Verteporfin photodynamic therapy for neovascular age-related ...

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16 MethodsPlan of analysisThe manual of operations recognised that the data set for the VPDT cohort study would havea complex structure, with varying numbers of visits/duration of follow-up across patients upto about eight visits/3 years of follow-up. It was also recognised that patients would be ‘nested’within groups of retinal specialists and DHs. Therefore, we planned to analyse the data set bymixed regression with multilevel modelling, an extension of conventional regression methodsto take into account statistical dependency between observations that are ‘clustered’ in the datastructure, for example observations within patients or patients within retinal teams.Follow-up of patients throughout the study period allowed repeated measurements of outcomesand changes over time to be described in detail. The main outcomes (BCVA, CS, HRQoL andlesion characteristics) were continuously scaled and could be analysed by mixed regressionwith multilevel modelling. We also planned to use similar models to quantify associationsbetween clinical outcomes and HRQoL. The analysis plan did not provide details of additionalanalyses but envisaged that outcomes might also be analysed in different ways, for example bydichotomising the change in BCVA to describe a deterioration of ≥ 15 ETDRS letters or not(a deterioration expected to occur in about 50% of participants) or using survival analysis todescribe the cumulative probability of a deterioration of this degree with increasing duration offollow-up.The analysis plan stated that, because of the complexity of the data set and the likelihood that thecomposition of the cohort would influence the nature of the analysis, a detailed plan of analyseswould be written after carrying out preliminary descriptive analyses. The preliminary descriptiveanalyses would characterise baseline clinical and treatment characteristics of patients recruited tothe cohort but not involve any comparative analyses. A number of baseline factors were expectedto influence outcomes independently following photodynamic therapy, including BCVA atpresentation, CNV composition and fellow eye comorbidities, and the analysis plan specified thatanalyses should take all of these factors into account.Consideration of predictors of outcome in the analysesAs described in Other predictors of visual function, known predictors of outcome were identifiedand collected. The use of adjunctive treatments was also documented, although it was not knownif these would influence outcome. The plan of analysis recognised that it would be importantto take into account differences in these predictors between subgroups that were of interestto compare.Estimating the effectiveness and cost-effectiveness of verteporfinphotodynamic therapyThe objective of estimating effectiveness and cost-effectiveness required comparisons to bemade with untreated patients. At the outset, we recognised that the lack of a concurrent controlgroup was an important limitation of the study and a number of strategies were discussed toestimate outcomes for untreated patients. We proposed to use the following three methods and toinvestigate the impact of using different methods on estimates of effectiveness, cost-effectivenessand cost–utility:(a) Extrapolation from trial data Existing trials of VPDT provide estimates of effectiveness.Longitudinal data for BCVA, CS and HRQoL outcomes also exist from a previouslyconducted UK-based clinical trial of CNV of AMD in which the intervention was noteffective at the specified outcome points. 42 Self-reported use of HSS resources in relation toAMD were also collected in the VPDT cohort study (see Appendix 2). We proposed to use
DOI: 10.3310/hta16060Health Technology Assessment 2012; Vol. 16: No. 617these data, together with the characteristics of participants, to model indirect comparisonsbetween treated and untreated patients.(b) Extrapolate use of health and social service resources The use of health and personal resourcescan be extrapolated from associations between the use of resources and visual functionand other outcomes in the groups documented in the study. For example, if a relationshipbetween the use of resources and amount of deterioration over time were observed inthe study, the use of resources could be extrapolated to the level of deterioration in acuityexpected without treatment, based on published data for sham/no treatment groups fromprevious randomised or non-randomised studies.(c) Estimate use of health and social service resources from the cohort This method assumed thatresource use for an untreated control group would be similar to that for patients observedin the cohort who received VPDT but who showed no benefit (i.e. whose BCVA andPelli–Robson Contrast Sensitivity outcomes deteriorate in a similar way to patients in thecontrol groups in trials). This method required estimates to be adjusted for any differencein clinical characteristics between patients who showed no benefit in the cohort study andpatients in the control groups of trials.We stated that cost-effectiveness estimates would be calculated by combining the estimatesof effectiveness with utilities derived from SF-6D scores and the association between use ofresources and visual function.Data management and statistical analysesTreating centres submitted clinical and HRQoL data to an independent data management centreat the LSHTM. The imaging data were submitted to the central angiographic resource facilitywhich managed the grading of the angiograms by NetwORC UK.© 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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66 Discussion of resultsStrengths a
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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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114 Appendix 18. Recording adverse
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116 Appendix 1level of benefit from
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118 Appendix 1• comparison of num
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120 Appendix 110.6 Sub-group analys
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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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154 Appendix 18. It is customary to
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166 Appendix 1Appendix 9:Site imple
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170 Appendix 1Dos and Don’tsDosDo
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172 Appendix 1Resource use question
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174 Appendix 1Appendix 11: Recommen
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176 Appendix 1ADVERSE REACTION AND
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178 Appendix 1acute Trust; note tha
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180 Appendix 1Ophthalmologistrespon
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192 Appendix 3manufacturer’s pers
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FeedbackThe HTA programme and the a
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