APPENDICES - NIHR Health Technology Assessment Programme

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202 Appendix 13 Study details Population details Treatment details Results Interpretation Authors’ conclusions When treated with both MAL–PDT and cryotherapy, patients significantly prefer MAL–PDT treatment for AK. MAL–PDT is an attractive treatment option for AK, with comparable efficacy and superior cosmetic outcomes compared with double freeze–thaw cryotherapy Brief study appraisal This study was generally well conducted and reported; however, it was an openlabel trial, which can lead to bias in favour of a particular treatment. The possibility of institutional differences and/or protocol deviation (25 centres in two countries) affecting the reliability of results was illustrated by the variation of freezing times used for cryotherapy Morbidity At wk 12 lesion reduction with MAL–PDT was 87% vs 76% (p < 0.001). Reduction in lesion count at wk 24 was 89% with MAL–PDT vs 86% with cryotherapy (p = 0.2, n = 108). At wk 12 CR was 83% with MAL–PDT vs 72% with cryotherapy. At wk 24 it was 86% (650/758) with MAL–PDT vs 83% (613/743) with cryotherapy. 21% of lesions with CR at wk 24 had needed re-treatment with cryotherapy at wk 12 vs 10% with MAL–PDT, results were independent of initial severity grade or location (ITT population) QoL and return to normal activity Overall participant preference (i.e. cosmetic outcome, efficacy, and skin discomfort) was 49% for MAL–PDT vs 21% for cryotherapy (p < 0.001, ITT analysis). Results reported for per-protocol population were 45% vs 10%, p < 0.001. Investigator preference for cosmetic outcome was 43% for MAL–PDT vs 12% for cryotherapy, p < 0.001, and for overall preference was 52% vs 16%, p < 0.001. Most subjects were ‘satisfied’ to ‘very satisfied’ with MAL–PDT (compared with cryotherapy and previous other AK treatments) for 7/11 questions of a satisfaction questionnaire. More than 90% were satisfied with MAL–PDT in terms of effectiveness of treatment, scarring, skin colour and appearance at 1- and 3-mth FU. Cryotherapy was preferred for time taken over treatment (92%) compared to 78% for MAL–PDT. 65% would prefer to be retreated with MAL–PDT vs 32% with cryotherapy (n = 108) AEs Skin discomfort VAS scores (mean) were 5.2 with MAL– PDT vs 4.9 with cryotherapy (p = 0.24) after 1st treatment. For re-treated lesions, mean VAS scores were 3.7 vs 4.4. Patients preferred cryotherapy in terms of skin discomfort after 1st treatment (45% vs 33%, no preference 22%, p = 0.07), but there was no difference for re-treated lesions. Skin-related AEs were reported by 62% MAL–PDT patients vs 72% for cryotherapy. There was one discontinuation with MAL–PDT due to a local reaction. Most skin-related AEs were mild to moderate and transient Trial treatments MAL– PDT vs cryotherapy (within-participant comparison) Intervention MAL– PDT: After scraping of lesions, a 1-mm layer of MAL 160 mg/g cream was applied (including 5 mm of surrounding tissue) for 3 hr (under occlusion). Following saline cleansing, lesions were illuminated with narrowband light (approximately 630 nm, dose 37 J/cm2 ) using a standard LED light source. Mean illumination time was 8 min 41 s. Lesions with a non-CR were re-treated at 12 wk Comparator Double freeze–thaw cryotherapy: Liquid nitrogen spray applied to achieve a 1- to 2-mm frozen rim around the marked outline of the lesion. Mean freezing time was 16 s (± 7 s) Treatment intention Curative Type(s) of lesion and histology Nonhyperkeratotic AK Main eligibility criteria Males and females over 18 yr (16 yr in Scotland) with clinical diagnosis of (at least three) nonhyperkeratotic AK on the face and/or scalp (of similar severity and number on both sides) were eligible for inclusion. Patients that received topical treatment within the previous 3 mth, regular UV therapy, patients with thick or pigmented lesions or porphyria were excluded Patient characteristics % Male: 91 Age range: 54–93 yr Mean age: 75 yr Mean no. of lesions per side: six Median lesion diameter: 7 mm Further patient characteristics were reported Concomitant treatment Not stated Authors Morton et al. (2006) 48 Linked publications167,168 Data source Full published paper Countries Ireland, UK Language English Study design RCT No. of participants Total: 119 (1501 lesions) Intervention: 119 (758 lesions) Comparator: 119 (743 lesions) No. of recruiting centres 25 Follow-up period and frequency FU at wk 12 and 24. Additional telephone FU was performed at wk 1 and 13 UV, ultraviolet.
