Placebo Medication and Sham Surgery Responses in Benign Prostatic Hyperplasia Treatments: Implications for Clinical Trials

Abstract

Placebo medications and sham surgeries have long been thought to be inert treatments. These groups served as a threshold to which an active treatment should be compared in a randomized trial to determine the true efficacy of the active treatment. However, surprising changes in subjective symptom scores and objective measures of voiding have been demonstrated in numerous placebo medication or sham surgery arms of trials. The exact mechanisms by which these inactive treatments augment patient outcomes are not clearly defined and multiple theories have been proposed to explain the often pronounced response. It appears that urologic outcomes are particularly prone to these effects and the astute physician should keep these responses in mind when interpreting any trial on a new therapy.

Two-year results after convective radiofrequency water vapor thermal therapy of symptomatic benign prostatic hyperplasia

“…Analyses of randomized, controlled clinical trials for LUTS/BPH with drugs, endoscopic procedures, and surgeries have shown that placebo effects are to be considered in evaluating the outcomes of active treatments 21,22. However, as the improvements in IPSS and Q max in this study are comparable to those observed in the prospective, controlled pivotal convective RF thermal therapy trial, and similarly durable,13 the validity of the therapeutic responses are substantiated.…”

Brain Mechanisms of the Placebo Effect: An Affective Appraisal Account

“…These include multiple pain conditions (Tuttle et al 2015, Vase et al 2002, such as osteoarthritis (Bannuru et al 2015, Moseley et al 2002, migraine (Kam-Hansen et al 2014, IBS (Kaptchuk et al 2010, Vase et al 2005, and labor pain (Liberman 1967). Substantial placebo responses are also observed in depression (Cuijpers et al 2012, Fournier et al 2010, anxiety (Bandelow et al 2015), Parkinson's disease (Goetz et al 2008), schizophrenia (Rutherford et al 2014), asthma (Wechsler et al 2011), urological conditions (Sorokin et al 2015), menopausal hot flashes (Freeman et al 2015), and other conditions.…”

“…Although placebo treatments can affect physiological outcomes, such as hormone production or urinary flow rate (Meissner 2011, Meissner et al 2007, Sorokin et al 2015, Wager & Atlas 2015, they are largest for psychological outcomes (Figure 2a) (Hróbjartsson & Gøtzsche 2010). For example, one study found that a placebo treatment for asthma improved subjective symptom severity but did not improve forced expiratory volume, an objective measure of lung function (Wechsler et al 2011).…”

Informed consent and clinical trials: where is the placebo effect?

“…25 Disclosures about placebo responses should be carefully formulated to be as illness and symptom specific as possible. For example, for treatments of conditions that are known to elicit placebo responses (eg, benign prostatic hyperplasia, 26 perimenopausal hot flushes 27 ), patients should be told that previous studies suggest that they may experience symptom improvement. If no placebo effects are expected-for example, in trials that add a second medication to standard of care for treating cancer tumours-participants might be told that placebos are unlikely to affect the tumour and are designed to help scientists to assess outcomes objectively.…”