WELCOME 2015.

Methods	Wessex Evaluation of Fatty Liver and Cardiovascular Markers in NAFLD with Omacor Therapy (WELCOME) RCT, parallel, (Omacor or placebo), 15‐18 months Summary risk of bias: low
Participants	Patients with NAFLD N: 51 intervention, 52 control (analysed, 47 intervention, 48 control) Level of risk for CVD: moderate Men: 49% intervention, 67% control Mean age in years (SD): 48.6 (11.1) intervention, 54 (9.6) control Age range: not reported (18‐75 years inclusion criteria) Smokers: 14.3% intervention, 11.8% control Hypertension: not reported Medications taken by at least 50% of those in the control group: lipid lowering drugs Medications taken by 20%‐49% of those in the control group: antihypertensives, metformin (data not provided by group) Medications taken by some, but less than 20% of the control group: none reported Location: UK Ethnicity: not reported
Interventions	Type: supplement (Omacor capsules) Comparison: DHA + EPA vs MUFA Intervention: 4 g OMACOR per day (providing 1.84 g EPA, 1.52 g DHA as ethyl esters)]. Dose: 3.36 g/d EPA + DHA Control: 4 g olive oil capsules/ day (providing; ALA1%, oleic acid 67%, palmitic acid 15%, stearic acid 2%, n‐6 fat: 15%) Compliance: was assessed by recording the returned unused capsules and quantification of erthrocyte EPA + DHA enrichment (a prespecified threshold of 2% for DHA & threshold of 0.7% for EPA enrichment) Duration of intervention: 15‐18 months
Outcomes	Main study outcome: changes in mean liver fat %, changes in 2 liver fibrosis scores, change in serum biomarkers Dropouts: 4 intervention, 4 control Available outcomes: weight, BMI, lipids, blood pressure, glucose, insulin sensitivity, body fat measures, liver enzymes, HbA1c, serum n‐3 FAs, authors provided details of diabetes diagnoses, % body fat, BP and carotid intima media thickness Response to contact: yes
Notes	Study funding: National Institute for Health Research (NIHR) Southampton Biomedical Research Unit grant and by a Diabetes UK allied health research training fellowship awarded to KGM (Diabetes UK. BDA 09/ 0003937). CDB, PCC and ES are supported in part by the NIHR Southampton Biomedical Research Centre. Omacor and placebo were provided by Pronova Biopharma through Abbott Laboratories, Southampton, UK
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants were block randomised by an independent clinical trials pharmacist to treatment with identical capsules by mouth of either n‐3 fatty acid ethyl esters (4 g/d Omacor; Pronova, Sandefjord, Norway) or placebo (4 g/d olive oil) for a minimum of 15 months and a maximum of 18 months (McCormick‐2015, p2). Patients were randomised according to standardised procedures (computerised block randomisation) by a research pharmacist at University Hospital Southampton NHS Foundation Trust. Simple randomisation in blocks of 4, either to trial medication or placebo was used. (Scorletti‐2014, p 2)
Allocation concealment (selection bias)	Low risk	Participants were block randomised by an independent clinical trials pharmacist to treatment with identical capsules by mouth of either n‐3 fatty acid ethyl esters (4 g/d Omacor; Pronova, Sandefjord, Norway) or placebo (4 g/d olive oil) for a minimum of 15 months and a maximum of 18 months (McCormick‐2015, p2). Only the clinical trials pharmacist was unblinded, and randomisation group allocation was concealed from all study members throughout the trial. (McCormick‐2015, p 2).
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Paper states that only the clinical trials pharmacist was unblinded, and randomisation group allocation was concealed from all study members throughout the trial. However, the trial register record states "single blind (investigator)". Although the capsules were identical, no information provided as to their smell and taste
Blinding of outcome assessment (detection bias) All outcomes	Low risk	As above
Incomplete outcome data (attrition bias) All outcomes	Low risk	The ITT analysis included all patients randomised who had complete data (baseline and end‐of‐study measurements), regardless of whether they were later found to be ineligible, a protocol violator, given the wrong treatment allocation, or never treated) (Scorletti 2014, p 4)
Selective reporting (reporting bias)	Unclear risk	Prospectively registered September 2008, study start September 2009, end February 2017. Outcome data for cardiac function not yet published, though other cardiovascular measures reported – take as ongoing as recent end date
Attention	Low risk	Both groups had the same attention
Compliance	Low risk	Assessed by recording the returned unused capsules and quantification of erthrocyte EPA + DHA enrichment (a prespecified threshold of 2% for DHA and threshold of 0.7% for EPA enrichment). Quote: "Enrichment was highly variable in the DHA+EPA group and 5 and 6 participants in the DHA+EPA group did not reach the prespecified threshold for EPA and DHA enrichment, respectively. In the placebo group, we expected no enrichment between baseline and end of study in all participants in this group, but 3 and 4 participants reached the thresholds set for the DHA+EPA group, for EPA and DHA, respectively. One participant in the placebo group admitted to taking cod liver oil during the study and another markedly increased consumption of fish." 10 of 95 non‐compliant
Other bias	Low risk	None noted