[prism (OP)]

Hi all!
You may have heard about this in the news recently.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1079669/
I was wondering what people make of this news?

http://www.healthypages.co.uk/newsitem.php?news=6380
Copied from the above article:-

Whenever you hear about a placebo-controlled trial you may well give it greater merit than those without. Generally, it is considered more acceptable when a trial is conducted against a placebo as the placebo is supposed to be a neutral ingredient that does not actively produce any effects. On that basis, placebos have been incorporated into trials for decades.
 
But strange as it may seem, there is no single standard for what a placebo is. In fact the Annals of Internal Medicine journal very recently published an article with the headline "What's In Placebos: Who Knows?"
 
In most placebo controlled trials, the volunteers are split into two groups. One is given the active drug or ingredient that is on trial and the other group are given a placebo; a pill without the drug in it. Both groups need to believe they are taking the drug so that human factors such as ‘belief’ or ‘expectation of results’ does not interfere with the trial.
 
There is however, one major problem with the placebo according to Professor Beatrice Golomb, MD from the University of California, San Diego School of Medicine, and that is: "There isn't anything actually known to be physiologically inert. On top of that, there are no regulations about what goes into placebos, and what is in them is often determined by the makers of the drug being studied, who have a vested interest in the outcome.”
 
Golomb first made these observations public in two letters sent to the Nature journal over 15 years ago.
 
The problem said Golomb is that "A positive or negative effect of the placebo can lead to the misleading appearance of a negative or positive effect of the drug," adding that "An effect in the same direction as the drug can lead a true effect of the drug to be lost. These concerns aren't just theoretical.”
 
As 15 years had gone by since she first wrote the letters, Golomb wondered it=f there had been any improvement in the use of the placebo. Golomb and colleagues checked the randomized trials over the last two years to find out how many had disclosed the contents of the placebo. They found that less than 10% of trials had disclosed the placebo contents.
 
Summing up, Golomb said, "How often study results are affected by what's in the placebo is hard to say -- because, as this study showed, most of the time we have no idea what the placebo is."

When it comes to the health industry, I tend to agree "to some extent" with this guy Mike Adams views (on this issue)
http://www.naturalnews.com/030209_placebo_medical_fraud.html

It's amazing how medical scientists will get rough and tough when attacking homeopathy, touting how their own medicine is "based on the gold standard of scientific evidence!" and yet when it really comes down to it, their scientific evidence is just a jug of quackery mixed with a pinch of wishful thinking and a wisp of pseudoscientific gobbledygook, all framed in the language of scientism by members of the FDA who wouldn't recognize real science if they tripped and fell into a vat full of it.

what does everybody else think of this?

[Don_1]

It does appear to be the case that placebo's can have some psychological effect, to what extent that might corrupt medical trials would be fascinating to discover.

Perhaps it would be an idea if some people were put into a situation where they believed they were taking part in some clinical trials and that half would receive a new drug, while the other half get a placebo. Then give them all a placebo and see what happens.

[SteveFish]

“Placebo fraud Rocks the very foundation of modern medical science” is a bit of an exaggeration, don’t you think? Applied science has some problems, but the JRSM opinion piece is an excellent example of the self-correcting nature of most medical science. The big drug industry requires even more scrutiny, but wouldn’t it be great if the same attention was paid to the, so called, natural or herbal, or holistic medicine claptrap? These folks rarely test their medicines and expect us to believe their profit motivated opinions. They rarely give accurate measurements of concentrations of the active ingredient, or even guarantee that there is anything in it at all! As for homeopathy, they purvey the ultimate placebo, plain water, and they don’t even guarantee its purity. Mike Adams wants to try to direct everybody’s attention away from his own immoral hobbyhorse and he should be ashamed.

Don_1, there is an active research area into how the placebo effect works. It will be fascinating to see what the mechanisms are and to find a way to apply it ethically, unlike how the natural medicine corporations use it. It isn’t really necessary to do a trial that is completely placebo because the placebo control in a study can be compared to the, usually already well-studied, group of people who don’t get any treatment at all for the condition under study. Also, what do you think that Miller and Kaptchuk, in the JRSM piece, would have to say about telling all the patients in a study that they were getting medicine when they were not? At least in many placebo control studies the researchers can arrange it so that one half get the real medication and the other half get the placebo in the first half of the study, and this is reversed for the second half. This way both groups of subjects participate in both treatment groups. EDIT- I should have also said that in placebo controlled trials the patients are told that they may get real medicine, or the placebo, so nothing is really hidden from them. I really value the ill patients who knowingly volunteer for a drug trial, they are making a very important contribution to medical care.

