Problems and solutions in the design of an active sham for randomized controlled trials vs. placebo

The term sham means a medical device with the only purpose of acting as a placebo in controlled clinical trials. Differently from drugs, where a placebo is very simple to design, in active devices different scientific problems emerge that are often difficult to overcome.

The sham traditionally used is a device without effective stimulation emissions. In theory this is the perfect solution, because by definition a sham must not have any active principle, in this case the stimulation. Functionally it is not hard for the participant to understand a placebo is being used, thus invalidating the results’ credibility.

A further step has been achieved with modified TENS devices capable of emitting output impulses only for a couple of seconds before being shut off. However, also in this case, the cure by illusion for many is still not considered sufficiently valid, even if strengthened by the short initial emission.

The reason why continuous emissions cannot be used is rather simple. Stimulation by its nature is an active principle, and just the fact the participant perceives it means it is interacting with his nervous system; thus, it is no longer a placebo. Some researchers considered the possibility of using continuous low-intensity stimulations, hoping to avoid these effects, but this is practically impossible to scientifically demonstrate for a few solid reasons:

- In order to be used without preliminary studies, a device must have well-known stimulation parameters, restricting the field to impulses of less than 1mS, consequently selective towards A-Beta fibers. In this field any type of stimulation chosen, even of low intensity, if perceived by the patient, leads to results in line with the Gate Control Theory. This sham de facto becomes a TENS device, which interferes with the perception of pain and can no longer be considered a placebo.

- Some consider using as a placebo a TENS device directly on neuropathic pain, due to an overall scientific agreement of its inefficacy for this type of pain. However, there is a similar agreement in considering TENS devices effective in muscle pain and other types of inflammatory pain, two of the normal components associated with neuropathic pain. Once again, this type of device cannot be considered a placebo.

- Lastly, one can consider studying and selecting “placebo” stimulations, but this calls for a burdensome effort both in costs and years of study. In theory there are no placebo stimulations (just by being felt, the stimulation produces an organic effect, differently from an inert pill placebo that is totally inactive). However, even by considering this remote possibility, clinical tests with the many variables in play should be based on thousands of cases, and this still would not be enough. In an inert pill placebo, there is no need for a control group to check whether it is really a placebo effect, since safety is implicit in the lack of active principle. With an active principle that must work as a placebo, the issue is completely different and can be solved only with a double-blind. How can a control arm be set up to address this issue? This brings us back to square one.

Active placebo designed for Scrambler Therapy

In the case of Scrambler Therapy, it is possible to take advantage of its specific “binary” response features to design a reliable and reproducible sham. By binary response we mean that if electrode positioning is carried out correctly, pain is immediately zeroed out independently from its nature and intensity. Whereas, when the procedure is carried out in the wrong way, the result is null. Another advantage for a reliable active sham directly by using the Scrambler Therapy is its action on stimulating surface receptors, and not the nerves, and corresponding dermatome type. Therefore, there are two key elements to solving the problem of a scientifically active sham valid and reproducible for Scrambler Therapy. This is currently the only solution that eliminates critics or scientific methodology mistakes and has been approved by the IRB for double-blind (virtual due to the need for an operator independent from the trial team) on neuropathic and oncological pain. In strengthening the placebo effect, it is important to highlight that the participant receives the same continuous stimulation and sees the same device he might have seen in ads, therefore creating complete suggestion.

Setting up an active sham device for Scrambler Therapy

To avoid publicly disclosing the sham design so that participants have no knowledge of the detailed procedure, I urge you to ask for the protocol by using the contact link.

Quick support on research and clinical best practice