The Placebo Effect Doesn’t Apply Just to Pills
nytimes.com
nytimes.com
False, the FDA doesn't actually have any requirement to prove that a treatment is better than placebo. Many trials don't even include a placebo arm, they only compare themselves against existing drugs that were grandfathered into the system without any efficacy testing. Or they compare themselves to inert placebos rather than active ones, even if they are psychoactive drugs. Or they only compare themselves against placebos for a few weeks, even if they are meant to be used for long periods of time.
This is how we have drugs like antidepressants and ADHD drugs on the market even the though research shows they are actually worse than taking no drug at all.
What do you mean?
The other thing to keep in mind is that this was a meta-analysis using data pooled across many different trials. It certainly isn't as rigorous as a RCT.[1]
You seem to be taking that demonstrate efficacy, when what they're actually saying is more like 'there is no evidence that this works, but if nothing works then why the hell not.' It's no different than doctors giving patients the go ahead to use alternative medicine or whatever when the doctors know the patient is already going to die from cancer regardless.
Isn't "active placebo" a contradiction in terms?
Because people know they could be taking a placebo, then having undeniable effect (psychoactive, redness, soreness, etc.) tells them that they are not using the placebo. Conversely, having no undeniable side effects lets them know that they are using the placebo. Thus, placebo usage is undermined.
"Active placebo" has an undeniable effect, but not the compound being tested, so that the test subjects cannot tell if they have the placebo or the real things.
There are probably many factors to depression which may include chemical or structural causes; however the human brain is a complex self adapting analog computer. It would be foolish to think that such a system can be reduced a single or even simple set of controlled variables.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003012...
Source - memory from having written a book on adult ADHD
What do you mean by 'work'? The research cited by Anatomy of an Epidemic shows that there is no affect on grades or other academic outcomes. And that while concentration itself improves somewhat in the short term, after 2+ years it is worse than if the person were never given the drugs to begin with. See also:
http://online.wsj.com/news/articles/SB1000142412788732336870...
Can anyone say if this article is reliable? I can't even read it on this computer.
The confounding thing with stimulants of all varieties is that even people without any problem tend to report improvement.
Or is there a case where one could "pass" this test, but still "lose" against a placebo?
For the rest, I didn't realize there was a difference between inert and active placebos.
The main issue is that a lot of the existing drugs aren't better than placebos:
- Some were never required to be tested for efficacy by the FDA before approval.
- Some were tested for whatever reason., but the methodology used by testing was flawed for whatever reason.
- In many the data was blatantly faked or manipulated by the company running the test. In general NIH tests show much lower efficacy for the same drugs as in pharma trials sponsored by the drug manufacturer. There is tons of research on this.
However, there are other tricks that pharma companies use when testing against existing drugs. One of the main ones is using non-effective doses of the older drugs... E.g. by using a higher than normal dose of the older drug in order to make it look like the newer drug has less side effects. This is how the newer generation of anti-psychotics got approved, and it's also how Nexium got approved even though it's basically chemically identical to Prilosec.
Yes they were used before the FDA had a formal approval process, but your comments doesn't make sense.
If the current standard of care is a drug and you test against it, aren't you showing it's more effective?
The main issue is that a drug can be more effective than an older drug but still be less effective than taking no drug at all.
But given all the problems, both theoretical and practical, with current drug trials, there is pretty much no guarantee of anything. Just because something makes sense on paper doesn't mean that it's actually true. There are a number of books about the issues with drug trials... Bad Pharma by Ben Goldacre, The Truth About Drug Companies by Marcia Angell, Overdosed America, etc. All of these books cover largely different issues, so imho it's worth reading them all.
No offense, but Marcia Angell has a tenuous grasp in terms of knowledge of the pharmaceutical industry. I would take her opinions with a grain of salt.[1]
[1]http://www.forbes.com/sites/johnlamattina/2012/12/14/marcia-...
> Angell’s attack came at the same time that the FDA was reporting that much like 2011, 2012 has proven to a great year for patients with the approval of 35 innovative drugs.
Here is the actual argument from the book:
"In the five years from 1998 through 2002 [...] 415 new drugs were approved -- an average of 83 per year. Of those, 133 (32 percent) were new molecular entities. The others were variations of old drugs. And of those 133, only 58 were priority review drugs. That averages out to no more than 12 innovative drugs per year, or 14 percent of the total."
"Over the four years beginning in 2000, there were just 32 innovative drugs out of a total of 314 approved drugs. Even in this small collection, only seven came from the top ten U.S. drug companies."
The book was published ten years ago, but if you look at the most recent data from the FDA then it's similar:
In the five years between 2007 and 2011, a total of 119 New Molecular Entities were approved by the FDA. Of these, only 50 were granted priority review, meaning they were classified by the FDA as having the potential to provide a therapy where none exists or providing a therapy which may be potentially superior to existing therapy. Of these 50 priority NMEs, 30 were orphan drugs, meaning they were approved for diseases that affect 200,000 or fewer Americans. Of these, it's not clear how many (if any) were created by large American pharma companies. [1]
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugs...
