Research Institute

HRI Science Division

As part of our mission to enhance our anecdotal and empirical understanding of the causes, implications, and solutions to reducing the insidiously high placebo and nocebo effects within CNS and general medicine clinical trials, Hassman Research Institute (HRI) has devoted itself to developing and funding our own Science Division focused on these phenomena. The researchers associated with this division meet on a regular basis to discuss and implement systemic strategies to help overcome what our clinical trial industry has identified as the primary causes of the placebo and nocebo responses or Placebo Response Factors (PRFs) (e.g., Alphs et al., 2012; Benedetti & Amanzio, 2011; Brazil, 2018; Cohen, 2012), namely subjects’ naivety of the placebo, expectation bias, misconception of expected interactions with research site staff, and uncertainty of their role in the trial.

A significant development toward this purpose from HRI’s Science Division is the copyrighted Placebo-Control Reminder Script (PCRS, now in Version 5). The PCRS is a methodical instrument which carefully reviews the PRFs with research participants and is diligently read to each study subject starting at the SCR Visit and at all study visits thereafter before any efficacy scales are administered. HRI is currently in the process of thoroughly empirically exploring the efficacy of the PCRS to manage placebo and nocebo responses among subjects with major depressive disorder (MDD), schizophrenia/schizoaffective disorder, and migraines. The below research posters presented at professional clinical trial industry conferences illustrates the studies we have conducted for this robust endeavor. In general, the findings do indicate that the PCRS significantly helps manage the placebo effect among subjects with MDD and schizophrenia/schizoaffective disorder (p<.01 and p=0.002, respectively) with also an expected (nonsignificant) trend for managing the nocebo effect. HRI and its associated esteemed sites are currently engaged in researching the PCRS’ impact in helping to control the placebo and nocebo effects among migraine sufferers (results expected Q4 2020, so please return to this webpage at that time).

Subsequent to HRI’s empirical findings of the PCRS, sponsors and CROs have expressed great interest in applying the script to their respective clinical trials, and as such, HRI does license the PCRS for such purposes. The license includes actual PCRS source specifically tailored for the respective clinical trial design and methodology to be read by the site staff member (typically the psychometric rater administering the primary efficacy scale in the study) as well as a PowerPoint slide deck training the site staff member on using the PCRS. For more information on HRI’s research in this crucial area within our industry and licensing the PCRS, please email Dr. Elan Cohen, HRI Principal Investigator, at

In conjunction with our PCRS and our concerted determination to stay current on recent literature regarding theories of what promulgates placebo and nocebo reposes, HRI has implemented our own proprietary Placebo-Control Daily Reminder Campaign (PCDC; see below) for subjects participating in our Single- or Double-Blind Placebo-Control clinical trials. The PCDC involves providing such subjects with a small (approx 4.5 x 5), convenient magnet participants take home with them at their Baseline Visit for them to place on their refrigerator (or any other convenient place for them to place where they will see the magnet on a daily basis and be reminded of its message). The campaign also involves reminding subjects of the intended message (see below) during their actual visits at our site, and as such, a banner was also created and hung in all HRI common areas (inpatient and outpatient facilities).

The magnet and banner indicate: “Speak Your Truth. No Expectations.*” with the smaller font at the bottom: “*Ask your Coordinator or Rater.” Why these words: research continues to strongly show that unchecked and any level of expectations from subjects about their own improvement in a study and what they perceive from study staff as wanting them to improve or not improve during their participation has the strong potential of generating a placebo effect. An expectation is also derived from subjects forgetting they may be on a placebo and thinking that they are receiving true medicine to help them with their respective indication. While there is arguably minimal empirical evidence that shows implementing actual interventions to control and educate subjects about such expectations subsequently reduces a placebo effect (with the exception of our multi-site study investigating the efficacy of the PCRS to reduce the placebo effect; see posters which present our findings), it makes rational sense to incorporate such continued education in our work at HRI. While our PCRS is read to all subjects at all of our Placebo-Control study visits, this script is only provided once a week / per study visit. In contrast, the PCDC is a continual reminder to our Placebo-Control investigation subjects that we have no expectations, that they should have no expectations, and that they should simply come to the site per their study visits reporting “the truth” of their symptoms. If a subject asks any of our staff what the message means, they ardently refer to the verbiage from our PCRS – i.e., to tell the subject none of us at the site have expectations of how you should or should not be feeling because none of us here at the site know if you are randomly assigned to receive the active medication or the placebo (remind subject what a placebo is) and that their role in the study is to simply come to each visit and be truthful in describing how they are doing in regard to their symptoms.

The above are just a few systemic examples, of many, regarding how HRI and its Science Division are dedicated to explore and implement strategies aimed to manage the placebo and nocebo effects within its awarded trials, and moreover, share its gained knowledge with other interested entities to reduce this effect overall within our industry. HRI genuinely welcomes ideas and partners to this venture and this can be done by emailing Dr. Elan Cohen at










HRI Placebo-Control Daily Reminder Campaign: