Homeopathic nosodes: A clinical trial of magic

As hard as it is for me to believe, I’ve been writing about homeopathy for more than a decade now. Regular readers, of course, know that homeopathy is quackery, utter pseudoscience based on prescientific vitalism based on two “laws”: the Law of Similars and the Law of Infinitesimals. The former states that, to relieve a symptom, you use a substance that causes that symptom in healthy people. There is, of course, no science or logic to support this as a general principle other than sympathetic magic. The latter Law states that to make a remedy stronger, you must dilute it. That in itself is silly enough and goes against much of what we know about how drugs work in the body, but it gets sillier. Homeopaths often dilute their remedies with serial dilutions of 100-fold each, usually designated as “C,” as in 1C = one 100-fold dilution. Between each dilution, a homeopath will tell you, you must vigorously shake (succuss) it in order to “potentize” it. The silliness gets even sillier when you consider that a typical homeopathic dilution of 30C = a 1 in 1060 dilution. Given that Avogadro’s number is only ~6 c 1023, which means that a 30C dilution is over 1036-fold greater than Avogadro’s number. Basically, any homeopathic remedy stronger more dilute than 12C or so is very unlikely to have a single molecule of starting compound left. Most homeopathic remedies are water.

That’s why skeptics like myself like to use homeopathy as an example of quackery. Once you explain the laws of homeopathy, it’s very easy for most lay people to understand why homeopathy is quackery and why it basically can’t work. As I like to say, for homeopathy to work, scientists would have to be not just wrong, but spectacularly wrong, about some very fundamental laws of physics and chemistry. Homeopathy also is a very good “teachable” example to illustrate how randomized double-blind clinical trials (RCTs) can go wrong. To put it very simply, using Bayesian considerations, in which the plausibility of a hypothesis and hence its prior probability of producing a positive clinical trials are considered, testing treatments like homeopathy, which has about as low a pre-trial probability or plausibility as I can imagine, can be very good at producing false positive trials. Heck, Steve Novella and I even managed to publish a commentary on this in a scientific journal under the title, Clinical trials of integrative medicine: testing whether magic works?

All of this is just a bit of background I wanted to lay down for those who might be relatively new to this blog before I discuss what I learned about a clinical trial of homeopathic nosodes discussed in a STAT article by Helen Branswell, Should researchers study bunk science? Among respected scientists, a debate ensues. Basically, it’s asking the same question that Steve Novella and I answered two years ago with a resounding “No!” Depressingly, the arguments for testing homeopathic nosodes are basically the same naive or discredited arguments that Steve and I discussed then and have been discussing on and off in our respective blogs for years.

But first, what are homeopathic nosodes? Basically, nosodes are homeopathic remedies prepared from a diseased animal or person and can consist of saliva, pus, urine, blood, or diseased tissue, diluted to various degrees according to the principles of homeopathy. Many homeopaths sell nosodes as being the equivalent of vaccines. Take to a ridiculous extreme, some homeopaths were known to take blood or bodily fluids from Ebola victims to make, in essence, nosodes, an incredibly dangerous thing to do, not just for the patient being possibly exposed to Ebola but for the homeopath stupid enough to handle actual bodily fluids from Ebola victims without proper training and, one worries, proper protection.

The STAT story basically reports on the tension and disagreement between two Canadian academics, neither of whom is a quack or crank and both of whom are well respected, over whether doing a clinical trial of homeopathic nosodes can be justified:

A disagreement between two respected Canadian academics is raising some fundamental questions about when a disputed scientific issue has been studied long enough.

The debate centers on whether it’s still valid — or even ethical — to do research on products called nosodes, which are marketed as homeopathic “vaccines.”

And this is what it’s all about:

Dr. Mark Loeb, an infectious diseases researcher at McMaster University in Hamilton, Ontario, is seeking volunteers for a study that he thinks will show nosodes don’t activate an immune response and therefore cannot protect against diseases.

Tim Caulfield, a professor of health law and policy at the University of Alberta in Edmonton and a zealous debunker of quack science, argues there’s no need to run such a study. Science already knows the answer, said Caulfield, whose most recent book — on the impact of celebrity culture on health — is entitled “Is Gwyneth Paltrow Wrong About Everything?”

“It is com-pleeeeeeeete scientific nonsense,” Caulfield said of homeopathy, drawing out the word for added emphasis.

“There is no need to study it. … I don’t need to run a physics experiment to demonstrate that flying carpets don’t fly.”

And:

One of these days Prof. Caulfield. and I need to meet. He’s showing some sweet, sweet Insolence, there, and I approve heartily. What Caulfield is saying is basically what Steve and I wrote two years ago when we compared a trial of this type to a clinical trial of magic. In fact, because homeopathy is basically very similar to the principles of sympathetic magic, I have a hard time thinking of a better example of exactly the sort of phenomenon that Steve and I were lamenting that this very clinical trial by Dr. Loeb. It is the very epitome of what Harriet Hall has labeled “Tooth Fairy science,” defined by her as seeking explanations for things before establishing that those things actually exist and frequently elaborates:

You could measure how much money the Tooth Fairy leaves under the pillow, whether she leaves more cash for the first or last tooth, whether the payoff is greater if you leave the tooth in a plastic baggie versus wrapped in Kleenex. You can get all kinds of good data that is reproducible and statistically significant. Yes, you have learned something. But you haven’t learned what you think you’ve learned, because you haven’t bothered to establish whether the Tooth Fairy really exists.

