What’s Wrong with Integrative Veterinary Medicine?

Posted on April 3, 2013 by skeptvet

The terminology associated with unconventional therapies has shifted a bit over the last 40 or so years. Initially, such therapies were often described as “alternative.” This fit well with the still widespread philosophical position that new or different ways of looking at health and disease which are not part of the scientific tradition are necessary or valuable. But it wasn’t the most effective marketing for these practices since it suggests substituting these therapies for conventional medicine. The dramatic effectiveness of science-based medicine is hard to ignore, and most people aren’t willing to give it up for the promises of unproven alternatives.

The term “complementary and alternative medicine” (CAM) emerged to suggest a more flexible approach in which unconventional therapies could add benefits along with, not only in place of, conventional medicine. This is still a popular term, but some advocates of CAM therapies dislike the implication it carries that science-based medicine is the mainstay of treatment and CAM simply “complements” it. And it can be quite clumsy to say.

So the latest term that seems to be gaining ground quickly is “integrative medicine.” This suggests a seamless merging of the best of conventional and unconventional medicine. Integrative medicine advocates often present this approach as focused only on the welfare of the patient and willing to use whatever tools are appropriate without any prejudice regarding their origins. What could be wrong with that?

Well, to begin with, there is a hidden and untrue assumption behind this approach; that individual practices from both CAM and scientific medicine are equivalent, equally likely to be useful regardless of the philosophies behind them. The problem with this assumption is that there is, in fact, good reason to believe that therapies based in science and validated by scientific research are far more likely to be safe and effective than therapies based on implausible or pseudoscientific theories and validated by historical use, individual anecdotes, and little to no controlled scientific research.

Among some skeptics, integrative medicine programs in academic medical centers have been labeled quackademic medicine. This is the integration of implausible and unproven alternative therapies into academic medical practice not, as is often claimed, with the intent of investigating whether or not such therapies are safe and effective but with a pre-existing faith in their benefits.  Such integrative medicine programs are founded on a desire to use the platform of an academic institution to give an aura of legitimacy to such practices, and to use the authority of a faculty position to convince veterinary students these are legitimate medical therapies regardless of the evidence for or against them.

There are a number of problems with such programs. As Mark Crislip from the Science-based Medicine blog has put it, “If you mix cow pie with apple pie, it does not make the cow pie taste better; it makes the apple pie worse.” In other words, integrating unproven therapies or outright ineffective nonsense with conventional medicine doesn’t improve patient care or outcomes, it makes them worse. And there is growing evidence of the harm this can cause, both directly and indirectly (e.g. 1, 2).

Such integrative medicine programs are also, alas, quite successful at conveying the impression that the therapies they promote are evidence-based or widely accepted as legitimate in the medical community even when they are not. And they tend to create this impression among doctors and medical students as well as the public, despite the lack of compelling evidence of effectiveness for most of these therapies. They are very successful public relations efforts.

These programs are not, however, very successful at stimulating the research needed to make truly evidence-based judgments about CAM therapies. The clinicians involved in these programs are themselves already convinced their practices are effective, so they tend to produce research at high risk for bias. And when research results are not supportive, they are ignored or rationalized away since the self-reinforcing clinical experiences and anecdotes most doctors rely on do seem to support what they are doing, and this has more psychological impact than less influential, but more reliable, objective research. Rarely do integrative medicine programs discourage even the most obviously useless of CAM therapies, such as homeopathy, but they tend to encourage acceptance of the whole mélange of unrelated and ideologically affiliated practices within the CAM family.

The folks at Science-Based Medicine and the James Randi Educational Foundation have recently published an e-book with a number of essays discussing the problems with the infiltration of unproven or bogus CAM therapies into academic medicine, which I highly recommend: Quackademic Medicine

The marketing and PR campaign under the label of “integrative medicine” have begun to appear in veterinary medicine in the last several years, thanks largely to the recent availability of significant funding from proponents of alternative medical practices. For example, I recently wrote about a grant of $10,000 the American Holistic Veterinary Medical Foundation gave to the veterinary school at the University of Tennessee (UT) to promote alternative veterinary medicine. Based on the fundraising and marketing materials of the AHVMF, this organization certainly seems to share the typical marketing and PR goals of most integrative medicine programs. There is some talk of research, but always with the emphasis of demonstrating to the skeptical mainstream that CAVM practices are safe and effective, which is already taken as a given. And there is much talk of widening the appeal and availability of CAVM therapies, regardless of whether the evidence supports their use.

And based on the blog post written for the AHVMF by the grant recipient at UT, this certainly seems to be the agenda for the leadership of the integrative medicine programs the AHVMF is supporting there. Dr. Donna Raditic, who runs the integrative medicine service, made it clear in a blog post on the AHVMF site that she has no doubts about the effectiveness of CAVM and seeks to make alternative therapies more popular and acceptable not by conducting objective research but by providing “hand-on” exposure and the opportunity for generation of anecdote and personal experiences that are, despite their unreliability, so persuasive for most of us.

