The placebo effect will have to be taken into account in the development of vaccines and treatments, according to this opinion in Stat News.
“The placebo response is a complex psychobiological phenomenon that describes the clinical improvement seen in patients taking dummy or sham medicines. It can also comprise some proportion of the measured effect among patients receiving active drugs. Multiple behavioral, psychophysiological, and neuroimaging studies have shown that the placebo response is a real, multifactorial effect associated with changes in biochemical pathways in the brain. The effect is patient specific and is influenced by patient expectations and certain well-defined personality traits.
While drug developers are attuned to considering the placebo response in areas like pain and depression, it may not be immediately apparent why it is so critical for the development of Covid-19 therapies and vaccines. What set the stage was the FDA’s regulatory guidance, released in May, directing how the biopharma industry should evaluate drugs and vaccines being developed to fight the pandemic.”
When is a placebo not a placebo? It seems that placebos are no as ‘unreactive’ as the literature would suggest. Research hastened and made more urgent by the rushed efforts to develop a Covid-19 vaccine have revealed the need to create a standard for the actual content/ingredients of the placebo used in a given trial.
“Some researchers conducting clinical trials on a COVID-19 vaccine have not revealed to the public what the placebo contains, but they should. This is because the placebo ingredients influence how effective or harmful the active treatment, with which the placebo is compared, appears.”
Later, the article continues:
“Placebo controls are rightly the gold standard against which new treatments are measured. If a new treatment proves to be better than a placebo, it is taken to be effective. Otherwise, it isn’t. The problem is that until today, there has been no standard for placebos, which made estimates of side-effects confusing. Our new guideline fixes this problem by encouraging rigorous reporting of placebo ingredients.
We’ve known about the failure – and need – to report what’s in placebos for 15 years. By following the new guideline, we can get more accurate information about how beneficial and harmful treatments tested in placebo-controlled trials are.”
We have posted for a while now on so-called ‘open label’ placebos, and the placebo effect engaged when someone actually knows they’re taking a sugar pill (or any other placebo treatment such as a saline injection).
This report, in Science Alert, claims that “across two experiments (…) during a highly arousing negative picture viewing task, non-deceptive placebos reduce both a self-report and neural measure of emotional distress.”
It seems that ‘open label’ placebos can also be described as ‘non-deceptive placebos’. This designation is of importance where researchers try to tackle the ethical issues involved in ‘lying’ to people about the test drug (or non-drug) being administered.
“What if someone took a side-effect free sugar pill twice a day after going through a short convincing video on the power of placebos and experienced reduced stress as a result?” says lead researcher and psychologist Darwin Guevarra from Michigan State University (MSU).
Scientists have known since at least the 1930s that a doctor’s expectations and personal characteristics can significantly influence a patient’s symptom relief. Within research contexts, avoiding these placebo effects is one reason for double blind studies — to keep experimenters from accidentally biasing their results by telegraphing to test subjects what they expect the results of a study to be.
Students in the doctor group had previously been conditioned to believe that one of the creams was pain reliever. But in reality both of the two creams that they administered were an identical petroleum jelly-based placebo. And yet, when the doctor actors believed that the cream was a real medication — the researchers even gave the pseudo-medication a name, “thermedol” — the patient actors reported experiencing significantly lower amounts of pain.
As well-documented as the placebo effect is, to see it play out so cleanly surprised the study’s authors themselves. “We did several more studies to convince ourselves it wasn’t just a fluke,” says the study’s primary author, Luke Chang of Dartmouth University. “I’m impressed at how robust the effect seems to be.”
It seems that this damned placebo effect is getting in the way of developing and authorising new psychiatric drugs. It creates a ‘therapeutic bias'(!) and so the experimenters are experimenting with ways of controlling for it in trials, for example ‘SPCD, sequential parallel comparison design’. These are proving to be not (yet) up to the task, sufficient to be acceptable by bodies such as the RDA. The following is from The Placebo Effect Is Hobbling New Psychiatric Drugs
“The FDA’s rejection cast doubt upon the design, still in use in more than a dozen trials, as a weapon against the placebo effect.
That’s big news because the effect, also called the placebo response, has been growing stronger over the years in clinical studies that randomly assign patients to either an active drug or placebo. When the effect is high, it’s hard to know if a drug just isn’t good enough, if there are errors in the data, or if the participants taking the placebo—an inert pill meant to make them believe they’re getting the real thing—fared unusually well because of their expectations.
It’s a testament to the power of our minds to improve our health, at least temporarily. Many factors boost placebo response. “Most people, whether they know it or not, are biased to believe that they will receive the active drug even if they are told that they have a 50 percent chance of getting placebo, and this ‘therapeutic bias’ increases the placebo response,” says John Krystal, the chair of the psychiatric department at the Yale School of Medicine in New Haven, CT.”
There is some evidence – for example, in this study – that simply receiving the results of DNA tests can have a physical impact. Why? Well, once more the Placebo Effect is mentioned (as well as its dark twin, the Nocebo Effect, also covered on this website.
DNA tests are becoming quicker, cheaper and more reliable, so this is an issue we’ll hear more about.
Pain is something of a mystery. While we all experience it, and experience it in degrees, there’s no ‘gold standard’ for estimating the degree of pain. It seems to be a ‘subjective’ experience. In some of the research literature, such as this study, the placebo effect is given a credible place in the landscape of pain and pain management.
“Placebo effects that arise from patients’ positive expectancies and the underlying endogenous modulatory mechanisms may in part account for the variability in pain experience and severity, adherence to treatment, distinct coping strategies, and chronicity. Expectancy-induced analgesia and placebo effects in general have emerged as useful models to assess individual endogenous pain modulatory systems.”
Meantime, in the category of ‘Out There But Maybe Not As Out There As You Might Think’ virtual reality may have the capacity to harness the placebo effect in pain management.
“Recently, Cedars-Sinai also published research on the clinical utility of a virtual reality intervention in the Inpatient setting. The results of the study were overwhelmingly positive with most patients receiving pain and stress relief from the VR experience.”
We’ve posted elsewhere about the placebo’s dark twin, the nocebo, the phenomenon of the mind provoking negative and damaging effects through the same mechanism that accounts for the positive effects of a placebo.
This paper brings focus to ‘nocebo algesia and hyperalgesia (ie, the occurrence and worsening of nocebo-induced pain, respectively)’ and makes practical suggestions for reducing the incidence of this. As always, these relate to the patient-practitioner relationships and interactions, and strongly reinforce the ‘subjective’ and ‘negotiated’ nature of the experience of pain.
‘In general, the literature shows that uncaring interactions that convey a message of invalidation and lack of warmth may trigger nocebo effects. Avoiding negative communication and interactions with a patient may help to shape a safe and positive environment that not only promotes placebo effects but that also reduces nocebo effects.’