Elan Cohen, Ph.D., Principal Investigator, CenExel HRI
The pervasive placebo effect observed within clinical trials, where drug and placebo demonstrate “comparable efficacy,” continues to have significance, with the slightly over 50% failure rate in the development of new psychiatric drugs (Greenberg, 2003; Khan et al., 2002; Kirsch, 2016; Mitte et al., 2005). General medicine studies are not immune to the placebo effect, where 30-40% of patients report improved subjective and objective outcomes in general medical studies (Hrobjartsson & Gotzsche, 2001). The high placebo response has been shown to be increasing as time progresses (Kemp et al., 2010; Loebel et al., 2010; Rief et al., 2009; Tuttle et al., 2015), with such ramifications as several pharma companies reducing or closing their psychiatric as well as general medicine R&D, increased costs for drug development, more inconclusive and failed trials, and delays in the development of new medications (Alphs et al., 2012).
To the rescue is the proprietary / copyrighted Placebo-Control Reminder Script© (PCRS) developed by clinicians in the trenches conducting clinical trials with study participants: Drs. Howard Hassman and Elan Cohen. The PCRS is a deceptively simple, yet highly effective one paragraph script read by designated trained site staff (typically the primary psychometric scale rater) to each study participant at each study visit. This tool crucially reminds study participants of key factors scientifically and anecdotally grounded as causing the placebo and nocebo effects – participant expectations of benefit, lack of understanding about what is a placebo, misconception of expected interactions with research site staff that enhance participants’ bias of “wanting to please their doctor,” and subject role uncertainty. The reading of the script, taking approximately 2-3 minutes, ends with the participant confirming in their own words a meta-understanding of the PCRS key concepts. Importantly, the investigator can justifiably withdraw a participant from the study if deemed having an inability to comprehend these factors. The PCRS has been empirically validated as demonstrating a significant reduction in the placebo and nocebo effects (Cohen et al., 2020, Neuropsychopharmacology; 2019a; 2019b) – meaning that the difference between active drug and placebo in rating scales of interest is larger with PCRS than without it. CenExel HRI Raters scored active drug subjects 24.5 points LESS on the PANSS scale compared to placebo subjects at primary endpoint visits.
In their review of the PCRS at an industry conference where the tool’s data was being presented, a regulator from the FDA expressed a personal view: “We [US FDA] found the approach interesting that a simple intervention like education can be quite impactful” (J. Toure, FDA Sr. Policy Advisor of Division of Psychiatry Products, email communication dated April 12, 2019).
In order to increase the reliability and success of clinical trials, application of the PCRS, a validated tool, is being implemented in clinical trials. The PCRS has been licensed and seamlessly implemented in over 30 global psychiatric and general medicine clinical trials, using both paper and electronic sources.
For more information about this exciting, essential placebo and nocebo mitigation tool for your study, please contact Dr. Elan Cohen at email@example.com.