Here’s what I mean. The clinical trial being run by Dr. Loeb can be found on ClinicalTrials.gov (NCT02825368). It will consist of three groups:

  • Controls, who will receive a calcium carbonate oral dose and two sterile saline injections (0.5 ml each, intramuscular) as placebo.
  • Active Comparator: Conventional vaccine group. These will receive one dose of Tdap, one dose of MMR, and calcium carbonate pellets as a placebo.
  • Experimental: Homeopathic vaccine group. This group will receive Diphtheria (Diphtherinum®), pertussis (Pertussinum®), tetanus (Tetanotxicum®), measles (Morbilinum®) and mumps (Ourlianum®) nosodes, as well as two sterile saline injections (0.5 ml each, intramuscular) as placebo.

Three weeks later, antibody levels for diphtheria, pertussis, tetanus, mumps, and measles will be measured in the subjects. There will be 150 subjects in the study, roughly 50 randomized to each group. Dr. Loeb will be looking at other measures of immunity as well.

Now, there’s nothing wrong with this study, as far as its design goes under the evidence-based medicine (EBM) paradigm. It’s a perfectly serviceable RCT looking at the response of a biomarker (in this case, measures of specific immunity) to an intervention. It’s just that Caulfield is correct. It’s a completely unnecessary clinical trial. Dr. Loeb has clearly fallen victim to methodolatry, which in medicine is the profane worship of the RCT as the only valid method of experimentation. Dr. Loeb states that his hypothesis is that “will be no different than placebo,” which is rather odd and makes me wonder how on earth he got funding for this study, as it’s uncommon for the hypothesis of a clinical trial to be that there will be no difference between the two interventions. After all, the purpose of clinical trials is usually to find a better treatment than standard of care or a treatment that is better than placebo.

Be that as it may, the second question I have is how this study got through the Canadian equivalent of the institutional review board (IRB); that is, the ethics committee overseeing clinical trials. The McMaster University IRB-equivalent truly messed up here when it gave its stamp of approval on this profoundly unethical clinical trial, as described in the STAT article:

Further, Caulfield argued that conducting the study may be unethical. His rationale: Research ethics require that there is what’s known as equipoise — scientific uncertainty — if a question is to be studied. There is no scientific uncertainty about nosodes, he insisted.

Loeb said he could find no previous study looking at whether nosodes triggered an immune response. And his arguments satisfied McMaster’s Institutional Review Board, which approved the study.

Dr. Ross Upshur, an ethicist and a professor at the University of Toronto’s Dalla Lana School of Public Health, disagreed with Caulfield on the issue of the study’s ethics — but agreed with him that regardless of the outcome of the study, it would not change the thinking of people who believe nosodes work.

Would he have approved the study if he had been on the McMaster review board? Upshur, who has conducted research with both Loeb and Caulfield in the past, said he could argue both sides of this debate, but said if pressed to make a call, he probably would have argued that the study wasn’t worth doing.

I argue more strongly than Caulfield: The study is unethical. Period. No doubt about it. Even Dr. Upshur seems to know that the McMaster IRB acceptance of the argument that there is no previous study looking at whether nosodes trigger an immune response was not appropriate, given that basic science alone is enough to show that homeopathic nosodes are utter nonsense. After all, he basically admitted that if he were on the McMaster IRB he would have argued that the study wasn’t worth doing. After all, there is a very small, but not zero, potential for subjects in the control group. Remember, this is a group whose members have, according to the trial protocol, already received their childhood primary DTaP and MMR vaccines and thus don’t need Tdap or MMR vaccine, to suffer a vaccine reaction. I suppose you could finesse their receiving the Tdap as their adult dose, but not the MMR. Then there’s also a small, but not zero, risk from receiving the homeopathic nosodes, which are not, strictly speaking, all water.

Basically, this is the very definition of an unethical clinical trial. There’s no expected benefit to the experimental group or, quite frankly, to the active comparator group, either. The control group is the only one without an expected risk is the control group. Even then, though, one can argue that receiving saline injections could result in a hematoma. That’s harm too. Granted, it’s small and not very likely, but it’s risk nonetheless. So, basically, 150 human research subjects are being subjected to varying degrees of risk for no benefit. Now, don’t get me wrong. Sometimes we do subject clinical trial subjects to low degrees of risk for biomarker studies, but we generally don’t do it when the hypothesis is that there is no difference between control and the experimental intervention. We do it for drugs for which we want to determine if they actually “hit” the molecular target, as determined by seeing the expected changes in biomarkers in either blood or tissue, the idea being to use this information to validate a promising drug and demonstrate its promise by proving that it does what it’s supposed to do on a molecular level before doing a large scale clinical trial.

Here’s a point Steve and I made in our article that’s relevant here:

Even so, the major assumption underlying EBM is that by the time an investigational treatment is ready for RCTs it has passed all preclinical tests and has thus demonstrated biological plausibility. Before, CAM or IM, treatments without biological plausibility and compelling evidence from preclinical studies and pilot clinical trials usually did not reach the stage of RCTs. Indeed, so integral to this process is biological plausibility based on preclinical data that the Declaration of Helsinki [8] states, ‘medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and adequate laboratory and, as appropriate, animal experimentation’.

Homeopathy fails that test. Miserably.

