The Physicians Health Study II.
| Methods | RCT of parallel group design | |
| Participants | 14,641 male participants were recruited in two phases. Starting in July 1997, 7641 participants were recruited from Physicians Health Study I. In July 1999 recruitment of physicians started. Invitational letters were sent to US male physicians identified from a list provided from the American Medical Association. 7000 willing and eligible men were recruited. Inclusion criteria: · Men · Age 50 years and older · Willing to forego any current use of multivitamins or individual supplements containing more than 100% RDA of vitamin E, vitamin C, β‐carotene or vitamin A Exclusion criteria: · History of cirrhosis, active liver disease, taking anticoagulants · A serious illness that would preclude participation 5.1% of participants had prevalent CVD at baseline (non‐fatal MI and stroke). *Some participants had a history of diabetes (approximately 6%), a history of high cholesterol (approximately 36%), a history of hypertension (approximately 42%), a BMI ≥30 kg/m2 (approximately 11%), were smokers (approximately 4%). Approximately 77% of participants were taking aspirin at baseline. *approximate percentages due to aggregated data |
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| Interventions | Intervention (Vitamin C (500 mg) taken daily, n = 7329) Control (Placebo, n = 7312) Mean follow‐up was 8 years. |
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| Outcomes | Major cardiovascular events, total MI, MI death, total stroke, stroke death, Ischaemic stroke, haemorrhagic stroke, cardiovascular death, congestive heart failure, angina, revascularisation, all‐cause mortality. | |
| Notes | This trial was a factorial 2 x 2 trial of vitamin E and vitamin C supplementation and it is therefore possible to compare two vitamin C arms (active vitamin C and placebo vitamin E and active vitamin C and active vitamin E) with two non‐vitamin C arms (placebo vitamin C and active vitamin E and placebo vitamin C and E). Funding source: commercial and non‐commercial (grants from the National Institutes of Health, investigator‐initiated grant from BASF Corporation. Study agents and packaging were provided by BASF Corporation, Wyeth Pharmaceuticals and DSM Nutritional Products Inc) |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "computer‐generated list of random numbers randomised in blocks of 16, stratified by age, prior diagnosis of CVD and cancer, and for the PHSI subjects, by their original β‐carotene assignment". |
| Allocation concealment (selection bias) | Unclear risk | Not stated. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | "Treatment and follow‐up continued in a blinded fashion", "All tablets were identical in appearance, size, and color". |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | End points were examined by physicians blinded to randomised treatment assignment. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Numbers for participants dead, alive and unknown status provided. |
| Selective reporting (reporting bias) | Low risk | All outcomes reported as specified. |
| Other bias | Unclear risk | Insufficient information to judge. Commercial and non‐commercial funding, authors clearly mention that commercial funding had no role in the study. |
BMI: body mass index CVD: cardiovascular disease DBP: diastolic blood pressure HDL: high‐density lipoprotein ITT: intention‐to‐treat LDL: low‐density lipoprotein MI: myocardial infarction RCT: randomised controlled trial RDA: recommended daily allowance SBP: systolic blood pressure