The AHVMF has also given a total of $110,000 to the Integrative Medicine program at Louisiana State University’s (LSU) School of Veterinary Medicine. The LSU integrative medicine folks have, of course, been actively promoting the AHVMF fundraising efforts, and they have hosted as speakers a number of prominent advocates of a variety of alternative therapies. The web site for this integrative medicine division, which was apparently made possible initially by a substantial private grant, also talks considerably more about promoting alternative therapies than about researching their safety and efficacy. The grant comes from individuals with a strong interest in promoting alternative therapies, and it has been used, in part, to send staff and students for training at the Chi Institute and the annual convention of the American Holistic Veterinary Medical Association, two of the biggest promoters of unproven and even clearly ineffective and pseudoscientific alternative practices.

Despite the numerous connections between these integrative centers and prominent advocates of unproven and pseudoscientific therapies, and the clear bias evident in the promotional materials which talk not about testing CAVM practices but promoting them, it is possible these centers could be useful if they have a commitment to rigorous scientific research and if they are willing to openly rejecting therapies which fail to prove their value in such research. I would like to think that the academics involved in these centers understand the indispensability of evidence-based medicine and scientific validation of claims for any therapy. However, starting from a position of embracing alternative therapies, talking about promoting rather than investigating them, and exposing students to the pseudoscientific rationalizations of homeopaths and other CAVM extremists from the AHVMA all suggest that these centers are more of a marketing and PR effort on the part of true believers than a genuine academic endeavor to find out the truth about these therapies.

So what sorts of services are these programs offering and promoting? The LSU center advertising a variety of therapies, including so-called Traditional Chinese Veterinary Medicine, which includes acupuncture and herbal therapies. I have written extensively about TCVM and acupuncture before. TCVM is a hodgepodge of pre-scientific and pseudoscientific vitalist myths used to identify not disease as it is understood in science-based medicine but “imbalances” in energies and other metaphorical entities which cannot even be proven to exist, much less to play a vital role in health and illness. These mythic concepts are then used to guide the application of therapies which undoubtedly have real physiological effects but which have not been demonstrated to be safe or effective in maintaining or restoring health. Herbal therapies, for example, are among the most promising CAVM treatments because they contain pharmacologically active chemicals. However very few have been consistently shown to be truly effective for any disorder in any species, and there is ample evidence that they, or contaminates they contain, can be very harmful.

Acupuncture is the most popular form of CAM after chiropractic (though still not as widely used as proponents would make it seem). Despite extensive research over decades, it has not been convincingly shown to be anything more than an elaborate and rather potent placebo. To be clear, that doesn’t mean it heals disease through the power of the mind. It means that it can cause us to believe we are better, and even to feel better, when our disease actually hasn’t changed, and it is no more effective than randomly poking us with needles or even toothpicks.

Such a placebo might have a meaningful benefit in treating subjective symptoms such as nausea or pain in humans, so long as it was not substituted for therapies that actually affect the disease directly. However, there are serious doubts about how effective such a placebo ritual and non-specific irritant might be in animals, particularly since they cannot report how they feel and must rely on us to judge their comfort, and it is clear that we experience a significant placebo effect on their behalf. I have seen patients in obvious and serious pain whose owners felt they were fine thanks to acupuncture treatment.

The LSU integrative service offers a few other therapies, some of which are a bit of a bait-and-switch in that they are frequently claimed as CAM even though they are widely used by conventional veterinarians (such as physical therapy and nutritional therapy). The most egregiously ridiculous kinds of therapies, such as homeopathy, flower essences, energy healing, and so on, are not listed and, I hope, not offered by the LSU integrative medicine service. And the folks at LSU are careful to emphasize that they do not restrict the use of established, science-based therapies. So while the hazards of direct harm to patients from unproven therapies are probably quite small (both acupuncture and herbal products can be dangerous), the bigger problem is that pseudoscientific practices such as TCVM are offered and presented to students and clients as if they were just as reasonable as science-based practices, despite the many reasons they are not.

There is less readily accessible information on the services offered in the integrative medicine department at UT. Dr. Raditic is certified in acupuncture (not, of course, a recognized medical specialty in human or veterinary medicine) and is apparently pursuing a board certification in nutrition (which is a recognized specialty area). As a member of the AHVMA, she is at least to some extent affiliated with proponents of other, less reasonable CAVM practices, but I have no way of knowing what her views are on these or the extent to which she practices, teaches, and promotes them.

