MRC 1968.

Study characteristics
Methods	RCT Medical Research Council (MRC) Summary risk of bias: moderate to high
Participants	Free‐living men who have survived a first MI (UK) CVD risk: high Control: randomised 194, analysed 181 at 2 years Intervention: randomised 199, analysed 172 at 2 years Mean years in trial: control 3.7, intervention 3.8 % male: 100 Age: unclear (all < 60) Ethnicity: not stated Statins use allowed? Unclear (anti‐coagulants allowed, but few other medications appear to have been used) % taking statins: Not reported (probably none as too early, pre‐1980)
Interventions	Modified fat vs usual diet Control aims: usual diet Intervention aims: reduce dietary fat to 35 g fat per day, add 84 g soya oil per day Control methods: usual diet plus reducing diet (reduced CHO) for weight management for overweight men Intervention methods: instructed to follow a dietary regimen removing saturated fat from the diet plus daily dose of 85 g soya oil; half of it had to be taken unheated. Reduced CHO diet for weight management in overweight men Intervention appears to be delivered and supervised by trial dietitian but unclear how often. Total fat intake, %E (at 3.5 years): int 46 (SD unclear), cont 43 (SD unclear) (mean difference 3.00, 95% CI 0.91 to 5.09 assuming SDs of 10) significant increase Saturated fat intake: not reported (mean difference unclear) PUFA intake: not reported PUFA n‐3 intake: not reported PUFA n‐6 intake: not reported MUFA intake: not reported CHO intake: not reported Protein intake: not reported Trans fat intake: not reported Replacement for saturated fat: mainly PUFA (based on dietary goals) Style: diet advice & supplement (soy oil) Setting: community
Outcomes	Stated trial outcomes: MI or sudden death Data available on total mortality? yes Cardiovascular mortality? yes Events available for combined cardiovascular events: cardiovascular deaths and fatal or non‐fatal MI Secondary outcomes: total and non‐fatal MI, stroke, cancer deaths, CHD mortality, CHD events (CHD mortality or non‐fatal MI) Tertiary outcomes: none (data for weight, total cholesterol and BP, but no variance info)
Notes	Study duration over 6 years Study aim: for intervention "saturated fats were replaced by polyunsaturated fats", but saturated fat intakes during trial were not reported. SFA reduction aimed Total serum cholesterol, difference between intervention and control, mmol/L: ‐0.64 (95% CI unclear), reduction > 0.20 For all, data at 4 years, control n = 89, intervention n = 88 Weight change: control ‐3 kg, intervention 0 kg Total cholesterol change: control ‐0.47 mmol/L, intervention ‐1.11 mmol/L Systolic BP change: control 0 mmHg, intervention +2 mmHg Diastolic BP change: control +3 mmHg, intervention ‐1 mmHg Trial dates: Study recruitment 1960 to 1965, analysed 1967 Funding: Medical Research Council Declarations of Interest of primary researchers: none stated, all authors worked for academic or health institutions.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "using random numbers, by blocks within hospitals"
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding of participants and personnel (performance bias) All outcomes	High risk	Big changes to fat intake in intervention group while control group ate their usual diet
Blinding of outcome assessment (detection bias) CVD outcomes	Low risk	Quote: "Suspected relapses were assessed at regular intervals by a review committee unaware of the patients diet group".
Blinding of outcome assessment (detection bias) All‐cause mortality	Low risk	Blinding is not relevant in assessment of mortality.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Data collection was thorough, but some participants dropped out and contact was lost, so some events may have been missed.
Selective reporting (reporting bias)	Low risk	Not relevant for primary and secondary outcomes as all trialists were asked for data
Free of systematic difference in care?	High risk	Unlikely as control group continued diet as usual, intervention group were likely to have had additional contact. See control and intervention methods in the Interventions section of the table of Characteristics of included studies
Stated aim to reduce SFA	Low risk	Aim to reduce SFA stated
Achieved SFA reduction	Unclear risk	SFA intake not reported
Achieved TC reduction	Low risk	Although statistical significance was not reported or calculable, TC in the intervention group was 0.64 mmol/L lower than in the control group, a large fall (and almost certainly statistically significant).
Other bias	Low risk	None noted