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

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.

An independent clinical research organisation used a computer-generated randomisation 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 randomised and assigned to active treatment or vehicle in a ratio of 8:2.

What was the risk of bias from the random sequence generation?

Low

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.

Study medication was labelled with a patient number before the trial commenced and patients were allocated sequentially at each centre according to the randomisation schedule.

Active and vehicle gels were physically indistinguishable and identical packaging was used to maintain concealment of both the investigator and patients regarding allocation to treatment.

What was the risk of bias from the allocation concealment?

Low

Blinding

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.

Active and vehicle gels had same packaging

What was the risk of bias from the blinding of participants and personnel and outcome assessors?

Low

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.

Arm A (n=30) Arm B (n=30)

AEs
2 patients (1x0.01% IM; 1x0.05% IM) in the Arm A group discontinued due to AE.

Response rates
No attrition/exclusions

What was the risk of bias from incomplete outcome data?

Low