Tumexal: Wonder Drug or Snake Oil?

Posted on March 26, 2014 by skeptvet

Introduction

Cancer is a common disease in our pets just as it is in humans, though not necessarily for the reasons often claimed by proponents of alternative medicine. While there are certainly environmental triggers for many cancers, smoking being a classic and important example, it is not an established fact that we are facing an epidemic of cancer because we live in an “unnatural” and “toxic” environment.

For one thing, some toxic causes of cancer are actually less of a problem than in the semi-mythical “old days” before industrialization and modern science. Not too many chimney sweeps are getting scrotal cancer from soot these days, thanks to the identification and control of this risk through scientific research. And stomach cancer rates have fallen dramatically since the early 20thcentury, possibly due to less reliance on salting and smoking meats for preservation and the increased availability of fresh fruits and vegetables in urban areas, both consequences of technological advancement.

Perhaps more importantly, cancer is clearly a disease most often associated with old age, and one reason we see so much of it in humans and in our pets is that we, and they, and not dying as young as we used to of other things, like infectious disease and malnutrition.

Nevertheless, cancer is still a serious problem in our pets, and one which is being intensively studied in an effort to find effective prevention strategies and treatments. Again in contrast to the simplistic and inaccurate characterization of science-based cancer therapy, the reality is that there are effective therapies for many cancers, even cures for some, and these therapies consistently improve the length and quality of patients’ lives. Sure, we are a long way from preventing and curing cancer with the kind of success we’ve had preventing and curing infectious diseases, but the best hope for getting there is good, rigorous science.

Unfortunately, for individuals with pets who have cancer and who either don’t have good results with existing science-based therapies, or who are afraid of them due to the propaganda from proponents of alternatives, there are all too many untested snake oils freely available. There are far too many for me to evaluate them all, but occasionally I am asked to look at a specific product, and I feel it is important to remind desperate pet owners that even in the face of a terminal disease for which there is no proven cure, gambling on some concoction from the internet is risky. While it is not impossible that some of these products may work, it is less likely than the folks selling them would have you believe, for reasons which I will discuss.

And it is absolutely possible to make a bad situation worse with an untested treatment. Human patients with pancreatic cancer, which is highly aggressive and for which there are no truly effective conventional therapies, have unfortunately demonstrated this danger for us. Subjected to a bizarre diet, untested supplements, and coffee enemas under the Gonazalez cancer regime, these patients not only did not live as long as those on conventional therapy, they had significantly worse quality of life. Even in a situation where it seemed like they had ”nothing to lose,” a quack cancer therapy made these patients’ remaining days fewer and more uncomfortable than standard care. This is always a risk, for us and for our pets, with unproven treatments no matter how many testimonials and anecdotes companies give us to suggest their treatments are safe and effective.

An example of just such an untested therapy is Tumexal™.

What Is It?

As was the case for the equally “miraculous” and unproven kidney failure treatment RenavastTM I wrote about recently, the short answer is “Who knows?” Once again, the company selling this product refuses to disclose what it contains. This is a key warning sign for snake oil, and it is a clearly unethical way to promote a medical therapy. It is hard to imagine the public tolerating a pharmaceutical company trying to sell us a drug not only without any clinical studies to show it is safe and effective but without even disclosing what is in it, yet for some reason people tolerate this from companies selling mystery potions like TumexalTM. It is also, as the American Veterinary Medical Association (AVMA) Principles of Veterinary Medical Ethics states, unethical for veterinarians to foist such nostrums on their clients:

It is unethical for veterinarians to promote, sell, prescribe, dispense, or use secret remedies or any other product for which they do not know the ingredients.

Does It Work? Is It Safe?

The company has published a Powerpoint presentation claiming to explain the “science behind TumexalTM.” This presentation spends a lot of time describing one of many pathways to cancer formation, involving inactivation of the p53 tumor suppressor gene. The author then claims that TumexalTM stops cancer by inhibiting an enzyme called G6PD and that it “duplicates p53 function.” Without knowing what the substance is and with no published data showing if or how it does this, the truth of this claim cannot be evaluated. A recent published scientific paper discussing G6PD suppressors, however, does state ”To date, only a few G6PD inhibitors have been available. However, adverse side effects and high [concentration needed for a significant effect] hamper their use as therapeutics and basic research probes.” This argues against the claim that this company has found a perfectly safe and effective G6PD suppressor that the rest of the scientific community doesn’t know about.

Of course, the company behind TumexalTM has an explanation for why they have succeeded where the rest of the biomedical industry has not:

How is it that the scientists of CanineCare.US have come up with a treatment like Tumexal™, and not one of the big pharma drug houses?…Big pharma scientists are encumbered by a business model that insists in an absolute manner that every drug put into active development have billion dollar sales potential…Tumexal™ is a natural product for which a new composition of matter patent is not possible. But since CanineCare.US scientists are focused not on sales potential, but rather upon using cancer biology discoveries most effectively, we have been able to make progress far out of proportion to our numbers. Tumexal™ may never be a billion dollar drug, but it very well could help more dogs than all the billion dollar drugs of all the big pharma companies combined.

In other words, money-grubbing pharmaceutical companies have ignored the potential of safe and natural cancer treatments because they fear they won’t be able to patent and make any money off of them, but CanineCare.US is far more altruistic and doesn’t care about profits but only about making life better for your dog.

This is a common, and in this case completely incredible, explanation for the supposed story of a lone genius discovering a wonder drug. For one thing, there is plenty of profit potential in unpatentable “natural” products, which is why dietary supplements and herbal medicines are a multi-billion dollar industry that Big Pharma is actively interested in participating in. For another, the owner of this company, Jonathan Nyce, has already been a lavishly compensated CEO of a multi-million dollar pharmaceutical company, Epigenesis Pharmaceuticals, which forced him out when the supposedly revolutionary asthma drug he was developing failed to prove viable.** So the idea that pure altruism has motivated CanineCar.US to produce a wonder drug that the rest of the biomedical industry could not have found due to a blind pursuit of profit is not believable.

There are plenty of other warning signs of snake oil associated with this product. It is advertised primarily by sowing fear and distrust of conventional cancer therapy, exaggerating the dangers of chemotherapy, surgery, and radiation and completely ignoring the manifest benefits of conventional treatment. The slide show touting the product has all sorts of pictures of soldiers in WWI suffering the effects of chemical weapons and implies that because some chemotherapy drugs were developed based on these compounds that chemotherapy is merely “poisons as cancer medicine.”

The logic here is as flawed as it is simplistic. Smallpox and polio vaccines are made from smallpox and polio viruses, so are they simply “infections” the way cancer drugs are “poisons,” doing more harm than good? Many antibiotics are derived from bacteria and fungi, so are they automatically harmful “molds” with no real benefits? Of course not. Such therapies have dramatically reduced suffering and death for millions of people. The source of the medicine does not tell us anything about the balance of risks and benefits of the medicine itself. Only good scientific research can do this. Such research tells us what the pros and cons of cancer medicines are, but there is no such evidence to tell us the risks and benefits for TumexalTM.

Another red flag of quackery for TumexalTM are the claims of dramatic benefits with little to no risk.

TumexalTM : Effective, Safe Monotherapy for virtually all forms of Canine Cancer

Tumexal™ is also remarkable for its lack of harmful side effects. Unlike standard chemo drugs that can significantly reduce the quality of life in a treated dog, Tumexal™ is virtually toxicity free because of its novel mechanism of action.

And with Tumexal™ there is virtually no toxicity! In fact, Tumexal™ will almost always restore a cancer-stricken dog’s appetite, spirit and energy!

Such claims are always unlikely to be true, but when presented in the absence of any evidence and with a refusal even to disclose the ingredient in the drug, there is simply no reason to take them seriously at all.

The Powerpoint Dr. Nyce has produced to sell the product does claim there is scientific research evidence that TumexalTM is effective, but this is highly suspect for several reasons. The evidence consists of a series of charts purporting to show laboratory beagles with cancer induced by researchers using toxic chemicals and then treated with TumexalTM or nothing. Invariably, they show that Tumexal works. Here is one example:

tumexal ppa chart

There is no evidence these experiments were ever published, or done at all for that matter. They also raise ethical questions about the use of these animals for fatal experiments since there is no information about the conduct of the studies or the care of the subjects, and since the studies were apparently never published to make the data useful to the scientific community but instead are used merely to promote a commercial product.

Dr. Nyce attempts to head off objections to these experiments by claiming “this work was done several decades ago using animals scheduled for destruction by animal control” and he “wouldn’t have the heart” to do this work today. Apart from the fact that this statement seems as implausible as the data themselves, it begs the question of why TumexalTM has only recently been developed, and only by Dr. Nyce, if  extensive and costly research from decades ago produced such dramatic data that it is a potentially effective therapy for many cancers? Who did this research? Why was it not followed up? How was Dr. Nyce involved, if at all? Why was none of the data published?

All of this is highly suspicious, but of course impossible to evaluate objectively since the company does not provide any of the usual information, in the form of published research or regulatory documents, by which the value of potential new cancer therapies are judged.

What CanineCare.US does provide, of course, are testimonials, the sine qua non of quack therapies. Undoubtedly, people will comment on this post by saying I can’t prove TumexalTM doesn’t work, and lots of anecdotes show it does so what’s the problem? The problem, of course, is that such anecdotes and miracle stories prove nothing. They are available for every therapy ever invented, including many which have been definitively proven not to work, and they are deeply misleading. A responsible scientist and company generate and provide scientific data to show their products work, rather than simply posting heartwarming and meaningless anecdotes.

