OBJECTIVEThis literature review investigated whether the reported efficacy was comparable or not for the same anti-hypertensive drug when used as treatment agent or reference agent in randomized clinical trials in China.

METHODThe randomized clinical anti-hypertensive trials for the treatment of mild to moderate hypertensive patients in Chinese-language journals between 1994 and 2004 were identified by searching the China National Knowledge Infrastructure in China Hospital Knowledge Database web (CNKI-CHKD). A clinical trial was selected for the present review if the same drug in the same dose was used either as treatment agent or reference agent in the trial with identical therapy duration and effects evaluation criteria. The anti-hypertensive efficacy of the same drug as a treatment drug or reference drug was compared.

RESULTSSix drugs (bisoprolol, benazepril, enalapril, felodipine, amlodipine and losartan) were used in 37 clinical trials and used as treatment drug in 18 trials and as reference drug in 19 trials. The rank sum test indicated that there is a significant difference in the total effective rate between the treatment groups (85.38%, n = 18) and the reference groups (77.17%, n = 19), P < 0.05. The effective rate for the same drug was significantly higher when it was used as treatment drug than that used as reference drug (P < 0.05).

CONCLUSIONThe anti-hypertensive effect of the same drug is often overestimated when used as a treatment agent and underestimated when used as a reference agent in randomized clinical trials. This grouping-related efficacy bias should be considered when evaluating the effects of a tested anti-hypertensive drug in clinical trials.