Steve

[rosy]

It does appear to be the case that placebo's can have some psychological effect, to what extent that might corrupt medical trials would be fascinating to discover.

Don... that's the entire point of the placebo arm of a trial!
The effect of any treatment is the pharmacological effect of the tested treatment plus the psychological effect of changing patients' expectations (and that applies both to benefits and side effects). If there were no comparator trial there would be no way of knowing what was the benefit of the treatment and what was the placebo.*

To DaveyBoy's original question:
There's been lots of study done of placebo effects - changing the size, or the colour, or the shape of the pill or injection can have a significant impact on the effect. So any remotely competent clinical researcher would know that it is essential to ensure that the pills given to the placebo arm must be as much like those in the treatment arm as is physically possible. I suspect that the reason why the content of placebo pills is not generally discussed in published papers is that it's taken to go without saying that readers will know that a pill will be formulated in exactly the same way and using exactly the same ingredients as the treatment pill, except for leaving out the ingredient whose properties are being tested.

When it comes to the health industry, I tend to agree "to some extent" with this guy Mike Adams views (on this issue)

To what extent? The man appears to me to be more-or-less foaming at the mouth. I cite only one example of a startlingly ill-considered "argument" in the article linked, but I saw several.
He says:

Fact: Placebos are usually provided by the very same company funding the clinical trial! Do you detect any room for fraud in this equation?

Well of course they're supplied by the same people who are funding the clinical trial! The people who are funding the clinical trial are the people manufacturing the drug. The form of the pill has to be identical, and the packaging has to be the same, so that the clinicians and patients don't know who's in the treatment arm and who's in the placebo arm. So the people supplying the drug, also supply the placebo.

Certainly there's an opening for fraud. But let's unpack what that fraud would entail... I won't put too fine a point on this - he's suggesting the drug company's employees - not the execs, not the shareholders, but the bench-top lab workers in their hundreds and probably thousands - are deliberately poisoning trial participants. And no-one's said anything to object. It's not a realistic hypothesis.

Also.... DaveyBoy - your first link discussed the ethics of non-double-blinded treatments such as sham surgery, and then you go on, without further mention of the sham trials article, to discuss the question of the contents of placebo pills etc. Any reason for this?

*Note that often trials are not actually against placebo but against the current standard treatment, because where the current treatment is known to work better than a placebo it is unethical, especially in cases of serious conditions, to use a placebo rather than that treatment.

[prism (OP)]

When it comes to the health industry, I tend to agree "to some extent" with this guy Mike Adams views (on this issue)

To what extent?

well its probably basically true, if you think about it theres far too many variables in any health experiment to say any drug is definitely good for you, 
long term effects of drugs are a concern,
for e.g can anyone say viagra is safe over a 30 year period? nope
also drugs cant cure chronic conditions, only deal with symptoms
e.g viagra might give you an erection but cant cure the cause of ED. All that time not dealing with the cause is damaging too.

your first link discussed the ethics of non-double-blinded treatments

sorry my mistake, i rushed.
 

[rosy]

well its probably basically true, if you think about it theres far too many variables in any health experiment to say any drug is definitely good for you,

Uh? For some drugs, this is probably true. But any drug? Nonsense. I don't think there is any question, at all, (at least not in the mind of anyone who both (a) is sane and (b) has thought for 2 minutes) for example, that antibiotics are good for people with bacterial meningitis. If you're suffering from a disease which is going to kill you in the next 24 hours and you're given a drug that stops you dying, even if that drug increases by 50 % your odds of developing cancer in the next 20 years (not that I know of any antibiotic to which this applies, I'm using an invented example to clarify my point), you're still coming out ahead. The same applies to chemotheraputics for cancer treatment. Individuals and their doctors have to weigh up the known risks and benefits. What's known about the risks and benefits evolves over time, and therefore so do the decisions people make. But that's how medicine works.

also drugs cant cure chronic conditions, only deal with symptoms

That's a beautifully circular argument. A condition is only a "chronic" condition if we don't have a cure for it. As soon as we do, it ceases to be chronic. In the meanwhile, and alongside research into a true "cure", using drugs to suppress symptoms seems sensible to me. Does it not to you?
Example: insulin injections for type I diabetics. The life-expectancy of a newly diagnosed type I diabetic has changed from months (19th c.), to ten or twenty years (1960s), to pretty much a normal lifespan (current state of affairs in countries with a good medical system). Sure it's a hassle. Sure it would be better if the pancreatic damage could be reversed (fingers crossed for the stem cell research), but in the meantime?

