Verteporfin photodynamic therapy for neovascular age-related ...

28 Key changes to the protocolClassification of treatment as active or completedFor objective A (see Chapter 2), we needed to define episodes of treatment as active or completedbecause, by including patients still receiving active treatment, we would have underestimatedthe number of treatments administered. This distinction was complicated by the fact that manyparticipants were discharged from or lost to follow-up before 1 year. Distinguishing betweenactive and completed treatment was also important when estimating BCVA 12 months afterstarting treatment (a prerequisite for addressing objectives B, C and E). We wanted to include inthese analyses data for patients classified as having completed their treatment before 12 months.However, patients who had not reached 12 months’ follow-up and who were still having activetreatment could have experienced additional benefit from ongoing treatment up to 12 months.Patients were classified as having completed treatment for year 1 if they satisfied one of thefollowing sets of conditions:■■■■■■visit with BCVA follow-up data ≥ 350 days after the first treatmentno visit with BCVA follow-up data ≥ 350 days after the first treatment and no visit recordedin the 150 days before 14 September 2007 (or the last date of data submission, if earlier)no visit with BCVA follow-up data ≥ 350 days after the first treatment and visit in the150 days before 14 September 2007 and explicit reason for loss to follow-up (planneddischarge, treatment failure, etc.).Other participants, that is those with no data for BCVA follow-up ≥ 350 days after the firsttreatment and a visit in the 150 days before 14 September 2007 and a further visit booked (or noreason for not booking a further visit, e.g. explicit reason for loss to follow-up), were classifiedas having ‘active treatment, with continuing follow-up’. Classification as active or completedtreatment was mutually exclusive.Definition of ‘TAP eligibility’We decided that the independent, reading centre gradings of baseline angiograms should bethe basis for the classification of patients as ‘eligible for the TAP trials’ (EFT) or ‘not eligible forthe TAP trials’ (IFT). As described in Chapter 3, Network of Ophthalmic Reading Centres theUK, this decision was made because the research team was concerned that ophthalmologists’ invivo clinical gradings might be biased in order to allow a patient to be classified as eligible fortreatment (e.g. percentage of classic CNV overestimated).This concern was substantiated by an unpublished interim subanalysis comparingophthalmologists’ classifications with reading centre gradings for 2441 eyes which showedthat, on average, the former classified a higher percentage of patients as having predominantlyclassic CNV lesions (Table 4). Agreement was poor (although substantially better than expectedby chance: κ = 0.093, standard error 0.010, p < 0.0001). Many more eyes were classified aspredominantly classic with occult by ophthalmologists than by independent grading; conversely,fewer eyes were classified as minimally classic (with or without occult) by ophthalmologists, thatis as ineligible for VPDT according to the NICE guidance. 6At the time of first treatment, eyes were classified into mutually exclusive categories based onthe proportion of classic and occult CNV (predominantly classic, minimally classic or occult noclassic) as independently graded. We grouped patients into three categories based on whether ornot the treated eye met the following eligibility criteria for the TAP trials:■■■■BCVA > 33 and < 74 letters at first treatment ANDevidence on FA of at least some classic CNV (> 1% of lesion) AND