APPENDICES - NIHR Health Technology Assessment Programme

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198 Appendix 13 Study details Population details Treatment details Results Interpretation Authors’ conclusions MAL–PDT showed inferior efficacy for treatment of non-face/ scalp AK compared with cryotherapy. However, both treatments showed high efficacy, and MAL– PDT conveyed the advantages of better cosmesis and higher patient preference Brief study appraisal The study was quite well conducted, but it was open in design and therefore there was potential for investigator/ patient bias. The possibility of institutional differences and/or protocol deviation (24 centres in four countries) affecting the reliability of results was illustrated by the wide variation of freeze–thaw timings used for cryotherapy Morbidity At wk 24 the mean reduction in lesion count from baseline was 78% for MAL–PDT and 88% for cryotherapy (per-protocol population) (p = 0.002), 95% CI of the bilateral difference (MAL–PDT/cryotherapy) was between –16.6% and 3.9%. ITT (last observation carried forward) analysis confirmed this (75% reduction with MAL–PDT vs 87% with cryotherapy, p < 0.001). 76% (455) of lesions were cured with MAL–PDT vs 88% (490) with cryotherapy. The difference was similar for mild- and moderate-thickness lesions QoL and return to normal activity Investigator-assessed cosmetic outcome was significantly better for MAL–PDT than cryotherapy (p < 0.001). In the MAL–PDT group, 79% of lesions had an excellent cosmetic outcome, 19% good, 3% fair and 0% poor (compared with 56% excellent, 36% good, 8% fair and 0.9% poor with cryotherapy). After 24 wk, 50% of patients preferred MAL–PDT in terms of cosmetic outcome compared with 22% for cryotherapy (p < 0.001). 28% had no preference (ITT analysis). Patients preferred MAL–PDT to cryotherapy for all questions in the patient questionnaire (between 12% and 58% of difference). The differences were marked apart from effectiveness of treatment (39% favoured MAL–PDT vs 26% cryotherapy, not significant). Patients preferred MAL–PDT in terms of comfort (60% vs 10%, p < 0.001), procedure (49% vs 28%, p = 0.05) and healing (64% vs 6%, p < 0.001). Overall patient satisfaction favoured MAL–PDT (49% vs 20%, p < 0.001). If re-treatment was required 59% would prefer MAL–PDT over cryotherapy (25%, p < 0.001) AEs There were 63% patients with 99 AEs with cryotherapy vs 45% patients with 67 AEs with MAL–PDT. Most were dermatological and related to treatment. The most commonly reported AE for MAL–PDT was photosensitivity reaction (43% of patients with 63 AEs) and cold exposure injury for cryotherapy (62% patients with 95 AEs). Most were of mild intensity. Two patients in the cryotherapy group reported severe cold exposure injury Trial treatments MAL–PDT vs cryotherapy (withinparticipant comparison) Intervention MAL–PDT: After scraping of lesions, a 1-mm layer of 160-mg/g MAL cream was applied to each lesion (including 5 mm of surrounding tissue) for 3 hr (under occlusion). After saline cleansing, a standard LED lamp illuminated lesions with narrow band red light (average 630 nm, dose 37 J/cm2 , mean time 8 min 36 s). Lesions with a non-CR were re-treated after 12 wk Comparator Cryotherapy: Double freeze–thaw cryotherapy using liquid nitrogen spray applied with a 1- to 2-mm frozen rim outside the lesion outline. Timing of freeze–thaw application was as per usual practice of each centre (mean time 20 s ± 14 s) Treatment intention Curative Type(s) of lesion and histology Nonhyperkeratotic AK Main eligibility criteria Males and non-pregnant women aged 18 or over, with a clinical diagnosis of non-hyperkeratotic AK, of mild or moderate thickness, on locations other than the face or scalp, were eligible for inclusion. Patients had to have at least four comparable symmetrical AKs, of similar severity and total number on both sides of the body. Further eligibility criteria were reported Patient characteristics % Male: 65 Age range: 38–89 yr Mean age: 68.9 yr Cancer stage: Grade I, 687; grade II, 656 Patients had (a mean of) six lesions per side. Further patient characteristics were reported Concomitant treatment Not stated Authors Kaufmann et al. (2008) 46 Data source Full published paper Countries Australia, Belgium, Germany, UK Language English Study design RCT No. of participants Total: 121 (1343 lesions) Intervention: 121 (691 lesions) Comparator: 121 (652 lesions) No. of recruiting centres 24 Follow-up period and frequency FU at wk 12 and 24. Additional telephone calls were made at wk 1 and 13 when patients were re-treated
DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37 Study details Population details Treatment details Results Interpretation Authors’ conclusions One treatment with PDT using topical 5-ALA appears to be as effective and well tolerated as 3 wk of twice-daily topical 5-FU, a cheap and widely available alternative Appraisal This study appeared to be too small to detect significant treatment effects. The methods and results were not clearly reported and measures to reduce bias (e.g. randomisation, blinding and allocation concealment) were not reported at all so the reliability of the conclusions is questionable Morbidity The mean lesional area before treatment for PDT was 1322 mm2 and 6 mth after treatment was 291 mm2 (a reduction of 73%, 95% CI 61% to 84%). For 5-FU, mean lesional area was 1390 mm2 before treatment and 297mm2 after (a reduction of 70%, 95% CI 61% to 80%). There was no statistically significant difference in reduction of lesional area between PDT and 5-FU at 6 mth (p = 0.72). No patients were completely cleared of AKs with either treatment QoL and return to normal activity Not assessed AEs All patients experienced mild to moderate pain at PDT sites. In wk 1, PDT sites were significantly more painful than 5-FU sites, but this difference was absent in wk 2 and reversed in wk 4. There was no significant difference between treatments overall over the 4-wk period. Daily symptom diaries were completed by 11 patients. In wk 1, PDT sites were significantly more erythematous than 5-FU sites but this difference was absent in wk 2 and reversed in wk 3 and 4. There was no significant difference between treatments overall over the 4-wk period. There was no blistering, ulceration, scarring or photosensitivity reaction after either treatment method. One patient experienced contact sensitivity to 5-FU Trial treatments ALA–PDT vs 5-FU (within-participant comparison) Intervention ALA–PDT: Thick surface scale was removed if present then 20% 5-ALA was applied topically and covered in a lightimpermeable dressing for 4 hr. PDT was administered with a halogen lamp (580–740 nm, 150 J/cm2 , mean fluence rate 80 mW/cm2 ) Comparator 5-FU cream (5%) was applied topically twice a day to one hand for 3 wk by thorough massage Treatment intention Curative Type(s) of lesion and histology AK Main eligibility criteria It appeared that patients with a long history of AKs affecting the forearms and hands were eligible for inclusion Patient characteristics % Male: 47 Age range: 53–79 yr Concomitant treatment Not stated Authors Kurwa et al. (1999) 47 Data source Full published paper Country UK Language English Study design RCT No. of participants Total: 17 Intervention: 17 Comparator: 17 No. of recruiting centres Not stated Follow-up period and frequency 1 wk, 4 wk and 6 mth © 2010 Queen’s Printer and Controller of HMSO. All rights reserved. 199
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Feedback The HTA programme and the
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APPENDICES - NIHR Health Technology Assessment Programme

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