Steve Novella, I, and others like to refer to "science-based medicine" (SBM) instead of EBM, the difference being that SBM takes into account what EBM does not. EBM relegates basic science to the lowest rung on its evidence ladder or pyramid, which is not inappropriate when dealing with clinical trials of treatments that have some scientific plausibility. But when we're talking about magic like homeopathy, with as close to zero prior probability and plausibility as I can imagine, what RCTs are testing is basically noise and bias in the clinical trial process. I realize that it goes against the grain of scientists like Dr. Loeb and many others, for whom the RCT is the be-all and end-all of clinical research, ever to conclude that there is no need for an RCT. They just can’t accept that basic science alone can be sufficient to rule out the need for an RCT, even in the case of homeopathy, which is to me one of the best examples, if not the best example, of an alternative medicine treatment that is so ridiculously, incredibly implausible that RCTs of homeopathy can pretty much never be justified. Nor is this a justification:

Dr. Peter Palese, a renowned influenza researcher at the Icahn School of Medicine at Mount Sinai in Manhattan, also understands Caulfield’s concern. He calls homeopathy “hogwash.” But Palese noted that Loeb conducts first-rate research, and there has been little of that done on homeopathy.

“If a guy like Mark Loeb does it, it is a service to the rest of us,” he said.

Loeb acknowledged the true believers will not be swayed by the findings of a clinical trial. But he said he hopes to generate evidence that will provoke regulators to take a harder line on nosodes.

As you can see, Dr. Loeb is far from alone. At one level, I can understand the naïveté and idealism of scientists like Dr. Loeb and Palese. What I can’t understand is how, even when someone like Dr. Loeb understands that a negative result will not sway true believers, he persists anyway. After all, given how good he is, what is cost of his doing this clinical trial? Leaving aside the issue that this trial is a complete waste of money, there is also the opportunity cost of having a good scientist devote his time and attention to designing, carrying out, and analyzing the results of a clinical trial like this, particularly when he expects it to be negative anyway and is only doing it in the naively misguided belief that one more negative trial of homeopathy will sway Canadian regulators. What far more worthy scientific questions could Dr Loeb have investigated with the time and resources he is wasting to ask this pointless question about homeopathic nosodes?

One wonders if Dr. Loeb has considered one final question. What will he do if, contrary to his expectations, he finds an increase in the specific immune response to the various antigens he’s testing for in response to the homeopathic nosodes? His hypothesis is that there won’t be such a finding, and he hopes that finding will provide ammunition for Canadian regulatory authorities to ban homeopathic nosodes. It probably won't, because, as Steve Novella put it, if 200 years of science is not enough to convince someone that homeopathy is bunk, or to convince regulators, then one more study is not going to do it. Also, such a false positive result is not as implausible as one might think; Dr. Loeb should read some of John Ioannidis' studies, if he doesn't believe me. As I’ve explained time and time again, when you test treatments with very low pre-test probability and plausibility, false positives are far more common than you might think. Dr. Loeb “knows” that homeopathy is “bunk.” But what will happen if his study is one of those false positives?

As you might expect, I side with Caulfield, although I don’t do it for the main reason he objects, that doing studies of quackery like homeopathy somehow “legitimizes” it (although certainly that’s a significant concern). As a physician, I’m more concerned about the ethics of the clinical trial process and how doing such studies is profoundly unethical, as much as Dr. Loeb might delude himself otherwise. There are more than enough data to conclude conclusively that homeopathic nosodes are complete and utter nonsense. Further clinical trials are unnecessary. The trial that Dr. Loeb is doing is the very epitome of quackademic medicine. It's also an excellent example of the pernicious influence of quackademic medicine, which can tempt an otherwise excellent researcher to believe that it is worth doing a clinical trial of magic like homeopathic nosodes.

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Another problem is that the results will have no impact on homeopathy. I can just imagine Dana et al telling us that nosodes are ENERGY MEDICINE and exert their influence by acting on the WHOLE BODY and cannot be evaluated by as crude a test as measuring immune response which is a measure used to test ALLOPATHY. Unless, of course, there is a postive result from the noise, in which case Dana et al will herald it as a triumph for the miracle that is homeopathy.

It is really very sad that people just pin out holes in homoeopathy and turn a blind eye to the treatments of various chronic diseases that are cured by homoeopathy when all other schools of medicine fail.Why don't you put those goodness of homoeopathy?Homoeopathy was discovered by a very famous allopathic surgeon Dr.Samuel Hahnemann.I don't think he was that unintelligent...

By Dr. Pooja Rai (not verified) on 11 Oct 2016 #permalink

It seems to me that the study assuming no difference, might be used to bludgeon regulators or politicians, Otherwise it looks like waste time and money.

BTW who's funding this? Internal funds or grant? I find it hard to imagine most funding agencies would spend the money.

By jrkrideau (not verified) on 11 Oct 2016 #permalink

Perhaps I overlooked it, but I couldn't tell if the victi...excuse me...volunteers in this study are expected to be immunologically naive.

If not, then how does one determine the effects? I'm up-to-date- on my vaccinations; got the flu shot and pneumonia vaccine a week ago - tetanus and shingles about two years ago, and so forth. Would I show a higher level of serum antibodies than expected if I were in the Vaccinated group, or would I be a false positive in the placebo or homeopathy groups?

If they are, then this is clearly unethical, denying patients proper care merely for the sake of an experiment.

fusilier
James 2:24

They are not immunologically naive. In fact, they must have had their childhood MMR and DTaP vaccine series. Not having had these vaccines is in fact an exclusion criterion, if I remember correctly.

Perhaps I overlooked it, but I couldn’t tell if the victi…excuse me…volunteers in this study are expected to be immunologically naive.

Yes, inclusion criteria is receipt of childhood vaccines. They didn't list this but are subjects going to be pre-tested for antibodies? What are they going to do to assure purity and potency of the homeopathic nosodes? Commercially-available homeopathic preparations contain wildly varying amounts of the so-called active ingredients along with frequent contamination with active pharmaceuticals. All in all I agree that this is a waste of money and shouldn't be needed to convince regulators that homeopathy is bollocks.

