Brown 1997a.
| Methods | The method of random allocation was not described | |
| Participants | Patients were men < or = 65 years of age at high risk for future cardiac events by virtue of: 1) an elevated apoprotein B > or = 125 mg/dl, 2) at least 1 coronary lesion > or = 50% stenosis or 2 lesions > or = 30% stenosis as documented by baseline angiogram, and 3) a family history of premature cardiovascular events | |
| Interventions | Regular niacin (4 times each day) versus polygel controlled release niacin (twice‐daily dosage (bid)). All patients received lovastatin 20 mg bid, colestipol 10 g bid, and niacin 500 mg 4 times each day for 12 months, with dosage adjustment to target cholesterol of 150 to 175 mg/dl, and to minimize side effects. At 12 months, patients were randomly assigned to 1) continue with regular niacin at a dose identical to that established during the 12‐month dose‐finding period, or 2) change to polygel controlled‐release niacin at that daily dosage, but given twice rather than 4 times/day. At 20 months, groups 1) and 2) were reversed (cross‐over). This regimen continued for 8 more months | |
| Outcomes | Compliance with the recommended (and variable) dosage was calculated for each drug using a computer program that accounted for all drug supplies given, the recommended dosage, and a count of returned medication. It is expressed as a percentage of the dose recommended for the patient at the time Clinical outcome measurements included plasma very low‐density lipoprotein (VLDL), low‐density lipoprotein (LDL), and high‐density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein B, and asparate aminotransferase measured at baseline and every 4 months. Other laboratory measurements included uric acid, fasting glucose, fasting insulin, creatinine kinase and fibrinogen at entry (before treatment), 6 months, 12 months, 20 months, 28 months, and 6 weeks after stopping the triple‐drug regimen |
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| Notes | ― | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details on randomization provided in article. (pg 112) At 12 months, patients were randomly assigned to: (1) continue with regular niacin at a dosage identical to that established in the 12‐month dose‐finding period, or (2) change to polygel controlled‐release niacin at that daily dosage, but given twice rather than 4 times/day. At 20 months, groups (1) and (2) were reversed (cross‐over). This regimen continued for 8 more months |
| Allocation concealment (selection bias) | Unclear risk | No details on allocation concealment provided in article. (pg 112) At 12 months, patients were randomly assigned to: (1) continue with regular niacin at a dosage identical to that established in the 12‐month dose‐finding period, or (2) change to polygel controlled‐release niacin at that daily dosage, but given twice rather than 4 times/day. At 20 months, groups (1) and (2) were reversed (cross‐over). This regimen continued for 8 more months |
| Selective reporting (reporting bias) | Unclear risk | No protocol available |
| Other bias | Unclear risk | No apparent bias but unclear |
| Blinding of outcome assessment (detection bias) Adherence measure | Unclear risk | (PRIMARY) PILL COUNT ‐ No information given in article about who collected the data |
| Blinding of outcome assessment (detection bias) Patient outcome | Low risk | (PRIMARY) LIPID LEVELS ‐ BLOOD TEST ‐ Probably unblinded ‐ trial is open‐label; there is insufficient information, but marked low risk because blood test is an objective measure not affected by blinding |
| Blinding of participants (performance bias) Adherence measure | High risk | (PRIMARY) PILL COUNT ‐ Patient would have been aware of their study group; open‐label trial |
| Blinding of participants (performance bias) Patient outcome | Low risk | (PRIMARY) LIPID LEVELS ‐ BLOOD TEST ‐ Laboratory outcomes are unlikely to be influenced by lack of blinding of participants |
| Blinding of personnel (performance bias) Adherence measure | Unclear risk | (PRIMARY) PILL COUNT ‐ No information given in the article about general blinding to study group |
| Blinding of personnel (performance bias) Patient outcome | Low risk | (PRIMARY) LIPID LEVELS ‐ BLOOD TEST ‐ Probably unblinded ‐ trial is open‐label; there is insufficient information, but marked low risk because blood test is an objective measure not affected by blinding |
| Incomplete outcome data (attrition bias) Adherence measure | Low risk | (PRIMARY) PILL COUNT ‐ Reason for missing data unlikely to be related to the outcome (2 patients left the study because of time constraints) |
| Incomplete outcome data (attrition bias) Patient outcome | Low risk | (PRIMARY) LIPID LEVELS ‐ BLOOD TEST ‐ Reason for missing data unlikely to be related to the outcome (2 patients left the study because of time constraints) |