The defenses provided by CanineCare.US for their unproven claim, use of testimonials instead of data, and secrecy are self-serving and unconvincing. They amount to just a repetition of their claims, with no actual evidence provided, and snide denigration of the rest of the biomedical industry and anyone not willing to take the company at its word alone:

Very few people who have tried Tumexal have been disappointed in its results… It can extend life, and maintain a high quality of life, sometimes in dramatic fashion. It is important to note that every testimonial on our website is an authentic, unsolicited report from an owner whose dog has been treated with Tumexal. When cynics say that these testimonials are “too good to be true,” they are merely comparing them with the results they are accustomed to with traditional chemotherapy, or no treatment. In comparison, to such a cynic, the results obtained with Tumexal may indeed appear “too good to be true.”

A patent is not possible for Tumexal, because it is a natural product that nature, not us, synthesized… As a natural product for which a NCM patent is not possible, Tumexal must be protected by trade secret law. This is why we do not disclose what it is, except to say that it is natural.

So once again, we should believe TumexalTM is a wonder drug without any evidence other than the claims of the company selling it and the testimonials they choose to put on their web site because they are goodhearted people focused on making pets healthier rather than making money and the product is “natural.” Anyone who asks for more than this is a “cynic” who, by implication, doesn’t care about the welfare of pets or is beholden to Big Pharma. A finer modern example of snake oil could not be found. And it is worth remembering, the product from which the term “snake oil” likely derives didn’t work, and didn’t actually contain any snake oil! CanineCar.US and Dr. Nyce have given us no reason to think any better of TumexalTM.

Bottom Line

TumexalTM is yet another purported wonder drug with a “secret ingredient” that has been discovered by a lone genius and offered to the public out of altruism. It is supposed to be very effective and perfectly safe, and anyone who doesn’t take the company’s word for this is a “cynic” with questionable motives or a lack of compassion. Such claims are cheap and easy to make, but they are worthless without real scientific data, and none are available for TumexalTM. While it is impossible to prove it doesn’t work based on the nothing the company will tell us about it, it is not the job of skeptics to prove such wild, implausible claims untrue. It is the job of those who make them to prove they are valid. Anecdotes aren’t data, and cannot be used to prove a medical therapy is safe and effective. So to date, the company expects us to buy their product and administer it to our ill pets based only on their word for the safety and effectiveness of TumexalTM. Does this seem like a good idea?

And while the lack of definitive evidence against TumexalTM makes it impossible to assert it is ineffective, that doesn’t mean it can be assumed to be safe. Unproven remedies are as likely to hurt your pet as to help them, especially when substituted for real medicine. And even in the face of a disease as terrible as cancer, it is possible to make your pet’s life worse by rolling the dice on a snake oil like TumexalTM. If your pet has cancer, please see a veterinarian, ideally one specializing in cancer care. There really are beneficial treatments available even when there isn’t a cure.

If you are looking for information about pet cancer on the internet, watch out for snake oil peddlers. Here are some real experts with real information for you if your pet has cancer:

Veterinary Oncolink, University of Pennsylvania
Pet Owner’s Guide to Cancer, Cornell University
The Cancer Center at Cares, Canine Cancer Library, National Canine Cancer Foundation
Animal Cancer Center, Colorado State University
**There is a vivid tabloid story in Dr. Nyce’s life, complete with books by and about him, but since this has little bearing on whether or not the claims made about TumexalTM are legitimate, I did not include this material in my post.

 

 

Posted in Miscellaneous CAVM | 44 Comments

New Study Shows Belief in Medical Conspiracy Theories Associated with Use of Alternative Medicine

Posted on March 19, 2014 by skeptvet

I was going to write a detailed post about a recent paper published in the journal JAM Internal Medicine, but since Dr. Novella at Science-Based Medicine has already covered it quite well, I just wanted to share a few tidbits.

Oliver J, Wood T. Medical Conspiracy Theories and Health Behaviors in the United States. JAMA Intern Med. Published online March 17, 2014

I have often pointed out that the advocacy and use of alternative therapies is primarily about ideology and belief rather than what is demonstrably effective at preserving and restoring health. People choose alternative therapies either out of desperation or out of a philosophical perspective that conflicts, to a greater or lesser degrees, with the philosophy of science and science-based medicine. I’ve reviewed this philosophical conflict before. There is a spectrum of degrees of conflict, but at its alternative medicine becomes a kind of religion or faith healing.

 

The significance of this is that such an ideology is often not responsive to conflicting facts or evidence, and criticism generates the kind of irrational anger usually seen when one criticizes a religious belief system. This has implications for how to effectively combat pseudoscience and quack therapies when simply pointing out the contrary evidence is likely to fail or even strengthen belief in them.

 

This JAMA paper explores a different aspect of the ideological nature of alternative medicine, the degree to which people believe in absurd medical conspiracy theories, and the extent to which this correlates with the use of alternative therapies.

 

The study presented people with six conspiracy theories about medicine. It should go without saying (though it clearly does not) that these theories are nonsense, and there is strong evidence contradicting each of them.

 

  1. The Food and Drug Administration is deliberately preventing the public from getting natural cures for cancer and other diseases because of pressure from drug companies. (37% agree, 32% disagree)
  2. Health officials know that cell phones cause cancer but are doing nothing to stop it because large corporations won’t let them. (20% agree, 40% disagree)
  3. The CIA deliberately infected large numbers of African Americans with HIV under the guise of a hepatitis inoculation program. (12% agree, 51% disagree)
  4. The global dissemination of genetically modified foods by Monsanto Inc is part of a secret program, called Agenda 21, launched by the Rockefeller and Ford foundations to shrink the world’s population. (12% agree, 42% disagree)
  5. Doctors and the government still want to vaccinate children even though they know these vaccines cause autism and other psychological disorders. (20% agree, 44% disagree)
  6. Public water fluoridation is really just a secret way for chemical companies to dump the dangerous byproducts of phosphate mines into the environment. (12% agree, 46% disagree)

 

My own experience as an advocate for science-based medicine, like Dr. Novella’s, would have led me to think belief in these ideas would be even greater than this survey indicates, so there is at least some reason for optimism. Still, this is a depressingly high level of belief is some pretty extreme, and manifestly absurd, ideas. Undoubtedly, the agreement would be even higher with more plausible, though still false, theories about the “Medical Establishment.”

In addition to the general assessment of belief in these theories, the study looked at associations between level of belief and use of alternative therapies. The kinds of associations evaluated were quite limited, and it would be interesting to tease out the relationship between belief in malign conspiracies in government and conventional medicine and the use of particular alternative therapies. Still, the results are intriguing.

For example, of those who did not believe in any of the six conspiracy theories, 13% said they use herbal remedies. However, for those who believed in 3 or more of the theories, 35% said they use herbal medicine. A similar correlation was seen for use of sunscreen and vaccines, purchasing of organic foods, and other alternative healthcare practices.

This does not, of course, suggest that using alternative therapies is a sign of being a conspiracy nut. It does, however, suggest there is a relationship between distrust of healthcare providers, scientists, and government and the use of alternative therapies. It also implies, though it doesn’t prove, that the more extreme this distrust, the more likely one is to turn to alternatives.

This isn’t surprising, of course, but it does challenge the notion of integrative medicine, which seems to be gaining wider popularity. This notion says that alternative and science-based medical therapies are all indistinguishable tools in a healthcare toolbox, and one can freely and rationally choose among them without prejudice. The reality, however, is that there are deep ideological and philosophical difference between the approach of science and the alternatives, and choosing one often involves some degree of rejection of the other. For the most ridiculous and pseudoscientific of alternative therapies, such as homeopathy, energy medicine, and so on, acceptance involves a fundamental rejection of the core principles of science. For more plausible interventions, such as dietary supplements, their use does not necessarily conflict in a fundamental way with a scientific approach, though it may still indicate a lack of thorough understanding of and commitment to the use of scientific evidence to make healthcare decisions.

I think exploring the relationship between ideology, philosophy, and faith and the use of alternative therapies is a productive way to understand the fundamental reasons some such therapies persist even when there is good reason to think they are useless or even harmful. A better understanding of why people turn to these methods can hopefully inform a more effective strategy for guiding people towards the most effective healthcare available, that based on good science.

 

 

 

 

 

Posted in General | 4 Comments

Clever New Study Illustrates the Importance of Placebo Controls In Veterinary Clinical Studies

Posted on March 18, 2014 by skeptvet

I recently ran across a fantastic web site, Testing Treatments, which explains clearly and simply how we use science to test our medical treatments. For anyone not already very familiar with this process, this site will explain why a lot of the evidence people offer on this site for their favorite therapies isn’t really evidence we should trust. One major problem with anecdote and other kinds of low-quality evidence, is the influence of the placebo effect. Contrary to what many people believe, this is just as big a source of error in veterinary studies as in human research.

One of the most entrenched fallacies used to defend the use of anecdotal evidence to validate veterinary treatments is the idea that any perceived effect must be real because the placebo effect doesn’t work in animals. While our veterinary patients don’t experience the perception of relief, when they actually aren’t getting better, solely because of their beliefs or expectations, as humans do, placebo effects do still fool us when trying to decide if our therapies are working in our pets.

Improvements associated with human contact, better care when involved in a clinical trial, operant conditioning, the natural course of disease, and many other factors do occur, and they can fool us into thinking an ineffective therapy is working. These are aspects of the cluster of errors usually labeled the placebo effect.