By Science Mom (not verified) on 11 Oct 2016 #permalink

"As I’ve explained time and time again, when you test treatments with very low pre-test probability and plausibility, false positives are far more common than you might think."
Maybe you need to explain it again,cause that sounds like the prior affects the p-value.

There's a Canadian physician who already has done a lot of work showing nosodes do not work. Dr. Peter Nieman, a pediatrician in Calgary, wrote in 2014 ( sorry--the original isn't on the Calgary Herald web site, so here is my archive of it at http://tinyurl.com/h86q22u )

Other pediatricians have opted for education, hoping to convince parents to use the traditional vaccine schedule. I have honoured the wishes of a number of parents who asked me to check their child’s immunity following the use of nosodes; in 100 per cent of the cases, objective blood tests showed a lack of appropriate immunity.

Parents who get blood test results back showing that homeopathic vaccines have failed to provide sufficient immunity often leave my office disappointed. My analogy, which consistently resonates well with most of these parents, is that the use of nosodes is a bit like closing the front door of your house, but leaving the door unlocked, thus giving a false sense of security.

Seems it would be worth contacting (and a lot cheaper than an RCT) to contact Dr. Nieman and obtain a summary of his titer testing following nosode administration given he states a 100% (as expected) failure rate for nosodes.

By Chris Hickie (not verified) on 11 Oct 2016 #permalink

Yep. Even if it's unpublished, this case series could easily represent a pilot study that does not support the scientific rationale for Dr. Loeb's study and would thus undermine its rationale.

I am very tired this morning and had a moment where I thought they were studying homeopathic noodles. Perhaps I have hit on a new diet craze. Wash your food and drink the water. The more you dilute it, the more nutrients you get! All with no calories!

I've been victimized by spell checkers changing "nosode" to "noodle" without my noticing it. :-)

How well do antibody assays work in terms of quantitative repeatability? If a particular person is tested multiple times over a span of, say, a few weeks, is it reasonable to expect all of the tests to yield the same numbers with little variation?

On a related topic, a physician in Illinois had his license suspended for "giving patients vaccines with cat saliva, vodka" ( http://wgntv.com/2016/09/29/suburban-doctor-accused-of-giving-patients-… )--aka nosodes (not that the word "nosode" was used). What he appears to have been in trouble more with the medical board for was forging vaccine records based on the above link and also what was listed on the Illinois Medical Board page for why his license was suspended on 9/28/16:

based on unprofessional conduct, to wit: failure to properly administer vaccinations to pediatric patients.

Sadly it sounds like he's been doing this for many years.

Are nosodes illegal in the US? There are unfortunately a lot of search results for nosodes for animals being promoted by "holistic veterinarians".

By Chris HIckie (not verified) on 11 Oct 2016 #permalink

@ Chris Hickie, nosodes are not illegal in the U.S.

By Science Mom (not verified) on 11 Oct 2016 #permalink

Take to a ridiculous extreme, some homeopaths were known to take blood or bodily fluids from Ebola victims to make, in essence, nosodes, an incredibly dangerous thing to do, not just for the patient being possibly exposed to Ebola but for the homeopath stupid enough to handle actual bodily fluids from Ebola victims without proper training and, one worries, proper protection.

I agree that Ebola is a ridiculous extreme, but the process in general sounds like something only would-be Darwin Award winners should be involved with, either in manufacturing, administering, or as a patient.

Yes, the McMasters IRB, if there is one, dropped the ball here. One also wonders whether the Canadian equivalent of the NIH has an agency comparable to NCCAM (or whatever they are calling it these days). Funding agencies usually don't spend scarce research money on proposals to verify null hypotheses, but maybe the Canadian CAM office didn't have anything better to spend their money on.

By Eric Lund (not verified) on 11 Oct 2016 #permalink

@2: It's true. Homeopathy is a sure fire cure for thirst. Since they use homeopathic water, it's piss useless, and likely dangerous, to try and use it to cure dehydration. None of that applies of course if they condense the magic, err I mean homeopathic water, down into a sugar pill. In that case I guess you could use it to counter-act excess insulin.

By Anonymous Pseudonym (not verified) on 11 Oct 2016 #permalink

Another problem is that the results will have no impact on homeopathy. I can just imagine Dana et al telling us that nosodes are ENERGY MEDICINE and exert their influence by acting on the WHOLE BODY and cannot be evaluated by as crude a test as measuring immune response which is a measure used to test ALLOPATHY.

Moreover, it doesn't take a very long perusal of, say, the comments at AoA to determine that antivaccine nuts don't "believe in" levels of neutralizing antibodies as a measure of immunity. Unless one is trying to avoid a vaccine requirement, in which case they're dandy.

@ 16 Eric Lund
Health Canada has the Canadian Institute of Health Research that doesn't have a NCCIH per se, but does accept complementary and alternative methods as acceptable criteria for research funding. There is also an Interdisciplinary Network for Complementary and Alternative Medicine Research (INCAM) whose website prominently displays the Health Canada and CIHR logos. The current head of INCAM is Heather Boon, the dean of pharmacy at the University of Toronto. We've met her before involved in questionable research of woo.

"Loeb said he could find no previous study looking at whether nosodes triggered an immune response. And his arguments satisfied McMaster’s Institutional Review Board, which approved the study."

I'm guessing there also aren't any previous studies looking at whether slapping people with fish triggers an immune response. Maybe he should study that as well.

By tonylurker (not verified) on 11 Oct 2016 #permalink

Whoa, whoa, whoa. Who told you about the Thorson Protocol for piscene therapy? That's proprietary information! I'm going to sue!

