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I loved both the article and your write-up here. I think there is one possibility you did not consider sufficiently. Say the British have a higher placebo response than the Australians. You suggest that this is irrelevant because - unless the actual drug effect is shown to vary by culture (or presumably genetic variations tied closely to culture in most of the world) then all that matters is the drug effect itself, which should remain the same once we subtract the placebos in each case.

But what about an ailment in which it is difficult to distinguish levels of improvement beyond a certain threshold - the line at which we say someone is cured. If the British placebo is enough to push them past, or sufficiently close to that line, then a British test would indeed be misleading with respect to the Australian market, and lead to a drug being unnecessarily rejected.


Nice writeup, I'll make sure to read the Wired article.

I recently read Ben Goldacre, "Bad Science" (http://www.amazon.co.uk/Bad-Science-Ben-Goldacre/dp/000728487X/). It very nicely exposes all the issues with drug trials and has some very interesting examples of placebo/nocebo effects. For example, it turns out that if a dentist administers a placebo, that the patient thinks is anesthesia but the dentist thinks will increase the pain in his patient, the patient actually experiences more pain than if the dentist thinks he's administering anesthesia. Weird! Maybe the patient picks up some subtle behavior in the doctor?


The arena of this podcast series is a critique of alternative medicines. One episode takes a look at the placebo effect, and offers some studies to consider:

QuackCast 5: Placebo Effect
"SCAM effects are often attributed to the placebo effect. Turns out the placebo effect does not exist. So when the effect of alt.med is equal to placebo effect, it is the same as saying it is equal to nothing. How true, how true."


I think the article was suggesting that the differences in placebo response across countries matter because what a drug company is testing is the effect of their drug relative to the effect of placebo. You mentioned an example in which the effect for the treatment group was 15 units and the placebo group 13 - imagine a place in which the placebo effect was 10 units smaller. The drug would now have an effect of 5 units and the placebo 3, i.e., the drug is nearly twice as effective as placebo and probably can be "passed." Those are the kinds of numbers the drug companies would be hoping for if they considered moving a trial location. However, I agree entirely about the importance of Theme #2, since the best treatment research would be trying to improve both placebo and drug response.


"If the fertilized plant is the same height as the unfertilized plant, you would say the fertilizer didn't work. Who would conclude that the unfertilized plant is "unexpectedly tall"?"

You would rightly conclude this if the unfertilized plants used to be much shorter in previous trials. If the control group used to consistently grow to 8 inches--but now grows to 10 inches--you have a phenomenon worth investigating.

This kind of effect would indicate that there was possibly something wrong with the methodology for your control group; the conclusions of the study would--at best--be suspect.


Reiterating Alex's point, the effects a drug have can be bounded by whatever our base health is - if placebo alone has an effect of 15, and placebo + drug has an effectiveness of 25, but our base health is 16, the drug appears to only have an effect of 1. It's possible for a drug to be super-powerful and not show any effects because the placebo effect is ALSO super-powerful.

Obviously for things like anti-cholesterol medication, blood pressure medication, and anything else where a value can change linearly this won't apply (and you would be correct). But for more subjective things like judgements of mental health, it's in the realm of possibility.


Thanks all for the thoughtful responses. Keep them coming

Alex, Lisa and hegemonicon: Your example works if the drug indeed performs better in one country compared to a different country. To me, that indicates poor test design, and it is a stretch to say the "control group did too well". Also, then the drug should be "passed" in the countries where it shows a large enough improvement, and should "fail" in the countries where the improvement is not sufficient.

Jes: If the base rate has increased from 8 to 10, the increase affects both groups and thus the interesting phenonemon is the general rise in plant heights, not just the rise in heights of the controls.

Some of this is semantics: glass half full or half empty. I's argue that a serious investigator would ask the question neutrally, whether the placebo effect was measured properly without assuming that it is over- or under-estimated. In trials in which drugs were shown to work better than placebo, could it be that the placebo effect is "unexpectedly too small"? Is anyone researching that?

hegemonicon: if the placebo effect is super-powerful, then any drug needs to be even more powerful, otherwise the patient is better off getting the placebo. I see nothing wrong with this but Steve tells us the pharmas do.

Cris: I do read and enjoy Ben's blog.

David: I haven't yet heard the podcast but the person uttering the quotation sounds confused. We don't need to invalidate the placebo effect to conclude that alt.med has no effect; it is sufficient to know that those getting alt.med has the same improvement as those getting placebo.


Regarding the podcast and invalidating the placebo effect, the commentator, in their podcast, refers to a study/studies (my memory is a bit hazy) exploring the placebo effect, the conclusion being that the placebo effect doesn't exist.
References: http://www.quackcast.com/page8/page8.html#5

I thought the study and conclusion were relevant to the topic here, as the opinion here seems to be that the placebo effect is definitely real.


Thanks for all of the posts. It makes for great reading. Having worked in the biomed field, I realise that the placebo effect is certainly understudied and potentially a very cost effective way of augmenting traditional treatment. The arguments you outlined against pharmas complaining that 'the placebo effect being too high' hold together very nicely when there are linear changes in the mediators and outcome variables.

Let's take the example of a drug that is designed to lower blood pressure and the risk of heart attack. If the relationship between the change in blood pressure and change in risk of heart attack is linear, then the true effect of the drug does not depend on the placebo effect, because hypothetically it should be the same for both groups. In these cases, pharma companies complaining of the placebo effect being too high are just playing with themselves.

However, if there is a non-linear relationship between the change in blood pressure and change in proportion who suffer heart attacks, this argument may not hold. For example, imagine that there is a law of diminishing returns for lowering heart attack risk as you lower blood pressure. That is, if you lower systolic blood pressure from 200 to 180 (20 points), you may see a 5% reduction in heart attack risk, however if you reduce blood pressure from 160 to 140 (20 points), you may only see a 2% reduction in heart attack risk. If this were the case, then the effects of the drug may appear lower studies with high placebo effects compared to no placebo effects when both the placebo. This of course only holds if both the drug and placebo act on heart attack risk through lowering blood pressure. In this situation, a pharma company may very well wish to no how to reduce placebo effects.

I admit this is an extremely simplified example and the actual figure on blood pressure and heart attack risk are purely fictional. It is just intended as food for thought.

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