In addition, there is good evidence for what is usually called the “caregiver placebo effect.” Since many of the measures for the effect of our therapies are subjective and assessed by owners and vets, not directly by the patients, the beliefs and expectations of owners and vets can often create an impression of improvement where none really exists. This is especially true when the measures are so difficult to objectively, consistently asses, such as pain, nausea, etc.

For these reasons, a placebo control is essential in any veterinary clinical study if we are to have confidence in the apparent effects of the treatment being tested. This is not controversial, except sometimes for folks pushing therapies they believe are effective but that haven’t been tested, or that have failed testing, in placebo controlled trials.

However, I have always assumed that with proper placebo controls, a clinical trial would usually be able to detect a real difference in outcome when the treatment being tested truly worked. Even though placebo effects would make the control group appear to be getting better, they would affect the treatment group to the same degree. And the real effects of a treatment that works ought to make the improvement in the treatment group significantly greater than those in the placebo group. However, a cool new study in cats suggests this may not be true, and that caregiver placebo effects may be masking the real effects of some treatments.

M.E. Gruen, E. Griffith, A. Thomson, W. Simpson, and B.D.X. Lascelles. Detection of Clinically Relevant Pain Relief in Cats with Degenerative Joint Disease Associated Pain. J Vet Intern Med 2014;28:346–350

The authors in this study were interested in whether the effect of a pain reliever in cats with arthritis could be better identified by looking for recurrence of symptoms after the medication was stopped than by looking for improvement in symptoms while the medication was being given. They compared meloxicam, an NSAID for which there is already good evidence of efficacy, to an identical placebo.

The study selected cats with significant symptoms of arthritis and used owner surveys to evaluate symptom severity. All cats got a placebo for 2 weeks, and the investigators and owners knew they were getting only placebo. This was to accustom the cats and owners to giving the medication and monitoring symptoms. Then the cats were randomly assigned to two groups, one getting meloxicam and one placebo for three weeks. During this time, both owners and investigators were blinded to which treatment each cat was getting, which reduced the influence of bias. Finally, the cats on meloxicam were shifted to placebo, but only the investigators knew this, not the owners.

During the treatment period, all cats appeared to get better according to the owner evaluations. This is consistent with placebo effects. The cats on meloxicam did not improve significantly more than those on placebo, which would seem to suggest that the meloxicam wasn’t working. However, when the cats on meloxicam were switched to placebo, without the owners knowing it, these cats got significantly worse while the placebo group did not change. This indicates that the meloxicam was having an effect, however it was swamped during the treatment period by the owner placebo effect, which influenced the results of both groups.

The authors do a good job of assessing the limitations of their own study, which is an important element in the discussion section for any scientific paper. The investigators were not blinded during the last three weeks, so potentially they could have influenced the owner evaluations in some way. There are also some weaknesses in how the diagnosis of arthritis was established, how the severity of disease was evaluated, and some other factors. But such limitations occur in every study, which is why no single paper can be definitive evidence. This was still an clever and illuminating project, and if it holds up when replicated, it may lead to a significant change in how placebo effects are controlled for in veterinary research.

Posted in Science-Based Veterinary Medicine | 1 Comment

RenAvast™ for Kidney Disease: Sloppy Science and Snake Oil Marketing

Posted on March 17, 2014 by skeptvet

A reader recently asked me to investigate yet another supplement product, this one marketed for treatment of kidney disease in dogs and cats. While there are thousands of such products, and a thorough investigation of each isn’t possible, there were some interesting features to this particular product, so I spent some time looking into it.

What Is It?

The short answer is, “Who knows?” The product is called RenAvast™, and first on the list of red flags of quackery is the fact that the company won’t say exactly what it contains. The ingredients are listed as “a proprietary combination of amino acids and peptides.” While I understand that intellectual property concerns are often valid, it is also appropriate to be extremely wary of any medical therapy that contains secret ingredients. The American Veterinary Medical Association (AVMA) Principles of Veterinary Medical Ethics specifically identifies selling or using such products as unethical:

It is unethical for veterinarians to promote, sell, prescribe, dispense, or use secret remedies or any other product for which they do not know the ingredients.

I did find one site purporting to have identified the ingredients as, “300mg: L-Aspartic, L-Carnosine, L-Glutamic Acid, L-Glutamine, Glycine, L-Arginine, L-Histadine,” though I have not been able to confirm that on any site associated with the company. The inventor of the product describes it in a radio interview as “amino acids and a peptide,” but again doesn’t provide any more details.

The company research report describes the substance as:

a powerful ROS scavenger, a cytoprotective agent which reduces damage to proximal renal tubules and increases glomerular filtration rate (GFR), stimulates gluconeogenesis and suppresses proteolysis in skeletal muscle, has strong anti-inflammatory properties, is a precursor for NO production, and induces BMP-7…

It is impossible to assess these claims without knowing what the ingredients actually are. Elsewhere in the document, reference is made to seven different “biomolecules” in the product and their supposed functions. The claims made here for these functions are supported with a reference to an unnamed publication listed in the references as “PLAW 104-294.” I have no idea what this means.

There is reference to another study which showed that the molecule BMP-7 has some effect on damaged kidney cells in mice with artificially induced renal failure. Supposedly, biomolecule 7” in RenAvast™ induces production of BMP-7, though no evidence for this is provided. This tenuous connection between the mystery ingredients in RenAvast™ and kidney disease hardly justifies using the product in actual patients in the absence of additional pre-clinical research and clinical trials.  As we will see, there really aren’t any such trials.

The company makes many bold claims for the product despite the lack of tangible support for them:

RENAVAST™ MECHANISM OF ACTION

Protects cells, particularly in renal tubules.

Increases glomerular filtration rate (GFR).

Increases gluconeogenesis.

Decreases protein breakdown, especially in skeletal muscles.

Has a strong anti-inflammatory effect.

Decreases renal blood pressure.

Increases renal vasodilation.

Increases hormone that promotes renal tissue repair.

[RenAvast™ is] SAFE – More than 4,000,000 doses have been given to dogs and cats with no negative side effects reported… It is 100% safe with no side effects.

[It is] scientifically proven in an open-ended two year clinical study to supplement and promote healthy renal function. Unlike other products and drugs, RenAvast™ does not treat the symptoms of renal failure, it treats the cause.

Along with these confident claims is, of course the required Quack Miranda Warning which reminds us that the company has not felt it necessary to provide the FDA with any real evidence to support them: “These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.” It always amazes me that companies put this disclaimer on their sites and then loudly (and illegally) proclaim that their products do treat disease.

The chutzpah necessary to do this is especially impressive in this case since the company, BioHealth Solutions, has already been warned by the FDA that their marketing of RenAvast™ is illegal:

 

WARNING LETTER

August 1, 2012

This letter concerns your firm’s marketing of the product RenAvast™.  The U.S. Food and Drug Administration (FDA) reviewed your website at the internet address www.RenAvast™.com, where you promote and sell this product.  We have determined that RenAvast™ is intended for use in the mitigation, treatment, or prevention of disease in animals, which makes it a drug under section 201(g)(1)(B) of  the Federal Food, Drug, and Cosmetic Act (the FD&C Act) [21 U.S.C. § 321(g)(1)(B)].  Further, as discussed below, this product is an unapproved new animal drug as defined by the FD&C Act and your marketing of it therefore violates the law.

Statements on your website that show these intended uses of your product include, but are not limited to, the following:

• RenAvast™™ can halt the progression of chronic renal failure
• RenAvast™™ may reverse the effects of chronic renal failure
• RenAvast™™ may help prevent kidney disease in healthy cats
• RenAvast™™ is a new, highly effective compound that has been proven through a two-year clinical study to halt the progression of Chronic Renal Failure (CRF) in cats and improve overall kidney function
• Unlike other products and drugs, RenAvast™™ does not treat the symptoms of renal failure, it treats the cause
• RenAvast™™ was highly successful in halting the progression of Chronic Renal Failure and in most cases improved kidney function.
• Finally a solution for cats with Chronic Renal Failure
• A two-year open ended clinical study proves that RenAvast™ can halt the decline in kidney function
• Until now, veterinary medicine could only manage symptoms in an attempt to maintain quality of life while the disease progressed relentlessly onward. All of that has now changed
• Chronic Renal Failure is no longer a death sentence

Because RenAvast™ is intended to mitigate, treat, or prevent disease in animals, it is a drug within the meaning of section 201(g)(1)(B) of the FD&C Act. Further, this product is a new animal drug, as defined by section 201(v) of the FD&C Act, [21 U.S.C. § 321(v)], because it is not generally recognized among experts qualified by scientific training and experience to evaluate the safety and effectiveness of animal drugs, as safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling.

To be legally marketed, a new animal drug  must have an approved new animal drug application, conditionally approved new animal drug application, or index listing under sections 512, 571, and 572 of the FD&C Act [21 U.S.C. §§ 360b, 360ccc, and 360ccc-1].   RenAvast™ is not approved or listed by the FDA, and therefore the product is considered unsafe under section 512(a) of the FD&C Act, [21 U.S.C. § 360b(a)], and adulterated under section 501(a)(5) of the FD&C Act [21 U.S.C. § 351(a)(5)]. Introduction of an adulterated drug into interstate commerce is prohibited under section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].

