Verteporfin photodynamic therapy for neovascular age-related ...

More documents

Recommendations

Info

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.
Page 5 and 6: DOI: 10.3310/hta16060Health Technol
Page 12 and 13: xExecutive summaryretreat on criter
Page 14 and 15: xiiExecutive summaryof data, with i
Page 16 and 17: 2 Introductionon-going or new clini
Page 18 and 19: 4 Introductionof VPDT in routine cl
Page 23: DOI: 10.3310/hta16060Health Technol
Page 31: DOI: 10.3310/hta16060Health Technol
Page 34 and 35: 20 Key changes to the protocolThese
Page 36 and 37: 22 Key changes to the protocolCentr
Page 38 and 39: 24 Key changes to the protocolADVER
Page 40 and 41: 26 Key changes to the protocolPlan
Page 42 and 43: 28 Key changes to the protocolClass
Page 44 and 45: 30 Key changes to the protocolFor i
Page 46 and 47: 32 Key changes to the protocolIn ad
Page 48 and 49: 34 Key changes to the protocolsites
Page 52 and 53: 38 Results (1) - study cohortTABLE
Page 60 and 61: 46 Results (2) - objectives A, B, C
Page 75 and 76:
DOI: 10.3310/hta16060Health Technol
Page 77:
Page 80 and 81:
66 Discussion of resultsStrengths a
Page 82 and 83:
68 Discussion of resultsThe VPDT st
Page 84 and 85:
70 Discussion of resultsOur analyse
Page 86 and 87:
72 Discussion of resultsA further c
Page 88 and 89:
74 Discussion of resultsVPDT. It is
Page 91 and 92:
Page 93 and 94:
Page 95:
Page 98 and 99:
84 References16. Stelmack J. Qualit
Page 100 and 101:
86 References49. Guymer RH, Chiu AW
Page 102 and 103:
88 References83. Margrain TH. Minim
Page 104 and 105:
90 Appendix 1THE VERTEPORFIN PHOTOD
Page 106 and 107:
92 Appendix 11. Overview of Manual
Page 108 and 109:
94 Appendix 1And, if also collectin
Page 110 and 111:
96 Appendix 1more patients in the v
Page 112 and 113:
98 Appendix 12.4 Limitations of the
Page 114 and 115:
100 Appendix 1Box 2 Key advantages
Page 116 and 117:
102 Appendix 14. Study population4.
Page 118 and 119:
104 Appendix 15. Recruitment to the
Page 120 and 121:
106 Appendix 16. Background data co
Page 122 and 123:
108 Appendix 1Table 1: Schedule of
Page 124 and 125:
110 Appendix 1The Verteporfin Photo
Page 126 and 127:
112 Appendix 1• Additional clinic
Page 128 and 129:
114 Appendix 18. Recording adverse
Page 130 and 131:
116 Appendix 1level of benefit from
Page 132 and 133:
118 Appendix 1• comparison of num
Page 134 and 135:
120 Appendix 110.6 Sub-group analys
Page 136 and 137:
122 Appendix 112. Data issues12.1 D
Page 138 and 139:
124 Appendix 113. Organisation13.1
Page 140 and 141:
126 Appendix 114. References[1] Ref
Page 142 and 143:
128 Appendix 1Barnes RM, Gee L, Tay
Page 144 and 145:
130 Appendix 1Appendix 1: Classifyi
Page 146 and 147:
132 Appendix 1Liverpool re-treatmen
Page 148 and 149:
134 Appendix 1Service StructurePlea
Page 150 and 151:
136 Appendix 1Has your photographer
Page 152 and 153:
138 Appendix 1There are many differ
Page 154 and 155:
140 Appendix 1testing on vision tes
Page 156 and 157:
142 Appendix 1something to do with
Page 158 and 159:
144 Appendix 1College of Ophthalmol
Page 160 and 161:
146 Appendix 1Appendix 5:Protocol f
Page 162 and 163:
148 Appendix 16.2 Subjective Refrac
Page 164 and 165:
150 Appendix 1• The patient shoul
Page 166 and 167:
152 Appendix 1Appendix 6:Protocol f
Page 168 and 169:
154 Appendix 18. It is customary to
Page 170 and 171:
156 Appendix 1Early or Transit Phas
Page 172 and 173:
158 Appendix 1
Page 174 and 175:
160 Appendix 1---------------------
Page 176 and 177:
162 Appendix 1---------------------
Page 178 and 179:
164 Appendix 1---------------------
Page 180 and 181:
166 Appendix 1Appendix 9:Site imple
Page 182 and 183:
168 Appendix 1Option 2 - units inte
Page 184 and 185:
170 Appendix 1Dos and Don’tsDosDo
Page 186 and 187:
172 Appendix 1Resource use question
Page 188 and 189:
174 Appendix 1Appendix 11: Recommen
Page 190 and 191:
176 Appendix 1ADVERSE REACTION AND
Page 192 and 193:
178 Appendix 1acute Trust; note tha
Page 194 and 195:
180 Appendix 1Ophthalmologistrespon
Page 197 and 198:
Page 199 and 200:
Page 201 and 202:
Page 203:
Page 206 and 207:
192 Appendix 3manufacturer’s pers
Page 209 and 210:
Page 211 and 212:
Page 213 and 214:
Page 216:
FeedbackThe HTA programme and the a
show all

Verteporfin photodynamic therapy for neovascular age-related ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?