Spiraling Empiricism: Antibiotic Use as a Model for Pitfalls in Medical Decision Making

Posted on February 14, 2011 by skeptvet

About two years ago, Mark Crislip over at Science-Based Medicine wrote about an article that had a profound impact on his practices as an M.D. specializing in infectious disease, Observations on Spiraling Empiricism. He recently mentioned this article again on his own infectious disease blog, which drew my attention to his earlier post and the original article. I strongly encourage anyone who has an interest and access to the medical literature to read the original article. Though it focuses particularly on empirical antibiotic therapy (that is, using antibiotics when an infection of some kind is suspected but no specific diagnosis is made), it provides an excellent general conceptual approach to therapy and an eloquent and cogent description of the dangers of initiating therapy in the absence of a definitive diagnosis or even a single prime suspect.

This problem is even more acute in veterinary medicine, where we have fewer resources and less detailed knowledge about our patients’ diseases. Even the case examples in the article which illustrates mistakes in medical decision making often have far more meticulous and thorough analysis done than we veterinarians can do at our best. The risks of acting on incomplete information are likely even greater for us since we are more often forced to do so and our information is often exponentially less comprehensive than that our MD colleagues have to work with.

The article begins by acknowledging that antibiotics have been a phenomenally successful medical therapy that have done by far more good than harm, and that advances in the drugs available since the first penicillins and sulfa drugs of the 30s have made them ever safer and more effective. It is important, especially when dealing with the pharmacophobia of much of the alternative medicine community, not to lose sight of the historical context when examining some of the problems with these drugs and how they are used.

The authors then state clearly, and with an unusual literary flair, the nature and complexity of the problem with inappropriate antibiotic use.

The imprecision of clinical practice establishes the context; the litigious nature of society unnerves; the absence of toxicity permits; and the sum of these encourages the incontinent, extemporaneous use of antimicrobial agents…

The term spiraling empiricism describes the inappropriate treatment, or the unjustifiable escalation of treatment, of suspected but undocumented infectious disease. Empiricism and empirical therapy, defined as the carefully considered, presumptive treatment of disease prior to establishment of a diagnosis, often are necessary in the proper practice of medicine. On the other hand, ill-considered or inappropriate use of antibiotics, incurring unnecessary risk and expense, should be indicted and condemned. The difficulty lies in distinguishing reasonable or appropriate from unreasonable or inappropriate therapy.

I would suggest that in veterinary medicine the role of “imprecision” is relatively greater and the role of litigation relatively smaller in driving inappropriate use of antibiotics, or indeed any therapy, but the general problem is broadly similar to that in human healthcare.

The article then presents a simplified conceptual framework for the options available to a clinician faced with the possibility of infection in a given patient. The examples (which I have omitted) are specific to human medicine, but the general approach is easily applicable to veterinary medicine, and provides a lot of insights into where medical decision making can go wrong.

Table I. Features and Objectives of Various Therapeutic Options

The first option, Observation, is often the hardest for both vets and clients. So many diseases get better without intervention (which is why so many ineffective therapies appear to work), but without being able to predict which will and which won’t, it is very hard to simply wait and see. There are, of course, clear reasons not to simply observe in many cases: the severity of the symptoms, the likelihood of specific diagnoses which are less treatable when treatment is delayed, and many other factors. But just as we don’t (or shouldn’t) go to our doctor and demand antibiotics for every little viral respiratory infection, since the drugs have risks and costs and won’t help anyway and since we will almost certainly get better on our own, so we as doctors should resist the temptation to treat illnesses that are mild and likely to get better on their own (feline upper respiratory viruses, mild acute diarrhea, low-grade fevers in otherwise normal patients, etc).

And not only should we resist the temptation to treat these patients with antibiotics or anti-inflammatories without a sound rationale for doing so, we should resist the temptation to pretend to treat them with “safe and natural” remedies that are likely to do nothing other than create the false impression we’ve fixed something when the patients spontaneously get better (homeopathy, energy medicine, many vitamins and supplements, etc).

Preventative use of antibiotics is a bit clearer an option, though it is still important to base our prophylactic use of these medications on sound evidence that they are needed. The prophylactic use of antibiotics in dogs with heart murmurs undergoing dentistry, for example is a commonly accepted practice, yet there is some evidence that it may be unnecessary. There are also other studies which cast doubt on the effectiveness of prophylactic antibiotic use before some kinds of surgery, so we must be careful not to indiscriminately use such drugs “just in case” or to compensate for poor surgical technique unless there is sound evidence to support the practice. Nothing with a benefit is without risks and costs, and we must balance this equation as carefully as possible given the available information.

Empiric Therapy, as defined above, is a common practice. Given some indication of an infection (fever, increased white blood cell count, etc), but before the necessary steps have been taken to establish a true diagnosis (or, unfortunately, in some cases instead of taking these steps), antibiotics are given to treat a range of possible causes of the clinical symptoms. This can be a mistake in a simple and direct way if the patient doesn’t have an infection but develops an adverse reaction to the antibiotics. However, a less obvious pitfall with this kind of approach is the possibility of delaying or missing the true diagnosis, especially when the symptoms improve after the drugs are given and we assume, sometimes mistakenly, that the drugs are responsible and that our suspicions of infection were correct. This post hoc ergo propter hoc bedevils us in medicine all the time, and this is one of the most common circumstances in which it does so. Just because we do something and the patient’s condition changes, it is not automatically true that we deserve the credit (or blame) for the change.

Empirical Therapy is distinct from a Therapeutic Trial, in which a specific infection is suspected and a specific antibiotic treatment is begun with the patient’s response used to support or contradict the presumed diagnosis. The difference is that the odds of a this-then-that relationship in time reflecting a true causal relationship is greater if there is a reasonable prior probability, based on factors other than the treatment, of there being such a relationship.

In a simpler example, if a dog has a cough and a chest x-ray shows a mass in the lung, the chance that the mass is truly relevant is fairly high. But if a dog with diarrhea has a chest x-ray that shows a mass, there is little reason to think the x-ray finding is relevant to the symptoms. A relationship between a potential cause and an effect is more likely to exist if there are multiple different lines of evidence supporting such a relationship. So if all the clinical symptoms are classic for a particular bacterial infection, and the symptoms go away on an antibiotic sited to that organism, then a cause/effect relationship between treatment and response is fairly likely. However, if the symptoms (such as a fever) could be due to any of a hundred diseases, and the symptoms go away after treatment for one of them, we cannot confidently use this fact to conclude the patient had that one disease.

Of course, even a therapeutic trial can lead to an erroneous conclusion. I once treated a young dog with a fever, neck pain, and a high white blood cell count with antibiotics, under the reasonable suspicion that it had an infectious meningitis (the owner declined the invasive and expensive tests to confirm my suspicion). The patient got better and I basked in the glow of my own self satisfaction. Until a few months later when it came back with the same signs and didn’t get better on antibiotics. Eventually, it became clear that the pet had symptoms every time it came into heat, and  that it was a non-infectious immune-mediated meningitis which responded to steroids. Once the dog was spayed it never recurred.

Finally, Specific Therapy is treatment of a particular disease we have actually diagnosed. Obviously, this is far more likely to be effective and to have a positive benefit to risk ratio than relatively blind empirical therapy.

The authors then go on to list a number of misconceptions doctors have about empirical antibiotic therapy, which again could apply just as well to many other kinds of medical intervention.

Table II. Fallacies in Antibiotic Therapy

In his discussion of the article, Dr. Crislip expands on each of these fallacies, and adds a couple. Some of his comments are worth reproducing here.

When in Doubt, Change Drugs or Add Another

Medicine is filled with uncertainty, and often it is the case that if an infection is thought of, it is treated, no matter how unlikely it is that it may be causing the disease. I have a fantasy where oncology is practiced like infectious disease. “It might be lymphoma, so lets start with CHOP, but we don’t want to miss adenocarcinoma, so lets add bleomycin, and in case its breast cancer we need to include tamoxifen and if could be prostrate so lets add etc , etc.”