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37 Study details Population details Treatment details Results Interpretation Authors’ conclusions PDT using topical MAL was a safe and effective treatment for AK with excellent cosmetic outcome. It is a promising treatment that could benefit from further study Brief study appraisal This study appeared to be generally well conducted Morbidity For the MAL–PDT group, patient response was 32/39 (82%) vs 8/38(21%) in placebo, treatment difference –61% (p = 0.001) For the MAL–PDT group lesion response rate was 209/236 (89%) vs 92/241 (38%) for placebo. Response rate was similar for mild and moderate lesions in the MAL group (90% and 84%, respectively); placebo response was higher in the mild lesions (44% and 25%) QoL and return to normal activity Investigator assessed cosmetic outcome in the MAL–PDT group was ‘excellent’ or ‘good’ in 31/32 (97%) patients and when assessed by patients this was 29/32 (91%). The outcome was not rated ‘poor’ by either investigator or patient. 73% of 32 patients preferred MAL–PDT to previous treatments (5-FU, cryotherapy, surgery) AEs 38 (90%) MAL–PDT patients had an AE vs 22 (58%) in placebo. One MAL–PDT patient discontinued due to AE. Common local AEs were: burning sensation of the skin (27 MAL patients vs 4); erythema (22 vs 8); crusting (16 vs 6); pain on the skin (10 vs 0); blisters (8 vs 2); skin oedema (6 vs 1); stinging skin (6 vs 1) and skin ulceration (5 vs 0). More details in paper Trial treatments MAL–PDT vs PDT with placebo cream Intervention MAL–PDT: Scales and crusts were removed using a curette MAL cream (160 mg/g) was applied (1-mm thickness and 5 mm around lesion) for mean 3 hr under occlusion. Cream was washed off using a 0.9% saline solution, then a non-coherent red light was applied: 570– 670 nm, dose 75 J/cm2 , mean intensity 155 mW/cm2 (range 50–200 mW/cm2 ). Treatment was repeated after 1 wk Comparator PDT with placebo cream: As for MAL– PDT but with placebo cream Treatment intention Curative Type(s) of lesion and histology Mild and moderate AK Main eligibility criteria Males and females over 18 yr with 4–10 previously untreated mild to moderate non-pigmented AK on the face and scalp (at least 3 mm diameter) were eligible for inclusion. Further eligibility criteria were reported Patient characteristics % Male: 88 Age range: 31–84 yr Mean age: MAL–PDT 64; placebo PDT 67 The majority of lesions were mild and located on the face. Most patients were Fitzpatrick skin type I or II Concomitant treatment Not stated Authors Pariser et al. (2003) 49 Data source Full published paper Country USA Language English Study design RCT No. of participants Total: 80 (502 lesions) Intervention 42 (260 lesion) Comparator: 38 (242 lesions) No. of recruiting centres Five Follow-up period and frequency FU was at 3 mth. AEs were assessed during, immediately after PDT, at wk 2 and 3 mth after the 2nd PDT treatment © 2010 Queen’s Printer and Controller of HMSO. All rights reserved. 203
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Feedback The HTA programme and the
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APPENDICES - NIHR Health Technology Assessment Programme

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