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NPR has a great interview with Jo Marchant on her new book “The Cure”. Excellent content. Now you could’ve gotten that also from my book Placebo 3.o. Published here. Adding the next section:

 

Strength of the Placebo Effect

A meta-analysis of 152 published reports found that placebos often have a similar benefit over no-treatment as treatments have over placebos (Howick, 2013). In other words

Compared to no-treatment patients in placebo groups get about 50% of the benefit of the treated patients.

Comparison of Benefits 100% = Treatment over No-treatment
Treatment over Placebo █ 50%
Placebo over No-treatment █ 50%

 

Why no-treatment groups matter

Even though the number of 152 studies reviewed is very large for a meta-analysis, the design of these studies was very unusual. Typically, clinical studies are designed to compare two groups: treatment group and placebo group. The studies reviewed also included a “no-treatment” group. A design with three groups is very insightful for the following reason. Even people who get no treatment can get better. In fact, this is often the case. Here are some common examples, someone…

  • gets the flu and recovers without treatment
  • suffers from episodic back pain that comes and goes
  • already feels better when seeing the doctor

These three examples actually describe effects that are well known by statisticians:

  • Natural History of Disease (people recover on their own)
  • Regression to the Mean (symptoms return to average values over time)
  • Hawthorn Effect (doctors makes people feel better)

Ideal clinical studies should have a non-treatment group to capture and compare these three effects. Patients who receive a placebo, benefit from these three effects in addition to the Placebo Effect. A person getting treatment, benefits from all four effects mentioned before and in addition gets the Treatment Effect.

Why we get better No treatment Placebo Treatment
Natural History
Regression to Mean
Hawthorn Effect
Placebo Effect
Treatment Effect

 

Taking all five effects into account the review found that

Placebo and Treatment Effect are about the same size.

Let’s just keep in mind that the term Treatment Effect is often used more loosely and captures several if not all of the effects mentioned here. As always, it’s important to look at the context.

Another interesting outcome from the meta-review:

The studies that showed the greatest benefit of placebo over no-treatment were those that used continuous outcomes measurements (0 – 10 pain scale) rather than binary outcomes (yes / no).

It matters how we measure the strength of the placebo effect.

Despite the rigor of the meta-analyses described here, the 50% effect for placebo is only an approximation that was derived from studies that were already available. To air on the safe side, keep these two points in mind:

  • placebo effects vary a lot and depend on many factors
  • we cannot predict who will respond to placebo

More about this in the chapters ‘Focus Matters’ and ‘Patient’s Placebo Manual’.

As a rule of thumb, in clinical pain studies patients who take placebo get an average pain reduction of 2 points on a (0 – 10) point pain scale (Hoffmann 2005, Levine 1984). This average includes participants who respond to placebo and those who do not. When looking only into the subgroup of placebo responders, pain reduction can be as high as 5 points on a (0 – 10) pain scale (Benedetti 1996).

Nocebo Effect

When receiving pharmaceutical treatments patients benefit from a combined effect that includes the effect from the drug’s active ingredient and the effect from the mind and body’s own placebo response. However, active ingredients of drugs can also cause undesired side-effects. For example, the medical treatments for common back pains often combines a painkiller and a muscle relaxant. The active ingredients in those drug’s can cause undesired side effects, such as drowsiness.

Pure placebos do not contain active ingredients. By design, pure placebos get around the issue of side-effects from active ingredients. However, it is very important to design pure placebo experiences in a way that is unambiguously positive and targets only beneficial effects. As we learned in the previous chapters, meaning and expectations matter. Here is an example for a placebo context that carries a positive message:

“I am taking this placebo pill for symptom relief, helping my mind and body to get relief from back pain.”

Honest and pure placebos can be ‘filled’ with any meaning and expectation that we want to give it. The design of open placebo experiences is a modern form of a Trojan Horse, or a mind and body hack, to get an entirely positive message conveyed to our subconscious mind and body.

On the flip side, when placebos are not received in this positive context, you may end up with un-desired effects. In those cases, we are sending an ambiguous message to the subconscious. Why is that? In blinded placebo-controlled studies that have uncertainty built in, patients know that there is a 50% chance that the pills they receive contain an active ingredient that could also cause side-effects. This situation can lead placebo responses that create negative effects. These phenomena that can occur in blinded, randomized studies are called Nocebo Effects.

However, when pure placebos are taken in an honest way, the expectations are clear: the patient is 100% sure that no active ingredient is at work that could cause side effects. The pure and open placebo design can send a message to our mind and body that is clear, focused, and positive.

Since studies involving pure and open placebos are recent and few, allow me to make the following statement in form of a hypothesis. Currently there is no experimental data to back this up, but I believe that this deserves further study:

Hypothesis: Honest placebo design using pure placebo enables focus on the beneficial effects and eliminates the Nocebo Effect.