This letter is not intended to be an all-inclusive review of your products and their promotion.  It is your responsibility to ensure that all of your products are in compliance with the Act and its implementing regulations. Failure to promptly correct the violations specified above may result in enforcement action without further notice. Enforcement action may include seizure of violative products and/or injunction against the manufacturers and distributors of violative products.

You should notify this office, in writing, within fifteen (15) working days of the receipt of this letter of the steps you have taken to bring your firm into compliance with the law. Your response should include any documentation necessary to show that correction has been achieved. If corrective action cannot be completed within fifteen (15) working days, state the reason for the delay and the date by which the corrections will be completed. Include copies of any available documentation demonstrating that corrections have been made.

Unfortunately, as I’ve discussed previously, regulatory control of veterinary quackery is not very effective. This warning appears to be more than a year old, and I was not able to find any information regarding how it was resolved. Regardless, the company continues to make clear treatment claims despite the warning and disclaimer.

 

Does It Work? Is It Safe?

The general claims about mechanism of action cannot be evaluated without any information about what is in the product. If there is any plausible reason to think it might work based on in vitro or lab animal studies, we cannot determine this without knowing what is in it.

Likewise, the safety cannot be assessed simply by accepting the company’s word for the fact that they have sold lots of it and no one has told them about any problems. All that I can say with certainty is that no medical therapy with any benefits at all is “100% safe,” so this is clearly nothing but marketing hyperbole. Such claims are a hallmark of snake oil therapies.

It is possible, however, to evaluate the claim that RenAvast™ is “scientifically proven.” I’ve talked before about what that means, and it is a good deal more complicated than the promoters of this product seem to understand.

The “research” that the company promotes as evidence RenAvast™ is safe and effective is a classic example of sloppy science used as a marketing tool rather than real scientific research. Information about the study can be found in a summary on the Bio Health Solutions web site and also a more detailed report which was previously made available online by the company and then apparently taken down, but which is available through a web archive.

19 cats with CRF were enrolled in an open ended 2-year study… All cats enrolled were diagnosed by their veterinarians with Chronic Renal Failure. None were on restricted diets. None were receiving fluids. All received 300 milligrams of RenAvast™ two times per day. All had periodic blood work…

There is no information about the cats, how they were selected, how long each was given the product, what other disorders most might have had, or any other details about the population studied or how the study was conducted. It is stated that the cats were enrolled “over a two year period,” but it isn’t clear how long each subject was treated and when or how often bloodwork was measured. Without this information, a huge number of possible errors and confounders could be present.

It is also not clear how the diagnosis of kidney disease was made. Two of the cats appeared to have a urine specific gravity of >1.035, which by the most common standard would not qualify them for a diagnosis of kidney disease. This critical value was not measured in three other cats, all of whom had near normal creatinine levels. This means at least 5/19 (26%) cats cannot be definitively said to even have had kidney disease at the start of the study!

Most cats showed little change in the various parameters measured, though again it isn’t clear how long each subject was followed over the total two-year length of the study. The detailed report indicates that these values were compared from the beginning to the end of the study for each subject. There are specific statistical methods needed to perform such a paired comparison, but no information is available to assess whether or not the methods used were appropriate, so it isn’t possible to say if the statistical tests reported are meaningful.

According to the report, declined or remained unchanged in 17/19 cats. (Of course, this includes the two that probably did not have kidney disease and the three that might or might not have but whose urine specific gravity was not measured at baseline.) Excuses are made for the cats whose creatinine values worsened (one was supposedly not compliant with treatment and the other was receiving medication for thyroid disease which can affect the kidneys). The fact that such possible confounders are not reported for any cats except those whose numbers didn’t change the way the author wanted them do suggests a significant risk of bias in these data. The same pattern is reported for the other variables measured, in which most improve or don’t change and those that get worse are explained away with information not provided for other subjects.

The implication here, of course, is that the failure of these variables to get worse for most cats means the RenAvast™ was working. While this is not a fair conclusion based on the limitations of this single report, the author of the report has no hesitation in making this claim:

These encouraging results prove that AB070597 can halt the advance of chronic renal failure in felines when given as an oral supplement. Supplementation with AB070597 halted increases in blood serum creatinine, blood serum urea nitrogen and blood serum phosphorus concentrations; while at the same time halted decreases in hematocrit and urine specific gravity.

Since cats with renal disease can remain stable for long periods, the fact that there is no control group is a huge problem. It is impossible to say whether or not the product did anything at all without a control group for comparison. In an unusual step, the company has provided some additional information in the form of responses to possible objections to their “study.” It is rare to have the opportunity to see such explicit arguments against what is generally considered appropriate scientific methodology, so I think it worthwhile to examine some of these arguments.

The company FAQ about the study begins by defending the very small sample size.

Many scientific studies are done with fewer subjects and over shorter time periods. In fact, there are thousands of human studies in peer reviewed journals with less than 19 patients. Nineteen patients in a study is acceptable; not to mention the fact that there are numerous over-the-counter medications used to treat humans and animals that are not based on any studies, peer reviewed or otherwise, with only subjective and anecdotal evidence as proof of efficacy.

This seems to me a fallacious argument. The fact that other studies have been done and published with no more subjects than this one isn’t itself a justification for the small sample size. Such studies may or may not have had appropriate samples sizes for the problem and population they studied, but that doesn’t tell us if this number is adequate for this population and problem. Just because others may have also used small sample sizes doesn’t mean doing so is appropriate or that the results are any less unreliable in this case. And there are specific statistical methods for evaluating whether or not a sample is large enough to answer a given question, none of which the company apparently employed in this case.

The argument that many remedies are marketed on the basis of anecdote alone is also not a justification for performing a study that isn’t capable of providing reliable information. Meaningless research is hardly a big improvement over no research at all!

The FAQ then states that biochemistry samples in the study were evaluated at a variety of laboratories. This is presented as a strength, but it may actually be a weakness. Using a variety of laboratories, each with different methods and quality control, introduces a source of variation in the data which can easily alter the findings.

Next, the FAQ attempts to answer perhaps the biggest objection to the so-called study, the absence of any control group. The response rests on two principles. First, it is claimed that a control group was unnecessary because any group not treated would undoubtedly have gotten worse, so any failure to get worse must automatically be due to the treatment:

In this particular case, a separate control group was uncalled for and would not have yielded useful information. The outcome of untreated chronic renal failure is already known: biochemical and hematological blood serum values deteriorate over time.

The problem with this argument is that it is simply false. While the general trend of chronic kidney disease is to worsen over time, the specific changes and the rate at which they happen in any individual are highly variable and unpredictable. Studies routinely show ranges in survival from days to years. Many factors can influence whether bloodwork values worsen and how fast, and none of those factors were accounted for in this study.

And there are many important variables other than bloodwork values, including body condition, appetite, and other clinical symptoms, which are only mentioned in passing but not specifically evaluated in this report.

We don’t even know from the information available whether these cats were properly diagnosed with kidney disease, what stage of disease, or any other relevant prognostic factors. Some of them, at least, clearly were not. And even if these cats all truly had some degree of chronic kidney disease, the progression of the disease over whatever unreported period of time each was followed cannot simply be assumed. Without a control group, no change or failure to change can be ascribed to the treatment in this study.

The second argument presented against a control group is that having such a group would be unethical since untreated cats would certainly die of their disease.

The use of a separate control group often raises questions of unethical behavior regarding withholding treatment from or giving placebos to the control group.

The FAQ then quotes a number of statements from the Stanford Encyclopedia of Philosophy concerning the ethics of placebo controls in clinical trials. It goes on to give an impassioned statement against the use of such controls:

The researcher does not question the superiority of randomized double-blinded studies over other forms. It is a well recognized fact, though, that their use in some situations is completely unethical. The researcher considered it completely unethical to create two groups of cats, both with CRF, and treat one group with RenAvast™ while giving the other group a placebo to merely satisfy statistical correctness. He already knew the outcome of the placebo group…. We fully support the researcher’s decision. We too, find it cruel and unethical to deny cats with CRF treatment with a product that could help them simply to create a statistic.

There are several problems with this argument. The first is that it is inconsistent with the little we know about how this trial was conducted. There is no evidence the cats placed on RenAvast™ were given standard care. Dietary therapy, for example, is well-demonstrated to improve outcomes for cats with kidney disease, yet these cats were not on dietary therapy. Other common therapies are less solidly evidence-based, but there is certainly a basis in plausibility and consensus for the use of fluid and for a number of other therapies depending on the details of the individual cases. The little information we have suggests these treatments were not provided to subjects. This study apparently substituted a completely untested supplement for standard care, which would certainly not be ethical. And if the product is not effective (and there is yet little reason to think it is), this amounted to simply not treating these cats at all, which is exactly what the author of this FAQ decries.

It is recognized practice in clinical research to test new therapies by comparing a group getting standard care plus the new therapy to patients who get only standard care. It would not have been difficult to run this study in this way, ensuring that both groups received accepted diagnosis and treatment and the only difference between them was the addition of RenAvast™ for the test group. This would have potentially provided actual information about the efficacy of this product, which the results reported here do not.

The ethical argument in the FAQ also fails because, as discussed above, the outcome was not actually known in advance as the company suggests. If we could safely assume that an experimental treatment worked before testing it, we wouldn’t need to run clinical trials at all! The reason that placebo controlled trials are ethical is because they are necessary to develop effective treatments. Without them, we simply guess and, as history and the cumulative results of thousands of such trials show, patients suffer from our ignorance. It is certainly not ethical to deny a known effective treatment to patients in a trial. But since RenAvast™ is not a known effective therapy, it is ethically questionable to give it in a clinical trial without having a control group, especially if standard care is not provided as well.

