned to run for 3 years so that, in total, data would be collectedfor 21,000 patients who, between them, would make up to 168,000 clinic visits.© 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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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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108 Appendix 1Table 1: Schedule of
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110 Appendix 1The Verteporfin Photo
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116 Appendix 1level of benefit from
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128 Appendix 1Barnes RM, Gee L, Tay
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130 Appendix 1Appendix 1: Classifyi
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FeedbackThe HTA programme and the a
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