Are Placebos Really Sugar Pills?

http://asserttrue.blogspot.com/2013/01/are-placebos-really-sugar-pills.html

by techdog • 13 years ago

471 138 13 years ago

asserttrue.blogspot.com

acchow2• 13 years ago

As an aside, sugars aren't biologically inert either.

Florin_Andrei• 13 years ago

So, is there anything that could be said to be biologically inert in any and every scenario?

cotsuka• 13 years ago

Chalk?

ahi2• 13 years ago

Probably not, but disclosure of placebo ingredients would be enough to determine if it was a wise choice for a particular study.

user24• 13 years ago

Gold?

trotsky2• 13 years ago

A quote from the press release about the paper the OP cites:

But, according to the paper's author, Beatrice Golomb, MD, PhD, associate professor of medicine at the University of California, San Diego School of Medicine, this standard has a fundamental problem, "there isn't anything actually known to be physiologically inert."

http://www.sciencedaily.com/releases/2010/10/101018174335.ht...

marvin• 13 years ago

Cellulose? Diamond? Glass? Ceramics?

sek• 13 years ago

Everybody consumes a huge amount of sugar every day, so the pill is not even measurable compared to your normal intake.

So on average the effect of this small amount of sugar disappears.

driverdan• 13 years ago

Unless you're studying something related to blood sugar, insulin, etc or the user has a condition impacted by sugar, such as diabetes, a small amount of sugar (pills would contain 100-1000mg) isn't going to have any impact.

cooldeal• 13 years ago

Aren't the side effects mimicked so that participants won't see the lack of them and then know that they're taking the placebo which will defeat the double blind study?

For example, if you're testing fish oil, you wouldn't use a sugar pill since it's easy to know what you're taking by looking at it. You would use something like olive oil.

newishuser2• 13 years ago

There are certainly ways to simulate fish oil with biologically inert ingredients.

pmelendez• 13 years ago

I think you're missing the point. He was talking about this section of the article:

>That way, of course, they can say things in their ads like "[drug name] has a low occurrence of side effects, such as dry mouth, which occurred about as often as they did with placebo."

cooldeal point is that you need to mimic the side effects to make the control group believable. Whether it is needed to use inert components or not would depend on the nature of the drug in test.

kragen2• 13 years ago

There are? What do you have in mind? If you use mineral oil or Olean, you get diarrhea as a side effect in doses of more than a few grams per day.

pygy_3• 13 years ago

Indeed. It is well known that SSRIs studies were biased because of this, because SSRIs have a lot of early side effects, which break the blinding. Knowing that you're in the treatment branch increases the placebo effect.

That being said, the opacity of the manufacture process is concerning.

Studies with active placebos should have a third branch with inert placebos, to assess the incidence of side effects.

Locke16893• 13 years ago

That presents massive ethical issues. One would have to knowingly not give subjects a drug that we know helps them (i.e., the current standard of care).

BHSPitMonkey• 13 years ago

Perhaps the real problem the article should hone in on is that drug companies are (allegedly?) permitted to compare side effect rates to that of the "placebos", when the public will undoubtedly not be aware that the placebos used were manufactured to provide those same side effects.

cowsandmilk• 13 years ago

incidence of side effects can frequently be judged by comparing to incidence rates in the general population. This is indeed how Phase I trials are done to gauge the safety of the molecule and decide what side effects need to be emulated by the placebo in later clinical trials.

pleiotrope• 13 years ago

I think you're correct. The example given in the linked article mentions dry mouth, but it's arguably important in double-blind studies to have both the controls and test groups develop similar side effects, to prevent both the patient and the administering physician from determining which is the placebo group. I don't think it's entirely due to nefarious motives from the drug company.

bestes• 13 years ago

True. Just a happy side effect for the advertising in that example.

Also, I'm not a huge fan of more regulation, but scientific integrity seems to demand the placebo ingredients be disclosed.

From the discussion, it seems clear the doctor-scientists have to think about and carefully consider what to use for the control. A single, simple answer cannot work.

pbhjpbhj• 13 years ago

>both the controls and test groups develop similar side effects, to prevent both the patient and the administering physician from determining which is the placebo group //

If the physician can effect the trial by knowing to whom they're administering the placebo it seems that the trial lacks in its design. Someone else said that the person administering the drug/control could repeat a test because they felt the result was wrong - why is such a person involved in a drug trial? If they lie about that then it seems they can pervert the trial any number of ways.