Just because it didn't get priority review, doesn't mean it's not innovative.
It just shows how little Angell understands the industry.
I'm not entirely sure what the plausible explanation for that one would be. Other than that the testing methods have changed to create a bias in favour of the placebos being successful.
I think that was just a Jonah Lehrer thing. (I.e. his article The Truth Wears Off in The New Yorker.) What's actually happening is more likely that if a new class of drugs makes it onto the market and becomes popular enough, then it eventually gets studied by people who don't have an economic incentive in 'proving' that the drug is actually effective.
Once you stop cherry picking the subjects of the trials, covering up bad data, and using dubious statistical methods, the drugs start looking much less effective than they did originally.
Earlier this year I re-injured the meniscus in my knee and was about to undergo surgery when a radiologist in the family mentioned this study. I cancelled the surgery and followed the alternative recovery method of ice, ibuprofen and rest. It took a long three weeks for me knee to feel normal again, but it would've been much longer had I undergone the surgery.
[1] "Dietary supplement industry says 'no' to more information for consumers (again)" http://www.sciencebasedmedicine.org/big-supp-resists-giving-...
http://www.stuffyoushouldknow.com/podcasts/how-the-placebo-e...
A friend of mine who repairs PCs occasionally finds nothing wrong with them and does the usual "I'll run some maintenance on it" and the client is always happier afterwards. He doesn't charge for stuff unless anything needs to be done.
http://www.nybooks.com/articles/archives/2011/jun/23/epidemi...
http://www.nybooks.com/articles/archives/2011/jul/14/illusio...
There is a feedback loop between abstract thoughts and effects on the body, so to make a proper distinction you want to ignore the feedback loop and look at where the inputs are.
A placebo's direct effect is not physical. The direct effect is that first thought that you are receiving treatment, before it even has a chance to affect your mood.
A kidney transplant's direct effect is mostly physical. It's filtering your blood at a rapid pace.
So technically mood has physical effects but by the time you reach that stage you've destroyed the meaning of the term "physical benefit" into meaning just "benefit". Feel free to suggest better terms, but please don't muddle the waters.
"No physical effect" means the same thing as "no effect", unless we are willing to discuss metaphysical effects.
The indirect effects are somehow the result of the user's expectation that there is a direct effect.
That is to say, "placebo effect" is not "the effect of the placebo object", obviously.
It's the emergent effect of the whole situation of someone being duped with a placebo.
Being duped with a placebo has direct, physical effects, while the placebo object has no effect.
See, that's the idea I'm not comfortable with. You are defining the term in a way which renders it basically meaningless, when there is an alternate definition that does have useful meaning.
Germany generally does a good job on evidence-based herbal medicine (like standardizing St. John's wort extract), but I worry that the line can easily be blurred between them and homeopathic products in the eyes of most consumers. You really have to look carefully - they're not clearly marked.
So honestly, you're probably quite right about it being a deliberate exploitation of the placebo effect. Because otherwise, there's no reason not to ban them.
I went home and looked it up: a homeopathic panacea with only a single "study". Not double blind, not even single blind -- they literally just gave the drug to some participants and the self-reported symptoms "improved".
I'm still not sure whether the GP was just trolling me.
On a more serious note, medicine has a general problem dealing with the mind. The "placebo effect" is just one case where this manifests itself, but in case of drugs at least this effect can be scientifically measured.
In case of psychosomatic ilnesses (e.g. ilnesses which manifest with real symptoms, but the underlying cause is in the mind) it is much harder to quantify anything. How do you create a control group, if each person is so different? There is no way to "look inside the mind", no universal way to influence the mind.
Having gone through several ilnesses which (as I later discovered) were psychosomatic, I know the issue first-hand. Doctors tend to avoid even considering the mind's role, just as if we were simple machines, with the mind completely separate. On one hand this annoys me, on the other hand I understand them: a doctor is supposed to deal only with what is measurable and quantifiable. Cause and effect should both be measurable.
I've noticed that the number of articles about placebo effects, mind-caused ilnesses and psychosomatic problems in general seems to be increasing. I'm glad this is happening, as we definitely need more research done on these kinds of problems and we need to find ways to deal with them. From what I can see around me (now that I know about psychosomatic illnesses), many people suffer from them, and only deal with the symptoms.
> We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed.
from "The moral case for the clinical placebo"
There are some known ways to take advantage of similar effects--for instance, helping patients find ways to lower stress as a means of mitigating risk factors like high blood pressure.
I remember one time I needed eyedrops. They were only listed as homeopathic in tiny print and were adjacent to real eyedrops in the pharmacy, so it was a bit hard to read them with my allergies going.