All that time not dealing with the cause is damaging too.

Well, sure. In some cases, like type II diabetes, relying heavily on the drugs as an excuse not to go to all the trouble of fixing diet and lifestyle, that's probably the case. On the other hand... do you have an answer for asthma? For eczema? For type I diabetes? For hypothyroidism? Or would you agree with me that it is not suppressing the symptoms of any of those, with drugs, that does more damage?
Sure eczema can often be improved by working out that it's caused by an allergy to something-or-other and eliminating it (as far as possible), but children die of infections due to untreated eczema, as in this tragic case:
http://www.smh.com.au/national/parents-guilty-of-manslaughter-over-daughters-eczema-death-20090605-bxvx.html

[Bored chemist]

It may be interesting to know what placebo was used but, of course, it shouldn't matter.
The whole point is that it's inert and that the patient can't tell the difference between the placebo and the active medication.
Who cares if they used sterile water or saline? Does it make any odds if they chose lactose or chalk

[SteveFish]

Daveyboy:

You say- "drugs cant cure chronic conditions, only deal with symptoms"- and I say, what is your alternative for dealing with a medical problem for which there is no cure?

Steve

[rosy]

Does it make any odds if they chose lactose or chalk

Well, potentially, I guess. If the patient is lactose intolerant, lactose-based pills can contain enough lactose to cause unpleasant side effects. So if the "treatment" pill is made from lactose plus a few mg of active ingredient then it might therefore be important that the placebo pill should be made from lactose, so that the side effects of the formulation, if any, are identical. But I would expect that this would be the default, and that in papers where there is no discussion of the content of the placebo treatment the reader is expected to assume that the placebo is formulated exactly as the treatment but without the ingredient under examination. As far as I understand it, Golomb et al. don't discuss whether they wrote to the corresponding authors of the papers they reviewed (really not rocket science, they'll all have e-mail addresses on the published papers) to ask what the placebo treatments actually contained. If they'd done that and not got (sensible) answers, then it might be an interesting story.

[Bored chemist]

I'd have to check, but I don't think the amount of lactose in a few pills would matter much, even to someone with lactose intolerance, because they use it as the bulking agent in a lot of pills.

[rosy]

Mm-mm. They certainly do use it as a bulking agent for pills. Which is fine for them as aren't intolerant of lactose.

However, I believe milk contains about 11g lactose per cup, I also know that a good deal less than a cup of milk would make Dave fairly miserable.. certainly it's also used as a carrier in spraying on crisp flavouring and I'm not sure what quantity would be used in a standard sized bag of crisps (which weighs maybe 25 g total?) but that's enough for him to notice that he's forgotten to check the packaging.

So I would think the half gram or so that might go into a pill as a bulking agent is quite probably sufficient to make some people who are intolerant of milk notice gastric side effects sufficient to be worth reporting, and which would therefore influence the outcome of the study if any of the test subjects in either arm were lactose intolerant (I suspect there probably aren't enough lactose intolerant people in the general population to be confident it would even out between the two arms), unless the selection of test participants asked about lactose intolerance in the screening questions before starting the study. Which I would expect in fact that it would..

(When we went on a walking holiday, I tried quite hard to find pills not bulked with lactose. Turns out all, but all, antihistamine pills available in Cambridge in August 2008 were lactose bulked, so we took children's antihistamine syrup instead. Not so light to carry, in its glass bottle.. That was quite annoying.)

[Variola]

Are we not missing the obvious point, that a lactose intolerant patient would not have been included in a drug trial where lactose was included in the placebo or pill?   [] People undertaking drug trials have their history meticulously recorded, it would be uncommon for a lactose intolerance not to have been noted.

Also the amount of lactose in pills, placebo or otherwise is only enough to effect severely lactose intolerant people, those people know about their intolerance and so does their GP, their medication is prescribed accordingly.