How do the patients know how the other members of the study are being affected? If they don't get a dry mouth, but the drug company thinks they should, how does the patient know?

Surely you need the physicians and patients to record exactly what happened, no more and no less.

It seems that you're doomed to fail if you don't know that this is what's happening: suppose you use an active control that dries the mouth (for 95% of patients), if you don't have the side-effect with the drug on test then you know you're part of the active group with a high enough confidence level to alter the results in a qualitatively similar way to using a non-active control (placebo).

So what you need is a placebo that matches exactly the profile of the side-effects of the drug. I'd warrant that's impossible - you don't know the side-effects of the drug that are expected in a wide scale longitudinal study because that's what you're testing isn't it?

What is entirely nefarious is any use of "no significant side-effects beyond that experienced under placebo" when in fact they don't mean placebo but "active-control".

Placebo may be synonymous with active control in Pharma circles but it's not in common usage and so this is still a fraud.

jat850• 13 years ago

Is it not possible that, via whatever mechanism placebo drugs have positive intended effects, that they could also cause side effects?

tedunangst• 13 years ago

Placebo effect is not a 100% effective substitute for the real deal. If the drug makes you pee more, you could convince yourself of that. If the drug makes your pee turn purple, that'd be harder to achieve just by willing it to happen.

newishuser2• 13 years ago

What this article leads me to think is that we need to legally protect the word placebo. It seems grossly misleading to use the word placebo to describe non biologically inert ingredients. To do so is to lie and nothing more.

wiredfool• 13 years ago

Just look for homeopathic remedies then. Guaranteed not to have any active ingredients.

joshuacc• 13 years ago

That's not strictly true. Homeopathic remedies do often include small amounts of alcohol or sugar.

plorkyeran• 13 years ago

Not everything that claims to be homeopathic actually is. One example is Traumeel. If you look at their ingredients ( http://www.traumeel.us/Products/ProductDetail.aspx?id=190100... ), there's enough active ingredients that are only 1X diluted that the total is over .5% active.

I assume it's just labeled as homeopathic because they failed to fake some clinical trials to get FDA approval (or didn't even try), but maybe it's actually an effective marketing choice.

jessriedel3• 13 years ago

Actually, I think "Placebo" has always meant "a thing used to make not taking a drug an indistinguishable experience to taking it" (which, it turns out upon reflection, requires it to inflict side effects). Inertness is just a popular misconception.

That said, I think capitalizing on that misconception is wrong and that it might be reasonable to take actions which prevent true but subtle statements like "drug had similar side-effects to a placebo" from misleading laymen.

amund• 13 years ago

is this like saying: we use the metric system (small print: but our 0 cm point starts at 50 cm)?

brunorsini• 13 years ago

This reminded me of a very good Wired article from a couple of years ago, "Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why" - http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo...

adcoelho• 13 years ago

This is not by any means my field of study but i do agree that placebo components should always be disclosed in order to turn these kind of tests more transparent.

However, how can we prove that something is 100% biologically inert? We can't account for all the unknown effects, is there any such 'ingredient'? I guess that at least the used placebo should be proven to not affect directly anything directly related to the hypothesis.

rxmatic• 13 years ago

It doesn't appear that anyone actually knows about the field here as this is really a non-issue for a simple reason (I chose you to reply to because you were at the bottom).

First of all, most immporant studies don't use a placebo because it would unethical when there are standard treatments out there already and you have to show that your new drug is just as good or better than those treatments (the proper terms are supperior vs. non-inferior trials).

But considering trials that do use a placebo - the whole point is to prove that their drug is superior to the placebo. If anything, when they design the placebo, it would have structurally similar molecules that would give the same side effects, and potentially the same results <-- which is key. A research DOES NOT WANT the placebo to do as well as their drug. The placebo can only hurt their results, not help them cheat.

You could also argue that since it's not regulated, maybe the active component does actual harm to make the test drug look better! No. There are too many studies showing what the controlled group should look like (whether they are on a placebo or on nothing at all).

abtinf3• 13 years ago

Having worked in the pharma industry, this article is complete bullshit.

For double and triple blind (the third blind comes from not even the pharma company knowing the blinding details until after the trial) placebo design is an extraordinarily complex undertaking. A placebo must match the drug in physical appearance, taste, texture, density, state (liquid/solid/gas), and anticipated side effects. Any material difference in any of these categories renders the trial completely and totally meaningless, because at a minimum it unblinds the doctors on the ground.

