
Placebos becoming too effective, pharma industry worries - gmac
http://asserttrue.blogspot.co.nz/2013/03/new-patents-aim-to-reduce-placebo-effect.html
======
ggreer
Ah, this site again. See <https://news.ycombinator.com/item?id=5327200> for
context.

The author's posts vary greatly in quality. Sometimes they're reasonable.
Sometimes they're stuff like "antidepressants in tap water cause autism"
([http://asserttrue.blogspot.com/2013/02/antidepressants-
tap-w...](http://asserttrue.blogspot.com/2013/02/antidepressants-tap-water-
and-autism.html)) and "Do warnings on cigarette packs cause lung cancer?"
([http://asserttrue.blogspot.com/2013/02/do-lung-cancer-
warnin...](http://asserttrue.blogspot.com/2013/02/do-lung-cancer-warning-
labels-cause.html)). When an article makes it to the front page of HN, a
domain expert usually comes along to tear it apart. See
<https://news.ycombinator.com/item?id=5140049> for a recent example.

Combined with the author's constant self-promotion (see
<https://news.ycombinator.com/submitted?id=techdog>), I tend not to believe
much written there. He's optimizing for page views, not scientific accuracy.

~~~
stygianguest
Good point! Though this one post does seem quite well reasoned its message is
an easy one (big pharma is evil) and suspect to confirmation bias.

If only my browser gave me something to tag the site with your comment, so
that next time it comes around I'll remember.

~~~
shrikant
I believe that's what Rbutr is trying to address: <http://rbutr.com/>

------
richardjordan
The real problem here of course, the unwritten and almost certainly valid
assumption in the piece is that our regulatory bodies will almost certainly
accept the fig leaf of these fudged trials as reason to grant license to drugs
of questionable medical benefit in order to reward big pharma and its generous
support of the political process through campaign contributions.

~~~
penny100
When did HN devolve into a place for conspiracy theorists? Your comment is an
embarrassment.

~~~
jdietrich
Read Dr Ben Goldacre's book "Bad Pharma". Scientific misconduct is endemic in
the pharmaceutical industry, most importantly in the form of publication bias.
Vast swathes of research goes MIA, with the statistical analysis showing
clearly that positive results are vastly more likely to be published than
negative results. Industry-funded research is more than twice as likely to
return a positive result than other research. This all takes place with the
implicit endorsement of the FDA - the FDA have far greater access to trial
data than any physician.

The pharma industry produces a lot of useful and important drugs, but they
also do a lot of seriously shady shit. GSK habitually lied about the risks of
Paroxetine and hid data showing serious safety issues. Merck committed fraud
on a grand scale by falsifying and concealing data related to Rofecoxib, which
led directly to around 60,000 deaths. It's quite clear that the ethical
standards of the pharmaceutical industry are close to nil - most large
companies are happy to kill patients with useless drugs as long as it's
profitable.

~~~
tinco
That might be. But reducing placebo effect is not shady shit. Publication bias
is a difficult phenomenon to fight, but when a pharmaceutical company invests
millions into a drug that does not significantly outperform placebo then that
product has failed. You can't keep repeating the research over and over again
until it succeeds if every research project costs millions.

You make it sound like a drug that performs as good as a placebo is useless.
Maybe you haven't read about the placebo effect, it is pretty damn effective.

~~~
LeeHunter
"You make it sound like a drug that performs as good as a placebo is useless."

But it is useless, is it not? The placebo effect is effective, cheap and safe.
If the new drug has the same effectiveness, it's probably just another
placebo, just far more expensive and probably nowhere near as safe.

~~~
tinco
Not necessarily. A placebo might perform as good as a regular drug in clinical
trials, where there is a 50% chance of it being the real thing and there is
significant personal interaction with researchers. Also for some reason people
always assume that if there is a clinical trial with humans involved the real
drug will probably work very well.

In real world scenarios however drugs might be bought with _no_ personal
interaction with professionals at all. Furthermore people are very sceptical
of the long-term effects of any psychology related drug. In this case the
placebo's might perform a lot worse than the actual drug, which may have an
actual noticeable effect.

The placebo effect is effective, cheap and safe, and might be present in both
the placebo and the tested drug. But the placebo can't be sold as medicine.
And the tested drug might still work without the placebo effect.

~~~
sekhat
Ultimately, I understand it as this.

Especially in terms of psychological effecting drugs

If the people getting the placebo get better (in the case of psychological
drugs.. feel better) as often as those on the actual drug, then it's quite
likely the drug is doing nothing and both sets of patients are getting better
because the belief of taking a drug that makes them better is causing them to
get better.

