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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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July 30, 2013

Apparently, Ads Make Antihistamines Work Better

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Posted by Derek

This PNAS paper's title certainly caught my attention: "Advertisements impact the physiological efficacy of a branded drug". The authors, from the University of Chicago, are digging into the business end of the placebo effect. After giving a set of subjects a skin-test panel to common allergans, here's what happened:

We conducted two randomized clinical trials to measure the impact of direct-to-consumer advertising on the objective, physiological effect of Claritin (Merck & Co.), a leading antihistamine drug. A pilot study assessed the efficacy of Claritin across subjects exposed to advertisements for Claritin, advertisements for Zyrtec (McNeil), or control advertisements. . .Among subjects with allergies, the efficacy was the same across the three advertisement conditions, but among subjects without allergies, efficacy was significantly greater in the Claritin advertisements condition than in the Zyrtec advertisements condition.

The heterogeneity of the treatment effect based on the allergy status was discovered only ex post facto, so we conducted a follow- up trial to replicate these initial findings. To maximize statistical power, the follow-up trial used a larger sample, assigned subjects only to Claritin advertisements or Zyrtec advertisements, and block-randomized subjects based on their allergy status. In ad- dition, we elicited subjects’ beliefs about the efficacy of Claritin to examine whether any difference in impact of the advertisements across the two subpopulations is driven by the relative malleability of their beliefs. . .

This reminds me of the various experiences that people have had with blind taste testing of wines. In the follow-up trial, they used a histamine challenge in the skin test, which will give a red reaction no matter what you're allergic to. The effect repeated:

In the subpopulation without allergies, we find that the efficacy of Claritin at 120 min is substantially higher for subjects who were exposed to Claritin advertisements. Claritin advertisements have no significant impact on efficacy 60 min after the drug is taken. This pattern is consistent with the observed changes in the subjects’ beliefs. Exposure to Claritin advertisements in this subpopulation greatly increases the belief in the efficacy of Claritin. At the same time, the realized efficacy of Claritin at 120 min (but not at 60 min) is strongly correlated with the change in beliefs.
In the subpopulation with allergies, we find no relationship between exposure to Claritin advertisements and the change in beliefs. Moreover, the advertisements have no impact on the efficacy of Claritin at 120 min. We do find a curious negative impact of Claritin advertisements on Claritin’s efficacy at 60 min in this subpopulation, but this effect cannot be mediated by the (nonexistent) impact of advertisements on beliefs.

Oh, boy. I truly wonder why this experiment hasn't been run before, but look for a lot of follow-ups now that it's out. As the authors themselves detail, there are several unanswered questions that could be addressed: does seeing the Claritin advertisements make the Claritin work better, or does seeing the Zyrtec ads make Claritin work more poorly? Why does this seem to work only in people without specific allergies in the first place? What's the physiological pathway at work here, in any case?

Here's the big one: does direct-to-consumer advertising actually increase the efficacy of the drugs it advertises? That is, does the effect shown in this experiment translate to real-world conditions? For how many compounds is this the case, and in what therapeutic classes is the effect most likely to occur? Is there an actual economic or public health benefit to this effect, should it prove to be robust? If so, how large is compared to the money spent on the advertising itself? And if people internalize the idea that advertisements make a drug work better, will advertisements continue to do that at all?

Comments (20) + TrackBacks (0) | Category: Business and Markets | Clinical Trials


1. Anon on July 30, 2013 10:21 AM writes...

I could see the placebo effect working for a subset of GI, GERD, and anxiety patients where stress is what is setting them over the edge.

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2. exGlaxoid on July 30, 2013 10:24 AM writes...

I would guess that the area of the most placebo effect is anti-depressants, anti-anxiety drugs, anti-ADHD, sleeping aids and similar areas. All of those are subject to large placebo effects, so if someone thought that they were getting the BEST drug, they often fell better no matter what. I did hear that in one study that if they pay more, they often have a better placebo effect; can't remember where I read that, however. But that makes sense.

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3. Mirjan on July 30, 2013 10:33 AM writes...

@2 - it was Dan Ariely

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4. petros on July 30, 2013 10:43 AM writes...

What about all the ads for ED products that seem so common in the US? easier to produce controlled measurments?

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5. Sili on July 30, 2013 11:32 AM writes...

