Critical appraisal:Siller G, Rosen R, Freeman M, Welburn P, Katsamas J, Ogbourne SM 2010 2

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Risk of bias assessment: Randomised Controlled Trial (Cochrane risk of bias tool)

Random sequence generation
Describe the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.Jutta's question mark icon.png
An independent clinical research organization used a

computer-generated randomization schedule with a block
size of eight to assign eligible patients to treatment on days
1 and 2 (Arm A) or days 1 and 8 (Arm B) and, within each
group, to treatment with ingenol mebutate gel, 0.0025%,
0.01% or 0.05%, or matching vehicle gel. Patients were
assigned to active treatment or vehicle in a ratio of 8:2.

What was the risk of bias from the random sequence generation?Jutta's question mark icon.png
Allocation concealment
Describe the method used to conceal the allocation sequence in sufficient detail to determine whether intervention allocations could have been foreseen in advance of or during, enrolment.Jutta's question mark icon.png
No clear.
What was the risk of bias from the allocation concealment?Jutta's question mark icon.png
Describe all measures used, if any, to blind outcome assessors from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective.Jutta's question mark icon.png
Study medication was labelled with a patient number before

the trial and patients were allocated sequentially at each
centre according to the randomization schedule. Study
medication assignment was double-blind and could be
revealed only in case of emergency. The active and vehicle
gels were physically indistinguishable, and identical packaging
was used to maintain blinding of both the investigator
and patients regarding allocation to active or vehicle gel.
Despite these measures, successful blinding could not be
guaranteed because of the skin responses expected with
active treatment.

What was the risk of bias from the blinding of participants and personnel and outcome assessors?Jutta's question mark icon.png
Incomplete outcome data
Describe the completeness of outcome data for each main outcome, including attrition and exlusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons for attrition/exclusions where reported, and any re-inclusions in analyses performed by the review authors.Jutta's question mark icon.png
Very complete data set.
What was the risk of bias from incomplete outcome data?Jutta's question mark icon.png
Selective outcome reporting
State how the possibility of selective outcome reporting was examined by the review authors and what was found.Jutta's question mark icon.png
oedema, erosion/ulceration, erythema, flaking/scaling/

dryness, hyperpigmentation, hypopigmentation, itch,
scabbing/crusting, scarring, vesicles and weeping/exudate.
LSR were classified as mild (easily tolerated), moderate
(associated with discomfort that was sufficient to interfere
with usual activities) or severe (incapacitating, with inability
to work or perform usual activities). The highest severity
experienced was recorded for each patient. Treatment was
withheld if a severe LSR occurred before the second scheduled
dose. LSR were recorded as adverse events (AE) if they
occurred outside the treatment area.
Efficacy was evaluated by the clinical and histological
response on day 85. The investigator determined the clinical
response at each visit by estimating the extent of lesion
clearance compared with baseline as follows: complete
clearance (no clinical evidence of residual disease),
marked clearance (50–90% improvement), slight clearance
(10–50% improvement), unchanged (�10%), worsened
(clinically observable growth), or unable to be assessed.
Pretreatment lesion photographs taken on day 1 were used
for comparison.

What was the risk of bias from selective outcome reporting? Assessments should be made for each main outcome (or class of outcomes).Jutta's question mark icon.png
Other sources of bias
Describe any other sources of biasJutta's question mark icon.png
Despite these measures, successful blinding could not be

guaranteed because of the skin responses expected with
active treatment.

What was the risk of bias from other sources?Jutta's question mark icon.png
Overall risk of bias
Low risk of bias Additional comments:

Jutta's tick icon.png This appraisal has been completed.

Siller G, Rosen R, Freeman M, Welburn P, Katsamas J, Ogbourne SM. PEP005 (ingenol mebutate) gel for the topical treatment of superficial basal cell carcinoma: results of a randomized phase IIa trial. Australas J Dermatol 2010 May;51(2):99-105 Available from:
Assigned to
Topic area
Guidelines:Keratinocyte carcinoma/Private
Clinical question
Form:Quality appraisal rct-cochrane

Section below only relevant for Cancer Council Project Officer

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Risk of bias assessment: cohort study

Subject selection
"New technology" group
No response
Comparison group
No response
Comparability of groups on demographic characteristics and clinical features
No response
Measurement of outcomes
Outcome measures blind to technology used
No response
Same method of measurement used across comparison groups
No response
Completeness of follow-up
Was follow-up complete and were all patients included in the analysis?
No response