Pointing out a few random oversights out of the thousands of clinical trials that occur every year is not proof of evil on the part of pharma; it is a testament to the care that goes into their design. It represents a defect rate virtually unmatched in any other industry.

But sure, go ahead and advocate irresponsible alarmism over a non-issue, as if though drug trials aren't already expensive enough, retarding scientific progress and costing millions of lives from drugs that would have been otherwise developed.

CodeMage• 13 years ago

I encourage you to post that in the comments on the blog itself. There are already comments saying "thank you for this" and "placebos should be regulated" and whatnot. Maybe I'm overly optimistic, but I believe it would be useful to have your comment close to the article text (instead of having to scroll down) to provide balance.

hellerbarde3• 13 years ago

I was about to write something similar. Thanks for formulating it so eloquently. I think it's this part that trips up some people:

> [...] at a minimum it unblinds the doctors on the ground.

It's very important that the person administering the drug/monitoring the patient can not tell the difference.

abtinf3• 13 years ago

The effects of unblinded doctors can be catastrophic and might not even be discovered.

There was one study where a drug was designed to improve motor response in patients with retarded motor skills. The doctors had found a way to determine which patient was receiving which drug.

So when it came time for the doctors to measure efficacy of the drug, they would do the motor skills test. If the patient was on the actual drug, and didn't show improvement, the doctors had a tendency to say things like "Well, that can't be right. Let me run the test again."

Disaster. Hundred million dollar trial down the toilet.

jpablo• 13 years ago

Of course we can't know who is telling the truth since ingredients on placebos are not disclosed. That's the part I think is the meat of the issue.

jennyjitters• 13 years ago

>That's the part I think is the meat of the issue.

I agree. I think the main issue the author wants the reader to take away is that since the ingredients in placebos are not disclosed, what's to say they can't add ingredients that will skew the results? I'm not saying that this happens, but what is stopping them? They obviously have financial, and other, incentives for their drugs to succeed, so why not take that extra measure to maintain integrity in studies that use placebos?

pygy_3• 13 years ago

Who controls the integrity of placebos?

refurb5• 13 years ago

If by "integrity" you mean "ensuring that the appropriate placebo was used in a clinical trial that was the basis of a drug approval", the answer is: the FDA.

jarito2• 13 years ago

I think you may have missed the point. You have stated that the article 'pointed out a few random oversights', but the actual point of the article is that _there is no data_. How can anyone, including you, know how effective the choice of placebo ingredients are if they aren't disclosed?

It doesn't seem an undue burden to ask that the placebo ingredients be documented so that their effect on the study, which is critical by any measure, can be understood. How can a separate group reproduce the results of a study if they don't have this type of information?

What you seem to have said is - trust us. We won't tell you what's going on, you can't evaluate how well we are doing, but this is a totally hard problem so don't worry about it. This is disingenuous when the drug companies have vested interests in the outcome of these studies.

If the drug companies are truly doing such a great job, then they should be recognized for the excellent work. The only way to do that is to release the ingredients used in the creation of placebos.

refurb5• 13 years ago

I don't think he's saying "trust us", he's saying "this is an issue that everyone knows about, thus it's a non-issue".

When you submit a drug for approval at the FDA, you need to list in exacting detail exactly how trials were run, including how they were blinded. The ingredients and form of the placebo are critical for this.

The paper referenced in this blog post examined journal articles to determine if the composition of the placebo was reported. Journal article are notoriously lacking in details and they have to be since no one want to read an article with pages upon pages of details.

If his comment was "Hey, you guys who write papers on clinical trials, it would be awesome if you'd list the placebo composition, since I'd be more likely to believe your findings" I would say "fair point".

But the blog post says "Hey! Drug companies are trying to pull a fast on all of you! Beware of what's in your medicine cabinet" which is a completely ridiculous statement. This "missing information" is available to the people that matter (the FDA).

This is truly an example of making a mountain out of a molehill.

larrys2• 13 years ago

"but the actual point of the article is that _there is no data_"

According to the OP whose is (just checked) a tech evangelist at Adobe. Additionally the sum of their research is "Over the weekend I was reading some medical studies involving placebos".

What I'm seeing is that someone wrote something (the OP) and made some statements and additionally pointed to one journal article (which I'm sure only a few HN'ers have even bothered to click through and glance at.)

