34 comments on “The Rising Placebo Effect&rdquo

1) If you think it works, and it doesn’t matter what the data say, what was the point of the trials?

2) If not working better than placebo is success, then why use something expensive that works no better than placebo? Why not use something cheap? Of course, someone else might think differently (http://www. theonion. com/article/fda-approves-sale-of-prescription-placebo-1606 ).

I’d actually love to try this. My daughter has been having mild stomach aches for a couple months. Doctors think it’s diet related. Wife thinks its Gluten (because… you know… Gluten).

I’d love to have a little placebo pill I could give her “from the doctor”. It would be worth it if it “cures” what I already think is largely in her head.

Some cruel and heartless person will propose that this is evidence that Americans are uniquely hysterical and suggestible. Whereas a cooler inspection suggests only that they are becoming increasingly hysterical and suggestible, which is a plain different thing.

Is there any chance that regression to the mean plays a role? ie, patients tend to enroll in trials when their pain is at its worst (and thus likely to get better)? Or have trials been done comparing placebo to “no intervention”?

Morten G says:

Oh, me me! I have theories galore.

1) Prescription strength painkillers are much more easily available in the US than Europe/Asia. And the people in the placebo group are likely to go take some. Patients lie.

This hypothesis is of course shot down if the clinical trial includes blood tests to ensure that the patients don’t take any other painkillers.

2) US Americans are better entertainers and more charismatic. The US school system includes a bunch of show-and-tell and debate teams and it’s generally in the culture to charm people. The US doctors might just be better at convincing the patients that the placebo is going to work.

3) European / Asian doctors might be better at explaining that while the patient enrols in a trial for an experimental drug, there is a good likelihood that the patient does not receive any of the drug. Or US American patients might have a harder time wrapping their heads around the concept.

Remedies:

Test patients for drugs and medications that might interfere with the outcome.

Perform double-blind head-to-head trials instead of placebo controlled.

Recruit patients on the autism spectrum since they lie less.

Crossover trials so that all patients are both on placebo (or the competition to beat) and the experimental drug.

And it is not completely dumb that a strong placebo effect obscures efficacy. If you get 100% response in both placebo and intervention group then you can’t say if the drug did anything or not. Doesn’t mean that it should be approved. If anything the placebo should be. If you still believe in the drug then you should redesign, resubmit, and redo the trial.

DCRogers says:

Maybe it’s because American doctors *underprescribe* placebos?

“Half of all German doctors prescribe placebos, new study shows”

anonymous says:

Ariely figured this out a long time ago, in a controlled study. The phenomenon is not limited to medicines, though it was demonstrated in a study using pain meds.

Perhaps the driving force for efficacy here is that we have trained our society to expect that new drugs will be astronomically expensive.

The Rising Placebo Effect

By Derek Lowe October 15, 2015

The placebo effect has many interesting and annoying features, among them the way that it varies so much among different therapeutic areas. There is no placebo effect for a broken leg, or for pancreatic cancer: these things are going to play out the way that they do, regardless of what you think about them. But for the pain of a broken leg, there you might have something. In general, the things tied most closely to self-awareness (pain, mood, etc.) show the strongest placebo effects.

Now a new analysis of clinical trials for pain medication shows that the placebo effect in this area has been getting stronger. (Here’s a Nature News article on the subject). The same also seems to be true for antipsychotics and antidepressants, but this effect seems to be mainly (or only) visible in large-scale US trials:

“We were absolutely floored when we found out,” says Jeffrey Mogil, who directs the pain-genetics lab at McGill University in Montreal and led the analysis. Simply being in a US trial and receiving sham treatment now seems to relieve pain almost as effectively as many promising new drugs. Mogil thinks that as US trials get longer, larger and more expensive, they may be enhancing participants’ expectations of their effectiveness.

That certainly could be it. People may also be raising their expectations of what modern medical science is capable of, and figure that in these days of modern times (as the Firesign Theater used to put it), new drugs must be quite a bit better than the old stuff. In a way, they’re right – that Jack Scannell article I linked to yesterday talks about what he’s called the “Better Than the Beatles” problem in drug discovery. That’s the competition we always face against our greatest hits, effective medications that have gone generic and are now cheap and well-proven. For simple pain relief, it’s not easy to beat the likes of aspirin, ibuprofen, naproxen et al.. so if you’re going into that market, you’d better have something good. Unfortunately, the harder-to-treat forms of pain are really, really hard to treat. And if you’d like to treat them without the possibility of addiction, then that’s just too bad. There’s not a heck of a lot between ibuprofen and opiates, although not for lack of trying.

So people may be expecting more out of pain medication trials, but they’re not getting it. This new study found that against neuropathic pain (a large and terribly underserved market), the drugs studied over the last 23 years have all been about the same: not too effective. But the placebo responses in these trials have been creeping up the whole time – well, the placebo responses in the US. Asia and Europe have been flat.

Thatsuggests placebo and drug responses may not always be strictly additive. This isn’t entirely unexpected, Mogil argues, because both placebos and pharmaceutical painkillers tap into similar biological mechanisms — such as the release of endorphins in the brain. But if true, it suggests that growing placebo responses are masking real painkilling effects. “There are a lot of people in the pain field who believe the drugs that are failing clinical trials actually work, it’s just that the trials can’t show it,” he says.

Hmm. I see where he’s coming from, but I think that’s a dangerous line of thought. If they worked really well, we wouldn’t be having this argument at all. If you start throwing out clinical trial results because the drug “actually works” anyway, where is there an end to it? I suppose one could draw some sort of placebo-control cutoff and say that if the placebo group responds to some high level, then the drug. no, actually, I still can’t see it. I’m going to remain an absolutist for now: if your drug can’t beat placebo, then there’s no way to say that your drug does anything for patients.