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. 2018 Nov 30;2018(11):CD003177. doi: 10.1002/14651858.CD003177.pub4

Brox 2001.

Methods RCT, parallel, 3 arms (n‐3 EPA + DHA from cod liver vs n‐3 EPA + DHA from seal oil vs nil), 14 months
 Summary risk of bias: moderate or high
Participants Subjects with moderate hypercholesterolaemia
N: 40 seal oil (SO), 40 cod liver oil (CLO), 40 control (numbers analysed vary by outcome)
Level of risk for CVD: moderate (dyslipidaemia)
Men: 53% seal oil, 50% cod liver oil, 48% control
Mean age in years: 53.2 seal oil, 55.0 cod liver oil, 55.8 control
Age range: 43‐66 years
Smokers: unclear
Hypertension: unclear
Medications taken by at least 50% of those in the control group: none allowed
Medications taken by 20%‐49% of those in the control group: not reported
Medications taken by some, but less than 20% of the control group: not reported
Location: Norway
Ethnicity: not reported
Interventions Type: supplement (oil)
Comparison: EPA + DHA vs nil
Intervention: Intervention: seal oil – 15 mL/d (2.6 g, 1.1 g/d EPA + 1.5/d DHA) (total n‐3 3.9 g/d, total PUFA 4.2 g/d): SO dose: EPA + DHA 2.6 g/d
Cod liver oil – 15 mL/d (3.3 g, 1.5 g /d EPA + 1.8 g/d DHA) (total n‐3 4.1 g/d, total PUFA 4.35 g/d): CLO dose: EPA + DHA 3.3 g/d
Control: nil, no supplement
Compliance: serum omega‐3 fatty acids, rose from around 1 mmoL/L to 2.4 (seal oil), 2.1 (cod liver oil) and 1.2 mmoL/L (control)
Length of intervention: 14 months
Outcomes Main study outcome: serum lipids
Dropouts: 8 seal oil, 2 cod liver oil, 1 control
Available outcomes: total and cardiovascular deaths, MI, combined CV events, lipids, adverse events
Response to contact: yes (author provided methodological details)
Notes Data of two intervention groups combined for dichotomous outcomes and CLO vs control data used for continuous outcomes
Study funding: the study was supported by the programme Medical Research in Finnmark County, University of Tromsø
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk J Brox stated (personal communication, January 2017): "The randomization of the 120 participants was done by first generating 3 groups (seal oil, cod liver oil, control), then giving each participant a number (1‐120), "'putting all the numbers into the same hat' and blindly drawing one number at the time from the hat. The first 40 numbers (1‐40) were allocated to the seal oil group, the next 40 numbers (41‐80) to the cod liver oil group and the rest (81‐120) were allocated to the control group."
Allocation concealment (selection bias) Low risk J Brox stated (personal communication, January 2017): "The researcher/clinician who invited the participants had no knowledge of to which group the participants would be allocated."
Blinding of participants and personnel (performance bias) 
 All outcomes High risk Quote: "controls were aware – not given a supplement"
Blinding of outcome assessment (detection bias) 
 All outcomes Low risk J Brox stated (personal communication, 2003): "All the persons involved in the drawing & analysing of blood were unaware of treatment. The technicians analysing the blood did not have any personal contact with the participants except K. Olaussen who did the FA analysis … she only had access to the sample numbers not names and code. The participants did not know their number (says elsewhere that K Olaussen did not know allocations). The only outcome assessor was J Brox who did not have personal contact with participants, randomising, collecting results or analysing process." "The only assessor was J Brox who did not have any personal contact with the participants, had nothing to do with the randomising or analysing process, or the collecting of results."
Incomplete outcome data (attrition bias) 
 All outcomes High risk Control group 3 dropouts, seal oil group 10 dropouts, cod liver oil 3 dropouts. So substantial differences in rates of dropouts between the groups
Selective reporting (reporting bias) Unclear risk No study protocol or trials register entry was found
Attention Low risk No suggestion of differential attention
Compliance Low risk Serum omega‐3 fatty acids, rose from around 1 mmoL/L to 2.4 (seal oil), 2.1 (cod liver oil) and 1.2 mmoL/L (control)
Other bias Low risk No further bias noted
HHS Vulnerability Disclosure