This is interesting to discuss and that's it (at this point at least).

api• 13 years ago

http://programinplacebostudies.org/

chasingtheflow• 13 years ago

This is a bit dense with legalese, but if you search for placebo it would seem to indicate that it /is/ required that they disclose placebos ...

"(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an "Investigational New Drug Application" (IND) including, in the following order:

...

(c ) A brief general description of the composition, manufacture, and control of any placebo used in a controlled clinical trial."

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRS...

adaml_623• 13 years ago

You've missed the point.

Once the placebo has been designed to 'match the drug in physical appearance, taste, texture, density, state (liquid/solid/gas), and anticipated side effects' it should still be described in the final paper.

droithomme• 13 years ago

Yes. If a placebo has active ingredients, you have no chance to replicate the study if you can't tell what those active ingredients are. And if you can't replicate a published study from the details given in the paper, then it's not a scientific study, it's bullshit. Yes, that's right, it's bullshit. And yes most studies fall into this category. Can't be replicated, shouldn't have been accepted for publication in the first place.

Havoc• 13 years ago

OK, but what do you measure the results against then if you distorted the benchmark with active ingredients? Surely the entire point of the control group is that it represents the unaltered baseline?

abtinf3• 13 years ago

This is a common misconception.

In fact, there are very few studies in which patients receive an "inert" placebo.

Consider a new drug that claims to treat heart disease. It would be obviously immoral to say, "we are going to take drugs away from the control group and give them sugar pills instead".

So a "Placebo" is usually the current standard-of-care, which might be a very powerful drug.

This works because we are not at all interested in the absolute effectiveness of a drug; we are only interested in whether or not it is better then the current alternatives.

ahoyhere5• 13 years ago

Why does the placebo complexity make a call for regulation and study disclosure "utter bullshit"?

tptacek7• 13 years ago

Again: it didn't simply call for "regulation" and "disclosure". It overtly accused pharma companies of using active placebos for marketing purposes, of haphazardly endangering participants in trials, and then later suggested that the whole concept of active placebos might reasonably be outlawed.

The post we're commenting on made a series of outlandishly ignorant assertions.

That there are reasonable challenges we might make to the way active placebos are handled does not make the article better. You're a great writer. Maybe you should write a good article on the perils of undisclosed/underdisclosed active placebos? Because this particular article doesn't appear to be good.

crpatino• 13 years ago

While the article might have pulled a few cheap shots at pharma companies, the point stands. We need disclosure of this incredibly complex placebo matching methodology (for lack of a better term), at minimum because the experiments cannot be replicated by a third party without it.

Another reason for disclosure is the ethical risk assessment. What is to prevent a misguided executive from arranging a placebo with minimal doses of active components that produce adverse effects... just to push the results of a marginally effective drug. I am sure that 99.9% of people in the industry would not do that, but there is no reason to avoid putting checks and balances in place, for the day when some random sociopath decides to push it a little bit and get away with it.

jessriedel3• 13 years ago

Do we know if it hasn't been disclosed in FDA filings (which are way more detailed), or just that it was disclosed in these research articles? Journal articles are meant to be terse for readability, and standard placebo techniques are just the sort of thing I would expect to be left out.

samstave• 13 years ago

So didn't you just state that a placebo needs to cause side effects?

Doesn't that mean that it's poison by nature if said side effects are negative?

Screw wanting to take part in that.

"Here's a pill that will cause oily discharge and nothing else" Yum!

saraid216• 13 years ago

Everything is poison by nature. Everything has negative side effects.

dalke• 13 years ago

Not all side effects are equally negative. Some negative side effects are acceptable and ethical.

Let's take DMSO as an example. Treatments with DMSO leave a particular garlic-like taste in the mouth. This is a negative side-effect. But DMSO is not a poison during normal treatments any more than ethyl alcohol is a poison.

A good placebo for DMSO would have the same side-effects as otherwise a patient and perhaps even the doctor could tell the difference based on taste/smell compared to the anticipated taste/smell. I believe this still isn't possible, which makes testing DMSO difficult. One solution, for example, is to look for a dose-response curve, which is a more complicated signal to extract.

bigfudge22• 13 years ago

Agreed the article is bullshit. However getting the issue 100% backwards the author actually raises an important point. Active placebos do make for a different comparator than inert placebos --- arguably a much better one. Given that north of 90% of patients and doctors have been found to correctly guess allocation in blinded trials of tricyclic antidepressants and other antipsychotics, it might actually help to add something to the placebo which does generate side effects to make it harder for people to pick which group they are in.