When in doubt, increase your diagnostic certainty.

Response implies diagnosis

This is the most difficult fallacy for people to abandon. Patient has a fever, no diagnosis is evident, but the fever went away at some point after the institution of antibiotics.

Most fevers go away. Many diseases that are not infectious will have a fever. This is the medical equivalent of the skeptical motto ‘association is not causation’. The worst cognitive error physicians and patients make is the assumption, the Rigorously absence of a good diagnosis, that the improvement when a therapy is given is due to the therapy.

Rigorously and consciously avoiding this error is key to being a good health care provider.[emphasis added]

Some antibiotics are a big gun, are strong, or powerful

There are few things in medicine with 100% sensitivity and specificity. However, if your health care provider uses the adjectives big gun, strong, or powerful in reference to an antibiotic, they are either 1) talking out their backside or 2) ignorant about antibiotic use. 100% sensitive and specific

If I had neurosyphilis…, the ‘strong’ or ‘powerful’ ciprofloxicin would do nothing to treat my infection, put ancient, weak old penicillin remains the treatment of choice. What you want is to give are appropriate antibiotics: something that will reliably kill the organisms in whatever space is infected. These adjectives are advertising ploys used on fool gullible rubes, er, I mean health care providers, to think they are doing what is best for their patient. They provide a false security that you are giving the patient the best therapy.

  

The primary reason a particular antibiotic is given is that “I like it.

I like to say that the three most dangerous words in medicine, especially when it comes to therapeutic interventions, are “In my experience.” In my experience you can’t trust anyone who uses that phrase. Remembering hits and forgetting misses drives antibiotic use more than I would like to admit. Infectious disease docs are sometimes the opposite. We put too much emphasis on the antibiotics that have failed us in the past. It is o e extreme or the other.

Patient is admitted with a complicated infection and started on X. Why X? I ask. It worked for me in the past is the reply. What are you trying to kill? I might then ask. Often, they say the boogie man of the ICU, Pseudomonas. What I will continue, is the chance drug X will be effective against Pseudomonas? They don’t know. So why again are you using X? It is what we do. They have used it successfully in the past, so it should work again.

Sigh.

Fortunately, most drugs work most of the time in most patients, but that rule is slowly being lost as the organisms become increasingly resistant to our current armamentarium of antibiotics and there are few, if any, replacements in the pipeline. At my institution there is 2% resistance for Pseudomonas to Ceftazadime and 4% to pipercillin/tazobactam. We get a few cases a year at best of a blood stream infection and sepsis from Pseudomonas. Most physicians are not going to see enough infections by a given organism to get a sense of what does and does not work. It is why you cannot trust your experience.

And finally, what could easily be a motto for the whole project of evidence-based medicine:

But often getting the right diagnosis and therapy is less about what you know and more about being rigorous about understanding how you know. Only when you are conscious of your ability to think poorly, can you compensate.

References

1. Kim JH, Gallis HA. Observations on spiraling empiricism: its causes, allure, and perils, with particular reference to antibiotic therapy. Am J Med. 1989 Aug;87(2):201-6.

Posted in General, Science-Based Veterinary Medicine | 2 Comments

Integrative Medicine or Bait-and Switch?

Posted on February 13, 2011 by skeptvet

For a while now, the Huffington Post has been providing a platform for a prominent voice in the alternative veterinary medicine community, Dr. Richard Palmquist. Dr. Palmquist is involved in the American Holistic Veterinary Medical Association (AHVMA), and has had some rather unkind things to say about CAM skeptics in general, and about my criticisms of the AHVMA in particular. It is unfortunate that someone whose ideas are so far outside the mainstream has been given such a prominent pulpit for disseminating misinformation, and that pet owners are unlikely to realize that Dr. Palmquist’s theories do not accurately represent the science of veterinary medicine or the opinions of most veterinarians.

He must be given credit, however, for representing his position skillfully. One element to putting a positive PR spin on unproven or disproven remedies is the technique known as bait-and-switch (though it is more commonly referred to as “integrative medicine”). This involves recommending or using widely accepted conventional therapies based on scientific reasoning and evidence, and then tagging on unproven therapies or pure nonsense treatments as if they were in the same category. In his most recent post, Dr. Palmquist discusses allergies, which in dogs and cats usually manifest as itching and infections of the skin in response to allergens from fleas, food, or environmental sources (such as dust mites, pollens, etc). There is a good deal of sound scientific research on allergies in pets, and the veterinary dermatology community regularly provides summaries of the research in statements on Evidence-Based Allergy Treatment.

Much of Dr. Palmquist’s post is perfectly consistent with a scientific understanding of the cause and treatment of allergies. He discusses antihistamines, corticosteroids, immunotherapy (aka allergy shots), limited antigen diets, and fish oil supplements, all of which are therapies supported by reasonable plausibility and research evidence. In this discussion, of course, he continuously minimizes the benefits and expounds at length on the potential risks, a clear effort to bias the reader against these therapies while ostensibly acknowledging that they have proven efficacy.

In particular, he harps on the notion that antihistamines and steroids “turn off” parts of the immune system. This sounds like a terrible thing, because everyone knows the immune system is necessary to protect us from infectious disease. So are we compromising the defenses of our patients with these drugs? If properly and judiciously used, no. The implication ignores the complexity of immune function and the effects of anti-inflammatory medications, probably deliberately in order to increase the negative associations people may have in their minds with these medicines.

In response to stimuli, such as infectious agents or allergens, cells in the immune system release chemicals, called cytokines, which lead to the classic inflammatory response: redness, swelling, itching or pain, and sometimes systemic effects such as fever or lethargy. Inflammation is not inherently a good thing. In fact, it can be quite harmful. While a mild fever may help fight off an infection, a high fever that causes brain damage is clearly doing more harm than good. And while activation of the immune system in an effort to fight off disease-causing organisms is a good thing, allergies are by definition an inappropriate activation of the system against proteins that are not inherently harmful. They are uncomfortable chronic diseases caused by excessive, unnecessary activity of the immune system. Even worse are auto-immune diseases, like lupus, hemolytic anemia, and so on, are serious, even deadly consequences of inappropriate immune-system activity. So the implication that turning off part of the immune system is a dangerous or unnecessary part of treating diseases that manifest as excessive immune system activity is nonsense. Suppressing excessive inflammation is exactly what is needed to treat the discomfort or even serious harm these diseases can cause.

It is possible, of course, to increase a patient’s susceptibility to disease with excessive or prolonged use of anti-inflammatories, and undoubtedly some doctors do not use these drugs judiciously. But anything in medicine that has a benefit has a potential risk, and it is disingenuous of Dr. Palmquist to focus primarily on the risks of conventional therapies and the unproven but assumed benefits of alternative methods regardless of the state of the evidence.

Of course, the agenda behind this damning with faint praise of conventional treatments is to build a case for the alternative treatments with which he concludes his article. He first includes limited antigen diets in his list of alternative treatments, though it is a widely accepted conventional therapy, probably because of the mistaken notion that any treatment that is not a drug must be a form of alternative medicine. He also includes fish oils, which are another treatment widely used in conventional medicine, though with only limited supportive evidence.

His descriptions of herbs and supplements, homeopathy and homotoxicology, and other such alternative therapies fairly glow with praise: “can be amazing,” “allergic responses can vanish entirely,” etc. And with the sole exception of high-dose Vitamin C supplementation, no potential risks or unwanted effects are mentioned for any of these treatments.