We don’t conduct trials “to create a statistic” or for “statistical correctness” but to generate the real and reliable knowledge that can only come from controlled scientific research. To conduct a trial that doesn’t produce such knowledge but merely facilitates marketing an unproven medical product is where the real ethical failing lies. This is a classic example of circular reasoning, assuming a therapy works before testing it and then claiming it would be unethical to deny this therapy to patients because it works. This is how one does faux science for marketing purposes, not real science designed to generate real growth in our knowledge and therapeutic tools.

 

Bottom Line

The ingredients in RenAvast™ are deliberately not disclosed by the company beyond the fact that they are amino acids and some sort of peptide. Therefore, it is impossible to evaluate the plausibility of the proposed mechanisms of action or any preclinical research on these ingredients.

The only data presented for safety and efficacy is a poor quality, small trial with clear and significant risk of bias that is essentially useless as evidence. There are, of course, plenty of testimonials and anecdotes suggesting the product works, but that is true for every therapy ever invented, so either no idea in medicine ever fails, or anecdotes are very reliable.

There is no way to determine at this point if the product is safe or effective. However, the way that it has been marketed shows a clear disregard for both the regulations intended to prevent inappropriate and unproven claims for dietary supplements and the basic principles of medical research. The combination of secrecy and misuse of sloppy science suggests a great deal of skepticism is in order when dealing with this company and its products.

 

What Else Do We Know?

In the absence of any real scientific evidence to evaluate the safety and efficacy of RenAvast™, it is impossible to draw any solid conclusion about the product. All we can say is that it is unproven, and even the basic plausibility of the proposed mechanisms is unclear.

While it won’t help us to evaluate the safety and efficacy of RenAvast™, there is some additional information worth considering using this product. As I have already discussed, there are a number of warning signs of snake oil, including claims of perfect safety, dramatic benefits not supported by real scientific evidence, misuse of the appearance of science to market a product, and others. I will not be surprised if we soon see another such sign in the form of a hostile response to this critique, though that is just a guess on my part.

The credentials of the folks making claims for this product are not directly relevant to the truth of those claims, but in the absence of any more specific evidence, they may be of some tangential interest. The detailed report on the cat study is attributed to “James Archer, Photo Research.” There are references elsewhere to a “Dr. James/Jim Archer” associated with Bio Health Solutions, the company marketing RenAvast™, and he has provided a radio interview on a program devoted to “integrative veterinary medicine” discussing RenAvast™.

According to this interview, Dr. Archer apparently invented prior to working with Bio Health Solutions. It is not clear what specific academic or research background Dr. Archer has. He appears to have worked largely for the Department of Defense, and though he is not a veterinarian, he indicates he has been a scientific consultant at a veterinary hospital in Southern California.

In his interview, he repeats many of the assertions for the effects of the ingredients in RenAvast™ without any additional details. He describes extensive research leading up to the development of this product, though apparently none of this has been published. He reports the results of the unpublished study and makes strong claims for the benefits of the product without addressing any of the limitations or problems discussed above. He recommends RenAvast™  be given permanently to all cats over 8 years of age! He does mention that a few of the cats had concurrent diseases or treatments during the study, and he confirms that the avoidance of diets for treatment of kidney disease was deliberate. He also reccommend using the product in dogs as well and mentions that there is research ongoing in this species.

The company web site only lists one other product, another nutritional supplement billed as an analgesic and anti-inflammatory for musculoskeletal diseases in animals. The marketing director, Mark Garrison, describes aggressive marketing of the product around the world. The company claims repeatedly on its web site to have a strong commitment to science, but this certainly is not consistent with the approach so far evinced in promoting RenAvast™.

Posted in Herbs and Supplements | 59 Comments

LEGS Glucosamine Study Shows Little Evidence of Real Benefit

Posted on March 16, 2014 by skeptvet

I have written extensively about glucosamine because it is a ubiquitous arthritis therapy that nearly everyone seems to believe in and use, yet the evidence for it is poor. Only two published clinical studies are available for dogs, one showing no effect and one showing a marginal effect far less than that of non-steroidal anti-inflammatory medications (NSAIDs). Overall, the evidence is poor for the use of glucosamine in dogs, though it is limited in quantity. There appears to be little evidence of harm, however, there is no question NSAIDs are more effective by far, and overall quite safe, so it’s a shame that the caregiver placebo effect leads some vets and pet owners to deny dogs an effective treatment for their pain in favor of one that probably isn’t doing anything.

There is a great deal more evidence concerning glucosamine in humans, and though it is often conflicting, the general trend is that older, smaller, lower quality studies show a benefit and newer, better quality studies do not. Systematic reviews and meta-analyses generally conclude there is little chance this supplement is effective, and this was supported by the largest and best trial, GAIT. A study out of Australia has recently been published which appears to challenge the generally negative conclusions of the current literature, though the results are not unequivocal.

Fransen M, Agaliotis M, Nairn L, Votrubec M. et al. Glucosamine and chondroitin for knee osteoarthritis: a double-blind randomised placebo-controlled clinical trial evaluating single and combination regimens. Ann Rheum Dis. 2014 Jan 6. doi: 10.1136/annrheumdis-2013-203954. [Epub ahead of print]

This study followed slightly more than 600 people over two years, comparing glucosamine and chondroitin individually and in combination with placebo. The main outcomes of interest were changes in joint space narrowing and in self-reported pain. A number of secondary outcomes were evaluated also.

There were no effects of either supplement individually. The combination supplement did show a small change in joint space narrowing over the length of the study. If consistently seen, this change could be clinically significant and results in a small proportion of patients with knee arthritis (1 out of 14) avoiding a knee replacement surgery over a 2-5 year period of treatment. This might be more significant over a longer period, say 10-15 years. However, the statistical significance of this finding was borderline (p=0.046), so it is possible it was only a chance difference  between the groups.

This interpretation is supported by the lack of similar effects found in other studies, and the lack of any significant difference in any other outcome evaluated in this study. The other primary outcome, pain, did not differ between the groups, suggesting no benefit of the supplement in terms of pain relief. While this study does show some potential benefit of glucosamine/chondroitin supplementation, in the context of the literature as a whole, it is not very impressive.

In terms of the veterinary use of these supplements, it is particularly concerning that this study and others consistently show no benefit over placebo in terms of pain. People frequently use glucosamine-containing supplements alone to treat arthritis pain in dogs and cats, and there is no convincing evidence they work. If we are being fooled into thinking they do, however, we are leaving our pets and patients to suffer with untreated pain. This is especially unfortunate given that safe and effective therapies for arthritis pain do exist. While there is likely no direct harm to using glucosamine, it is most likely a waste of money, and there is definitely a risk of indirect harm if it is substituted for weight loss, NSAIDs, and other arthritis therapies with better evidence of benefit.

 

 

Posted in Herbs and Supplements | 15 Comments

Falconer Strikes Back: A Veterinary Homeopath Refutes the Skeptics and Reveals the Emperor’s Nakedness

Posted on March 12, 2014 by skeptvet

It can be very instructive when proponents of alternative medicine respond to comments or criticism from skeptics. Sometimes, they respond with reasoned, even evidence-based defense of a specific practice. This is a good sign and can lead to productive discussion. More often, they respond with passionate but empty rhetoric simply asserting that they are right and their critics are ignorant, greedy, or simply terrible people. This is not a good sign, but it is still instructive because it often reveals, in their own words, underlying beliefs or attitudes that inform their practices and give the lie to any impression they may try to create that they are offering evience-based therapies.

Such is the response of Dr. Will Falconer to “skeptics,” which I suspect may mean me given his blog post comes a few months after several of mine mentioning him and his dangerous rejection of science-based medicine in favor of homeopathy (here and here). Dr. Falconer’s posts are regularly recommended on the Facebook page of the Academy of Veterinary Homeopathy, so I think it fair to say he is not a lone extremist but a representative of a perspective widely accepted among veterinary homeopaths, and I suspect the larger holistc veterinary medical community.

The core of his response to skeptics is a straightforward rejection of science in favor of personal experience, which is one of the key philosophical underpinnings I have previously identified as a characteristic feature of alternative medicine. He calls this “Common sense vs The Age of Science,” and makes it clear that when science is in conflict with belief and intuition, science is to be rejected. He uses one of the classic examples of quackery to suggest that what science says is untrue is patently obvious to anyone with common sense–the disproven but still widely feared link between vaccines and autism:

The “science” drum is beaten loudly when skeptics enter a conversation. Instead of being open minded and inquiring, these minds have snapped shut like a steel trap, rebuking anyone who doesn’t toe the line they’ve drawn on what’s real.

“Where’s the research, the double blind studies?!” “There’s no scientific proof that homeopathy is anything more than water. Anyone who gets well from it is making it all up! It’s a placebo response!!” “Vaccinations do not cause autism.” Etc. etc.

Meanwhile, mothers are seeing their perfectly normal, well adjusted toddlers lose all vestiges of normal life shortly after getting vaccinated. The rising autism incidence parallels closely the rise in vaccine requirements for children over the last 20-30 years. Any careful medical research could uncover this.

The evidence is overwhelming that vaccines do not cause autism and that the irrational fear of vaccines has sickened and killed many children, but Dr. Falconer believes we are all so infallible that simple, everyday experience outweighs the evidence of hundreds of studies involving millions of children. Except, of course, for the everyday experience of those of us whose common sense tells us vaccines have nothing to do with autism.