It always made me laugh reading about 'double blinded' trials of cannabis extract for MS... In this and many other cases the blind is a complete fiction.

Xion• 13 years ago

> (...) as if though drug trials aren't already expensive enough, retarding scientific progress and costing millions of lives from drugs that would have been otherwise developed.

Isn't testing a vital part of this development, and by extension a crucial part of what you call scientific progress? The fact that we need more and more sophisticated testing techniques is because we understand more about the intricacies of human body and the ways it can interfere with treatment process. Placebo is an obvious example of such interference.

To me, calling a scrupulous testing process a factor that's retarding scientific progress is like saying QA is retarding software progress.

einhverfr3• 13 years ago

> A placebo must match the drug in physical appearance, taste, texture, density, state (liquid/solid/gas), and anticipated side effects.

This makes the following statement: "When compared to a placebo, this drug had rare incidents of the following side effects..." translate as "We guessed correctly at the incidents of side effects before we started the trials," correct?

If so, then that's false advertising.

z92• 13 years ago

"A placebo must match the drug's ... anticipated side effects" --- that's what he is saying too. Placebos are not inert as I had been assuming till date. And then comes the after story...

mapt• 13 years ago

Not necessarily true; The veil of ignorance can be induced for doctors, if some care is taken. Direct psychological effects of the pill's appearance on patients can't be measured, but the effect of the doctors spoiling the study based on that certainly can.

Doctor hands patient sealed opaque pill blister pack, tells them to take two, nurse watching on a CCTV or via webcam sends a text message that they've verified the patient taking the pill.

refurb5• 13 years ago

This seems like a ridiculous blog post.

Only 6% of clinical studies list what their placebo was, so the conclusion from that is that there is a concerted effort by drug companies to unscrupulously modified the outcomes of their studies by choosing biologically active placebos. That's a bit of a stretch.

Typically what is done for a study is that drug company will manufacture the drug for the study in tablet form, complete with fillers and binders (inert ingredients used to make the pill). Then they will manufacture the same tablet without the active ingredient. The drug has to be identical in shape and color or else the study isn't really blinded, physicians could tell that patients were getting two different drug. That's the reason why drug companies make their own placebos.

Also, the example of using olive oil instead of clofibrate has two possible explanations: 1) clofibrate is soluble in olive oil so they likely gave one set of patients clofibrate +olive oil and the other just olive oil (negating the effect of olive oil) OR the study was just poorly done (yes it happens) and it would be obviously to anyone familiar with clinical trials (including the people at the FDA).

I could go on, but it doesn't really seem necessary. The article speaks for itself.

pygy_3• 13 years ago

Not playing in the conspiracy here, but the lack of transparency is concerning. I know the weight and complexity of the process of designing a clinical study, and I don't doubt that, in most cases, the placebos are well crafted.

However, I'm sure that, in some cases there are oversights in the placebo choice (we do make mistakes), and we don't know which ones.

There are also big financial stakes, and pharmaceutic firms are known to cheat while attempting to bring drugs to the market. The burial of negative studies come to mind.

xenophanes2• 13 years ago

They should list placebo ingredients after the trial is done so it's possible to duplicate the trial and get the same results, right?

If you don't provide enough information in your paper to repeat the experiment (and get the same results!!), then it's not good science. Good scientific studies need to be repeatable and need to provide enough information to do it.

And even if people don't want to repeat the full experiment, being able to review the details of how it was done will help them spot mistakes. You can't have things like "peer review" without saying what you did.

So this is a serious problem, even if the rest is breathless hype.

refurb5• 13 years ago

If your argument is that journal article should include more details so that they are reproducible, that's fine but there is no need to pick on the ones published on clinical trials. I would say it's a rare paper that is so exhaustive in detail that you can easily reproduce the results. Many times I've had to contact original authors to get more details. You'd be amazed at what gets left out.

ahoyhere5• 13 years ago

Even above duplication, it's important to document what's in the placebos because these clinical trials are used by the FDA to approve the drug for consumer use… or not.

ahoyhere5• 13 years ago

so the conclusion from that is that there is a concerted effort by drug companies to unscrupulously modified the outcomes of their studies

Did we read the same blog post? The author didn't claim any such thing. In fact, he referenced a study where (if you ascribe intent) it sounds like the drug company was undermining itself by using a placebo that worked better than the drug (the olive oil).

