ELSEVIER THE SO-CALLED “PLACEBO EFFECT” IN BENIGN PROSTATIC HYPERPLASIA TREATMENT TRIALS REPRESENTS PARTIALLY A CONDITIONAL REGRESSION TO THE MEAN INDUCED BY CENSORING SCOTT M. SECH, JUAN D. MONTOYA, PABLO A. BERNIER, EMMA BARNBOYM, SHERRIL BROWN, ALLISON GREGORY, AND CLAUS G. ROEHRBORN ABSTRACT Objectives. To study the variability of assessment instruments (symptom questionnaires and flow rate recordings) in healthy volunteers during repeat administration in short intervals. To study the effect of inclusion criteria-based censoring of patients during screening for benign prostatic hyperplasia (BPH) treatment trials on the outcome of subsequent tests. Methods. One hundred forty-five male volunteers without known prostatic diseases with a mean age of 52 years (range 23 to 83) were given the American Urological Association (AUA) Symptom Index (SI), BPH Impact Index (II). Quality of Life (QOL) score, and a flow rate recording twice 10 to 20 days apart without any healthcare intervention. Data were collected and analyzed after typical BPH trial criteria were applied to the first test, and patients who did not “qualify” were censored. Results. Good correlation exists between two closely spaced administrations of the AUA SI, BPH II, QOL score, and flow rate recordings in healthy male volunteers with correlation coefficients between 0.73 and 0.89. Censoring patients and excluding them from the analysis of the second test based on typical BPH trial criteria induces a regression to the mean phenomenon, which results in an artificial improvement in these outcome parameters. The magnitude of the improvement increases as the selection and censoring criteria tighten. The mean differences between the first and second test range from 1.4 to 1.7 mUs for the peak flow rate, from - 1 .O to - 1.4 for the AUA SI, and from -0.4 to -0.8 for the BPH II. All these differences induced solely by censoring with resulting regression to the mean are statistically significant. Conclusions. Censoring of patients based on inclusion and exclusion criteria is typical for BPH treatment trials. One of the under-recognized effects of censoring is a regression to the mean, which leads to an apparent improvement in the outcome parameters assessed. In both placebo or sham-controlled trials, as well as in clinical series without controls, one must keep this effect and its relative magnitude in mind, and interpret the data from such trials with appropriate caution. UROLOGY 51: 242-250, 1998. 0 1998, Elsevier Science Inc. All rights reserved. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 0 ver the past years a tremendous interest in the diagnosis, evaluation, and treatment of be- nign prostatic hyperplasia (BPH) and the associ- ated lower urinary tract symptoms (LUTS) has re- From the Depnrtment Urology, The University Texas South- 0 1998, ELSEVIER INC 242 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA ALL RIGHTS RESERVED sulted in the publication of numerous clinical studies. In fact, at the time of publication of the Agency for Health Care Policy and Research (AH- CPR) Guidelines for the Diagnosis and treatment of BPH,l only about 200 articles were available for review and analysis, but this number has increased more than twofold in the years since then. The interest in BPH and LUTS is based first on the aging male population, with more patients presenting with LUTS and clinical BPH for treatment and sec- ond on the competition between pharmaceutical companies involved in the research and develop- ment of new compounds with efficacy in this dis- 0090-4295/98/$19.00 PII SOO90-4295(97)00609-Z