Thursday, 20 April 2017

A Little Note on Placebo and Meaning

What are placebo effects?

There is a common misconception that "placebo effect" is the label given to cases of people believing they've recovered or perceiving their symptoms to have decreased or gone, when those people have received no medically active intervention: so, they've received a sugar pill perhaps, or a sham surgical intervention of some kind and in response perceive their symptoms to have improved or believe themselves to have recovered. However, this is not what we mean by "placebo effect", it's actually far more mind-blowing than that! 

It is not simply that people believe or perceive themselves to have recovered or believe that the condition has gone into remission, it is that they HAVE, as a matter of clinically verifiable fact, recovered as if having received a pharmaceutically active or surgical intervention. Daniel E. Moerman’s book Meaning, Medicine and the "Placebo Effect" is replete with examples, as are many other papers and books on placebos. This much about placebos is uncontroversial, even though it is, as noted above, pretty mind-blowing.

When Randomised Controlled Trials of drugs or surgical interventions are carried-out, there are two phenomena that have to be controlled for, in addition to existing treatments, so that we might ascertain whether the intervention under scrutiny has genuine medical efficacy: these are "placebo effects" and regression to the mean.

Regression to the mean is basically the statistically significant fact that some people just get better over time anyway, so we need to control for these people and not confuse measurement of this phenomenon in our trial data with a response to the intervention on trial.

What is referred to as the "placebo effect" is something else: people respond as if they have been treated with a medically active treatment when we know they have not received such (they’ve been given a sugar pill or sham surgery, for example). As I noted above, this isn’t merely about them believing themselves to be better, nor is it about them perceiving their symptoms to have gone; it is that they have recovered in ways physiologically comparable to those who have recovered in response to receiving treatment, and they have done so in ways that cannot be accounted for by regression to the mean.

So, an RCT will have a control group which receives no treatment at all (the regression to the mean control group) and one or more control groups who are administered sham treatments (the placebo control(s)), in addition to the groups who receive the intervention being trialled and groups receiving the competing intervention(s), such as, perhaps, the current market leading drug for that condition.

Explaining Placebo

So, what is the explanation for the placebo response? What is the explanation, for example, for why the person (the body) actually produces dopamine when administered a sham treatment, what is called endogenous dopamine release, and which mimics the dopamine that would have been introduced had that person received the medically active intervention? For, putting this another way: the person's biochemistry endogenously mimics the introduction of clinically administered exogenous dopamine. Indeed, there are many many more examples of such biochemical and physiological changes which come about through the administering of what have been called "placebos", which have been shown to mimic or replicate the changes that the active medical interventions are designed to introduce or cause. Such interventions can take the form of surgical or pharmaceutical interventions.

Well, the standard folk explanation for this has perhaps been to assume this is a n example of a conditioned response: i.e. to assume that there is something akin to classic Pavlovian conditioning taking place.

However, there are a number of reasons not to accept this: first, there are a wealth of arguments which show that actually there is no such thing as Pavlovian conditioning, as traditionally conceived and as it takes hold in the folk imagination; rather, there is the learning of associations.  Second, even if there were such a thing as the 'conditioning of popular psychological mythology', the necessary conditions for such conditioning in many cases of placebo responses just are not present. And third, such conditioning cannot account for the cultural indexicality/variance widely observed in studies of placebo responses, because cultural differences often generate different responses in people who might otherwise be depicted as having had the same conditioning or learning.

So, in the 1980s Irving Kirsch (the guy who is probably better known to those outside placebo studies for his critique of antidepressants: I.e. he demonstrated that FDA approved and widely prescribed antidepressants were no more effective than placebos) proposed the response-expectancy explanation for placebo responses. This explains placebo responses as responses to expectations: for example, you expect to find it difficult to sleep having had a double espresso late at night, and your expectation is based on your beliefs that caffeine is a stimulant and that a double espresso gives you a strong shot of caffeine. In response to this expectation you do indeed suffer disrupted sleep. However, unbeknownst to you, your host last night had run out of your favoured Java blend and, so as to avoid the shame which would inevitably follow from such a social faux pas, had elected to give you a Swiss water decaffeinated double espresso, without informing you. So, your poor sleep was a placebo response, based on our expectation, which in turn was based on your (false) belief that the coffee was caffeinated.

The response-expectancy explanation is the dominant explanation to date. In fact, when I attended the big placebo conference in Leiden earlier this month (April 2017 - the inaugural conference of the Society for Interdisciplinary Placebo Studies - SIPS) the vast majority of those speaking at the conference proceeded as if this was the explanation: placebos are expectancy responses. I was one of only two dissenting voices (of which I was aware) among the speakers, the other being  the cognitive psychologist, Jan De Houwer (...I found common intellectual ground with a cognitive psychologist.)

For my part, I just don't think the response-expectancy explanation works. Here are the problems, as I see them.

To expect something one has to represent, in the form of a belief, the putative state of affairs one is expecting and the problem is that in many documented cases of placebo responses there is simply no evidence that those responding to the sham treatment have such a belief (unlike in the coffee example). However, and this is the more telling point, there are many cases of placebo responses where those responding to sham treatments in placebo-type ways do not have the epistemic resources, or even access to them, such that they might form the required belief. So, it is not merely that there are cases of "placebo responses" where those who respond do not appear to have the beliefs that would be required in order to form the expectation, it is that they don't have access to the data that would be required to serve as the 'building blocks' for such an expectation.  

So, what of expectation now? If, as the response-expectancy crowd want to do, we hold on to expectancy as an explanation for "placebo responses", then we need to provide warrant for our having extended the grammar of “to expect”, such that in this use it is not internally related to, it does not invoke, a propositionally structured belief, a representation of a state of affairs. This, in turn entails having access to the epistemic resources, which, recall, we have seen are simply unavailable in many cases of placebo responses.

We can put the argument of the last paragraph less abstractly: if you want to stick with expectancy, you owe us an explanation as to how someone can expect something while not being in a position to know what it is they are expecting, i.e. how can one expect something without being able to specify or represent the something they are expecting?

Alternatively, we can leave the grammar of 'to expect' as it is, stop trying to square this particular circle, and instead drop the overly restrictive reliance on response-expectancy as a global explanation for "placebo responses". Then, instead, we might talk more broadly about meaning responses (as Dan Moerman does), and set about, via ethnographic investigations of people responding in medically significant ways to pharmaceutically and surgically inert interventions, gaining better understanding of medically significant meaning responses.

Here we are talking about the world having meaning in a way that does not demand that we first have the resources to form beliefs about (possible) states of affairs in the world, for we don't need to expect something to cure us for us to be cured when we have received a sham treatment. Rather, we move beyond such a representationalist picture of cognition, to more enactive or even ethnomethodologically-informed accounts.

That’s the issue, and that is why I’m so preoccupied with this right now.

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