And I've tried washing my eyes with water, but it's not as effective as real eyedrops. Moreover, these contained "aspis", allegedly some extract from bees, which I might be allergic to. One would hope that they'd diluted it enough, but it actually listed a fairly low dilution factor so I couldn't even be sure the damned things weren't harmful.
https://www.youtube.com/user/thehealthcaretriage
He does a great job covering a variety of subjects & explaining research to the layman.
Is it just me, or does this seem ethically dubious? A sugar pill placebo does no harm, but when you are cutting people open to "fake" surgery...just doesn't sit right.
> The ethical issues aren’t easily dismissed. Theoretically, a sugar pill carries no risk, and a sham procedure does. This is especially true if the procedure requires anesthesia. The surgeon must go out of his or her way to fool the patient. Many would have difficulty doing that.
> But we continue to ignore the real potential that many of our surgical procedures and medical devices aren’t doing much good — and might even be doing harm, since real surgery has been shown to pose more risks than sham surgery.
Too many medical studies, and almost all "alternative medicine" testimonials, are based on soft endpoints (patient self-reports of improvement) rather than on "hard endpoints" (longer healthier life after reduction in all-cause mortality, or resuming walking after being paralyzed, or something observable objectively and lastingly important).
Pretty much all studies by all authors of whatever researcher background that appear to show a "placebo effect" show that only for patient-reported subjective symptoms that are usually temporary anyway like pain and nausea. Nobody asks for a placebo treatment for a broken leg or a life-threatening infection. The medical researchers who look at the issue with proper study designs and statistical controls know that placebos are essentially useless, as they at most have influence just on self-reported subjective symptoms, not on any sign that affects the progression of a disease or maintenance of good health.[2]
Findings on placebo effects by researchers who have considered the issue carefully include
"Despite the spin of the authors – these results put placebo medicine into crystal clear perspective, and I think they are generalizable and consistent with other placebo studies. For objective physiological outcomes, there is no significant placebo effect. Placebos are no better than no treatment at all."[3]
"We did not find that placebo interventions have important clinical effects in general. However, in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting. The effect on pain varied, even among trials with low risk of bias, from negligible to clinically important. Variations in the effect of placebo were partly explained by variations in how trials were conducted and how patients were informed."[4]
So, yes, let's make sure that studies of surgical techniques include studies of sham surgery. (Studies of acupuncture had better always have sham acupuncture arms in which "real" acupuncture points are disregarded or other aspects of supposedly ancient Chinese technique are intentionally omitted without the patient knowing that.) This will improve the evaluation of safety and effectiveness of new surgical techniques. Just don't assume that ANY placebo is ever good for ANYTHING that you couldn't achieve just by giving yourself a good pep talk.
[1] http://www.bmj.com/content/348/bmj.g3253
[2] http://www.sciencebasedmedicine.org/michael-specter-on-the-p...
http://www.sciencebasedmedicine.org/ted-kaptchuk-versus-plac...
[3] http://theness.com/neurologicablog/index.php/the-rise-and-fa...
from: http://jme.bmj.com/content/40/4/219.full
"The moral case for the clinical placebo"
The same team's updated Cochrane review[2] still sums up the evidence by saying, "We found an effect on patient-reported outcomes, especially on pain. Several trials of low risk of bias reported large effects of placebo on pain, but other similar trials reported negligible effect of placebo, indicating the importance of background factors." They add a caution about experimental methods consistent with the article submitted here on HN: "The use of placebos in blinded randomised trials is a precaution directed against many forms of bias, and not only against effects of placebo. Unblinded patients may differ from blinded ones in their way of reporting beneficial and harmful effects of treatment, in their tendency to seek additional treatment outside the study, and in their risk of dropping out of the study. Furthermore, unblinded staff may differ in their use of alternative forms of care and in their assessment of outcomes. Thus, even if there were no true effect of placebo, one would expect to record differences between placebo and no-treatment groups due to bias associated with lack of blinding."
[1] https://math.dartmouth.edu/~doyle/docs/40/PlaceboArticle.pdf
[2] http://summaries.cochrane.org/CD003974/COMMUN_placebo-interv...
I agree with this:
"It is evident that placebo effects are real and that they have therapeutic potential. Laboratory evidence supports the existence of numerous placebo mechanisms and effects in both healthy volunteers and patients with a variety of medical conditions. Furthermore, clinically relevant evidence demonstrates that placebo effects can have meaningful therapeutic effects, by virtue of magnitude and duration, in different patient populations. Although substantial progress has been made in understanding placebo effects, considerable scientific work remains to be done in both laboratory experiments and translational clinical trial research, ---> with the ultimate aim of harnessing placebo effects to improve patient care."
Damien G Finniss,corresponding author Ted J Kaptchuk, Franklin Miller, and Fabrizio Benedetti
"Placebo Effects: Biological, Clinical and Ethical Advances"