Dr. Falconer then goes on to try and show that scientific research is worthless, and that even leading figures in science and evidence-based medicine don’t believe in it. His failure to understand what he reads, and his ability to twist it to fit his ideology despite the fact that the people he discusses are in direct and active opposition to his view, is truly amazing.

He begins by citing John Ioannidis’ work showing that false positive findings and exaggerated effect sizes are common in publishes scientific research. Quacks love to cite this study because they believe it means science is worthless and they are free to ignore it. As others have discussed in detail, this is not at all what this research means or what Dr. Ioannidis believes. Science, unlike “common sense,” intuition, and personal faith is an ongoing, self-correcting process. We are constantly identifying each other’s mistakes and working as a community towards better understanding. Identifying and correcting the sources of error in the conduct and reporting of research is part of this processes. Dr. Ioannidis is not suggesting we give up on science. In fact in his latest paper, which I wrote about last week, he lays out a strategy for using scientific research to do precisely what faith-based practitioners like Dr. Falconer are so unwilling to do: to identify and abandon ineffective therapies using scientific research.

Dr. Falconer also cites one of the founding figures of the evidence-based medicine (EBM) movement, Dr. David Sackett, stating that he has given up on evidence-based practice. However, even the quote Falconer uses shows that the reason Dr. Sackett has quit teaching EBM is precisely because he’s afraid his status as an expert might inappropriately lead others to value his opinion and experience as an individual over objective data.

Sackett is not doing this because he has ceased to believe in evidence based clinical practice but, as the BMJ comments, because he is worried about the power of experts in stifling new ideas…

Dr. Sackett has twice announced he is quitting a specialty in which he has been recognized as an expert, and in a recent interview he explains why. He feels that recognition of expertise too easily leads to the fallacy of appeal to authority, in which the personal experience and opinion of the expert is given too much credence and contrary arguments or evidence is ignored.

Yet this is exactly what Dr. Falconer is arguing for, the rejection of scientific evidence in favor of the opinion and experience of supposed experts. He lauds Andrew Wakefield and Samuel Hahneman for the wisdom of their experience and ignores the fact that extensive scientific research has proven them both to be wrong. Rather than a brave, independent thinker challenging dogma and orthodoxy, Falconer is advocating uncritically accepting and following the word of supposed experts based on their individual experience. And rather than humbly accepting human fallibility and accepting the need for mechanisms to guard against our own errors and misjudgments, he, like Dr. Fallek and so many other alternative practitioners, believes his own experiences and perceptions to be so reliable that no amount of data or evidence to the contrary can cause him to question his beliefs.

And then, without a trace of self-consciousness or irony, he concludes his response to skeptics by asserting his proud refusal to listen to anything that challenges his beliefs and his adherence to two of the most definitively false beliefs of alternative medicine, and he bizarrely tries to turn the world on its head and call this attitude “evidence-based medicine.” Bizarre but instructive:

Just as you’ll never convince mothers of autistic children that vaccinations are harmless, you’ll never convince veterinary homeopaths that animals are getting well by delusion. We’ve got volumes of patients that speak otherwise. Animals don’t live in delusion.

We don’t have time for the skeptic’s blathering. We’ve got work to do. Medical research marches on, pet by pet, horse by horse, tot by tot: real patients, real results.

Homeopathy: Evidence based medicine at its finest.

 

 

Posted in General | 8 Comments

Holistic Veterinary Medicine: A Variety of Faith Healing

Posted on March 9, 2014 by skeptvet

Early on in my effort to understand and evaluate alternative veterinary therapies, I had the naïve notion that learning about their mechanisms of action and the research evidence behind them would enable me to tell which were safe and effective and which weren’t. In some cases, there turned out not to be any plausible mechanism and no evidence, or even evidence against these therapies. I was, again naively, surprised to find that not only were most self-described “holistic” veterinarians not disturbed by this, they were offended that I would ask for such evidence or that I would see the lack of it as a reason to distrust their practices.

It was at this point that I came to realize the primary difference between conventional medicine and alternative/holistic/integrative medicine is one of philosophy. Science-based medicine relies on the processes of science to understand how the world works and what is an effective way to protect and restore health in our patients. Being human beings, conventional vets and scientists are not immune to the kinds of thought errors and emotionally driven reasoning that leads us astray, but we have at least the philosophical approach that scientific research methods intended to compensate for these work and should be relied on whenever possible.

Alternative practitioners, on the other hand, have much greater faith in their own experiences and those of others, especially those they trust or those who agree with them. They tend to see scientific research as a nice extra at best, or entirely irrelevant or misleading at worst, but not in any way a necessary part of evaluating the effectiveness and safety of their therapies. Intuition, revelation, tradition, and other subjective and experience-driven methods of evaluating treatments are more meaningful and compelling to them that science.

This creates the appearance of a conflict about facts which is really a conflict about values and beliefs. Most alternative veterinarians pay lip service to the need for a value of science, and yet their actions are inconsistent with their words. They see science as most useful for marketing therapies they already believe in and convincing or battling skeptics, not as a necessary step towards a true understanding. They are, in essence, asserting the primacy of faith over reason in understanding health and disease and our responses to them.

Such a philosophical position is fair enough, though obviously I feel it is mistaken and leads away from a true understanding of the world. However, it is disingenuous or deceptive when it is presented not as a philosophical, essentially a religious, point of view but as the practice of medicine. Pet owners have a right to know that they are being seen by a doctor with a faith-based approach to medicine that essentially rejects the basic foundations of science and modern healthcare.

In an effort to expose this underlying difference in philosophies, so pet owners will have a fair choice of which approach to follow, I occasionally discuss examples of veterinarians openly promoting this perspective. The latest that I have run across comes from Dr. Marcie Fallek, a veterinarian currently promoting a new book, Krishna’s Flute: The Spiritual Journey of a Holistic Veterinarian. The promotional materials begin with a fairly straightforward example of fear mongering:  “Are Vets Killing Pets?” Asks Holistic Veterinarian in New Book….’Trust your intuition for your dog’s survival,’ warns Dr. Marcie Fallek.” No unreasonable appeal to emotion there, eh? Oh, but it gets better. Dr. Fallek goes on to ask a series of inflammatory rhetorical questions with a clear message and little regard for facts:

  • Are prescription drugs killing pets? Are they necessary? Is there a better, safer way? Are yearly or triennial vaccinations really necessary? Are they safe?

  • Why are dogs and cats now ‘old’ at 8 years, when 30 years ago, they lived until their late teens and early twenties?

  • Are the thousands of dollars spent on diagnostic tests worth it? Are the tens of thousands of dollars spent on therapies like chemo and radiation effective? Isn’t there a cheaper and most importantly, safer and more effective way to treat disease?

  • Why do elderly clients say their old family dog lived ‘til 18 and was rarely at the vet’s? With vet bills often more than yearly mortgage payments are pets really better off?

  • Why do many animal companions have the same chronic diseases as people? Why don’t squirrels have allergies? Deer skin infections? Crows asthma? Raccoons ear infections? Why don’t wild animals share human illnesses, while domestic animals do?

  • Do pets really have to die?

There is plenty of recourse to the usual misrepresentation of science-based veterinarians as greedy and unconcerned about the well-being of their patients, and the usual unsupported assertions that conventional medicine is harmful and alternative medicine superior, but the core of this approach is to undermine the very idea that science can be a useful way to approach healthcare.

The notion that there used to be a Golden Age before modern science and medicine in which animals were healthier and lived longer and which has been ruined by money-grubbing doctors sowing disease and poisoning our pets for gain is the rankest sort of ignorant historical revisionism imaginable. There are few reliable data on the historical health and longevity of pets, but all the voluminous data for humans shows our lives to be longer and healthier by far in the last century than ever before in history, and there is no reason to believe this is different from the pattern in our pets.

Similarly, the ridiculous appeal to nature fallacy that suggests wild animals frolic in an Eden of health and well-being and outlive their captive brethren stuck in a toxic artificial environment runs counter to all the data and evidence. Life for wild creatures is, in the classic words of Hobbes, “nasty, brutish, and short,” and it is a deep delusion to envision it as Dr. Fallek apparently does.

So how is such a blithe disregard for fact and reality maintained? Why through faith, of course. The “spirituality” invoked here is simply an ideological a get-out-of-jail-free card employed to excuse substituting wishful thinking and fantasy for reality. Dr. Fallek clearly explains that intuition trumps all other sources of knowledge because it is ultimately the voice of God speaking to us:

Please listen to your inner voice. This inner voice is our God-given intuition, it is our birthright, ingrained in our DNA, installed to protect us and our loved ones….With LOVE and TRUTH as the bottom line, not marketing masquerading as medicine, following the heart leads to a safer truer path of healing.

She goes even farther in the sample chapter of her book offered for free, asserting that this inner voice is infallible:

The most important lesson we can learn in life is to trust our inner voice. It is never wrong.

This sample chapter consists almost entirely of an anecdote. This story purports to describe a dog seen by three conventional veterinarians, including board-certified specialists, and wildly misdiagnosed. After many expensive and useless diagnostic tests and multiple harmful and unnecessary treatments, Dr. Fallek diagnosed an obvious congenital abnormality and relieved his symptoms with a few acupuncture treatments.

