Date: November 20, 2023 Reference: Jones et al. Time to reflect on open-label placebos and their value for clinical practice. PAIN October 2023 Caitlin Jones PhD Guest Skeptic: Dr. Caitlin Jones is a Postdoctoral Research Associate at Sydney University’s institute for Musculoskeletal Health. Her research evaluates the benefits and harms of treatments for musculoskeletal conditions with a particular interest in high-risk treatment options such as opioid medicines and spinal cord stimulators for pain. She has a goal to improve patient outcomes and reduce harm from inappropriate treatments. We have an interesting back story on how we met. Dr. Sergey Motov and I did a structured critical appraisal of the OPAL trial (SGEM#419). You were the lead author on that study. You pointed out we missed some details in our review and provided some additional information. We were happy to hear from you and updated the SGEM episode based upon your comments. Not everyone has been so receptive to your study and your feedback. Thanks for appraising OPAL and for engaging with me about it. There were lots of varied responses to OPAL. Most were positive and interested. Some had opinions that the trial doesn’t reflect their practice or their patients, so it’s not relevant to them (reasonable position). Some are furious that we would even suggest that opioids don't work and they are certain this is part of a corrupt evil agenda (I don’t engage with this stance because nothing I can say will change their minds). I do engage when it’s just a genuine misunderstanding, or someone has missed some details.Everyone is free to make up their own mind about how they will or won’t apply these findings into their clinical practice, but I do feel an obligation to correct misunderstandings when I see them. After our exchange I looked up some of your other publications. One of them caught my eye as being very thought-provoking. It looked at open label placebo being used in clinical trials. The title of the paper was Time to reflect on open-label placebos and their value for clinical practice [1]. What got you interested in that topic? A lot of my research compares treatments for MSK pain to placebo to establish efficacy (how well it works). In my field we often find, sadly, that some of the treatments used for decades in clinical practice don’t show effects above that of the placebo when someone finally tests them properly. There’s been increasing chatter about OLPs with a few editorials written in big journals, and an increase in publications on the topic, so it is clearly gaining traction in the clinical and research community. A lot of my work so far has been about testing treatments that have been used for decades without proper testing, and then when we finally test them, we discover we were doing more harm than good all this time. Open label placebos as a clinical treatment are new enough that there is time to intervene and advocate for some thorough testing before they become common place in clinical care. I don’t want this to be another thing where we realize in 50 years’ time that we were harming not helping. SGEM listeners are probably familiar with the placebo effect, but can you give us a brief definition or description? The placebo effect is the positive effect on outcomes stemming from positive expectations around receiving a treatment, but not the treatment itself. Placebo in a research context is the gold standard comparison in efficacy trials that can provide an estimate of the treatment effect, filtering out all the biases and contextual effects that aren’t directly caused by the treatment of interest, so we are left with an estimate of the direct effects of the treatment itself. Then along came some research which caused some excitement. They reported that you could elicit a placebo effect without deceiving the patients (ie telling them it is a placebo) [2]. Yes,