His actual conclusion, for non-readers, is:

Placebos aren't documented, and they're not included in studies, and many times they're active in causing side effects deliberately and yet they're barely regulated -- "current anarchy" -- and this casts doubt on the validity of studies.

His call to action sounds pretty reasonable to me:

> FDA needs to review its policies on placebos and either outlaw "active placebos" or rigorously define acceptable conditions for their use.

peeters• 13 years ago

>> so the conclusion from that is that there is a concerted effort by drug companies to unscrupulously modified the outcomes of their studies

> The author didn't claim any such thing.

Actually, the author did claim any such thing:

> Active placebos are designed to mimic the side-effects of drugs under study. So for example, if a new drug is known (or thought by the drug company) to produce dry mouth, the drug company might use a placebo containing ingredients that produce dry-mouth. That way, of course, they can say things in their ads like "[drug name] has a low occurrence of side effects, such as dry mouth, which occurred about as often as they did with placebo."

The author here is accusing drug companies of using active placebos to make the side effects seem less critical, when there's no evidence of that presented.

Goronmon• 13 years ago

I'd argue these are the main points of his blog posts. Or at least the ones he emphasized.

Active placebos are designed to mimic the side-effects of drugs under study. So for example, if a new drug is known (or thought by the drug company) to produce dry mouth, the drug company might use a placebo containing ingredients that produce dry-mouth. That way, of course, they can say things in their ads like "[drug name] has a low occurrence of side effects, such as dry mouth, which occurred about as often as they did with placebo."

and

The current anarchy that prevails with regard to placebos calls into question the reliability not just of drug-company research but of virtually every placebo-controlled study ever done. Which is a hell of a thing to have to say, or even think about. In fact it's nauseating.

Sounds to me like he's saying drug companies are manipulating the outcomes of studies and implying that any study containing a placebo shouldn't be trusted.

Ingaz2• 13 years ago

>>That's a bit of a stretch. Can you imagine an "active placebo" for LSD, THK, methamphetamine (for example) ?

"Placebo" must be a potent psychedelic or stimulator itself.

davidtanner• 13 years ago

I think that amphetamine has been used as a placebo for LSD in some studies. I've also heard of researchers using threshold doses of the psychedelic as the active placebo. This is probably the best option most of the time.

rdl2• 13 years ago

I'd probably go for 2C-T-7 directly against LSD (but ending the trial after ~4h; after 12+ hours, it would be obvious who had taken what), but I could easily imagine psychedelics as a class having a common effect.

DanBC• 13 years ago

Ben Goldacre says that testing against placebo is sub-optimal. You're testing that a medication is better than nothing. What you want is a medication that tests better than whatever we're currently using.

I don't know how that fits in with blinding everyone involved. As abtinf and refurb mention, designing placebo is a difficult process.

And you don't need to include anything to create side-effects; people taking sugar pills will happily report having a range of side effects.

quasque• 13 years ago

"What you want is a medication that tests better than whatever we're currently using."

This is also done, depends on the trial. For example, new vaccines are often tested against the existing one(s).

trotsky2• 13 years ago

This blog seems to be rather senselessly hyperbolic and misleading. For example, it attributes an anecdote in which HIV patients are "dropping like flies" due to lactose intolerance to the research paper it cites. According to other sources [1] [2] the paper actually discusses a situation in which cancer patients were administered a lactose placebo in which the author speculates their predisposition towards lactose intolerance could have influenced the study. The gap between the two situations could hardly be larger.

Certain placebos, they add, may skew results in favor of the active drug. The researchers referenced a trial for a drug used to treat anorexia linked with cancer in which a lactose placebo was used. Since lactose intolerance is common among cancer patients, the fact that some suffered stomach problems from the placebo may have made the actual drug look more beneficial.

[1] http://articles.latimes.com/2010/oct/18/news/la-heb-placebo-...

[2] https://en.wikipedia.org/wiki/Placebo-controlled_studies#Pla...

oneandoneis2• 13 years ago

His cited example of a placebo that could skew data is olive oil, which by reducing heart disease would make the drug appear less effective than it might actually be.

Pointing out a study where the pharma company might have used a placebo that made their drug harder to approve is hardly in keeping with the insinuation that they're using placebos for "disturbing" ends.

Seems more like a case of "throw all the mud and hope some of it sticks" to me. Sorry.

gwern• 13 years ago

More importantly: if the tested drug can't beat olive oil on the very thing that the drug is meant to treat, then why should it be approved at all?

