APPENDICES - NIHR Health Technology Assessment Programme

DOI: 10.3310/hta14370 Health Technology Assessment 2010; Vol. 14: No. 37
Study details Population details Treatment details Results Interpretation
Authors’ conclusions
ALA–PDT is an easy to
handle one-step procedure
for therapy of isolated mild
to moderate AK lesions.
Compared with current PDT
procedures, pre-treatment
is not needed and handling
is considerably facilitated.
A single PDT treatment
results in efficacy rates being
statistically significantly
superior to placebo and
cryosurgery
Brief study appraisal The
study appears to be generally
well conducted but reporting
of some of the methodology
and results was unclear
Morbidity The complete clinical clearance rates
(lesions) were 89% (664/750) for ALA–PDT, 77%
(530/692) for cryosurgery and 29% (75/259) for
placebo. PDT was significantly better than placebo
PDT (p < 0.001) and cryosurgery (p = 0.007).
Clearance rates (patients) were ALA–PDT 67%
(86/129), cryosurgery 52% (66/126) and placebo 12%
(5/43). PDT was significantly better than placebo and
cryosurgery (p < 0.001 for both)
QoL and return to normal activity Patients’
and investigators’ assessment of cosmetic outcome
of cleared lesions was significantly better for ALA–
PDT than cryosurgery (p < 0.001). 95% of ALA–PDT
patients were very satisfied or satisfied with the
overall cosmetic outcome vs 82% with cryosurgery.
It appears to be reported that ALA patients
were significantly more satisfied than placebo
and cryosurgery (p < 0.0001). Pigmentation status
classed as ‘normal’ in the ALA–PDT groups was
88%. Hypopigmentation was seen in 33% of lesions
with cryosurgery. Hyperpigmentation was seen in
9% PDT patients vs 4% placebo. Pigmentation status
was significantly different between ALA–PDT and
cryosurgery (p < 0.001) but the difference between
ALA–PDT and placebo was not significant (p = 0.87)
AEs Three per cent in the ALA and cryosurgery
arms and 2% placebo reported an AE related to
therapy. 99% of ALA patients experienced an adverse
reaction at some stage of treatment (placebo data
was pooled with trial AK03)
Trial treatments ALA–
PDT patch vs cryosurgery vs
Placebo PDT patch
Intervention ALA–PDT patch:
4–8 patches (4 cm2 ) containing
8 mg of 5-ALA were applied to
lesions without preparation,
one patch per lesion. After
4 hr, illumination with red light
(37 J/cm2 , 630 ± 3 nm) with
Omnilux (11 centres). Patients
were instructed to protect
lesions from light for 48 hr after
therapy
Comparator cryosurgery:
A standardised protocol was
used. Open spraying procedure
with liquid nitrogen in 1 cycle
was used (with size C nozzles)
and freeze time (of 5–10 s)
started after ice ball formation
2nd comparator Placebo
PDT patch: As for ALA–PDT
but with placebo on the
patches
Treatment intention Curative
Type(s) of lesion and histology AK
Main eligibility criteria Caucasian
males and females (at least 18 yr old)
with skin types I–IV were eligible for
inclusion. AK lesions had to be mild to
moderate (Cockrell definition) with
a maximum diameter of 1.8 cm and
interlesional distance of at least 1 cm.
The following were excluded: women of
child-bearing potential, non-responders
to previous PDT, patients with
particular dermatological conditions,
porphyria, dementia or clinically relevant
immunosuppression, topical treatment
that may affect response 4 wk before
and during the study (various criteria),
treatment with cytostatics or radiation
3 mth prior to/during study and
intolerance to ingredients of placebo or
known reactions to cryotherapy
Patient characteristics
% Male: 72
Mean age: PDT 70, cryosurgery 71,
placebo 72
Age range: 41–94 yr
Skin type: I 18%, II 66%, III 15%, IV 1%
Concomitant treatment Not stated
Authors
Hauschild et al.
(2008), 60 Trial
AK04
Linked
publications166 Data source
Full published
paper
Country
Germany
Language
English
Study design
RCT
No. of
participants
Total: 349 (1950
lesions)
Intervention: 148
Comparator: 149
(cryosurgery)
2nd Comparator:
49 (placebo)
No. of
recruiting
centres 29
(unclear whether
this was for each
trial)
Follow-up
period and
frequency FU
after 12 wk
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