Placebos becoming too effective, pharma industry worries

http://asserttrue.blogspot.co.nz/2013/03/new-patents-aim-to-reduce-placebo-effect.html

by gmac • 13 years ago

38 62 13 years ago

asserttrue.blogspot.co.nz

tlarkworthy2• 13 years ago

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

Swizec2• 13 years ago

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

phreeza• 13 years ago

Congratulations, you just invented "alternative medicine"

Swizec2• 13 years ago

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.

Samuel_Michon5• 13 years ago

Plenty of techniques that were once considered alternative medicine have found their way into Western medicine, so it's not all as cut and clear as you present it.

hamax4• 13 years ago

Because it (mostly) doesn't actually work.

It looks like it works because it exposes bias in both patients and researchers.

This is why it's more effective with subjective and self reported symptoms like pain, nausea, etc.

A great short article about placebo: http://www.sciencebasedmedicine.org/index.php/the-placebo-ef...

Felix21• 13 years ago

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_• 13 years ago

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• 13 years ago

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

neilkimmett• 13 years ago

If the drug makes the condition worse?

lifeisstillgood2• 13 years ago

It is unlikely to work less than the placebo, just for 20 people you happened to choose some just got better anyway - and we're in the wrong group

That's why it's important to publish all trials - if the 20 people who got better anyway were receiving the active drug do you think they would be saying our drug might not be that effective?

DanBC2• 13 years ago

Some prostate cancer is very slow growing. The man will die with it, not of it.

Treatment is harsh and aggressive and carries risks and has unpleasant side effects.

In that case doing nothing is better than doing something.

A very good question to ask of a doctor is "What happens if I do nothing?"

rmc3• 13 years ago

It could be chance. Remember if you have a small sample size, it's possible that (by chance) the placebo control group just happen to get better faster, making it seem like the placebo works 'better'.

richardjordan4• 13 years ago

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.

penny1003• 13 years ago

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

3amOpsGuy2• 13 years ago

I don't buy it.

>> 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

Is a fair (although not proven) interpretation of the available data:

    1. Big pharma make very large political campaign contributions, sometimes via indirect routes which has the effect (even if not the intention) of disguising the funding source.
    2. Drugs are being tested against placebo, instead of the best available alternative. We know that unfavourable trial results are frequently not reported. It's fair to cast question on the medical benefit of such drugs.
    3. The final question is the FDA's motivation to approve such borderline drugs - ostensibly it's to provide options to doctors where the preferred treatment is not possible (perhaps adverse reaction in the patient or everything else has already been tried), your parent posits that it could be as favour to these companies.

While there's certainly no proof presented, i don't go along with the idea it can be cast aside as conspiracy theorist without some counter evidence.

One side needs to provide evidence - you or your parent, your parent's point is left open otherwise and your response doesn't counter it.

jdietrich• 13 years ago

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.

richardjordan4• 13 years ago

Hah. It is hardly conspiracy theorist to observe that industries which donate vast sums in campaign contributions get favorable legislative and regulatory treatment.

You can pop up with your throwaway account and hurl insults but I'm fairly sure that it is a well observed pattern that US campaign contributions correlate with the direction if policy and enforcement. Of course that could just be a placebo effect - they may actually have no effect whatsoever. That being said I am persuaded by the balance of evidence that large campaign contributions are a rational and effective expenditure by industry to secure favorable treatment rather than money squandered by corporations out of idealistic democratic intentions.

So now the ad hominem is out of the way? Did you have a broader point? As someone with a background of scientific training I'm comfortable holding the position that I fail to be persuaded that this is a valid and unbiased statistical approach, rather from what I read I see this as a rather transparent attempt to justify huge expenditures on speculative potential drug investments which unfortunately delivered products for which there is not strong evidence of significant benefit.

When you get over your embarrassment at a comment on a discussion forum which your account has been registered on for 16 hours perhaps rather than try to shut down discussion with personal insults you can make a more sophisticated argument as to why you believe in the validity of this approach and why you believe that campaign contributions to politicians are an ineffective way to influence policy and regulation contrary to all evidence.

He who pays the piper calls the tune.

uvdiv6• 13 years ago

How is SPCD a "fig leaf of a fudged trial"?

richardjordan4• 13 years ago

I view the situations under which drug trials happen today to already be highly favorable to the drug companies. If even in those circumstances they're not getting strong signals that their drug is effective then changing the experiments until they show what you're hoping for is not the right approach. Indeed I think it's a good use of the term fudging.

ggreer• 13 years ago

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...) and "Do warnings on cigarette packs cause lung cancer?" (http://asserttrue.blogspot.com/2013/02/do-lung-cancer-warnin...). 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.

stygianguest2• 13 years ago

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.

Samuel_Michon5• 13 years ago

http://tldr.io/ occasionally helps.

shrikant• 13 years ago

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

lifeisstillgood2• 13 years ago

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

stygianguest2• 13 years ago

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• 13 years ago

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.

uvdiv6• 13 years ago

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.

mtrimpe• 13 years ago

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.

hamax4• 13 years ago

The biggest problem A/B testing is ethical.

Every patient deserves the best medicine we can provide, so A/B testing, even though it would work in the long run, is unethical.

DanBC2• 13 years ago

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

> 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.

3amOpsGuy2• 13 years ago

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.

gruseom3• 13 years ago

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.

uvdiv6• 13 years ago

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.

gruseom3• 13 years ago

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.

Placebos becoming too effective, pharma industry worries

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