Dr. Palmquist does state that, “The scientific evidence varies for these methods,” and he supports this statement by reference to the summary of evidence-based allergy treatment I referred to above. However, with the exception of diets and fish oils (neither truly alternative) and phytopica (which Dr. Palmquist doesn’t mention), this review does not provide any evidence in favor of alternative therapies, and in fact it mentions almost none of those he recommends. There is no legitimate scientific evidence to support the utility of acupuncture, Traditional Chinese Medicine theory, homeopathy, homotoxicology, glandular extracts, or digestive enzyme supplementation in the treatment of pet allergies. And most of the herbs and supplements he recommends have little to no evidence to support veterinary allergy use. And yet he discusses these therapies as if they were as effective, and certainly safer, than the proven conventional therapies he so lukewarmly discussed at the beginning of the article.

No question this is a slick bit of propaganda designed to cast doubt on the safety of conventional therapies and to guide readers towards unproven or outright useless alternatives that are presented as if they were legitimate, accepted therapies of proven safety and efficacy. There is an impressive list of supporting references, though many of them are either books written by other proponents of alternative therapies, or articles which, like the dermatology task force review, don’t actually support the safety and efficacy of the alternative therapies being promoted. Some are legitimate studies investigating the safety or efficacy of conventional treatments, but the purpose is clearly not to review the available treatments fairly but to build a public relations case for alternative and against conventional science-based allergy treatments. Though I’m sure Dr. Palmquist feels this is for the greater good, since he is a true believer in the therapies he promotes, in reality such misinformation presented as if it were established fact and biased towards the unproven is not truly in the best interests of our patients or clients.

Posted in General | 10 Comments

From Science-Based Medicine: Complementary and Alternative Medicine in Hospice Care

Posted on February 3, 2011 by skeptvet

From the Science-Based Medicine Blog: Complementary and Alternative Medicine in Hospice Care

A number of news outlets (e.g. Bloomberg Business Week, MSN.Com, US News, etc) have recently reported that use of complementary and alternative therapies (CAT) is widespread in hospice care facilities. This is based on a report from the Centers for Disease Control, Complementary and Alternative Therapies in Hospice: The National Home and Hospice Care Survey, Untied States, 2007. According to most news reports, about 42% of hospice care providers offer some kind of CAT.

I was initially inclined to find this a little worrisome. In my own field of veterinary medicine, advocates of alternative therapies are prominent among the organizers of the nascent hospice care movement. And while I am strongly supportive of better and more available veterinary hospice care, the involvement of CAM advocates raises the concern that animals at the end of their life might receive ineffective palliative care, or be denied the benefits of conventional treatments by some CAM providers, who often characterize “allopathic” treatments as “unnatural” and harmful.

In practice, I have seen this happen to patients with terminal diseases. I will never forget a Rottweiler dog I diagnosed with osteosarcoma, a very painful bone cancer, whose owner was convinced that homeopathy was adequate to control his pain and refused to use NSAIDs because of her conviction they were “toxic.” I have also seen my patients denied euthanasia even in the face of great suffering because so-called “animal communicators” claimed the pet was “not ready to leave” and had expressed a desire to remain with their owner as long as possible.

Perhaps these experiences have made me overly sensitive on this subject, but I saw these recent news reports and pictured people at the end of their lives being similarly denied effective palliative care or subjected to pointless therapies like homeopathy and “energy medicine,” or even more worrisome treatments like chiropractic or herbal remedies with real risks. However, a little digging into the details suggests that the headlines are a bit misleading, and these fears are probably unfounded.

As always, when trying to assess how popular alternative medical therapies are, the tricky issue arises of defining “alternative.” In this study, the authors referenced the MedlinePlus definition:

Complementary and alternative medicine (CAM) is the term for medical products and practices that are not part of standard care. Standard care is what medical doctors, doctors of osteopathy and allied health professionals, such as registered nurses and physical therapists, practice. Alternative medicine means treatments that you use instead of standard ones. Complementary medicine means nonstandard treatments that you use along with standard ones. Examples of CAM therapies are acupuncture, chiropractic and herbal medicines.

Personally, I prefer Dr. Novella’s definition:

CAM is a political/ideological entity, not a scientific one. It is an artificial category created for the purpose of promoting a diverse set of dubious, untested, or fraudulent health practices. It is an excellent example of the (successful) use of language as a propaganda tool.

In any case, in order to measure the popularity of something, one has to define it in some way, and in the past assessments of how popular or widespread CAM use is have created misleading impressions due to dodgy definitions. For example, the 2007 National Health Interview Survey (discussed in detail here) reported 30% of Americans to be regular CAM users. A closer look at the details of the survey, however, showed that very little of this self-reported usage involved the application of the usual dubious CAM approaches (e.g. acupuncture, chiropractic, homeopathy, various herbal traditions, etc) to treat specific medical problems. Much of this supposed CAM usage involved the non-medical application of massage, yoga, tai chi, prayer, and so on to provide psychological comfort or facilitate relaxation.

Of course, if one argues that massage, yoga, or even prayer are effective in reducing the objective signs or disease, or even bringing about a cure, then one could argue these are forms of alternative medicine. But such methods are mostly employed to provide comfort and help patients cope with their illness, and as such they can be valuable and legitimate interventions. This does not make them medical therapies, however, alternative or otherwise.

The hospice care survey suffers from the same kind of problematic definition for “complementary and alternative.” According to the report’s technical notes, providers of hospice care were asked first to choose all the services they offered from a list, and “Complementary and Alternative Medicine (CAM)” was one of the choices. Those that indicated they offered CAM were then asked to indicate “Which of these complementary and alternative medicine therapies does this agency use?”

Here is the list:

  1. Acupuncture
  2. Aromatherapy
  3. Art therapy
  4. Guided imagery or relaxation
  5. Massage
  6. Music therapy
  7. Pet therapy
  8. Supportive group therapy
  9. Therapeutic touch (a westernized version of reiki)
  10. TENS (Transcutaneous Electrical Nerve Stimulation)
  11. Other

Personally, I see little on this list that I would classify as CAM. Acupuncture, certainly, along with therapeutic touch (like reiki) and aromatherapy. But most of the rest, unless specifically marketed as treatments for disease, seem more like benign, pleasurable activities designed to provide comfort, relaxation, and enjoyable stimulation. As a veterinarian, I work with a lot of pet therapy dogs, and I have yet to run across a handler of one who thought they were practicing alternative medicine! (Though I suppose there might be some such folks out there). And TENS is a perfectly conventional intervention, often somewhat disingenuously confused with acupuncture.

The most popular of the “true” CAM therapies offered was therapeutic touch, available at 48.3% of facilities. Aromatherapy was offered by 39.7% of hospice providers. I cannot even find a number for acupuncture in the report. And by far the most popular “alternative” therapies offered were massage (71.7%), group therapy (69%), music therapy (62.2%), and pet therapy (58.6%).

The report also indicates that only 8.6% of patients discharged from a hospice facility that offered CATs actually received one of these therapies. So even under such a loose definition of alternative, there is no evidence that large numbers of hospice patients are receiving alternative medical treatments.

It wouldn’t surprise me if we begin to see advocates of alternative medicine proclaiming that this report shows CAM is widely available, popular, and even indispensible in hospice care. The 2007 National Health Interview Survey results were frequently used this way to create the impression that CAM is becoming mainstream and that resistance to it is the province of extremists and ultimately futile. The details of both surveys, however, indicate that even with aggressive expansion of the definition of CAM to include conventional therapies such as TENS and non-medical interventions like pet therapy, CAM is not truly as popular ubiquitous as its proponents claim.

There is little objectionable from a science-based medicine perspective in most of the therapies hospice care providers are offering, according to this study. I enjoy a good massage, relaxing music, and the company of a friendly dog as much as anyone. And those elements that are truly nonsense, such as therapeutic touch and aromatherapy, are unlikely to do harm or replace appropriate conventional therapies, and they seem in any case not to be especially popular with patients even when they are available. So regardless of what PR use is made of this study, it does not suggest that human hospice care is becoming predominantly the domain of CAM providers, as I might have feared. I only hope the same will be true of veterinary hospice care as that becomes, hopefully, more commonplace.