By Mark Thorson (not verified) on 11 Oct 2016 #permalink

@7 rork
When we know something about the experiment in question, it turns out that p-value (a "frequentist" method) is not always the most appropriate thing to look at. Consider the following example:
Given a set of drugs, of which 1% works and the other 99% doesn't. Suppose we test the drugs and say they work if there's at most a 5% chance that a useless drug would have gotten a result that good by chance (this is the definition of p<0.05). Let us further allow, generously, that a drug that works is identified correctly 100% of the time.
Now, in the frequentist world, we run an experiment, the result says it works, and we assume it's correct because there's only a 5% chance we'd have gotten such a result if the drug didn't work. The Bayesian, on the other hand, notices that if we had run the test on all the drugs in the set, we would have identified (1.0)*1%+(0.05)*(99%)=5.95% of the drugs as working, out of which only 1% actually works. In other words, a drug that was identified as working by the test has only a 1/5.95=16.8% chance of actually working; not a great seal of approval, by any stretch of imagination.

The reasoning above also applies to, for example, screening for rare diseases in the population, which Orac writes about at great length.

*"Frequentist" and "Bayesian" is not a distinction in reality. Any statistician would apply whatever method they judge to be the most appropriate for the problem at hand.

One major problem with this study is that many homeopaths admit that their 'nosodes' do not elicit an immune response, thus no elevated antibody levels are expected in the homeopathy group -- much in the same way that homeopaths admit that their 'remedies' do not contain even a trace of an active substance.
The claim is that the immune system is somehow 'made aware' of the pathogen in a homeopathic way, i.e. through means that elude scientific detection. So even the measurement method in this trial would be useless, at least according to homeopaths.
Here, the best trial indeed seems to be an abandoned trial. There already is a huge body of evidence showing that nosode homeopathy does not work, e.g. this bit of Insolence, dating back from 2010. In the meantime, it seems that even mr. Isaac Golden himself discovered to his dismay that previously 'immunized' Cubans contracted leptosirosis in much the same numbers as before his experiment (can't readily find the link, though).

@ 2, dear mrs. Pooja Rai,
Mr. Hahnemann was not unintelligent in his time, where personal observation was about the best method a medical researcher could rely on for establishing treatment efficacy. Yet even then, it quickly became clear to the rest of the scientific world that mr. Hahnemann suffered from multiple chronic conditions affecting his good judgment, specifically self-delusion, an overactive fantasy, a lack of critical thinking, and an unwillingness to acknowledge evidence contrary to his beliefs, among others. You may also want to look at the Nuremberg salt test of 1835 for an early but very thorough trial utterly discrediting the very foundations of homeopathy. There is, of course, vastly more evidence for the notion that homeopathy cannot cure anything, and is literally a placebo: "I shall please". A homeopath's only true service is personal attention, making their customer feel good. Now 'feeling good' can of course mean that a headache or other unpleasant sensation is 'cured', but that is about as far as homeopathy can cure anything.

when you test treatments with very low pre-test probability and plausibility, false positives are far more common than you might think.

Hmmm. What does that even mean?

‘The plain fact is that 70 years ago Ronald Fisher gave scientists a mathematical machine for turning baloney into breakthroughs, and flukes into funding. It is time to pull the plug.’

https://aeon.co/essays/it-s-time-for-science-to-abandon-the-term-statis…

Totally OT but seriously ( I have to leave to attend to my other...er..literary duties... )
*Pardonez moi, s.v.p.*
(AND someone has to do it so why not me?)

In my continuing series concerning the political escapades of woo-meisters - since 2008 or so-
loons Null and Adams ( prn.fm show and Natural News) today continue in their attempts to woo Trumpsters and other reality deniers.
I surmise that they express sentiments in agreement with the
anti-everything crowd in order to attract their business.
Perhaps they sense a linkage in various forms of gullibility.

By Denice Walter (not verified) on 11 Oct 2016 #permalink

They'll just fall back on the "individualized treatment" excuse.

By Christine Rose (not verified) on 11 Oct 2016 #permalink

Given a set of drugs, of which 1% works and the other 99% doesn’t. Suppose we test the drugs and say they work if there’s at most a 5% chance that a useless drug would have gotten a result that good by chance (this is the definition of p<0.05).

Only in the sense that the null hypothesis is known to be "true" in this case.

@ 27, Christine Rose

They’ll just fall back on the “individualized treatment” excuse.

Well, the funny thing is that in this particular practice of homeopathic prophylaxis, their vict er, 'patiënts' all get given identical nosodes in identical quantities. Which is not surprising, of course, since even according to homeopathic principles, there are no symptoms to treat in a healthy person, so no personalized symptoms either, thus no personalized treatment.
(not to mention the fact that many homeopaths reject this whole notion of 'nosodes' for much the same reason, i.e. that homeopathy should not be applied when in a state of good health).
It really is a very convoluted, messy belief system, with almost more inconsistent 'explanations' made up ad hoc than in, say, creationism.

Sounds like tongue clucking to me, since you folks are already over 90% of the way to homeopathy yourselves. Seriously.

I suspect that if the MDs gave lots more vitamin C and D, pre- and post vax, preferably along with an enhanced daily formula, you'd have less reactions with the kids and less resistance from the parents.

@25 Gilbert
I respectively disagree with the article you linked. The term "statistical significant" is only a problem if people see a result that is "statistical significant" at whatever significance threshold was chosen for the paper and call it a day. This problem arises from a misunderstanding of mathematics, which would pose an issue no matter what method they are using.