Fairly sure Ben Goldacre discusses this in his first book, but for aspirin:

Branded works better than generic (the actually tablets were of course the same). Taking two tables works better than one (when the same amount of active component is delivered).

The colour plays a role as well. Red placebo is a stimulant while blue placebo works to calm patients.

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6. Helical Investor on July 30, 2013 12:49 PM writes...


I may have recently experienced an anti-placebo effect. I was on the road (boy scout camp dropoff in NH) and 'feeling the allergies' so I bought a single dose of a loratadine (Claritin generic) at a gas station convenience store. I recall thinking that packaging looked a bit dodgy. So ... despite taking the med, I still had watery irritated eyes for the rest of the day. Guess I was predisposed to consider the med as a potential fake.


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7. Helical Investor on July 30, 2013 1:04 PM writes...

@5 - Sili,

The colour plays a role as well. Red placebo is a stimulant while blue placebo works to calm patients.

Not a surprise. I recall reading the (now very dated - 1969) book Color Test as a kid. [enter B000UDY3UU into Derek's Amazon box above]. The book had you arrange color tiles by preference, and then give a 'tarot like' reading on your ordering. What was nice though, was an explanation of some of the psychology, and studies behind it, of the different colors. Kind of a fun read for a then teen.

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8. RKN on July 30, 2013 1:12 PM writes...

Not my area so I'm a little confused. How does one measure the physiological efficacy of an antihistamine drug in a patient without allergies?

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9. Paul on July 30, 2013 1:19 PM writes...

I should have had my poor dear kitty, who recently died of shock w. a mast cell tumor, watch these ads.

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10. Anon on July 30, 2013 1:47 PM writes...

I can't believe no one noticed the submission date...2010!

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11. Canageek on July 30, 2013 2:28 PM writes...

In Canada the rules say you can either say a drugs name, OR describe what it does. This has led to some brilliant Viagra ads, since everyone already knows what it does anyway. Anyway, that should eliminate some of the effects shown, shouldn't it?

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12. Anon on July 30, 2013 2:39 PM writes...

@11: If the effects are beneficial, why would you *want* to eliminate them?

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13. matt on July 30, 2013 3:48 PM writes...

I'm with RKN: how are you measuring amounts of physiological response in non-responders?

If this only helps people who didn't actually have an underlying condition needing treatment, i.e. it is only modulating a normal response slightly up or down, what difference does it make?

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14. PrairieBoy on July 30, 2013 3:52 PM writes...

Sounds like we have an episode for Mad Men.

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15. C-drug on July 30, 2013 6:58 PM writes...

@13: They did a skin prick allergy test, and classified people with large responses as "allergic", however non-allergic subjects would still have had sufficient responses to measure a difference with and without drug. I once helped run a lab for pharmacy students using a similar protocol, and we could see drug effects in basically all students (although that was with histamine solutions instead of allergens).

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16. Dan on July 30, 2013 7:18 PM writes...

I published a short story in Nature a couple years ago on this topic:

Life imitates art!

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17. cliffintokyo on July 31, 2013 2:31 AM writes...

"Oh Boy!" indeed. I am with #14.
Corollary: if you don't believe that your medicine is good for you, it won't work.
Another thought: Pharma could just make placebos and advertise them ad nauseam to the public using strongly assertive language, such as:
"Take Cebo for your headache, you KNOW it works for YOU!"

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18. matt on July 31, 2013 3:31 AM writes...

@cliffintokyo #16: but the medicine DID work, exactly the same, for people who actually had an allergic reaction. It "worked" better only in people for whom it wasn't doing anything in the first place.

@C-drug #15: There's a clear and large difference when an individual has a reaction. But this study is measuring and comparing the size of response in individuals where by definition it was small. Does this test support gradations of normal response, i.e. is there a response scale with enough resolution where significant differences can be measured between normal individuals? And was there enough statistical power to overcome variations in response in non-allergic individuals?

My skept-o-meter tingles when research too neatly confirms expectations on a hot-button topic. In this case, when physiological effects are claimed based on "significant" differences in a small range of a fuzzy subjective test.

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19. Da Vinic on July 31, 2013 8:55 AM writes...

And this is why direct-to-patient ads are banned in civilised countries!

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20. not a chemist on July 31, 2013 7:15 PM writes...

So, why did clemastine fumarate (sp?) work so well for me, and why is it no longer made?

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