My inner voice tells me this is a grossly biased and self-serving misrepresentation of what actually happened. But since I prefer to rely on facts when possible, and there are none available to corroborate or challenge this narrative, I will simply have to refrain from judging the accuracy of the story. However, even if it is true exactly as told in Dr. Fallek’s book, it is merely an example of individual incompetence, not proof that conventional medicine is useless and harmful and the alternatives Dr. Fallek sells are safe and effective. Stories are just stories, not evidence, though of course the whole point here is that alternative medicine prefers compelling narrative to evidence.

So what does Dr. Fallek offer as an alternative to conventional medicine, which she dismisses blithely as “an endless cycle of cortisone and antibiotics?” Apparently, the usual hodgepodge of practices which are, in their own theoretical justifications, incompatible with one another but which share the only important characteristic: a preference for faith, intuition, and personal narrative over controlled research data as the guiding principle. Homeopathy, which is the quintessential faith-based medical practice completely incompatible with reality and already convincingly disproven. Acupuncture, which might have some reasonable basis for scientific study if not practiced, as by Dr. Fallek, according to the mystical nonsense that is mislabeled Traditional Chinese Medicine. The dubious and as yet unproven dogma of raw diets. Hysterical and exaggerated fear mongering about the dangers of vaccination.

In other words, this independent thinker committed to listening to her own inner voice espouses nearly all the core dogma of the alternative veterinary medicine community. While there is, of course, some diversity of opinions among veterinarians promoting alternative medicine, just as there is among proponents of conventional medicine, there are common ideological themes which lead to common practical approaches. These themes include:

  1. The trope of science and technology as      dangerous and “natural” or historical approaches as benign.
  2. Science-based vets as money-driven dupes or      shills of the malign pharmaceutical and pet food industries compared to      the purely caring and spiritually-guided alternative practitioners working      only for the well-being of their patients.
  3. A misty-eyed misreading of history to suggest      the past and the natural world as healthful and benign and the modern,      technological world as toxic and harmful.
  4. A deep suspicion of scientific research and a      blind trust of personal experience.

As I said previously, it is perfectly fine for Dr. Fallek and anyone else to believe whatever they wish to about the nature of the universe and about health and disease. Her approach to medicine is her religion, and everyone is entitled to their religious beliefs. However, our society has generally chosen to expect our doctors to provide care based on science and evidence to the greatest extent possible, largely because these approaches have created the dramatic improvements in our health and longevity that Dr. Fallek denies have happened. Improvements in sanitation, nutrition, public safety, and both preventative and therapeutic healthcare have given us more and better life than any previous human generation, and the evidence of this is voluminous and has led to a societal contract with healthcare providers that emphasizes science-based care.

The days of medical anarchism, where any and all medical approaches were treated as equally legitimate, ended in the early 20th century, and the scientific approach was given precedence. If we choose to retreat from that and emphasize spiritual, faith-based medical approaches above scientific ones, we deserve to at least understand that is what we are doing and make an informed choice to do so. When members of the Academy of Veterinary Homeopathy, such as Dr. Fallek, vociferously deny in public that homeopathy is inconsistent with science and claim it is in fact scientifically proven to work, they are not only factually wrong, but they are being deceptive. Elsewhere, they clearly describe the spiritual nature of this practice and fundamentally treating not the patient’s but their “energy” or “emotions” or “vital force,” in short their soul. If they would honestly admit homeopathy is a spiritual practice, not a scientific medical treatment, then at least pet owners would get an honest and fair choice between medicine and faith healing.

 

 

 

 

 

 

Posted in General | 14 Comments

Evidence-Based Medicine: Separating the Wheat from the Chaff

Posted on March 5, 2014 by skeptvet

As I have discussed before, evidence-based medicine is the formal, explicit application of the philosophy and methods of science to generating understanding and making decisions in veterinary medicine. Science shows us how the world works, and in medicine it shows us which of our therapies are effective. But perhaps even more importantly, it shows us which are ineffective or not safe. A key to practicing truly science-based medicine is accepting that our perceptions and appearances can be deceiving, and often we will be wrong in our assessment of which therapies work and which don’t. This means we must have the humility and courage to give up cherished beliefs and practices when science clearly shows us our faith in them is wrong.

This is one of the key differences between science-based and alternative medicine. The very category of complementary and alternative medicine (CAM) exists precisely to protect from scrutiny and criticism those therapies that have either been shown not to work or that haven’t been adequately tested. As I have discussed previously, CAM proponents often have a fundamental philosophical distrust of science and the hierarchy of evidence, and they often believe personal experience, intuition, tradition, and other low-reliability Potential considerations in prioritizing the testing of unproven medical practices.kinds of evidence are as good as or superior to scientific research. There is a general human tendency to resist change and to cling to beliefs and habits even when there is good reason to abandon them, but this is an even greater problem in CAM than in conventional medicine because it is part of the philosophical rationale of alternative medicine.

A recent paper by John Ioannidis, one of the most productive critics of the scientific literature and process, emphasizes the natural and important role of rejecting the disproven and targeting our research efforts to most effectively and efficiently separate the safe and effective from the unsafe and ineffective.

Vinay Prasad and John PA Ioannidis. Evidence-based de-implementation for contradicted, unproven, and aspiring healthcare practices. Implementation Science 2014, 9:1

In this paper, the authors illustrate how identifying ineffective or unsafe practices, and contradicting current practices, is a common and intrinsic part of the process of science-based medicine. There are hundreds examples of such practices being identified and abandoned, just as there are examples of new ideas being treated skeptically and then accepted once adequate supportive evidence is developed. It would be difficult to demonstrate a similar pattern for most alternative disciplines, where new ideas are often accepted on theoretical or anecdotal grounds alone, and where few ideas are rigorously tested or rejected even when negative evidence is available.

The authors also discuss how the natural human resistance to change plays out and affects both the scientific literature and the response to evidence about existing practices. The purpose of the article is specifically to develop and advocate for a strategy to efficiently use scientific research to change medical practices. Such a strategy would not be necessary if people naturally made decisions in a rational, disinterested, and evidence-based way. However, the difference between science-based medicine and alternative medicine lies largely in the fact that compensating for our innate cognitive biases is built into the very fabric of science, whereas following the guidance of these biases is the favored approach in much of the alternative medical community.

The authors also review the issue of how truly evidence-based conventional medical practices are. This is often raised by defenders of alternative medicine with the goal of invoking the tu quoque fallacy, that proponents of science-based medicine cannot legitimately criticize the poor evidence base for alternative medicine while scientific medicine has an imperfect evidentiary foundation. The authors do identify significant deficiencies in the evidence base of conventional medicine, reporting for example that a review of Cochrane systematic reviews found 49% of interventions could not be definitively validated or contradicted based on the evidence, and 48% of recommendations from the American Academy of Cardiology were based only on expert opinion. This is still quite a bit better than the claims made by proponents of alternative medicine, and there is reason to believe that when all forms of scientific evidence are considered, most conventional medicine has a significantly more solid foundation in evidence than the bulk of alternative medicine. Nevertheless, it is clear that there is significant room for improvement in the degree to which conventional medicine is evidence-based.

This paper also addresses the issue of how to prioritize research on unproven therapies. While it doesn’t address alternative medicine directly, and so doesn’t deal with the issue of prior plausibility, it does lay out an interesting approach. While there is room for debate about the specifics, I appreciate the general approach. It is not appropriate to say that before rejecting any therapy we must always have high-quality and high-level evidence. The resources for scientific studies are limited, and we cannot test every approach no matter how unlikely to be useful simply because someone believes in it. And there are ethical problems with subjecting people or animals to studies of therapies that are irrational or not adequately evaluated at the preclinical level, as demonstrated by the awful experience of patients with pancreatic cancer treated with the Gonazalez Regime. Deciding how much effort to put into testing specific unproven therapies is a complex balance of different considerations, and this paper addresses several of these.

           
Potential considerations in prioritizing the testing of    unproven medical practices

Factor    to consider

 General principle How to implement this factor

Prior   evidence base

Priority   should be given to practices where the present evidence base is weakest.

For   instance, a tiered system may be utilized: Level 1 (Weak) Randomized trials   of interventions claiming subjective benefits, that are unblinded or fail to   use proper controls. 2 (Weaker) Historically controlled studies of   interventions that purport survival benefits, case series documenting   improvements in subjective endpoints and quasi-experimental studies. 3   (Weakest) Practices based on pathophysiology and expert opinion alone. In   many cases, professional conflicts may also prove problematic; thus, it may   be reasonable to pursue this technique using content-specific experts in   strictly an advisory capacity

Cost/ubiquity

Priority   should be given to interventions with significant net financial burden on   health payers.

For   instance, orthopedic procedures for chronic back and joint pain, including   knee and hip replacement surgeries are widely utilized in the United States,   incur large financial burden on payers, but have little evidence of sustained   long term benefits.

Alternative   options

Priority   should be given to practices for which there are several alternative options,   particularly if alternatives are of completely different mechanisms (thus   unlikely to also be overturned), or of low cost or bolstered by stronger   evidence.

For   instance, consider the market for anti-rheumatologic agents. Maintenance   treatment of rheumatoid arthritis (RA) with disease modifying agents (DMARDS)   has historically relied upon oral anti-immunologic agents such as   methotrexate, azathiaprine, cyclosporin, and hydroxychloroquine. Recent years   have witnessed a boom in novel drugs, typically expensive monoclonal   antibodies against circulating cytokines or cell surface receptors. To date,   this market has been limited by paucity of head to head trials, and, of   trials that have been conducted, the majority are industry-sponsored studies.   Collectively, there remains clinical uncertainty about how best to use these   agents [20].