@28 Narad
I'm not sure I follow. In hypothesis testing, we start out assuming the null hypothesis is true and ask "how likely are we to get a result as extreme as the one we got?" The answer is the p-value and we reject the null hypothesis if the p-value is less than whatever we are willing to accept (the significance threshold); i.e. the result is too extreme (unlikely) assuming the null hypothesis.

I suspect that if the MDs gave lots more vitamin C and D, pre- and post vax, preferably along with an enhanced daily formula, you’d have less reactions with the kids and less resistance from the parents.

And I suspect that you have pulled this idea out of your nether regions. There has been lots of talk of vitamin C being a wonder drug, but actual studies do not support the idea. The vitamin D suggestion is new to me, but one danger here is that, since vitamin D is fat soluble, it may be possible to overdose (I know that vitamin A toxemia can and does happen--vitamin A is also fat soluble).

By Eric Lund (not verified) on 11 Oct 2016 #permalink

In hypothesis testing, we start out assuming the null hypothesis is true and ask “how likely are we to get a result as extreme as the one we got?”

That's pretty much how I understand it. The point of significance testing (whether p-values or other method) is to rule out the null hypothesis. The p < 0.05 threshold is commonly used as a compromise between the available statistical power and the desire to minimize false positives. It is not by any means a universal standard: some fields set higher thresholds, mainly because they can. For instance, particle physics requires a 5σ significance (for comparison, p < 0.05 is about 2σ) to accept a phenomenon as real. They have been burned by too many false positives at the 3σ level. But particle physicists can afford to repeat their experiments enough times to insist on that level of significance. Medical doctors, and other fields that tend to study human subjects, can't get that kind of statistical power, so they have to accept a higher risk of false positives.

The thing to be careful of is that it is never possible to disprove the null hypothesis; one can only estimate a nonzero, but hopefully small, probability that the observed results are consistent with the null hypothesis.

By Eric Lund (not verified) on 11 Oct 2016 #permalink

@ 30, prn:

I suspect that if the MDs gave lots more vitamin C and D...

Erm, you mean as in how this kid was 'treated' with vitamin D?

you’d have less reactions with the kids and less resistance from the parents.

Erm, exactly what reactions are you referring to, and what resistance from the parents do you mean?
Do you suggest that children suffer significantly more and more serious adverse reactions from vaccination than the known and accepted side effects? Can you substantiate that with e.g. scientific research?
And do you suggest that kids should be administered unnecessary vitamins and supplements in conjunction with their scheduled vaccinations in order to accommodate or soothe their parents' belief in antivaccination myths? This is exemplary of the way CAM folk try to sneak pseudoscientific nonsense into proper medicine, one step at a time...

prn @30: Of for pity's sake, we're not talking about vitamins! If you're so into mega-dosing go eat a polar bear liver (whole thing!) and get back to us after.

Seriously, the idee fixe thing is starting to bug me.

(Actually, no, please don't eat a polar bear liver. If acquiring one doesn't kill you eating it will.)

By JustaTech (not verified) on 11 Oct 2016 #permalink

JT@35
What, you want to grow a Ni-Cd battery substrate with PCBs in your liver?? Or get high on retinol ? If polar bear hunting reflects some secret desire, remember, meals are free in the federal detention system...
----
JT, you have rather old, fixed ideas about vitamins. I would encourage you to look at some papers from the last 20 years that examine higher vitamin D dosages in light of earlier MSM errors in fact and applications. The old 200 iu vitamin D RDA, now creeping up to 600 iu per day, is, and has been, a disaster for many people. There are other threads to follow on therapeutic levels of vitamin D3 about excesses of calcium supplementation, deficiencies of magnesium and menatetrenone.

Consider this:
- A Canadian pediatric endo society endorsed even over 1000 iu for infants (age/wt based) to achieve adequate to optimal blood levels. http://www.cps.ca/documents/position/vitamin-d
- Advanced CRC cancer patients, a substantial percentage need 10,000 - 20,000 iu per day just to normalize their blood levels around 30-32ng/ml. A lot of them were in the less than 2 to 10 ng/ml range when tested for vitamin D.

RichardR
Why accept the "...accepted side effects" if you can do better?

Back in the 1800s surgeons "accepted" surgical infections, and even wanted the right kind of infection (different colors) asap in order to be considered a successful surgery.

Your other comments suggest you are pretty clueless about what can be done with C, D3 and other parameters. The literature is thin but growing. It reflects a reality that most here are n=0, both in personal experience and w.r.t. literature.

And I suspect that you have pulled this idea out of your nether regions.
Others - MDs, parents and nutritionists have suggested, and practiced several variations.

There has been lots of talk of vitamin C being a wonder drug, but actual studies do not support the idea.
The purported studies seem to always fall far short of the reported therapeutic ranges w.r.t. to time and formula concentrations.

You know, one of the reasons individuals thumb their noses at "skeeptics" is that in many cases, they are able to routinely and reliably achieve physiological changes in minutes to hours, not days, consistent with earlier reports for acute conditions. Chronic diseases are longer and more complicated, although often successful too.

The vitamin D suggestion is new to me, but one danger here is that, since vitamin D is fat soluble...

By far, the primary concern is calcium toxicity. Most people, with requisite magnesium and menatetrenone intake, avoiding calcium supplementation can take stupendous doses of vitamin D3. 50,000, even 100,000-300,000 iu per day for several years are matters of simple historical record and trials, even without the Mg-K2 fortification.. It is the willy nilly supplemental calcium that is considered a science based problem in CAM.

oops. add addressee

JustaTech: "(Actually, no, please don’t eat a polar bear liver. If acquiring one doesn’t kill you eating it will.)"