[rosy]

On the question of trials specifically:

Are we not missing the obvious point, that a lactose intolerant patient would not have been included in a drug trial where lactose was included in the placebo or pill?   roll eyes People undertaking drug trials have their history meticulously recorded, it would be uncommon for a lactose intolerance not to have been noted.

That's what I meant by this bit:

unless the selection of test participants asked about lactose intolerance in the screening questions before starting the study. Which I would expect in fact that it would..

On the question of prescribing to people with lactose intolerance issues more generally:

Also the amount of lactose in pills, placebo or otherwise is only enough to effect severely lactose intolerant people, those people know about their intolerance and so does their GP, their medication is prescribed accordingly.

Hm. Maybe. It depends what quantity of lactose they're putting in. I reckon half a gram would be enough to upset Dave's digestion slightly. But he certainly wouldn't, of his own accord, think to ask about the bulking agent of a pill (although he does know some pills are bulked with lactose, and if he was having milk-type effects he might think to look at the packaging...).

And whilst I think he did once tell his GP he'd stopped being able to eat milk, about 5 years ago, but he's an adult in good health in a large practice, so I doubt he's ever seen the same GP twice. I'd be utterly astonished if a prescribing GP knew about the lactose intolerance unless it was in the standard questions to ask before prescribing the drug.

I grant you, Dave's a pretty odd guy, and probably most people would involve their GP more in working out that the problem is lactose intolerance (if only because mucking about to find out if it's lactose intolerance would be likely to take up time which might perhaps be important in identifying any alternative, more sinister explanations). Most people probably wouldn't turn up the feed rate of their own saline drip because they were thirsty in hospital after having their appendix out, either.

[Bored chemist]

Half a gram is rather big for a pill.

[rosy]

One paracetamol tablet typically contains 0.5 g of paracetamol, and an ibuprofen tablet is approximately the same size... which is what I based my guess on - I guess that is a fairly large tablet, but if someone were taking several smaller pills it didn't seem to me to be a bad ball-park figure. I guess thinking about it that contraceptive pills are much smaller, and may be more representative, but I've thus far been fortunate in that my experience of these things is pretty limited.

[SteveFish]

I dug up a little information to help give this discussion some context. There have been quite a bit more than a thousand research studies of people with lactose intolerance. There have been reviews of this area that discussed findings from studies with, overall, good methodology. Good methods include studies with a large enough subject pool, appropriate statistics, the double blind method, randomized selections of the treatment and control groups, and treatments of lactose in the amount typically consumed in a single meal (around 6 to 26 grams of lactose, roughly equivalent that contained in one cup of dairy product).

Across multiple studies, the findings show a consistent tendency for those who are lactose intolerant to have the usual symptoms (including cramping, flatulence, frequent bowel movements and diarrhea, sorry about that), but not always and frequently the tendency is not statistically significant. This doesn’t mean that some individuals don’t suffer symptoms from small amounts of lactose, but it does mean that, on average, this fairly large amount of lactose has a relatively mild effect on most with this condition. These findings also don’t suggest that people with lactose intolerance don’t suffer, just that the actual cause of their symptoms isn't due to just lactose. Interesting. In any case, it would appear that concern over the small amount of lactose that may have been in some placebo pills definitely doesn’t “rock the very foundations of modern medical science.”

Steve

[Bored chemist]

Paracetamol tablets are pretty big as pills go. Most drugs are more potent than that.
Of course drugs that need large doses (like paracetamol) don't need bulking out with lactose.
Drugs that need bulking out only need to be made big enough to be easy to count  but not so big they are hard to swallow.
I can't see why you would have a pill with half a gram of lactose in it (unless it was as the placebo for a relatively low potency drug- possible but hopefully unlikely. I guess/ hope they would use starch for those.)

[rosy]

BC:
Yes... I think that's more or less the conclusion I was coming to having thought about it a bit further, I guess a typical tablet size might be more like 100 mg or less. A paracetamol sized pill is actually big enough that some people do find them hard to swallow, so no-one would make one that big if it wasn't necessary.
 