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Handlers Can Unintentionally Influence Detection Dog Performance

Posted on February 2, 2011 by skeptvet

A recent study in the journal Animal Cognition involving drug and explosive detection dogs has been widely reported in the online media (e.g. Medical News Daily, Sacramento Today, etc). The study, conducted at the University of California at Davis, was cleverly designed to explore the unconscious influence of detection dog handlers on their canine partners. It provides an excellent example of how greatly the beliefs and expectations of humans can unintentionally affect the behavior of dogs, even when both the human and the dog are highly trained professionals. The study is interesting in its own right, but it is also relevant to veterinary medical research since the problem of the unintended effects of human beliefs and expectations creates significant challenges for assessing the efficacy of veterinary medical therapies.

In this study, 18 detection teams were tested in each of 4 different rooms, none of which contained any explosives or drugs as a target. Therefore, any positive alert response from the dogs was an incorrect (or false positive) response. Handlers were told that a red piece of paper would be present in some rooms and would indicate the location of a substance the dog should detect. In reality, this piece of paper was a decoy intended only to create and expectation in the mind of the handlers that their dogs should exhibit a positive response. The 4 rooms contained the following:

1. No target, no paper decoy for the handler, no scent decoy for the dog

2. No target, a paper decoy for the handler, no scent decoy for the dog

3. No target, no paper decoy for the handler, a scent decoy for the dog (sausages and tennis balls)

4. No target, a paper decoy for the handler at the same location as a scent decoy for the dog (sausages and tennis balls)

Each of the teams was tested in each room, and there were a total of 225 incorrect responses (in which the dog sat/lay down and/or vocalized as it had been trained to do to indicate it had detected a target substance). There were false responses in all rooms, but interestingly there were more mistakes in the rooms with only a paper decoy for the handler than in those with a scent decoy for the dog. This would seem to suggest that the unconscious behavioral cues given by the handler affected the dogs’ performance even more than the presence of food or toys!

It is easy to see the implications of this finding for veterinary medicine. Many of the symptoms we look at in evaluating the effect of treating a patient, and many of the variables we measure in research studies of medical treatments, rely on owners or veterinarians observing the behavior of our animal patients. Most attempts to assess pain, itching, activity level, nausea, appetite, behavior and many other key indicators of health are ultimately dependant on subjective interpretation by owners and veterinarians.

We already know that our own expectations and biases can influence what we see and how we interpret it. That is, after all, the major basis for the placebo effect, and why it disappears when we don’t know if the patient is getting a real treatment or a placebo.

But what this study suggests is that the patients’ behavior is likely also affected by our expectations and biases. This is yet another element to the placebo-by-proxy effect, in which ineffective therapies are believed to be working because of non-specific treatment effects (aka placebo) on the owners or the doctors evaluating the treated patients. One of the best examples of this is the use of glucosamine for arthritis in pets, which the balance of the evidence pretty clearly shows doesn’t work but which many veterinarians and owners cling to tenaciously as a useful therapy regardless.

A study like this one shows quite clearly how our expectations and beliefs strongly effect the behavior of our dogs. And this was a study of experienced professional handlers who undoubtedly had been trained in how to avoid misleading their canine partners. Those of us without such training or unaware of the risks of such unconscious influences are likely at even greater risk for unintentionally changing our pets’ behavior in ways that conform to our beliefs. Could our dogs play more, scratch less, eat better, seem happier, or otherwise appear to benefit from treatments we give them partly because we want them to and we expect they will? This study suggests the answer is “Yes!” and reinforces the importance of properly controlled research in evaluating medical therapies.

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California Veterinary Medical Association Campaign Against Unlicensed Treatment of Animals

Posted on January 30, 2011 by skeptvet

There must be something in the air. Lately, I’ve run across a number of stories about regulatory agencies trying to crack down on illegal or unsupported medical claims, in Switzerland and the United Kingdom. I am a bit pessimistic about the practical effects of these efforts, but it is always good to see any attempt to promote science and reason as key elements in the regulation of medicine. Now a private veterinary group, the California Veterinary Medical Association (CVMA) is getting into the act (well, sort of).

Professional veterinary associations such as the CVMA and the national AVMA, are lobbies for veterinarians, and they are membership organizations. As such, they tend not to take strong stands on issues about which there is any controversy among their members. For example, since proponents of “holistic” and other alternative veterinary medical approaches are active members of such groups, the organizations rarely make any but the most superficial and vague statements about the scientific legitimacy of CAM practices or the importance of evidence-based standards of care. However, such lobbies are aggressive in protecting the turf of veterinarians, which tends to lead to a tacit position of “Anything goes, so long as it is a licensed vet doing it.” As disappointing and irresponsible as this is, it is probably an inevitable outcome given the internal politics of these groups.

The CVMA recently announced a vigorous Illegal Practice Campaign. According to the organization’s statement:

The CVMA is strongly opposed to the illegal practice of veterinary medicine by unlicensed persons providing illegal services in unregulated locations. We further promote and support efforts by the California Veterinary Medical Board and the Department of Consumer Affairs to enforce criminal sanctions against unlicensed activity, thereby protecting the consumer and safeguarding the health and welfare of animals.

The CVMA conducted a survey of its members, and many reported illegal treatment of animals by unlicensed individuals. Most of these reports came from clients, who told their veterinarians about having used such services, or from advertisements. The largest single treatment was anesthesia-free teeth cleaning, reported by 62% of veterinarians. This is a procedure once commonly offered by veterinarians, but it is now generally believed to be useless in the prevention or treatment of dental disease and so it has been replaced by dental cleanings performed under anesthesia 

Interestingly, the next most commonly reported activity was chiropractic treatment of animals, reported by 32% of veterinarians. As I have discussed before, the California Veterinary Practice Act is very specific about the requirements for chiropractic treatment of animals. The full text is copied at the end of the post, but in brief:

1) First that a vet examine the pet, determine that MSM is appropriate and safe, and take official responsibility for supervising the treatment.

2) Then the owner is supposed to sign a form as follows: (This is a direct quote from the regulations) “The veterinarian shall obtain as part of the patient’s permanent record, a signed acknowledgment from the owner of the patient or his or her authorized representative that MSM is considered to be an alternative (nonstandard) veterinary therapy.”

3) Then a licensed chiropractor can examine the pet, determine that MSM is appropriate, and then consult with the supervising vet before performing treatment.

Other common unlicensed activities reported by small animal veterinarians included vaccination and acupuncture. And in its report on the subject to veterinarians, the CVMA emphasized that veterinarians are violating the law when they refer clients to unlicensed providers of veterinary services.

This campaign is being marketed in terms of “protecting the consumer and safeguarding the health and welfare of animals.” I have no doubt this is a genuine motive behind this campaign. I have seen the harm irrational therapies can inflict on pets, both directly and by interfering with the use of appropriate scientific diagnostic and treatment interventions.

Unfortunately, it is hard not to suspect that protection of the territory and livelihood of veterinarians is  also part of the motivation for this campaign. The campaign is very specific in targeting interventions performed by unlicensed individuals, which is appropriate, while also ignoring the problem of veterinarians utilizing bogus, unscientific therapies, which is not appropriate. As an organization made up of veterinarians, this inconsistency is probably unavoidable, but it is disappointing nonetheless.

Nevertheless, if veterinary licensure and regulation is to have any meaning, and to be of any value in protecting animals and their owners, the regulations must be enforceable, so I thoroughly support the CVMA campaign. Hopefully, this campaign will improve enforcement of these consumer protection laws and discourage these practices, though I fear it may only shift the application of unproven or useless therapies to the domain of veterinarians, which would largely undermine the benefit for the public.

