Feb 05, 2019

Greenberg on the placebo effect & healer-patient alliances

Related, tangentially.

The placebo effect is complicated. Gary Greenberg dives in, on EconTalk (a):

Greenberg: It's called the double-blind, placebo-controlled method. What that means is that neither the experimenter nor the subject knows whether they are getting drug or placebo. And that, in turn, reflects the hope that they've managed to make the two treatments exactly equivalent with the exception of the molecule that's in the active drug.

Roberts: It's a strange test when you think about it, because, if it weren't for the so-called placebo effect, you wouldn't have to give anybody the sugar pill. Right? You'd just say, "You're not on the trial. We're going to see how your health goes over the – you're not getting the medicine."

Or, "You're getting a sugar pill, and we're just doing that just to kind of have you kind of come in and go through the same kind of stuff that the other people are going through. But, by the way, you've got a sugar pill."

That's not what they do, typically.

Greenberg: No. And... there are a couple of reasons for that. One is that the idea, the general received wisdom about placebo is that it works somehow or other by deception. That is to say: if you know that you are getting a placebo, somehow that's going to diminish its effect. Or change its effect. And so, telling people that they are getting a placebo theoretically would reduce the placebo effect. Now, interestingly, to the extent that that question has been researched, it doesn't necessarily prove out.

So, the ongoing use of the placebo in the clinical trial is really just there to reassure everybody that they are actually seeing the work of the drug and not the work of treatment in general – not simply the work of being exposed to a healer or to the medical industry in any way.

Roberts: One of the things I took away from your article is that that's something of an illusion: that they are only getting the medicine. And, of course... it also means the way we conduct clinical trials that the people who get the "real medicine," the people who are getting the molecule that purports or trying to figure out whether it helps or not – those people have some awareness they might have a placebo.

Greenberg: Well, part of the process of being in a clinical trial is being informed that you have a 50% chance of getting a placebo. So, presumably everybody in a clinical trial that's placebo-controlled knows that that's a possibility. They just don't know whether or not they've got the drug.

Roberts: So, if I told half the group, "Oh, you've got the placebo," and I told the other half, "You've got the real drug," you'd think you'd get a different result than if everybody thought it was a 50-50. Because some of the people getting the real drug are thinking, "This might not be the real drug." And that psychological awareness, perhaps, has a negative impact, just like the people who get the placebo are sometimes getting an improvement in the trial at all just from the possibility that they might have the real drug.

Greenberg: That's right. And so, what you are really getting at there is the fact that every clinical trial has a placebo group – virtually, every one – and therefore is a study of the placebo effect as well as of the drug, there hasn't been a whole lot of inquiry into the placebo effect itself.

So, the scenario that you just described – you could actually find that out fairly easily. You would have to have a group that you tell you are giving a placebo, but give them the real drug; and another group that you tell that to but you are honest; and then the same with the drug – a group that gets it thinking they are getting it and a group that gets it thinking they are not getting it. And that would really answer a lot of questions, once you crunched the numbers.

The problem with that is, (a) who are you going to get to pay for that? And, (b) even if you get somebody to pay for it, you have to deceive your subjects. And, while that's not impossible, that's a higher bar to cross than most researchers are willing to go in order to get the research approved by the government funders or the university or whoever is providing the funding for the study.

Examples of placebo effects doing work, from Greenberg's article:

Give people a sugar pill, they have shown, and those patients – especially if they have one of the chronic, stress-related conditions that register the strongest placebo effects and if the treatment is delivered by someone in whom they have confidence – will improve.

Tell someone a normal milkshake is a diet beverage, and his gut will respond as if the drink were low fat.

Take athletes to the top of the Alps, put them on exercise machines and hook them to an oxygen tank, and they will perform better than when they are breathing room air – even if room air is all that's in the tank.

Wake a patient from surgery and tell him you've done an arthroscopic repair, and his knee gets better even if all you did was knock him out and put a couple of incisions in his skin.

Give a drug a fancy name, and it works better than if you don't.

Russ Roberts throws in a placebo example:

Roberts: "Oh, it's this amazing thing. These people come in with back pain, and we put this cement in their joints. And it's magical. Their pain just totally disappears." ... [but] there is no difference between doing the treatment, where you actually go into this person's back and inject cement, versus laying him down, opening this cement so they can smell it, and then injecting saline into their vertebrae.

On the importance of ritual:

Greenberg: However, medical treatment, no matter what it is, is a ritual... So, what we learn is that, in addition to that there's more things under heaven and earth than you've dreamt of, is that the ritual is very, very important to the outcome.

Also this:

Greenberg: So, there's a theory out there is that what's happening in the healing encounter is that the healer – the physician – is, in order to do his or her work, has to try to understand the patient's situation from the inside.

Now, we know that there are many, especially as you get into rarified, specialties that the stereotype is exactly the opposite. That, the subspecialist is more interested in the particular disease or the symptom or the surgery or whatever it is that the person needs than he or she is in the whole person.

But, at the level of primary care for sure, medical care involves being empathic with somebody who is suffering. And the idea there is that, when you do that, you set off a series of events that – and this is real preliminary – but that may modulate the body's own healing abilities.

For instance... we know there's something called mirror neurons. And, mirror neurons are networks of brain cells that respond to watching somebody do something that you're familiar with as if you yourself were doing it. So, somebody having an experience like sadness that you yourself are familiar with, your brain actually looks like the brain of the person who is sad. And that's thought to be related to empathy. I would go so far as to say it's the cause of it. But it may be the signature of it in the brain, loosely speaking.

And so there's research that's emerging – it's in the very early stages – which shows that when there's a successful therapeutic alliance between a healer and a patient is that one of the things that's going on is that their mirror neuron networks are being activated. And so that's very suggestive that if there is what they call brain concordance between a healer and a patient, that that may help the healing process.

Which isn't to say that whatever the treatment is isn't also part of it. But that in a way the treatment is the occasion for this expression of empathy or care or concern or whatever you want to call it. And that that isn't just window dressing, and that isn't just their making you feel good for a moment. It's somehow related to the fact of healing. You know, we can look at, I don't know, an antibiotic eat a bacteria in a test-tube; and that will tell us that antibiotics eat bacteria. But nobody with an infectious disease can say exactly why that treatment is what makes you feel better. Or get better. We're pretty close to being able to state it as a fact, but if you think about it, there's still a little bit of a gap even in that most objective kind of medicine, of, say, giving somebody penicillin for an infection. There's still a little bit of a gap there that we just don't fully understand. And it's possible that that placebo effect is part of what's in that gap.