The UT Facebook page recently promoted an “educational” event in which the “National Acupuncture Detoxification Association” will be teaching “ear acupuncture” Both the concept of detoxification, through acupuncture or other means, and the various systems of ear acupuncture are pseudoscientific and unproven concepts that certainly shouldn’t be promoted at a veterinary medical college. Dr. Raditic is also reported to offerchiropractic, cold laser, and herbal/dietary supplement therapies. These are all fairly typical CAVM therapies with mixed, but generally poor, evidence concerning their effects. Cold laser and some herbal or supplement therapies are at least plausible and might have benefits in some cases. Chiropractic, however, has little claim to any legitimate veterinary use based of the bogus theory behind it (the “vertebral subluxation complex”) and the lack of reliable evidence of safety or benefit.

Reportedly, the University of Florida College of Veterinary Medicine has also received $10,000 from the AHVMF for its acupuncture program. Some of the faculty members associated with the integrative medicine program at UF are also affiliated with the Chi Institute, the largest organization teaching TCVM and acupuncture in the U.S., and other organizations promoting all aspects of TCVM, not merely acupuncture. Educational materials provided by the UF integrative medicine web site promulgate some of the common myths about veterinary acupuncture (that it is an ancient practice validated by this history, that there are identifiable specific points along “energetic channels” that can be stimulated to achieve specific therapeutic effects, that it has been validated for specific indications, such as pain, by controlled research, etc). This does not suggest an open, evidence-based approach to TCVM but a pre-existing belief that it is effective despite the lack of compelling research evidence to that effect. 

Bottom Line

So the efforts of proponents of integrative veterinary medicine appear directed at the same goal as such programs in human medical centers. They are not so much concerned with finding out if these therapies are safe and effective since they already believe this to be true based on their underlying theories, personal experiences, historical use, and other non-scientific sources of evidence. Instead, they wish to make such therapies comfortable and familiar to students and practitioners of scientific medicine so they will be more readily accepted, regardless of the state of the evidence. And while for now they are avoiding promotion of the most egregious nonsense, such as homeopathy, energy healing, dowsing, they do not appear to be making any effort to distance themselves from such practices or those who do promote them. TCMV and acupuncture share much philosophical and ideological ground with these sorts of practices, in particular a feeling that validation through scientific research is a nice extra with PR value but not essential to judging the value of a therapeutic practice. It is difficult, then, to see how these centers can be anything other than marketing efforts or contribute the kind of rigorous data and unbiased evaluation needed to separate those CAVM therapies that may have real value from the useless nonsense.

 

 

 

 

Posted in General | 32 Comments

The Ethics of Referring Patients for Alternative Medical Therapies

Posted on March 22, 2013 by skeptvet

I recently ran across an editorial on the subject of the legal and ethical issues associated with conventional doctors referring patients for alternative medical therapies. It does a nice job of highlighting an issue which I think gets too little attention. If a therapy is unproven, implausible, or has been clearly shown not to work, can one ethically refer a patient for that therapy?

CAM practitioners are always suggesting that conventional doctors skeptical of their practices “leave it to the experts.” We are expected to declare ourselves incapable of giving reasoned judgments or recommendations and simply allow believers in a particular CAM therapy to be the only source of information for clients about that therapy. This is the fox guarding the henhouse in its purest form. My recent series of articles about veterinary homeopathy illustrates this claiming of expertise and the right alternative medicine practitioners claim to be the only voice patients get to hear on the topic of their methods.

One problem I’ve pointed out with this approach is that the label of “expert” is generally self-applied in CAM. There are no “CAM specialties” in medicine recognized as legitimate by anyone other than CAM practitioners. Astrologers and psychics may declare themselves to be experts in their fields, but it would be ridiculous to suggest that the rest of us should defer to their judgment about whether astrology and psychic phenomena are legitimate. The same is true for CAM practices.

Another question that arises for the conventional doctor considering referral for CAM therapy is what the patient (or in the veterinary field, the client) wants. Does it matter if my client wants homeopathy? Does that make it legitimate to refer them to a homeopathy even if it is clear homeopathy is nothing but a placebo? Is the right therapy for your patient always whatever therapy the patient (or owner) wants? These are some of the issues addressed in this commentary.

Timothy Caulfield, Ubaka Ogbogu, Gerald Robertson. Commentary: the law, unproven CAM and the referral challenge. Focus on Alternative and Complementary Therapies Volume 18(1) March 2013 1–7

The authors begin by pointing out that conventional medicine has certain well-defined and widely accepted standards of evidence, based on the methods of science, that a doctor is expected to understand and rely on in judging all therapies. They then show, as I have previously, that CAM practitioners and advocates often have a different set of standards:

compared to conventional physicians, ‘[p]roviders of CAM may conceive of “evidence” in broader terms – including their own clinical experience – and place less emphasis on population-based empirical data’. While there has been a push to gain more evidence on the efficacy of various CAM therapies and approaches, a significant portion of the most popular therapies remain unproven or, alternatively, there is disagreement about the nature, quality and value of the relevant data.