I think it is significant that two prominent alternative therapies are among the most commonly offered illegally to pet owners. Proponents of such therapies often believe passionately in their value despite the evidence against them, and they are ideologically inclined to view any regulatory limitations on their activities as solely protectionist rather than as an attempt to protect the public from unproven or unsafe treatments. This makes ignoring the law seem almost like a moral duty. And despite the fact that groups such as the CVMA may have some self-serving motives in acting against such practices, this is no different from the self-serving motives chiropractors and acupuncturists have in offering their therapies to pet owners illegally, so this issue doesn’t alter the fact that providing such services is illegal and not supported by legitimate scientific evidence.

The CVMA also states that in addition to encouraging enforcement of existing laws and regulations, “Our next step is to introduce legislation to strengthen the laws…” This campaign could be improved, and made more effective in protecting animals and their owners, if this new legislation included language setting rational, science-based standards of veterinary care. As I recently discussed with respect to the AVMA model practice act, language in medical practice acts regulating MDs would be appropriate for veterinary regulations as well, such as sanctioning “employing methods of treatment or diagnosis that do not conform to the standards of acceptable and prevailing scientific medical practice.” It would be a powerful (and surprising) act of principle for the CVMA to propose such language in veterinary practcie laws, since this would involve actually regulating the therapies offered by licensed veterinarians, which veterinary organizations have historically been loath to do.

California Veterinary Practice Act: Animal Chiropractic (Musculoskeletal Manipulation)

2038.  Musculoskeletal Manipulation.

(a) The term musculoskeletal manipulation (MSM) is the system of application of mechanical forces applied manually through the hands or through any mechanical device to enhance physical performance, prevent, cure, or relieve impaired or altered function of related components of the musculoskeletal system of animals. MSM when performed upon animals constitutes the practice of veterinary medicine.

(b) MSM may only be performed by the following persons:

(1) A veterinarian who has examined the animal patient and has sufficient knowledge to make a diagnosis of the medical condition of the animal, has assumed responsibility for making clinical judgments regarding the health of the animal and the need for medical treatment, including a determination that MSM will not be harmful to the animal patient, discussed with the owner of the animal or the owners authorized representative a course of treatment, and is readily available or has made arrangements for follow-up evaluation in the event of adverse reactions or failure of the treatment regimen. The veterinarian shall obtain as part of the patients permanent record, a signed acknowledgment from the owner of the patient or his or her authorized representative that MSM is considered to be an alternative (nonstandard) veterinary therapy.

(2) A California licensed doctor of chiropractic (chiropractor) working under the direct supervision of a veterinarian. A chiropractor shall be deemed to be working under the direct supervision of a veterinarian where the following protocol has been followed:

(A) The supervising veterinarian shall comply with the provisions of subsection (b)(1) prior to authorizing a chiropractor to complete an initial examination of and/or perform treatment upon an animal patient.

(B) After the chiropractor has completed an initial examination of and/or treatment upon the animal patient, the chiropractor shall consult with the supervising veterinarian to confirm that MSM care is appropriate, and to coordinate complementary treatment, to assure proper patient care.

(C) At the time a chiropractor is performing MSM on an animal patient in an animal hospital setting, the supervising veterinarian shall be on the premises. At the time a chiropractor is performing MSM on an animal patient in a range setting, the supervising veterinarian shall be in the general vicinity of the treatment area.

(D) The supervising veterinarian shall be responsible to ensure that accurate and complete records of MSM treatments are maintained in the patients veterinary medical record.

(c) Where the supervising veterinarian has ceased the relationship with a chiropractor who is performing MSM treatment upon an animal patient, the chiropractor shall immediately terminate such treatment.

(d)(1) A chiropractor who fails to conform with the provisions of this section when performing MSM upon an animal shall be deemed to be engaged in the unlicensed practice of veterinary medicine.

(2) A veterinarian who fails to conform with the provisions of this section when authorizing a chiropractor to evaluate or perform MSM treatments upon an animal shall be deemed to have engaged in unprofessional conduct.

Posted in Law, Regulation, and Politics | Leave a comment

Book Review: At Home by Bill Bryson

Posted on January 25, 2011 by skeptvet

For my infrequent book reviews I have tried to focus on books that are explicitly relevant to the issues and themes of this blog. However, I wanted to call attention to a very enjoyable book that, honestly, is only marginally related to science-based and alternative medicine, At Home by Bill Bryson.

It is an entertaining, historical buffet of domestic life that uses, as a very loose framing device, a tour of Mr. Bryson’s house to set up fascinating meanderings through the history of domestic life. What did people eat, wear, sleep on and so forth in the centuries leading up to modern diet, clothing, and furniture? Who really thought up the flush toilet? When was childhood invented? All sorts of intriguing and loosely related questions such as these are raised and at least partially answered. Most of this has little to do with my usual subjects. However, the book does offer a few illustrative examples of medical history which I want to share.

Two of the core problems in getting people to recognize the superiority of scientific methods over traditional ways of investigating health and disease are 1) a lack of appreciation for how dramatically more successful scientific medicine has been compared to the thousands of years of pre-scientific medicine and 2) a failure to understand how unreliable our commonsense and personal experience are when it comes to medicine. A knowledge of history can be a powerful tool in overcoming these problems. And Mr. Bryson provides a few very telling examples of pre-scientific medical theories and practices that persisted for hundreds or thousands of years despite being wildly wrong.

It is very important that I stress the true significance of these examples. It is not simply that previous generations had a lot of stupid or crazy ideas and gosh isn’t great that now we know better. Since the evolution of at least the Cro-Magnons, people have been just as smart as any of us around today. The wheel and the stirrup required just as much brain power to think up as the semi-conductor. Or, looked at from a different angle, we are just as blind and likely to be fooled as our ancestors. The lesson of medical history, how foolish ideas were born, spread, and became intractable dogma, is not that we are smarter now than our ancestors. The lesson is that we are, in fact, the same as the cavemen or the Sumerians, or the Romans, or the Victorians, and that foolish ideas can just as easily be born, spread, and become intractable dogma now as they ever could if we fail to accept our limitations and use the tools of science bequeathed to us.

What we have now that is fundamentally different from what preceding generations had is not a feature of ourselves. It is a method, an approach that our ancestors discovered and which we are still improving. And we have the information this method has generated, which we can preserve and transmit more easily than ever before and which we can build on. In short, we have science and the technologies it has helped us to produce.

One example of ideas about health that are now well-known to be false, but that made perfect sense to former generations is the relationship between sexual and reproductive functions and health. The Victorians, in particular, despite a technological sophistication greater than had previously been achieved, had some bizarre notions concerning sex and health. For example:

For men, the principal and preoccupying challenge was not to spill a drop of seminal fluid outside the sacred bounds of marriage–and not much there either, if they could decently manage it. As one authority explained, seminal fluid, when nobly retained within the body, enriched the blood and invigorated the brain. The consequence of discharging this natural elixir illicitly was to leave a man literally enfeebled in mind and body. So even within marriage one should be spermatozoically frugal, as more frequent sex produced “languid” sperm, which resulted in listless offspring. Monthly intercourse was recommended as a safe maximum.

It is relatively easy to imagine how such notions could arise, and in the absence of rigorously controlled observations they would be perpetuated by “authorities” in medicine. Case studies (a “sciency” word for anedcotes or testimonials) were used to support such notions, just as they are all too often used to justify medical theories and practices today:

Case studies vividly drove home the risks. A medical man named Samuel Tissot described how one of his patients drooled continuously, dripped watery blood from his nose, and “defecated in his bed without noticing it.”

It may seem obviously ridiculous to assign blame for such symptoms to a history of masturbation, as this “authority” did, but the apparent correlation was undoubtedly just as obvious to medical practitioners of the time, and it is only through systematic, controlled observations that we can weed out such spurious, fanciful connections from true cause/effect relationships.

Another bizarre and quite long-standing notion about health that we have fortunately discarded, concerns the subject of cleanliness. The Romans were fond of frequent, lengthy, and complicated bathing practices for many reasons, including the belief it promoted health. However, with the rise of Christianity in Europe, and the loss of classical knowledge during the Middle Ages, this idea was reversed.