(Drugs should be tested against the best existing alternative treatment, not merely a placebo. We are not interested in whether a new drug has a non-zero effect - but whether it is an improvement on the state of the art in some way.)

kragen2• 13 years ago

It might be an improvement on the state of the art in some other way. For example, a new antibiotic might be less effective than existing antibiotics, but have no cross-resistance with them and therefore be useful in treating antibiotic-resistant strains in the future (the magainin case), or a new antipsychotic might be less effective than existing antipsychotics for average patients, but more effective or less damaging for a few. Finally, you might be able to get synergistic effects by combining the drug with the best existing alternative treatment.

lwat• 13 years ago

Also: The placebo effect is stronger if the placebo used has side effects. Again this works AGAINST drug companies.

hermannj314• 13 years ago

From the article: It's inconceivable (to me, at least) that there are no laws requiring drug companies to list placebo ingredients.

From CFR 21 Part 312.23 (a)(7)(iv)(c): A brief general description of the composition, manufacture, and control of any placebo used in a controlled clinical trial. [is required to be supplied for an Investigational New Drug Application]

What is the difference? It seems the law clearly states that for new drugs, you must list the composition of your placebo to the FDA. It would seem the article is mistaken. I am not a lawyer nor do I work in the pharmaceutical industry. I just did a google search for "placebo composition site:fda.gov"

alayne• 13 years ago

The blog title is "Are Placebos Really Sugar Pills?". Was "Or Something Worse?" editorialized on? The thrust of the article isn't that placebos are bad, it's that they are inert and not regulated or reported on consistently.

tokenadult• 13 years ago

It appears that a lot of participants on Hacker News are interested in the role of placebos in treatment trials. I have some recommendations for background articles on the use of placebos in clinical trials and the pitfalls sometimes encountered in interpreting results from such trials. The articles are all by expert authors who practice frequently writing on this topic for general readers.

August 2009 "The Rise of Placebo Medicine" by Steven Novella, M.D.

http://www.sciencebasedmedicine.org/index.php/the-rise-of-pl...

December 2010 "Placebo Effects without Deception? Well, Not Exactly" by David Gorski, M.D.

http://www.sciencebasedmedicine.org/index.php/placebo-effect...

January 2013 "Is acupuncture as effective as antidepressants? Part 2. Blinding readers who try to get an answer" by James Coyne, Ph.D.

http://www.sciencebasedmedicine.org/index.php/is-acupuncture...

There are many more good articles about placebos and how they are used in clinical trials on the site where these articles come from. The issue the blogger whose post is kindly submitted here seems so upset about is simply an issue of making a placebo (sham) treatment indistinguishable from the treatment under investigation, so that doctors and patients are properly "blinded" during the trial. Another comment already posted here on HN has pointed out that the FDA does oversee what ingredients are put into placebos, whether or not those detailed ingredients are published in a peer-reviewed research study. The blogger's concerns are legitimate, but not proportionate to the actual problem.

Disclosure: I have been a subject of FDA-regulated medical trials. I was very impressed by thoroughness of data collection in those trials, and by my inability to distinguish whether I was receiving placebo or genuine medicine in one of those trials. My oldest son, now a hacker for a start-up, had work experience while in college at a medical device company, and he was impressed that every line of computer code he wrote during his summer job was reviewed line-by-line by FDA computer scientists as part of the review process for the medical device he worked on.

guelo• 13 years ago

It makes no sense that the FDA receives extra information that is not available to peer reviewers. Why would that be?

kvb2• 13 years ago

The purpose of the FDA is quite different from that of a journal; why would you expect the information needed for each to perform its function to be the same? Among other issues, how much time to you expect a journal reviewer to spend vetting a study, compared to the amount of effort that the FDA spends reviewing the same study?

kuenx• 13 years ago

http://imgur.com/a/7Vfnc

Here are some Alzheimer placebo samples (pictures) from Pfizer, handed out to doctors in Switzerland. Sorry for the bad quality. Pictures taken with a phone.

rdl2• 13 years ago

It would be interesting to do placebo vs. placebo trials (telling patient A he's getting a specific drug and giving him a placebo instead, and telling patient B he's getting another drug which treats the same condition, and also giving him a placebo).

i.e. would you subjectively report more pain relief when given ibuprofen (placebo) vs. vicodin (placebo).

But, pesky IRBs :(

Are Placebos Really Sugar Pills?

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