I laughed out loud... but very quietly, dear hubby is trying to sleep.

@ Eric
Statistics make sense only if integrated in the scientific method. If your hypothesis says that you are expecting a specific result, as a scientist, you should be able to discard it if the experimental data go against it, but in this case you will have hard time to publish. If you are not able to discard your hypothesis, there is always one way to find an experimental set in agreement with your hypothesis, but it takes more time, and your hypothesis is dubious.
On the other hand, if you don’t have any hypothesis, you can build the hypothesis in agreement with the data and have a good chance to publish. Either there is a statistical threshold that is reached, most likely by chance, or you endorse the fallacy of the conclusion that there is no difference when p is greater than 0.05 (confusing statistically not significant with absence of difference). In any case you have a paper you can submit.
Doing science is being replaced by the ability to get fundings to collect data, with the belief that they speak for themselves.

By Daniel Corcos (not verified) on 11 Oct 2016 #permalink

@prn

I have always been curious of the Vitamin A,Vitamin D, Vitamin K, and Calcium dynamic.

I personally think that the RDAs for Calcium and Vitamin A are set too high thanks to the political maneuvering from the Dairy Industry. It seems likely that the Vitamin C RDA is set too low as well.

Could you elaborate on how Vitamin D effects Calcium? I want to know how much Vitamin D to take.

By James Crawford (not verified) on 11 Oct 2016 #permalink

Could this study be a subtle vax vs unvax one. After all, one group Injected with saline, t'other with a dirty vaccine...?

@37, prn:

Why accept the “…accepted side effects” if you can do better?

The thing is, can you do better? Vaccines are already physiologically matched in terms of pH and ion concentrations to keep tissue damage and discomfort from the injection to a minimum. To my knowledge, there is no evidence that administering vitamins further reduces side effects, e.g. those caused by the immune response, nor is there a plausible mechanism why an extra dose of vitamins would have any effect in that respect in a healthy individual. Or do you have evidence to the contrary? Routinely administering unnecessary vitamins is orthomolecular quackery, not good medical practice, regardless whether it is basically harmless or not.

@23: I understand about the issues of multiple testing, and false discovery rates. It was not the point I was making. I am saying that under the null, p-value will be less than P exactly P of the time, and how likely I believe that null to be or not doesn't affect that (cause I'm conditioning on the null when I compute a p-value). Orac's expected come-back would likely be that people with very outlandish alternative hypotheses do stuff like repeat the experiment and only publish the ones that looked like they worked (so they get to announce that p was less than P more often - publication bias).
I agree with your later comment, and raise you: That author is boring, and perhaps self-mystified, and certainly self-aggrandizing. You can see him toot his horn on blogs like this. Rarely has so little been said with so many words in such a muddled way.

@33 Eric Lund
I like your point about never being able to disprove a null hypothesis. As many of my science teachers/professors have said, proofs only exist in the realm of mathematics. What we are doing in science can probably be thought of as a search for "truth", where the search process is heavily constrained by time and funding. Consequently, we need to aggressively prune branches of the search that doesn't show great promise. Any threshold value we use for pruning is going to be arbitrary to some extent, and it lies on the shoulders of practitioners skilled in the art to say "they had p=0.01 here, but the design of the study was junk and it doesn't say what it does" or "p-value was only 0.80, but the data was really noisy and they were only able to collect a small amount of it. I wouldn't call it a wash yet."

@42 Daniel Corcos
I agree with most of your points, but I believe that sometimes it is useful to conduct observational studies with no prior idea of what we would find. For example, in a scenario where an extremely well-established theory seems to be contradicted by data. We are unable to tell whether we are being too naive in our reading of the theory (i.e. the theory can explain the observations using emergent properties that arise out of interactions of complex systems) or if there are previously unknown processes at play. Well, in this case, we have to start somewhere.

That said, I have once seen a paper make both of the mistakes you describe at the same time. First the protocol writes overestimated the power of their design, then they engaged in subgroup analysis to try to salvage the sunk cost.

prn @36: The point I was attempting to make in my joke about polar bear liver is that polar bear liver contains sufficient vitamin A to cause death by vitamin A toxicity, if you were to eat the whole thing. You are such a proponent of huge amounts of vitamins, I was curious to see if you would acknowledge the possibility that there is such at thing as too much of a vitamin.

As for the Canadian pediatricians and infants: it's not like you can take those babies out into the sun to make vitamin D for most of the year in most of Canada, right? So of course they are going to need to get it some other way.

Again, you are so fixated on this vitamins thing, you're not capable of having a conversation about the topic at hand (homeopathy and clinical trials).

By JustaTech (not verified) on 12 Oct 2016 #permalink

I just clubbed this baby polar bear and ate some of its' liver; Is that why I can't get my celebratory junk up?

By sullenbode (not verified) on 12 Oct 2016 #permalink

Yeah. Someone should tell Hanibal Lector that Chiante can actually exacerbate Hypervitaminosis A.

By James Crawford (not verified) on 12 Oct 2016 #permalink

@prn

Thanks for that link! Vitamin D seems to be one of the most underappreciated vitamins/hormones.

I also found out today that the INTERSALT Study found a tribe of native Brazilians who only consume 12% of the RDA for sodium.

They remain in sodium balance.

The RDA for sodium has been grossly overestimated. In one study, people kept for 12 hours per day in a 104 degree sauna (sweating bucketloads) maintained sodium balance at 1.5g (the RDA).

They didn't measure if this was possible on a lower sodium intake, but it seems likely. Natural food has all of the sodium we need, but the salt cultists continue with their stupid "animals seek salt-licks" and "we need salt" arguments.