Documented   harms

Priority   should be given to test practices where the harms are well documented and   confer substantial morbidity.

For   instance, there is growing awareness of strut fracturization, embolism, and   migration of IVC filters. At the same time, the IVC filter has never shown to   improve any patient-centered outcome for any patient population in a   prospective trial, and traces its approval through the FDAs 510 k   mechanism [21].

Testing   the intervention makes financial sense

Priority   should be given to test practices where the cost to test is far less than   ongoing expenditures of the practice.

In   some respects, trialists should think like CEOs, weighing the costs of   conducting a study, which may find a practice ineffective versus the ongoing   expenditures for that practice. At times, such calculations may favor costly   trials where the existing evidence base is weak, observational studies   suggest inefficiencies, and the ongoing costs are large [22]. At   other times, small trials that eliminate boutique practices may be employed [23]. Whose   financial bottom line is being affected is important to consider. For that   reason, nonconflicted bodies should make these determinations, utilizing   investigators without financial conflicts of interest.

Proponents   are open-minded

Priority   should be given to test practices where negative results may truly gain   traction.

Some   specialties (primary care providers) may be more ready to abandon   contradicted medical practices, and it is reasonable to test practices when   there is genuine belief that contradiction can gain traction. Furthermore,   some practices may be cumbersome (tight glycemic control in the ICU),   time-consuming (routine gown and glove precautions) or unpleasant, and their   contradiction may also be palatable. Finally, as payment structures shift   from fee for service towards bundles [24], costly   components may lose faithful disciples. Other fields, those with numerous and   hyperbolic third party advocates, have been notoriously unwilling to trust   results that undermine their worldview, no matter how robust the science.

Value   of information gained

Priority   should be based on the expected value of funding a specific study that may   inform de-implementation, at the size and cost proposed.

Value   of information (VOI) offers a decision-making framework that tries to capture   several of the above issues, at least the ones that can be best quantified [19]. VOI   can be used to prioritize and power clinical trials taking into account the   costs of increasing study sample size, the potential number of persons   affected by changes in that practice, the costs of the practice, including   downstream costs, and the increased knowledge of marginal changes in health   outcomes that may result from testing — converting all to the final common   denominator of cost per favorable outcome gained.

I particularly appreciate the consideration of the impact of the evidence gained from research. If negative results are not going to have any impact, is research really justified? Clearly, we do not need more research on homeopathy for many reasons, for example, but a big reason is that additional research will never dissuade true believers but will simply add to the illusion that there is some scientific legitimacy to the ideas or practices they employ. Likewise, the money spent through the National Center for Complementary and Alternative Medicine has failed to validate most of the therapies studied, yet it has not apparently led to the rejection of any therapies despite the negative evidence generated.

Skeptics like myself are often accused of blind, unthinking defense of conventional practices and closed-mindedness. The exact opposite, however, is the truth about skepticism. It is the process of demanding evidence for all practices, including those I personally rely on. Articles like this illustrate that truly science and evidence-based medicine is as rigorous and critical in approaching its own practices as those under the label of CAM. This kind of critical scrutiny and adherence to the evidence, whatever it reveals, is necessary for progress and improvement in medicine, and is the acceptance of that that distinguishes science-based medicine from alternative approaches to developing and employing medical knowledge.

 

 

Posted in Science-Based Veterinary Medicine | 1 Comment

Dog Food Logic–A Great New Guide to Dog Foods for Dog Owners

Posted on February 20, 2014 by skeptvet

I was recently asked to review a new book for dog owners called Dog Food Logic: Making Smart Decisions for Your Dog in an Age of Too Many Choices by Linda Case. I was very impressed, and I encourage anyone interested in a rational, science-based approach to feeding our pet dogs to read this one. Here is the original review I provided for the book.

Dog Food Logic is an indispensable book for any pet owner who wants to make thoughtful, informed decisions about what to feed his or her canine companions. The dog food industry is a bewildering, ever-changing landscape of companies and brands, and dog owners are inundated with marketing masquerading as science, with rigid advice from self-declared experts, and with fads every bit as intense and short-lived as those in the human weight loss business. Dog Food Logic cuts through the noise and chaos and provides pet owners with a rational, science-based approach to evaluating their pets’ dietary needs and their feeding choices.

Rather than simply telling dog owners what food to buy, Dog Food Logic provides a concise and comprehensible guide to the three main subjects we must understand in order to make sound feeding choices: the science of canine nutrition, the nature of the dog food industry, and the pitfalls in our own ways of thinking that make us susceptible to marketing hype and irrational decisions. Rather than trying to tell us what to feed, Ms. Case empowers dog owners to make choices consistent with the needs of our individual pets and our own values.

In Dog Food Logic, the author displays a deep understanding of not only the science of nutrition but of the human-animal bond. Feeding our pets is more than providing them with essential nutrients. It is an expression of love and one of the most enjoyable shared experiences between pet and owner. Ms. Case understands that the emotional nature of feeding our animal companions must be appreciated and nurtured, but that it can also make us vulnerable to manipulation. Advertising and advice about what to feed our pets often plays on our anxieties about their health and happiness and our desire to do everything possible to ensure a long and healthy life for our dogs. Ms. Case is able to help us see through such manipulative marketing and make sound feeding decisions based on science while still respecting the role of feeding in the deep bond between owners and our pets.

As a veterinarian, a scientist, and a dog owner, I have waited a long time for a book like Dog Food Logic, one which I can enthusiastically recommend to my clients and colleagues. After reading Dog Food Logic, you will of course have a deeper understanding of canine nutrition, the pet food industry, and how to make good choices about feeding your pet. But you will also have a greater understanding of yourself as a pet owner and a consumer. Understanding how we make choices, and how those choices can be influenced by the quirks of our own thought processes and by the manipulative power of marketing, enables us to make better decisions about all aspects of our pets’ care. If we apply the same critical thinking and evidence-based approach to behavior and training, veterinary care, and all the other decisions we make as pet owners, we will better caretakers with happier, healthier pets.

Posted in Book Reviews, Nutrition | 26 Comments

Nutrition Resources for Pet Owners

Posted on February 18, 2014 by skeptvet

There is, as we all know, a tremendous amount of misinformation on the internet concenring virtually any subject. Yet the internet is an unqeustionably powerful information resources, likely indispensible for anyone seeking to be an informed consumer. For pet owners, the quantity of information about pet nutrition is overwhelming. Yet the quality of most of this infomration is poor, with little in the way of scientific evidence backing claims made, and with advertising and other commercial messages often indistinguuishable for legitimate and useful information resources.

So I have put together a brief list of useful informational resources for pet owners concerning dog and cat nutrition. These resources are produced by board-certified veterinary nutritionists and academic institutions or consortia with solid credentials in veterinary nutrition. I may not necessarily agree with every single statement in these resources, but I consider the sources trustworthy and the information reliable.

The objection will inevitably be raised that many of these individuals or organizations have some connection with the commercial pet food industry. This industry does support the majority of the research and education in veterinary nutrition, which raises the legitimate question of potential bias. That said, the claims and statements made by academic veterinary nutritionists are most often backed by research evidence, and this evidence does not become magically irrelevant just because of potential funding bias.

While any industry-funded research must be scrutinized carefully to ensure appropriate methodological techniques are employed to reduce the risk of bias, and while in a perfect world all research would be sponsored by independant government agencies or through funding mechanisms that prohibited any connection between funder and researcher, this is not our current reality.

All individuals have their biases, whether ideological, financial, cognitive, or other, and the purpose of the techniques of science are to minimize the influence of such biases on our understanding. The opinions of individuals promoting and/or selling unconventional diets or disparaging commercial diets are not free of bias, but they are often free of real scientific evidence. It is not the individual nor their affiliations that is ultimately the most salient feature in evaluating the reliability of factual claims, it is the quality of the data.

I invite anyone who is legitimately concerned about the influence of industry on the veterinary profession’s understanding and approach to nutrition to do more than complain. Provide real evidence to support your own claims or those of others you believe have a better approach.  Support the generation of better evidence with less risk of funding bias. Encourage the highest standards of research design and reporting to minimize the risk of bias.

World Small Animal Veterinary Association

Nutrition Toolkit–

Selecting the Best Food for your Pet

The Savvy Cat Owner’s Guide to Nutrition on the Internet 

The Savvy Dog Owner’s Guide to Nutrition on the Internet 

Calorie Needs for Healthy Adult Cats

Calorie Needs for Healthy Adult Dogs 

Pet Nutrition Alliance

Pet Owner Resources–

Frequently Asked Questions

Assessment

Nutritional Guidelines

Preventive Care

Body Condition Score Chart

Muscle Condition Score Chart

Nutrition Calculators & Charts

Food Safety

Food Safety Guidelines

ASPCA and Pet Poison Helpline

Pet Food Recall Alerts

Pet Food Information

Home-Cooked Diets

Ingredients in Pet Food

Nutrition Myths

Pet Health

Feeding Guidelines For Dogs and Cats

How to Evaluate Nutritional Health Claims and Detect Fraud on the Internet

Keeping Your Pet Healthy

Nutritional Consultation Services

Nutritional Needs for Specific Diseases

Nutritional Supplements

Weight Management and Obesity

Tufts Veterinary School Nutrition Service

Frequently Asked Questions

Home-cooked Diets

Raw Diets

The Ohio State University Veterinary Nutrition Support Service

Pet Owner Resources

Posted in Nutrition | 12 Comments