[prism (OP)]

well its probably basically true, if you think about it theres far too many variables in any health experiment to say any drug is definitely good for you,

Uh? For some drugs, this is probably true. But any drug? Nonsense. I don't think there is any question, at all, (at least not in the mind of anyone who both (a) is sane and (b) has thought for 2 minutes) for example, that antibiotics are good for people with bacterial meningitis. If you're suffering from a disease which is going to kill you in the next 24 hours and you're given a drug that stops you dying, even if that drug increases by 50 % your odds of developing cancer in the next 20 years (not that I know of any antibiotic to which this applies, I'm using an invented example to clarify my point), you're still coming out ahead. The same applies to chemotheraputics for cancer treatment. Individuals and their doctors have to weigh up the known risks and benefits.

Yep, fair point.

When I talked about "too many variables" i was mainly questioning whether drug trials should be classed as truly "scientific", since
for example, if they use say 30 different people, they are all going to have different fat indexes, different blood types, different hormone levels, and over the trial different room temperatures, experience different foods, different water intake, different personal stresses, different muscular tensions etc.
There's 9 variables there. You get the point.
When you add this Placebo revellation, that even they are not consistant, personally I think it starts to get abit laughable really.
Maybe, Im wrong(?)

Anyways, to be honest Im not "Mr.Anti-drug", because as you say, they can be life changing in the right circumstances.
And actually it is of my opinion that the long-term side effects of drugs are probably less to do with actual drug and more due to the fact the cause is not being treated, only the symptom.
 
When you ask what I suggest to solve the cause, well there's a myriad of ways which can switch the 'flight or fight' mechanisms in the body in the positive favour.
I went down the Somatic Education route, which eventually cured me of 12 years of "chronic" back pain, RSI, ED, PE and POIS (anything embarrassing I had it, lol). 
I subscribed to Alexander Philosophy that it is bad 'use' and poor movement patterns that is the cause of all health symptoms. Once properly looking into it all, its general theory appears air-tight to me.

What I find most tragic is this idea of writing people off or not giving people the right information, which is effectively the same thing.
This is a good example of this,
behind the cheesy production is an important message (made by the dad) that his daughter was written off by doctors, which would have meant a life of hell,

To you, someone curing themselves of celebral palsy-type brain damage might be seen as an unbelieveable (if not dubious) story, but to me, its not a surprising story at all. (Esp. if Anat Baniel is involved).
I also find it quite tragic that someone should be told drugs are the only thing for Asthma and the other conditions you said.

Plenty Alexander Techniques teachers are ex-Asthma, and I know one that says his Diabetes problems are non-existant.
Do i think Somatic Education should be on the NHS..mmm...well yes.. and no.. it would be better spent in schools, getting young children exposed to it as much as possible.
Unfortunately there is only one school in the UK, which does this, Educare School in Surrey gives all the kids Alexander lessons everyday. (I'd be very surprised if a child leaves there with Asthma, or if not the condition immeasurably improved by the school).

Can Somatic Education cure Asthma? Yes. Hypothyroidism? Yes. Diabetes? Yes (definitely not an easy task and it would illegal for the organisations to say they can!)
(of course Diabetes is not something you just wake up with, you can have years of other health problems before it develops, an Alexander Teacher once told me by the age of about 8 years you can tell what the persons ill-health will be over a lifetime, if things arent corrected) 

You might ask whats the link with Cerebral Palsy, Asthma, Diabetes, Hypothyroidism?
well they are all symptoms of living "fight mode" instead of "flight mode".
In my situation, there's many different terms which would describe my recovery from my 12 years of living hell...
an alexander teacher would call it "staying free and up", a reflexologist would say "balanced reflexes", an acupuncturist would call it "unblocked Chi", a biofeedback practitioner would call it "accessed blocked neurological pathways", a Taoist would probably call it "kundalini awakening", a neurologist would probably call it something like "better functioning of damaged nerves"...

..either way they just different words describing the exactly same thing...staying in "flight" mode.

[Bored chemist]

"When I talked about "too many variables" i was mainly questioning whether drug trials should be classed as truly "scientific", since
for example, if they use say 30 different people, they are all going to have different fat indexes, different blood types, different hormone levels, and over the trial different room temperatures, experience different foods, different water intake, different personal stresses, different muscular tensions etc.
There's 9 variables there. You get the point."
You have just illustrated why they do trials on large groups of people. The effects you talk about get "averaged" overthe group. The effects of the drug - which are similar in all the people are not washed out in this way.