(apologizes for the confusing paragraph)

And hence, the drug is deemed worthless and thrown out, time to get on with a
trial of another drug.

~~~
tinco
"it is quite likely the drug is doing nothing"

The only way to be sure that the drug is doing nothing is to repress the
placebo effect as much as possible.

There are people dying or suffering that could be helped with drugs that
failed the placebo test. (Some of them could even have been helped with the
placebos themselves)

------
uvdiv
This looks genuinely useful. Getting more statistical power out of clinical
trials, for free, means they can use smaller sample sizes and save millions.
Lower entry barriers means more drug trials.

Not sure what the author finds "repulsive" in this.

------
gruseom
This is an interesting article about something important. I'm sad that it got
flagged out of view and that the discussion was derailed by middlebrow
dismissals (man am I envious that I did not think of that phrase!), tedious
name-calling about "alternative medicine" and the like.

The idea of rigging a clinical protocol to titrate out placebo responders and
redo the study on successively more favorable terms seems like a new variety
of intellectual corruption — like epicycles, except these epicycles are worth
billions of dollars. Now admittedly I got that impression by reading a
tendentious blog post. What this thread ought to be for is a neutral
discussion of how accurate and fair what the author is saying is. There are
people here who could help with that, but I'm not sure the ecosystem of HN can
tolerate it.

~~~
uvdiv
_The idea of rigging a clinical protocol to titrate out placebo responders and
redo the study on successively more favorable terms seems like a new variety
of intellectual corruption_.

They're not more favorable terms. A drug which has no effect will still
perform identically to a placebo. What changes is the level of noise, and
hence the sensitivity of the test.

The spread in placebo responses (the standard deviation of the binomial
distribution) is sqrt(N p (1-p)). For N=100, if 20% of the sample has a
placebo response, the s.d. of this is 4%. If you have only 5% placebo
responses, it's half that: 2.2%. Higher signal-to-noise ratio. You find that
more drugs work, because it's easier to tell _if_ they work -- not because
you're corrupting the test to show that work when they actually don't.

~~~
gruseom
Sorry, I'm not getting it—it sounds like tampering with a random sample after
the fact. How does this not amount to throwing out data one doesn't like?
Suppose I have a stock trading algorithm. I test it on random stocks, discard
part of the data set, and run the tests again. Now it's easier to show that my
system works. Is this ok?

 _You find that more drugs work, because it's easier to tell if they work_

Previously, the definition of "works" was "can be shown to be significantly
better than placebo". Why should that definition be changed? It seems very
reasonable to me, whereas relabeling placebo effects "noise" to throw them out
seems like eliminating the competition.

~~~
uvdiv
_Previously, the definition of "works" was "can be shown to be significantly
better than placebo"_

That's what they're testing -- except, on a subgroup which is less sensitive
to placebos. If a drug works on this subgroup, and if (the assumption) the
drug effect is independent of the placebo effect, then you infer it's better
than a placebo on the _whole_ population, though you haven't directly tested
this.

Placebo effects don't vanish when you're given a real drug. Roughly, when
you're testing a drug against a placebo, you're measuring {drug effect +
placebo effect} against {placebo effect}. If drug and placebo are independent,
than subtracting some "placebo effect" from _both_ sides, equally, gives you
the same comparison except with less statistical variation -- less "noise".

It's still possible that the drug and placebo effect are interacting in an
unknown way -- if the drug works, _and separately_ it weakens the placebo
effect, then this test gives you the wrong inference. This adds some epistemic
uncertainty, though maybe less uncertainty than the statistical uncertainty in
the ordinary trials. Obviously an issue.

What this is isn't is biased. It's not set up in a way to make drugs _seem_
systematically better: it's set up to _find_ more drugs that _actually_ are
better.

~~~
gruseom
This thinking seems to me fraught with dangerous non sequiturs, or at least
unproven assumptions. You mention one: on what basis can we assume that the
drug effect and the placebo effect are independent? We don't understand the
placebo effect. We should make as few assumptions about it as possible.

Here is another. If the drug is approved, it won't be given only to the
"subgroup which is less sensitive to placebos" on which it was tested. It will
be given to the general population. On what basis can you assume that since
the drug beats placebo on the subgroup, it must also beat placebo on the
general population?

It seems weird to allow a random sample to be taken from a population that is
not the population you're trying to make claims about. Are there precedents
for this in other fields?

------
Felix21
How can a drug work LESS than a placebo? Like if the drug does nothing then it
should at least be as effective as a placebo shouldn't it?

~~~
pygy_
It can have adverse effects worse than the _nocebo_ effect ( _nocebo_ in Latin
means "I will harm". It is the negative twin of the placebo effect).

~~~
jsilence
I thought the nocebo effect described that a placebo even worked when the
patient knew he was getting a placebo.

~~~
Samuel_Michon
“In medicine, a nocebo is a harmless substance that creates harmful effects in
a patient who takes it.”

<http://en.wikipedia.org/wiki/Nocebo>

------
3amOpsGuy
Ben Goldacre makes a strong case for not using placebo. If there's already a
widely used alternative, surely they should test against the best currently
available treatment, instead of testing against nothing (placebo).

