Paller 2008.

Methods	Study design had a 12‐week randomised, double‐blind, placebo‐controlled period, thereafter a 24‐week open‐label phase, and lastly a randomised, double‐blind withdrawal–retreatment period from week 37 to 48
Participants	211 participants (106 in the treatment arm, 105 in the placebo arm) with paediatric psoriasis from 4 to 17 years of age were recruited at 42 sites in the United States and Canada Inclusion criteria: Moderate to severe plaque psoriasis at screening (defined as a PASI score of at least 12); stable disease; PGA of at least 3; BSA‐psoriasis involvement of at least 10%; history of psoriasis in the last 6 months; and previous or current treatment with phototherapy/systemic psoriasis therapy (e.g. retinoids, methotrexate, or ciclosporin) or poorly controlled psoriasis with the use of topical therapy
Interventions	Participants in the treatment arm received a dose of 0.8 mg per kilogram of body weight up to a maximum intended dose of 50 mg of reconstituted etanercept in syringes for once‐weekly subcutaneous injections; participants in the placebo arm received matching placebo
Outcomes	The primary outcome was PASI 75 (improvement in the PASI of 75%) at week 12. Secondary efficacy endpoints were PASI 50 (improvement in the PASI of 50%), PASI 90 (improvement in the PASI of 90%), and a PGA of clear or almost clear (score of 0 or 1), which were evaluated at weeks 2, 4, 8, and 16 and every 4 weeks thereafter The following participant‐reported outcomes were assessed during the double‐blind period in this study: The CDLQI was administered at baseline and at weeks 2, 4, and 12. Children aged 4 to 12 completed a cartoon version (children aged 4 to 7 years had caregiver or parental assistance), and adolescents aged 13 to 17 years completed the written version The PedsQL was administered at baseline and week 12; 4 age‐specific versions of the PedsQL were administered: 4; 5 to 7; 8 to 12; and 13 to 17 years of age. Participants aged 8 to 17 years completed the questionnaire without assistance, whereas participants < 7 years of age were assisted by a caregiver or parent The Stein Impact on Family Scale, which assessed the impact of psoriasis on the lives of participants' families, was completed by parents or caregivers at baseline and at week 12 during the double‐blind period The 2 age‐dependent versions of the Harter Self‐Perception Profile for Children, which assessed the impact of psoriasis on participants' self esteem, was completed during the double‐blind period Safety outcomes included non‐serious adverse events, serious adverse events, non‐serious infections, serious infections, malignancies, reactions in the injection site, laboratory findings, etanercept concentration in serum, and disease recurrence during the withdrawal period, which was defined as "the worsening of PASI by more than 125% from baseline within 3 months after discontinuation of treatment" (Paller 2008)
Notes	The analysis of the study was designed by Amgen Inc and funded by Immunex Corp, a wholly owned subsidiary of Amgen Inc, and by Wyeth, which was acquired by Pfizer Inc in October 2009. Financial support for the preparation of the manuscript was provided by Amgen Inc
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	In the included study participants underwent randomisation at a 1:1 ratio by an interactive voice‐response system
Allocation concealment (selection bias)	Low risk	Not specifically stated in paper, therefore we contacted the trial authors for further details about allocation concealment; since the main investigator was not able to provide further data, we contacted Pfizer. According to information provided by Pfizer, the allocation sequence was generated by Amgen and provided by the interactive voice‐response system by an unblinded randomisation group within Amgen According to the pharmaceutical lab response, the identity of  the investigational product assigned to participants was concealed using an "interactive voice response system"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Stated as "double‐blind" in abstract and methods of the original study. We therefore contacted the main author and Pfizer, who confirmed that all participants, study site personnel, and Amgen staff were blinded until the data through week 12 were finalised
Blinding of outcome assessment (detection bias) All outcomes	Low risk	It was not clear whether blinded outcome assessment was attempted in the original study. We therefore contacted the main author and Pfizer, who confirmed that outcome evaluators were dermatologists or dermatologists in training who were certified on PASI training materials and were also blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	In the included study, analysis was performed according to the intention‐to‐treat principle during first 12 weeks, thus, avoiding bias, at least in this phase of the study
Selective reporting (reporting bias)	Low risk	There was no evidence of selective reporting in the included study
Other bias	Unclear risk	Paediatric participants (aged 4 to 17 years) had stable moderate to severe plaque psoriasis at screening (defined as a PASI score >= 12); stable disease; PGA of at least 3; BSA‐psoriasis involvement of at least 10%; a history of psoriasis in the last 6 months; and previous or current treatment with phototherapy/systemic psoriasis therapy (e.g. retinoids, methotrexate, or ciclosporin) or poorly controlled psoriasis with the use of topical therapy When compared to the intervention arm, the control group had slightly lower disease duration at 5.8 years versus 6.8 years, slightly more participants with history of previous systemic therapy or phototherapy (59% vs 55% in the intervention group) and more psoriatic arthritis (13% vs 5%) at baseline. In addition, even though participants were required to have a PASI ≥ 12 at baseline, a PGA ≥ 3, and a BSA ≥ 10%, the median baseline PASI was 16. Also, an important percentage of participants in both arms (45% in the etanercept group and 41% in the placebo group) had no previous systemic or phototherapy history This was a industry‐sponsored trial with positive results. We therefore sought out missing or unclear information by contacting the pharmaceutical laboratory (Pfizer). They provided clearer information in April and May 2013 regarding sequence allocation, allocation concealment, blinding of participants and personnel, and blinding of outcome assessment

BSA: body surface area.
 CDLQI: Children's Dermatology Life Quality Index.
 PASI: Psoriasis Area and Severity Index.
 PedsQL: Pediatric Quality of Life Inventory.
 PGA: Physician's Global Assessment.