Absurd.

The RDA was set very generously, as can be seen in this book written by the very people who set the RDA: https://www.nap.edu/read/10925/chapter/8#365

I am going to read the chapter on Vitamin C next.

By James Crawford (not verified) on 12 Oct 2016 #permalink

@28 Narad
I’m not sure I follow.

I was getting a whiff of the base-rate fallacy.

but the salt cultists continue with their stupid “animals seek salt-licks” and “we need salt” arguments.

The 80's called, they want their buffon back.
Next you are going to tell us to avoid sugary food and alcohol.

Mainstream physicians have been warning their patients about the danger of too much salt in food like, forever.
Also, loss of electrolytes is a real concern for sport people.

By Helianthus (not verified) on 12 Oct 2016 #permalink

@Helianthus

I know. Some people haven't got the memo yet. You tell them that 99% of land mammals cannot possible get the RDA for sodium and bring up the stupid "salt-lick" gibberish. I have yet to see an exposed salt-formation anywhere besides Utah.

I am just venting. I have been dealing with absurd arguments on this matter for way too long. It's almost like listening to apocryphal Lemming stories the way they describe how wild animals covertly obtain large amounts of sodium through these hidden salt deposits.

High Potassium intakes can attenuate the hypercalciuric effect of high sodium intakes, and even more so when it is given as the carbonate salt.

By James Crawford (not verified) on 13 Oct 2016 #permalink

@James Crawford: you'll get my salt when you can pry it out of my cold, dead, hands. I happen to LIKE the taste of salt on my food. (I hate salt water - go figure) but do very little cooking with it.

Studies have shown you use less salt when you apply it after cooking, so the taste buds can sense it. So even though I seem to eat a lot of salt, in reality, I don't. (I don't eat a lot of processed foods that contain salt; I do a lot of cooking from scratch because I like to cook).

James Crawford, thanks for your link to the Academies Press site. Looks like some interesting reading there. I really appreciate internet library resources.

JT@50...Again, you are so fixated on this vitamins thing, you’re not capable of having a conversation about the topic at hand (homeopathy and clinical trials).

The infinite dilution theme on homeopathy is far more repetitive here than me. Pretty boring. It seems to aimed to politically discredit all other subjects on some theory that one anachronism falsifies all. However part of the licensed homeopathic MDs venue seems to concern nutritional therapies - herbals and various nutrition. So I think the perpetual focus on the watered down goods part can be misleading.

FYI, yes you can overdose on different kinds of vitamins, particularly under some conditoins. Some forms that have been sold before, have been particularly inferior or defective. Vitamin A and caratenoid precursors are an area of concern for form, amounts, overdose, conditions, and opportunties.

The problem here is that some have very little understanding about the therapeutic opportunities and the conditions to achieve them. This accompanied by various phobias, myths, attacks or adversarial comments. I do appreciate a good discussion that uncovers something new, I've kind of been missing Kerbiozen.

RichardR@46: is there a plausible mechanism why an extra dose of vitamins would have any effect in that respect in a healthy individual.
A large dose of vitamin C can address excess histamine and febrile patients. Vitmain D modulates pro inflammatory cytokines.

"I think the perpetual focus on the watered down goods part can be misleading."
If a discipline can't admit the absurdity of one of its core planks, then clearly we can't expect anything else produced by that discipline to be reliable.

"I agree that Ebola is a ridiculous extreme, but the process in general sounds like something only would-be Darwin Award winners should be involved with, either in manufacturing, administering, or as a patient."
All users of Homeopathy are potential contenders for a Darwin Award. Placing a belief in magic above a belief in the scientific method exposes them all to the chance of coming into contention.

By Craig Thomas (not verified) on 16 Oct 2016 #permalink

Oh, dear G-d, I thought my opinion of extremely short tenured AAAS publisher Kent Anderson couldn't fall any lower, but over at the inaptly titled "Scholarly Kitchen," while responding to Jeffrey Beall, he's delivered an imbecilic defense of Elsevier's Homeopathy:

Let’s talk homeopathy. I am not a fan, but studying homeopathic treatments is not necessarily pseudo-science. With 200 million people using homeopathic treatments, understanding the possible risks, emerging trends, and emerging approaches can be important, especially to practitioners with patients using them. The worst thing is to stigmatize it, because then you drive it underground. Better to study it and at least acknowledge it and deal with the risks and trends in a scholarly and scientific manner.

Narad: That sounds like a reason to study pop music, or fashion, or social media, not 'medicine'.

By JustaTech (not verified) on 19 Oct 2016 #permalink

That sounds like a reason to study pop music, or fashion, or social media, not ‘medicine’.

You don't want to get me started about some of his of other misadventures, one of which was downright creepy. At least he's no longer one of the regular "chefs" (the purported reason for his quick departure from the AAAS was the commute, which seems like something one would take into account beforehand).

The worst thing is to stigmatize it, because then you drive it underground.

If popular delusions and scams can be so easily driven underground by stigmatising them, then BRING ON THE STIGMATA.

By herr doktor bimler (not verified) on 19 Oct 2016 #permalink

Better to study it and at least acknowledge it and deal with the risks and trends in a scholarly and scientific manner.

So all these studies failing to replicate water's memory or showing that homeopathy drugs work no better than placebo don't exist.
Also, I'm confused. Shouldn't be saying "it's not working, and sometimes the product is dangerously not diluted enough to be safe" be a big part of "deal with the risks and trends"?

By Helianthus (not verified) on 20 Oct 2016 #permalink