Gottlieb 2003

Methods	RCT, placebo‐controlled, double blind Date of study: August 2000‐January 2001 Location: multicentre (locations not specified)
Participants	Randomised: 112 participants (mean age 47 years, 70 male) Inclusion criteria Participants with moderate‐severe psoriasis (BSA ≥ 10), age ≥ 18 years Had previously received phototherapy or systemic psoriasis therapy at least once Exclusion criteria Quote p 1628) "Patients were excluded if they had guttate, erythrodermic, or pustular psoriasis; other skin conditions; or other significant medical conditions that might interfere with evaluations of the effect of study medications on psoriasis" Dropouts and withdrawals 19/112 (17%): etanercept 4/57 (7.0%), placebo 15/55 (27.3%) Time and reasons: etanercept: AE (1), lack of efficacy (3) placebo: AE (4), lack of efficacy (9), lost to follow‐up (1), patient refusal (1)
Interventions	Intervention A. Etanercept (n = 57), SC, auto‐administered, 25 mg twice a week, 24 weeks Control intervention B. Placebo (n = 55), SC, auto‐administered, twice a week, 24 weeks
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PASI 75 Secondary outcomes of the trial At 4, 8, 12, 24 weeks PASI 50 PASI 75 PASI 90 DLQI PGA Safety Participant global assessment of psoriasis
Notes	Funding source, quote (p 1631): "This study was sponsored by Immunex Corp, a subsidiary of Amgem, Inc.) Declarations of interest not stated except "Dr Zitnik is an employee of Amgen" (p1627)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 1628): "Patients ... were to be randomised in block of 6 with equal allocation between the treatment group...Patients were assigned numbers based on randomisation tables verified by Immunex Pharmaceutical Planning" Comment: probably done
Allocation concealment (selection bias)	Unclear risk	Quote (p 1628): "Patients ... were to be randomised in block of 6 with equal allocation between the treatment group...Patients were assigned numbers based on randomisation tables verified by Immunex Pharmaceutical Planning, after which the Immunex Clinical Distribution Department shaped blind‐labelled vials of study drug to the pharmacies". Comment: we don't know whether the investigators were blinded or the numbers of participants per block. This probably was a centralized randomisation; however, it's not stated.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 1628): "... performed blinded labelling and packaging of the study drug. ... multicenter, randomised, double‐blind" Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 1628): "... performed blinded labelling and packaging of the study drug. ... multicenter, randomised, double‐blind" Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	High risk	Randomly assigned 112, 112 participants analysed for the primary endpoint Dropouts and withdrawals Etanercept 4/57 (7.0%), placebo 15/55 (27.3%) Time and reasons: etanercept: AE (1), lack of efficacy (3) placebo: AE (4), lack of efficacy (9), lost to follow‐up (1), patient refusal (1) Management of missing data: Quote (1628): "Patients were analysed on an intent‐to‐treat basis... If a patient discontinued treatment before the end of the study, the last observation was carried forward for efficacy analyses" Comment: high rate of withdrawal in placebo group and imbalanced reasons for withdrawal
Selective reporting (reporting bias)	Unclear risk	Comment: no protocol was available. The pre‐specified outcomes mentioned in the methods section appeared to have been reported.