Critical appraisal:Farrell B, Godwin J, Richards S, Warlow C 1991

Risk of bias assessment: Randomised Controlled Trial (Cochrane risk of bias tool)

Random sequence generation

Describe the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups.

Eligible patients were randomised by telephoning the Clinical Trial Service Unit in Oxford. A two letter code was allocated which matched coded medication packs held by the local hospital pharmacists. Each four month patient pack contained 20 one week foils of 28 tablets; two tablets were to be taken in the morning and two in the evening (preferably with or after food) and each pair of tablets was specifically labelled by the day of the week and whether it was to be taken in the morning or evening.

Patients who were randomised to "high dose" aspirin received two 300 mg tablets twice daily, those randomised to "low dose" aspirin received two 150 mg aspirin tablets in the morning and the two evening tablets were placebo, and those randomised to "placebo" received two placebo tablets twice daily.

What was the risk of bias from the random sequence generation?

Low

Allocation concealment

Describe the method used to conceal the allocation sequence in sufficient detail to determine whether intervention allocations could have been foreseen in advance of or during, enrolment.

Eligible patients were randomised by telephoning the Clinical Trial Service Unit in Oxford. A two letter code was allocated which matched coded medication packs held by the local hospital pharmacists.

What was the risk of bias from the allocation concealment?

Low

Blinding

Describe all measures used, if any, to blind outcome assessors from knowledge of which intervention a participant received. Provide any information relating to whether the intended blinding was effective.

Placebo used and taken at the same frequency as active drug.

What was the risk of bias from the blinding of participants and personnel and outcome assessors?

Low

Incomplete outcome data

Describe the completeness of outcome data for each main outcome, including attrition and exlusions from the analysis. State whether attrition and exclusions were reported, the numbers in each intervention group (compared with total randomized participants), reasons for attrition/exclusions where reported, and any re-inclusions in analyses performed by the review authors.

Follow-up seem to be very complete.

Patients were seen every four months until after the scheduled end of the trial (30 September 1986), their prior death or emigration. If they could not, or would not, come to the neurological clinics, follow up was continued by postal or telephone contact with their general practitioners. In addition, each patient was flagged with the Office of Population Censuses and Surveys so that we received a death certificate in the event of their death. All the surviving patients were reviewed after the 30 September 1986. This was to ensure that all important events had been recorded and to inform the patients of the interim trial results (but not of their own treatment as the collaborators were still "blind" at that time).

What was the risk of bias from incomplete outcome data?

Low