ELSEVIER SAFETY AND EFFICACY OF DOXAZOSIN IN BENIGN PROSTATIC HYPERPLASIA: A POOLED ANALYSIS OF THREE DOUBLE-BLIND, PLACEBO-CONTROLLED STUDIES CLAUS G. ROEHRBORN AND RICHARD L. SIEGEL ABSTRACT Objectives. To present the results of a pooled analysis of three double-blind, placebo-controlled studies of doxazosin in benign prostatic hyperplasia (BPH). Heterogeneous symptom and bother score data collected using different symptom indices were transformed to enable a comparison of the data and to conduct a pooled, in-depth analysis. Methods. Urinary flow rates, and symptom and bother score data were shown by analysis of covariance methods to give consistent estimates of the efficacy of doxazosin across different studies, thus confirming the validity of pooling the results. Prior to analysis, symptom and bother score data were transformed so that all scales started from zero (least symptoms or bother) and were expressed as a percentage of the maximum score. Results. Doxazosin produced a significantly greater improvement than placebo in peak urinary flow rate (P = 0.0017), symptom severity (P ~0.0001 ), and bother caused by symptoms (P <O.OOO 1). Stratification showed that a greater improvement was obtained during doxazosin treatment by those with more severe symptoms at baseline (P = 0.0001). Stratification by age showed that age did not affect the capacity to benefit from treatment. Analysis of the pooled peak flow-rate data showed that doxazosin produced a con- sistently greater increase in flow compared with placebo. Doxazosin was well tolerated, with 10% of patients having withdrawn due to adverse events versus 4% with placebo (P ~0.05). Conclusions. Doxazosin is well tolerated and effective in the treatment of BPH. Pooling of data has enabled more extensive and robust conclusions to be drawn than was possible for each one of the individual three studies. UROLOGY 48: 406-415, 1996. I mprovement in the lower urinary tract symp- toms associated with benign prostatic hyper- plasia (BPH) , although a subjective measure of treatment outcome, is of more immediate con- cern to the patient than objectively measured pa- rameters such as improvement in urinary flow rates. The improvement in symptoms obtained with a new medical treatment for BPH is, there- fore, of prime clinical interest. However, the measurement of symptoms in BPH is difficult. A From the University of Texas Southwestern Medical Center, De- partment of Surgery, Division of Urology, Dallas, Texas; and Pfizer, New York, New York Reprint requests: Claus G. Roehrborn M.D., The University of Texas, Southwestern Medical Center, Department of Surgery, Division of Urology, 5323 Harry Hines Boulevard, 18-l 48, Dal- las, TX 752359110 Submitted (Rapid Communication): April 4, 1996, accepted (with revisions): May 15, 1996 COPYRIGHT 1996 BY ELSEVIER SCIENCE INC. 406 ALL RIGHTS RESERvED number of different scales have been used for this purpose; this has made comparison of data from different studies difficult. For example, some of the scales run from zero to an endpoint, whereas others go from a number other than zero to an endpoint. Some scales go up, others go down, and different scales are based on dif- ferent questions. The first published scale for assessing symptoms suggestive of bladder outlet obstruction was the Boyarsky Scale.’ Eight symptoms are rated on a scale from 0 (absent/occasional) to 3 (always present/severe) : nocturia, hesitancy, intermit- tency, terminal dribbling, urgency, impaired size and force of stream, dysuria, and sensation of in- complete emptying. In addition, daytime fre- quency is rated on a scale from 0 (1 to 4 times) to 3 ( 13 or more times). The Boyarsky Scale is still a widely used instrument and has been vali- dated in recent studies.2 0090-4295/96/$15.00 PII SOO90-4295(96)00208-7