Bauer et al.2 reported on their use of an interesting strategy, little used in urology but well known to statisticians: a double-blind, placebo-controlled, multiple-crossover trial (known as an n-of-1) in men who were continuous users of tamsulosin for at least 12 months for treatment of BPH. The objective of this study was "to determine if placebo-controlled 'n of 1' deprescribing trials can identify older men who are likely to benefit from stopping ineffective chronic tamsulosin therapy for lower urinary tract symptoms." The time intervals for treatment with drug or placebo were based upon published pharmacokinetics, pharmacodynamics, and the expected time frame of symptomatic relief from the drug. The protocol included a one-week placebo run-in followed by two 5-week cycles, each cycle including two 2-week treatment periods of drug or placebo in a randomized sequence, separated by a placebo washout. The primary efficacy outcome was the American Urological Association (AUA) Symptom Index with an adapted recall period of 24 hours. The effect size was based on the upper boundary of the individual drug-placebo difference in daily score and characterized as minimal or none, moderate, or strong effect. The population consisted of men aged 55 to 80 years, and one exclusion criterion was a symptom index less than 5 or greater than 25. The overall conclusions and relevance as stated by the authors were "...one in 3 older men who had minimal symptomatic relief from tamsulosin may be high-priority candidates for deprescribing." The actual findings were that 36.7% of the population demonstrated minimal or no effect, 36.7% demonstrated what was described as a moderate effect, and 13.3% demonstrated a strong effect. However, 13.3% did not tolerate the placebo run-in, presumably because their symptoms worsened, and therefore it seems that this percentage should be added to those who demonstrated a strong effect, making the total percentage in that category 26.6%.
The invited commentary by the former Chair of Biostatistics at Brown University School of Public Health3 emphasizes the point that even though treatment was determined to be statistically significant on average, about 1/3 of participants received little benefit. He points out that the focus of the manuscript on patients for whom treatment is not indicated is unusual but suggests another benefit of this type of trial: to provide information to the clinical practitioner. The "n of 1" seems to be a great tool, and was originally heralded, as the commentator suggests, as an attempt "to scientifically operationalize the clinical practice of trying different treatments to determine which works best," seemingly additive to the concept of truly "personalized medicine." Such a trial, if properly conducted as this one, would conceivably minimize placebo effect and expectation bias, regression to the mean, and symptom variation. The questions are: how practical is such a trial in clinical practice? Are there other objective variables besides symptom evaluation (such as urodynamic values in a neurogenic or non-neurogenic population) that might influence a clinician to feel that a treatment was conferring benefit in the absence of symptomatic change? And, if one is considering only a symptomatic evaluation, how different are the results going to be from simply asking the patient, after a sufficient trial, "Are you overall better, worse, or unchanged?" and "Do you want to stay on this medication?" The same questions would apply after a "drug holiday." Performance of this type of trial seems most compatible within an academic medical center with strict adherence to protocol. This type of trial would seem ideal for a head-to-head study of two drugs with similar pharmacologic characteristics, both for the same indication. Such a trial would not replace the usual randomized trial but complement it, and such results would nicely "round out" a meta-analysis or detailed review.
Written by: Alan Wein, MD, PhD, FACS, Professor of Clinical Urology, Department of Urology, Desai Sethi Urology Institute (DSUI), University of Miami Miller School of Medicine, University of Miami Health Systems, Miami, FL.
References:
- Gill, H et al. Benign Prostatic Hyperplasia and Related Entities. Penn Clinical Manual of Urology, Guzzo, T and Wein, A, eds. 2024, Elsevier Press, Philadelphia.
- Bauer, S et al. Tamsulosin deprescribing for lower urinary tract symptoms in older men: A randomized trial. JAMA Network Open, 2026. doi:10.1001/jamanetworkopen.2026.21639.
- Schmid, C. Invited Commentary: Personalizing N-of-1 trial results to facilitate decision making. JAMA Network Open, 2026. doi:10.1001/jamanetworkopen.2026.21651.