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Tuesday, July 20, 2010

Placebos: All you never wanted to know (Part 1)

Well, its that time of the week again when I cant put off blogging any longer. I have a terrible habit of putting off blogging (which i enjoy) to ensure that i actually complete my Phd. Therefore, I've decided to start blogging about my actual research.

To whit, everybody's favourite sugar pill: placebo!.

This will be a relatively long series, with about seven parts. Essentially, I'm updating my literature review this week, so I'll blog about each section as I do it (perhaps before, if i get really into this series).

Anyway, we'll start with the hard part: definitions. The placebo is something that most people in our society have an idea about, but it's a surprisingly difficult phenomenon to define. That being said, almost everyone in the field has had their hand at it, so there's a lot to choose from.

The first, classic definition is from Shapiro & Shapiro (1997) - the placebo effect is the result of a placebo treatment.
Pretty illuminating eh? The sad part is that this definition was the end of their long and ultimately fruitless search for a good way of describing the phenomenon.

That being said, it has its good points. Firstly, it can account for all placebo effects, it doesnt presuppose any mechanisms, and it doesn't limit the phenomenon unduly.

However, its bad points are legion also, the largest being that its a tautology, and not in the universal truth sense.

Probably the definition most people are familiar with is this one: the placebo effect is the effect seen in the placebo arm of a double blind trial. However, this one also has large problems. The major issue with this definition is that not all of the response in a placebo arm will be down to the placebo.

One thing that can happen to mess up this definition is a funny little phenomenon called regression to the mean. Regression to the mean is a statistical phenomeon that works as follows. There are sick people, whom you select for a trial on the basis of their sickness. Say if the sickness was measured on a ten point scale, they would be a seven. Now, even if the treatment you give them is harmful, it is likely that some of them will report less sickness after a week, because its more probable that the next measurement will be closer to the mean. I'm relatively sure that this could be eliminated with a perfectly reliable instrument, but we don't have any of those (certainly not in psychology).

Warning: previous example requires a normal distribution. If in doubt, consult a friendly statistician ( if you can find one). Update: apparently it only require a distribution with equal marginal probabilities - i do remember seeing an explanation that used the normal distribution though.

Another feature that can cause issues in estimating the placebo effect is the natural history of a sickness. The major problem here is that people's health may wax and wane, and again if you select a person for inclusion on the basis of sickness, the natural history effect could cause them to report feeling better even in the absence of any real effect from your treatment.

So, if you actually want to estimate the placebo effect accurately, you need a no treatment group. These poor suckers are recruited into the trial on the basis of sickness, and then don't get anything to help, except to be poked and prodded by doctors and nurses. Many clinical trials don't include these groups, and its easy to see why. Bad enough that you have to give half the participants placebo, but to give another group of people nothing, thats way too harsh. (We'll get back to clinical trials with no treatment groups later, i promise).

So, following on from this long and rambling excursion into clinical trials, we can update our definition of the placebo effect to as follows: the placebo effect is the improvement seen in the placebo arm less the improvement in the no treatment arm.

So, this is the workhorse of placebo definitions, but it still won't do. This definition requires a particular setting which does not fit where many placebo effects take place. For example, the response shown by a patient to the archetypal sugar pill after a visit to the doctor cannot be accounted for with this particular definition. So, we'll have to move on.

A more recent definition came from Price et al (2008) where they claimed that a placebo was any effect which simulated a treatment.

A fascinating recent study by Oken et al gave us some interesting findings. Essentially it was an RCT which randomised seniors (65-80 years old) to either placebo or no treatment. They were told that the pill would improve their memory, and lo and behold it did. They scored better on measures of verbal and working memory (interestingly enough only the men showed this effect).

This is a problem for definitions of the placebo which rely on the notion of treatment. I can't really see how the effects of this pill could be considered such, they were a neuro-enhancer rather than something to stave off decline. So, it looks like we may have to confine the Price et al definition to the fire.

A definition which can account for the experiment noted above is that of Daniel Moerman, an anthropologist: a placebo is the positive mental or physical effects induced by the meaning of a substance or procedure. He prefers to call placebos the meaning response, which is a much nicer phrase than placebo (or at least has less negative associations).

I really like Moerman's definition (and his book is really very good, even if you're not a specialist). However, there are some weasel words in there, the main culprit being "meaning".
So, boys and girls, what does meaning mean?

Presumably it refers to the interpretation one gives to something, but its a hard word to define, and even worse, its a horrible word to attempt to operationalise (i.e. figure out how to define or measure it). Although, that being said, i suppose we could just substitute meaning for expectancy and get on with our research.

That, dear readers, would probably be letting you off a little lightly though. So, lets move on to another defintion, this one by a wonderful scientist and human being, Dr Zelda Di Blasi (2001) she and her colleagues renamed placebo (everyone loves doing this this) to context effects (which again, is nice and doesnt have negative associations) and said: a placebo is an inert substance which has an effect due to context.

This is nice, it again leaves open the mechanisms and wonderfully enough, doesn't preclude none health related placebos. However, context (to me at least) means what surrounds the patient, and this ignores the fact that focusing on bodily sensations increases the size of the placebo effect

The other issue with this definition is that it somewhat marginalises the role of the person who experiences the placebo effect, as it implies that all the impetus comes from outside, when clearly the internal experience is perhaps the defining characteristic.

Moving on, I think that the term placebo is growing more and more useless. These days, its used by many and seems (in psychology at least) to be a convenient shorthand for the effects of the mind on the body. My first exhibit for this kind of thing is the 2007 paper by Crum and Langer (if you're Irish you probably giggled at that last name, otherwise, carry on), which is called: mind set matters: exercise and the placebo effect.

The study itself is really interesting, they took a large group of hotels, matched them, and randomised hotels to either control or treatment. In each of the hotels which were in the treatment, they told the cleaning people how many calories they burned in the course of their work. In the other hotel, they just talked to them for a while and got them to fill out some forms.

The really interesting part was that the women (i believe the entire sample was female) who were told about their calorie burning habits lost more weight over the next month, and were both healthier and happier by the end of the study. I suppose the take home message from this study is that you should learn how many calories you burn in your daily activities if you want to lose weight.

However, my point here is that the use of the term placebo effect here is confusing and causing problems with our understanding of the concept. I personally would much prefer to have a placebo effect that only related to healthcare and medicine, along with mind/body effects or expectancy effects for the Oken and Crum studies I noted above.

To be honest though, I'm not going to lose too much sleep over the definition of the effect. Having read some of the Shapiro papers where they grapple with the construct over the years, I've come to the conclusion that its a waste of effort and time that could better be spent trying to figure out how to induce the damn thing (whatever we call it) reliably.

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