Christianity was always curiously ill at ease with cleanliness anyway, and early on developed an odd tradition of equating holiness with dirtiness. When Thomas a Becket, archbishop of Canterbury, died in 1100, those who laid him out noted approvingly that his undergarments were “seething with lice…”

Then in the Middle Ages the spread of plague made people consider more closely their attitude to hygiene and what they might do to modify their own susceptibility to outbreaks. Unfortunately, people everywhere came to exactly the wrong conclusion. All the best minds agreed that bathing opened the epidermal pores and encouraged deathly vapors to invade the body. The best policy was to plug the pores with dirt. For the next six hundred years most people didn’t wash, or even get wet, if they could help it–and in consequence they paid an uncomfortable price. Infections became part of everyday life. Boils grew commonplace. Rashes and blotches were routine. Nearly everyone itched all the time. Discomfort was constant, and serious illness was accepted with resignation.

Again, it is easy but misguided to snicker at such notions and congratulate ourselves on our more enlightened understanding. It is not our superior intelligence, nor even solely the invention of the microscope and its aid in the discovery of germs, that allows us to scoff at such beliefs. Even with the technological and historical advantages we possess, equally absurd notions concerning hygiene exist today: from colon cleansing to detoxification to the surprising number of chiropractors and other alternative medicine advocates today who still deny the germ theory of disease.

Interestingly, the notion that clogging one’s pores with dirt is healthy was replaced by the equally bogus notion that clogged pores were themselves a cause of disease. This seems eerily familiar to those of us confronted with contemporary theories about “toxins” and “accretions” in our colon promoted by advocates of some CAM methods.

Now instead of it being bad to have pink skin and open pores, the belief took hold that the skin was in fact a marvelous ventilator–that carbon dioxide and other toxic inhalations were expelled through the skin, and that if the pores were blocked by dust and other ancient accretions natural toxins would become trapped within and would dangerously accumulate. That’s why dirty people–the Great Unwashed of Thackery–were so often sick. Their clogged pores were killing them. In one graphic demonstration, a doctor showed how a horse, painted all over in tar, grew swiftly enfeebled and piteously expired.

Without systematic, controlled methods for observing how healthy and ill patients respond to preventative and treatment measures, were are destined to lurch blindly from one wild theory to another, even accepting mutually incompatible notions in sequence or at the same time, as so often happens in the world of CAM.

One of the classic examples of the critical importance of systematized observations and record-keeping, is the discovery of the cause of cholera. When cholera was rampaging through the cities of England in the 19th century, nobody understood what caused it.

“What is cholera?” The Lancet wrote in 1853. “Is it a fungus, an insect, a miasma, and electrical disturbance, a deficiency of ozone, a morbid off-scouring of the intestinal canal? We know nothing.”

The most common belief was that cholera and other terrible diseases arose from impure air.

Many smart, educated people accepted this miasma theory, which had been around at least since classical times. The individual who first identified the real source of the cholera infection was John Snow. But more than this, he was a founding figure of modern epidemiology, a key component of modern evidence-based medicine.

Snow’s lasting achievement was not just to understand the cause of cholera but also to collect the evidence in a scientifically rigorous manner. He made the most careful maps showing the exact distributions of where cholera victims lived. These made intriguing patterns. For instance, Bethlehem Hospital, the famous lunatic asylum, had not a single victim, while people on the facing streets in every direction were felled in alarming numbers. The difference was that the hospital had its own water supply….while people outside took their water from public wells.

Of course, the habit of trusting conclusions derived from systematic observation wasn’t yet established (and isn’t always present today), so Snow’s explanation was dismissed during his own lifetime. And even today, relics of the miasma theory persist in some CAM disciplines, such as homeopathy which views microorganisms as causing disease not through their effects on the body but through changes in the spiritual “vital force” that are then transmitted to offspring; changes called miasms.

Finally, Bryson paints a picture of childhood that is horrific to the eyes of most modern citizens of prosperous industrial nations, but that represents the reality of the overwhelming majority of human history.

Life was full of perils from the moment of conception. For mother and child both, the most dangerous milestone was birth itself. When things went wrong, there was little any midwife or physician could do. Doctors, when called in at all, frequently resorted to treatments that only increased the distress and danger, draining the exhausted mother of blood (on the grounds that it would relax her–then seeing loss of consciousness as proof of success), padding her with blistering poultices or otherwise straining her dwindling reserves of hope and energy.

Such therapies were not employed because doctors were callous or stupid, but because they had only the authority of their mentors and the evidence of their own experience to guide them, and these things made such treatments look as though they were working even when they were killing the patient.

It is frequently claimed that among children in the pre-modern age, “one third died in their first year of life, and half failed to reach their fifth birthday.” Bryson discusses some more scientific statistics that suggest,

infant mortality was not quite as bad as figures now generally cites would encourage us to suppose. [In one city with detailed records], slightly over a quarter of babies died in their first year, and 44 percent were dead by their seventh birthday…Not until seventeen years had passed did the proportion of deaths…reach 50 percent.

When the most optimistic figures show 25% of infants dead by 1 year, 44% by 7 years, and 50% dead before what we now consider to be adulthood, it is a powerful statement about how dramatically the scientific method, applied to sanitation, nutrition, and healthcare, has changed the world as nothing before it ever did.

It is a cliché to say that those who are ignorant of the past are doomed to repeat it, but it is an apt and applicable cliché when it comes to much of modern unscientific medical theory and practice. The history of medicine has a lot to teach us about the dangers of relying on intuition, tradition, authority, anecdote, and personal experience in trying to understand and influence health and disease. And the dramatic impact of scientific methods on the well being of humankind is impossible to properly appreciate without an understanding of how people suffered before the advent of scientific medicine, and how ineffectual most approaches to understanding and relieving this suffering were in pre-scientific times. Winston Churchill is credited with saying, more or less, “Democracy is the worst possible system of government, except for all the others that have been tried.” The same is very much true of science and science-based medicine. It is full of flaws and shortcomings and is thoroughly imperfect. Yet it is far more effective than anything else we’ve ever tried, and history can teach us this.

Most of Bryson’s book is not about health and disease, or even science, but the myriad aspects of domestic life that we tend to take for granted. Whether or not one is interested in the history of medicine, it is a worthwhile book to read.

Posted in Book Reviews | 2 Comments

Neutricks(tm): Another Nutraceutical for Canine Cognitive Dysfnction

Posted on January 19, 2011 by skeptvet

Yet another product has entered the market aimed at treating Canine Cognitive Dysfunction Syndrome (CDS). This age-related brain disorder is analogous to dementia in elderly humans, and it involves a number of significant behavioral changes. Affected dogs may get lost in the house, they may have disrupted sleep and restlessness at night, they may show changes in social interactions with people and other animals, and they may experience a breakdown in housetraining. All of these are important symptoms that can adversely affect the quality of life for both pets and owners.

There are no dramatically effective treatments for this disorder, but there are plenty of remedies for sale. The prescription mechanism selegiline has been approved by the FDA for use in this condition, and there is some limited clinical trial evidence to support a benefit, however it is not by any stretch of the imagination a cure. As is typical for incompletely understood diseases with no clearly effective conventional treatment, CDS presents an attractive target for marketers of alternative therapies. And while it is laudable to seek to discover and promote a remedy for an otherwise untreatable disease, unfortunately most of the products targeted at CDS are brought to market well before adequate legitimate research confirms they are safe or effective. Rather than seeking an FDA label approval, which requires significant efforts to prove safety and efficacy, many companies prefer to market their remedies as supplements or nutraceuticals, taking advantage of the lack of effective regulation of such products.

I have previously written about nutraceuticals and CDS (updated here), but the newest product takes a novel approach. Rather than vitamins, antioxidants, or herbs, this product contains as its “active” ingredient apoaequorin, a protein found in certain jellyfish that has long been used in molecular biology research as a tool for monitoring the level of calcium inside of cells. The cleverly named Neutricks (as in “teach an old dog new tricks,” though I can’t help hearing an echo of the unrelated product Neuticals), supposedly reduces the symptoms of CDS by protecting nerve cells in the brain from damage associated with excessive calcium levels.