The more concerning point Goldacre raises is that unflattering trial data goes
missing, and this is completely ok with the FDA.

------
mtrimpe
I'm still curious what would happen if we:

a) have a pill for every disease

b) give placebos if we don't have anything better

c) A/B-test viable new alternative drugs (or maybe multi armed bandit's
minimum regret is appropriate here ;)

That way patients might get the benefits of placebo without resorting to
alternative medicine and you would be able to test effectiveness of drugs much
more accurately.

You could even offer people different tracks, such as 'conservative',
'regular', 'progressive' and 'experimental' where different (new) drugs with
different risk profiles can be issued.

If you'd make regularly contributing data (completing questionnaires) on your
progress / health status a requirement for participation we could even start
doing big-data analysis on this (massively valuable) data set quite soon.

~~~
DanBC
When ethics comittees kill ([http://www.badscience.net/2011/03/when-ethics-
committees-kil...](http://www.badscience.net/2011/03/when-ethics-committees-
kill/))

> _At present there is a bizarre paradox in medicine. When there is no
> evidence on which treatment is best, out of two available options, then you
> can choose one randomly at will, on a whim, in clinic, and be subject to no
> special safeguards. If, however, you decide to formally randomise in the
> same situation, and so generate new knowledge to improve treatments now and
> in the future, then suddenly a world of administrative obstruction opens up
> before you._

------
lifeisstillgood
But it is simple - medicine has long demanded 95% confidence levels.

Keep them.

Do not budge. Do not allow drugs to come through that fail to meet those
standards

Now offer really big X-prizes for malarial drugs

Now allow holistic treatment as part of the drug trial - drug plus recorded
CBT, drug plus exercise regieme monitored

~~~
stygianguest
While I'm not against them, prizes are not enough to sustainbly drive research
as they only reward the winners. It is the reality of research (as opposed to
engineering) that outcomes are uncertain. Meanwhile researchers have to eat
and typically have good (well-payed) alternatives.

~~~
Retric
It's normal for drug research to be prize driven after all if Viagra caused
heart attacks none none of those billions would have shown up.

------
tlarkworthy
Seperating out the effects of mind and chemistry is a good thing for
understanding our bodies better.

------
Swizec
Question: If it works, why not heal with a [active] placebo?

~~~
phreeza
Congratulations, you just invented "alternative medicine"

~~~
Swizec
I mean, why not use placebos in real medicine? They obviously work, their rate
of working is measurable and we have a list of specific diseases they work on
and to what extent they work.

~~~
rmc
Because it opens up a lot of very important medical ethics problems.

During trials, the doctor and the patient don't know that the patient is
getting a placebo (it's called "double blind"). If people know that what they
are getting is a placebo, I don't think it works as well. So the only way to
get an effective placebo is to lie to the patient and tell them it's a good
drug.

 _But_ there is a long history of abuses in medicine (Nuremburg, Tuskegee
syphilis experiment, etc.), so "informed consent" is very very very important
in medical ethics. This means you can't lie to patients. To use placebos as
you suggest, you'd have to throw that out. This is a dangerous path.

~~~
pella
_"Can the recommendation for a treatment intended to promote the placebo
effect be made without deception and also without undermining its therapeutic
potential? Consider, for example, the case of a clinician who recommends
treatment with acupuncture for a patient with chronic low back pain who has
not been helped by standard medical therapy. Aware of the results of the
recent acupuncture trials, described above, this clinician thinks that
acupuncture may work by promoting a placebo response. The clinician might
provide the following disclosure to the patient: “I recommend that you try
acupuncture. Several large studies have shown that traditional acupuncture is
not better than a fake acupuncture treatment, but that both of these produce
considerably greater symptom improvement in patients with chronic low back
pain condition as compared with those patients who receive no treatment or
conventional medical therapy. Although the specific type of needling doesn't
appear to make any difference, it is likely that acupuncture works by a
psychological mechanism that promotes self-healing, known as the placebo
effect.” On its face, this disclosure appears honest. A patient who received
this disclosure and subsequently got better after undergoing acupuncture might
nonetheless develop a false belief about why it worked. This does not mean,
however, that the patient has been deceived by his physician."_

from:

Placebo Effects: Biological, Clinical and Ethical Advances (Damien G Finniss,
Ted J Kaptchuk, Franklin Miller, and Fabrizio Benedetti

PMCID: PMC2832199 / NIHMSID: NIHMS169379

<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832199/>

~~~
rmc
But does the placebo effect work _as well_ if the patient is told that type of
words?

~~~
pella
_"Placebo effect works even if patients know they're getting a sham drug Study
suggests patients benefit from the placebo effect even when told explicitly
that they're taking an 'inert substance'"_

[http://www.guardian.co.uk/science/2010/dec/22/placebo-
effect...](http://www.guardian.co.uk/science/2010/dec/22/placebo-effect-
patients-sham-drug)

