A PROSPECTIVE COMPARISON OF 4 STUDY DESIGNS USED IN ASSESSING SAFETY AND EFFECTIVENESS OF DRUG-THERAPY IN HYPERTENSION MANAGEMENT

The objective of the study was to compare prospectively the impact of study design on drug therapy safety and effectiveness data obtained in hypertension management. The main study was a randomized controlled c linical trial of four different prospective study designs used in post marketing assessment involving 1008 primary care practices in nine Can adian provinces. Two thousand nine hundred sixty-four patients with mi ld to moderate hypertension received an angiotensin converting enzyme (ACE) inhibitor daily for 14 weeks in one of four postmarketing studie s-a randomized double-blind clinical trial (RCT) (10 to 40 mg fosinopr il daily v 5 to 20 mg enalapril daily), two structured open label tria ls of 10 to 40 mg fosinopril daily (one with free drugs), or an unstru ctured open label trial of 10 to 40 mg fosinopril daily. Patient demog raphic and baseline characteristics, systolic and diastolic blood pres sures, adverse events reported, and data quality were recorded as the outcome measures. The results showed that the RCT patients were titrat ed to higher doses of ACE inhibitor than patients in the open studies, P <.008; patients in the open studies were more likely to receive adj uvant diuretic therapy, P <.008. The decrease in blood pressure was si milar for patients in all four studies, mean decrease in systolic BP w as between 18 and 20 mm Hg, mean decrease in diastolic BP was between 11 and 13 mm Hg. Fewer patients in the unstructured open trial reporte d adverse events than patients in the RCT: a 55% relative reduction in reported adverse events (P <.008) was associated with the unstructure d trial. There were also fewer drug-related adverse events per patient reported in the unstructured study (17 per 100 patients) than in the other studies (27 to 41 per 100 patients), P <.008. Physician preferen ce for rounding off blood pressure measurements to 0 or 5 occurred mos t often in the unstructured open trial (P <.008). In conclusion, despi te differences in dose titration and in the use of adjuvant therapy, a ntihypertensive drug therapy effectiveness observed in an RCT may be s imilar to uncontrolled postmarketing studies. Open trials with schedul ed follow-up visits are as effective in detecting severe adverse event s as RCT, but postmarketing studies with unstructured schedules of fol low-up are insufficient in identifying drug-related adverse events and have poorer quality data. (C) 1997 American Journal of Hypertension, Ltd.