The company web site references a number of studies showing that injecting apoaequorin into rat brains can protect nerve cells from death when they are later removed from the rat and deprived of oxygen in test tubes (1, 2, 3). This is an interesting finding, but obviously a long way from showing that the product has any clinical benefits in dogs with CDS. Such preliminary animal model research is a necessary first step on the road to proving such a real-world benefit, but by itself it is totally inadequate to justify putting the product into your dog.

One very important step that the maker of Neutricks seems to have skipped (though, as always, I may simply not be able to find all the relevant information, so I am certainly open to being shown additional evidence) is demonstrating that the protein can be absorbed and get to meaningful levels in the brain of dogs when given orally. Proteins are usually destroyed in the stomach (that’s primarily what this organ is for), so many compounds that have significant effects when injected are useless taken orally. A classic example is rattlesnake venom, which can easily kill you when injected by the snake’s fangs into your body, but which is perfectly safe to drink.

The same company also markets apoaequorin as a supplement to treat symptoms of Alzheimer’s and dementia in humans, under the name Prevagen. The company is apparently enrolling and planning a large number of clinical trials studying apoequorin as a treatment for Alzheimer’s disease, other cognitive and memory disorders, autism, multiple sclerosis, Parkinson’s, and apparently any disorder whatsoever involving nerves and calcium. There is apparently only one clinical trial actually completed, and as another blogger has also already pointed out, this pilot trial of 56 participants was uncontrolled, unblinded, and methodologically quite weak. Again, such preliminary studies are appropriate to identify possible side effects or benefits that influence the decision to continue with further research, but they prove nothing and certainly do not justify marketing a product for actual use in patients.

(The company has also issued several press releases discussing “promising interim results” from a human trial involving apoaequorin and memory, but the details of the trial are not yet available, and no peer-reviewed publications of any results have appeared, so it is impossible to evaluate the quality or significance of the results)

As for veterinary research, the company apparently contracted an outside research firm to run a trial of Neutricks in dogs. The study involved 24 laboratory Beagles 9-17 years of age. The subjects were randomly assigned to a placebo group, a low-dose treatment group, and a high-dose treatment group. The subjects were selected from a larger group on the basis of preliminary testing to find animals that  reliably performed certain cognitive testing tasks but which “tended to perform at below maximal levels to allow for the possibility of seeing memory enhancement.” The treatments were given and testing done in a properly blinded manner.

The results of pre-treatment testing showed no difference in performance between the three groups. There were three cognitive tests administered: a delayed non-matching to position task (DNMP), a discrimination task, and an attention task. The results were as follows:

1. DNMP Task- No significant difference was seen in performance of the three groups. The report lists some post-hoc manipulation of the data which also show no statistically significant differences but the notorious “trend” often used to imply an effect where the data doesn’t actually show one.

2. Discrimination Task- The low-dose group showed a score and error rate statistically greater than the control and the high-dose group, which did not differ. This is, of course, the opposite of what you would expect if the agent worked since a dose-response relationship, in which the effect increases as the dose increases, is by far the most common result seen with effective medications. It seems most likely that this was simply the inevitable apparently positive result one sometimes sees when testing multiple effect measures in a clinical study. If it is repeatable in multiple studies and by different investigators, then it could turn out to be a real finding.

3. Attention Task- No significant differences between groups were seen in overall performance. The report keeps mentioning results that were “marginally significant” or “approaching significance,” but these are meaningless spin terms. The purpose of significance testing is only to decide, with a pre-determined level of assurance, whether the result could be due to random chance or not. If the usual cutoff of 5% (P=0.05) is used, then a significant result only means that the finding would appear by chance alone only 5 out of 100 trials. It doesn’t mean that the result is due to the effect of treatment or any other specific hypothesis. And when test results don’t reach this 5% level of probability, they are by definition not significant, period.

Some additional post-hoc manipulation of the data yielded a significant difference between the high-dose and the control groups in 1 out of 3 different conditions, with no difference at the other conditions or for the low-dose group.

No adverse events were reported.

Overall, the results of this trial clearly do not justify the clinical use of apoaequorin in treating CDS. The company has not apparently demonstrated even the most basic element in building a case for such use, that the product is absorbed when taken orally and reaches meaningful concentrations in the brain. They have not reported in vitro or laboratory model results that have any direct relevance to the pathology or clinical features of canine cognitive dysfunction. The clinical trial they are using as a marketing tool was conducted on healthy laboratory research Beagles, not owned pets with CDS, and even in this trial there were almost no significant effects seen in subjects getting the product.

Could it work? Sure.

Is there clear evidence it doesn’t work? No.

Is there any significant evidence of risk? No.

And finally, is there any meaningful evidence of beneficial effects? Nope.

So while I certainly would love to see additional, and more relevant testing of apoaequorin and the underlying hypothesis behind its  use, at this time it is just another example of selling wishful thinking to people without a lot of better options. I understand why desperate pet owners are willing to grasp at such straws, but I consider it ethically questionable, and certainly scientifically insupportable, to sell them.

Posted in Herbs and Supplements | 51 Comments

U.K. Veterinary Medicines Directorate Promises Crackdown on Unproven Alternative Remedies

Posted on January 17, 2011 by skeptvet

In December John Fitzgerald, the Director of Operations for the British Veterinary Medicines Directorate, announced that the regulatory agency will begin more aggressive supervision of medical claims made for alternative medicine products. According to the announcement,  

Some of these products are claiming to be effective and safe when no scientific evidence has been presented to us to show they are

Animal owners have a right to know if a product does what it claims. The products claim to treat diseases which can cause serious welfare problems and in some circumstances kill animals if not properly treated. So in some cases owners are giving remedies to their pets which don’t treat the problem

The agency will begin contacting manufacturers of homeopathic and herbal animal remedies and nutraceuticals to request scientific evidence of safety and efficacy. Unfortunately, if such evidence is not provided, the products will still be legal to sell, however they must remove any label claims suggesting a medical use of the product. Likely, manufacturers will then switch to the vague yet still misleading “structure and function” claims the FDA allows in the U.S. for herbs and supplements without adequate evidence to support true health claims.

Still, it is encouraging to see a government agency somewhere at least making the statement, which is bizarrely controversial in some circles, that before selling pet owners a medicine for their animals the manufacturer ought to prove the medicine actually works and isn’t harmful. Whether or not the VMD will be able to effectively enforce such a regulation given the ease of Internet marketing and distribution of home remedies is uncertain, but it’s nice to see them making the effort.

If nothing else, the publicity surrounding any attempt to sanction a company selling an unproven remedy, and the likely outcry from devoted users, will bring greater attention to the discussion of what is or is not real scientific proof, and will make it more likely that pet owners will at least know that scientists and the government do not accept the manufacturer’s claims. I suspect there are significant limitations to what government regulation can accomplish in terms of protecting the public from ineffective medical therapies, but it can certainly serve as a source of reliable information and a “bully pulpit” for the science-based perspective.

Posted in Law, Regulation, and Politics | 9 Comments

Complementary & Alternative Medicine in Veterinary Hospice Care

Posted on January 17, 2011 by skeptvet

There is a brief commentary (subscription required) in the current issue of the Journal of the American Veterinary Medical Association (JAVMA) on the subject of veterinary hospice care. I’ve written about this subject before, and I think it is one that deserves more attention and effort in the veterinary medical community.

Thanks in large part to the successful advances in preventative healthcare and treatment of disease, our pets are living longer. The natural consequence of this is that we are more frequently faced with the challenges of complex geriatric medicine and with individuals at the end of their lives who have multiple, often chronic diseases. These disease are generally not curable, but they can often be managed to provide a good quality of life for our patients. When we are able to accept the inevitability of death, which is difficult in our culture, then we can focus on trying to maintain a comfortable, satisfying life for our pets even as they are approaching the end of their lives. This is a worthy goal which presents a number of scientific, psychological, and logistical challenges.

The concern I expressed when I first wrote on this subject, about the role of CAM and associated ideologies in hospice care, is alluded to in the JAVMA commentary.

Hospice care may be more popular among those interested in alternative and complementary therapies. Thus, veterinarians engaged in hospice care should be comfortable working alongside individuals offering these therapies and be aware of the potential for conflicts and deleterious interactions between these therapies and conventional medical treatments.

Though I am not aware of any objective research data to support it, I tend to agree with the contention that pet owners interested in comprehensive hospice care, and often reluctant to consider euthanasia when their veterinarian suggests it is appropriate, are also owners more inclined towards CAM therapies. Much of CAM is vitalistic philosophically, emphasizing the “spirit” or “life force”  of the individual as the primary focus of health and disease, with the physical body considered secondary. And from such a perspective, death is likely to be seen primarily as a transition of the spirit from one state to another, with the dysfunction and breakdown of the physical body as a secondary concern.

This blog, and certainly the veterinary consultation room, are not appropriate places to debate religion or metaphysical philosophy. I don’t see it as at all my role as a veterinarian to challenge my clients’ attitudes about the fundamental nature of life and death. However, I do see my role not only as a source of support and comfort for the client but as an advocate for the welfare of my patient.

Pet owners clearly want the best for their pets, but they also are influenced by their own feelings and needs, especially at intensely emotional times like the end of life. Under such conditions, it is not difficult to project one’s own needs and beliefs onto an animal companion, especially with the facilitation of “animal communicators” or others who claim to have mystical insight into the wishes or thoughts of animals. This can lead to decisions about care which are not truly in the best interests of the pet.

Insofar as CAM is sometimes more successful at meeting people’s psychological and spiritual needs than science-based medicine, and that it is most often employed in the treatment of chronic diseases for which there is no definitively effective conventional treatment, I am not surprised that CAM and CAM providers are playing a significant role in the nascent veterinary hospice movement. CAM providers are among the most active promoters of hospice care.

While I applaud these efforts, I am concerned that ineffective, pseudoscientific therapies may come to dominate end-of-life veterinary care, and that the consequence of this may be inadequate palliation of  our pets’ physical suffering. I have had clients who were struggling to accept the inevitable loss of an animal companion and who sought any and all therapies that offered the promise of a benefit. Even when these therapies were clearly ineffective, or caused increased suffering, these clients have difficulty seeing and accepting this fact at the time (though they often come to me later and lament having persisted too long in the face of their pet’s suffering because letting go was too painful). There are plenty of examples in human medicine of ineffective alternative therapies that actually worsened the quality of life for terminally ill patients using them, and I believe this is a real risk for veterinary hospice care.

I have also seen clients whose pets were in great pain but who refused conventional pain therapy and persisted in the belief that homeopathy and other alternative therapies were effectively managing their pet’s discomfort despite clear and obvious evidence to the contrary. Again, this is not due to any lack of intelligence or compassion, but simply to the innate tendency of all human beings to see what they want and expect to see. Unfortunately, without legitimate scientific research it is not possible to know how effective a medical therapy really is, and I am concerned about patients in veterinary hospice care being denied effective palliative care in favor of bogus therapies because of a philosophical predisposition of some pet owners and hospice providers towards  CAM approaches.

I would certainly not suggest that veterinarians who wish to provide comprehensive hospice care automatically refuse to work with CAM providers or accommodate their clients’ interest in such therapies. This would likely be counterproductive as it would drive these clients away from conventional care or lead them not to disclose the CAM therapies they are using, making it harder to monitor for possible adverse interactions.

However, I do think veterinarians have an ethical responsibility to advocate for the welfare of their patients, even if this means telling clients things they don’t want to hear. If an owner is unable to see or accept that their pet is suffering, or mistakenly believes they are providing effective care, their veterinarian must try, as kindly but clearly as possible, to help them see the true situation. And in extreme cases, where a CAM provider is actively discouraging an owner from taking advantage of appropriate conventional care, it may not be possible to serve that owner and one’s conscience at the same time.

And while there are some people who have a philosophical or religious objection to euthanasia, I think most veterinarians and pet owners see it properly as an act of kindness to relieve otherwise untreatable suffering. If a client is unwilling to consider euthanasia, then their veterinarian may have to accept this and do whatever they can to ensure that the pet is kept as comfortable as possible while dying. But there is nothing wrong with discussing the role of euthanasia in high quality, compassionate end-of-life care. And I vehemently reject the caricature promoted by some CAM advocates of veterinarians who practice science-based medicine as callous and forcing euthanasia on their clients prematurely.   

Veterinary hospice care is a concept that needs to be developed and promoted more widely, and in order to best care for our pets as well as their owners, we need to ensure that the philosophy and techniques that make up hospice care include effective, evidence-based medicine. Offering comfort to clients in the form of therapies that don’t truly benefit our patients is not true compassion, and advocating aggressively for what we believe is the best, most effective scientific treatment available for our patients is not closed-mindedness but conscience. My hope is that conventional veterinary medicine will embrace the hospice concept, and that veterinarians committed to science-based medicine will continue to be involved in its development and implementation so that our pets get the best care possible at the end of their lives.

Posted in General | 1 Comment

Truth is a Popularity Contest (Again): This Time in Switzerland

Posted on January 15, 2011 by skeptvet

In Switzerland, as in many other European countries, the government pays for extensive health insurance coverage for its citizens. Naturally, the government and the citizenry want cost-effective healthcare for their money. One important aspect of achieving this is not to pay for therapies that don’t work. So it is understandable that in 2005, the Swiss Interior Ministry stopped paying for several alternative therapies, including homeopathy and Traditional Chinese Medicine (TCM), that failed to meet their criteria for adequate scientific proof of efficacy.

What is less understandable, is that in 2009 60% of the voters in Switzerland voted to force the government to pay for these therapies. Apparently, these voters were, as so often proponents of alternative medicine tend to be, less interested in whether the therapies worked than in their “right” to use them, even if other taxpayers had to foot the bill. The government’s own review panel recommended outright rejection of these therapies, but in a pragmatic political move the government has decided to continue funding them for a 6-year trial period, during which a supposedly independent review of existing scientific research is supposed to be conducted to determine, yet again, if there is adequate evidence of efficacy to justify providing these therapies at taxpayer expense.

One possible candidate for this external review agency is the National Center for Complementary and Alternative Medicine (NCCAM) here in the U.S. Given that NCCAM has spent over $1 billion dollars of U.S. taxpayers’ money, has failed to find solid evidence to support any specific CAM approach, and is nevertheless actively promoting an entire academic industry dedicated to researching CAM therapies (see these posts at Science-Based Medicine for details), it hardly seems a neutral party. Another candidate is the British National Institute of Clinical Excellence (NICE). This seems a better choice in that the organization exists to evaluate all medical therapies froman evidence-based perspective.

However, the unfortunate reality is that the negative findings of the original Swiss government panel were not sufficient to dissuade Swiss voters from demanding the government pay for CAM. And the extensive work NICE has done in Britain, along with strong statements from British physicians organizations about the complete fiction that is homeopathic medicine, the British National Health Service still pays for homeopathic hospitals. The negative findings of NCCAM here in the U.S. have had no discernable impact on the popularity of CAM therapies here. So the hope that a balanced, rational review of the evidence, which I have no doubt would lead to the conclusion that these methods are unproven at best or, as in the case of homeopathy, complete nonsense, is a slim one indeed.

The more I look at the evidence and people’s responses to it, including the vicious hostility of so many comments posted here by those who feel I am wrong about the evidence, the more CAM begins to look like a religion, not a rational approach to healthcare.

Posted in Law, Regulation, and Politics | 6 Comments