The fact is that very little within CAM can be considered evidence-based, and most of the practices exist in that vaguely defined group of practices precisely for this reason. CAM practitioners are only interested in scientific evidence when it supports their claims, but they have no fundamental philosophical problem ignoring such evidence when it does not. CAM is almost never judged by the same standards as conventional medicine. Therefore, conventional doctors have to decide whether to adhere to the standards they use for their conventional practices, or to accept a separate-but-equal set of standards for CAM.

Can physicians, who are bound by the (increasingly) evidence-based ethos of their profession, refer patients to CAM practitioners known to provide a range of unproven treatments? Could such a referral be construed by the patient as an endorsement of all the services offered by the CAM practitioner?

The authors answer these questions for physicians the same way I would answer them for veterinarians:

We conclude that physicians have a legal and ethical obligation to adhere to a consistent evidence and science-based approach to referral decisions regardless of the type or nature of the therapy in question.

Many vets I know who are don’t accept the claims for most CAM methods as legitimate nevertheless feel uncomfortable telling clients this. They often simply claim not to know anything about these methods and refer the client to a vet who practices CAM. I cannot see how this could be seen by clients as anything other than an endorsement of the practices they are being referred for. In my opinion, it is a complete abdication of ethical responsibility to the client and the patient, to refer for a therapy you believe to be ineffective or even possibly unsafe.

So why do conventional doctors who are skeptical about CAM claims refer for CAM services? The main reason for physicians to do so is likely the same reason vets do so, a misguided belief that clients want these services and that doctors are bound to give clients what they want, whether or not this is what is in the best interests of the patient.

I’ve written previously about the perceived demand for CAM services. While there is no question many people will express some interest in these therapies when asked, and while self-administration of over-the-counter dietary supplements and herbal products is quite widespread, studies consistently show that only a tiny minority of Americans regularly use most CAM services such as acupuncture and homeopathy, and even the most popular, chiropractic, is only rarely used for anything other than its one reasonable indication, back pain. So the notion that there is widespread aggressive demand for these services is simply inaccurate. People are always interested in something that might help them or their pets, but they are also very interested in their doctors’ help in deciding what is and what is not a safe and useful therapy.

And even when people actively request CAM therapies for themselves or their pets, this does not relieve a conventional doctor of the obligation to recommend only appropriate therapies based on scientific standards of evaluation.

The law is clear that ‘[i]f a patient requests treatment which the doctor considers to be inappropriate and potentially harmful, the doctor’s overriding duty to act in the patient’s best interests dictates that the treatment be withheld’…use a CAM therapy that does not meet requisite evidentiary standards for therapeutic use would conflict with the physician’s overriding legal and ethical duty to act in the patient’s best interests.

The authors of this editorial explore briefly the legal implications of CAM referral. While the details of this discussion relate primarily to laws for physicians in Canada, the ethical and legal principles are broadly similar in human and veterinary medicine and in Canada and the U.S. There is case law that demonstrates physicians are responsible for the harm done by therapies they recommend if they ought to have reason to believe these therapies are inappropriate for their patients. In one example,

a family physician was held to have been negligent in referring a patient to a chiropractor for treatment of his neck injury. The Court held that the physician ought to have known that chiropractic treatment was contraindicated in the circumstances. In addition, it was no defence for the physician to claim that the chiropractor was negligent. In the words of the Court, the physician ‘generated the risk of injury by referring [the patient] for inappropriate treatment. It is no answer that the treatment was administered negligently.’

Conventional doctors are legally, as well as ethically, responsible for knowing that unproven or inappropriate treatments have risks, and this responsibility does not disappear if a patient is injured because a CAM practitioner they were referred to does something inappropriate once the patient is in their hands.

This is especially important since CAM therapies, and a disdain for conventional treatment, tend to cluster together. Even if chiropractic therapy might be appropriate, for example, for a patient’s back pain, the physician has some responsibility if they send a patient to a chiropractor knowing they may be subjected to colonic irrigation, untested herbal remedies, and other unsafe practices or that the patient may be discouraged from using conventional healthcare methods, such as vaccinations or pharmaceutical medications.

I often tell clients, when they appear skeptical of something I recommend, that they are paying for my advice and I am obligated to give it, though they are not obligated to follow it. This is a somewhat casual and humorous way of expressing a very powerful and serious ethical duty. I owe my patients, and their owners, the most accurate, informed, and honest advice I can provide. It is not ethical for me to simply plead ignorance of therapies I don’t practice and pass the patient on to someone who claims expertise in those practices. It is my duty to, at a minimum, be familiar with the balance of the evidence regarding most therapies available to my clients and whether they are proven or unproven, safe and effective or useless and harmful. This holds for alternative therapies just as it does for conventional practices.

And it is not ethical for me to simply give clients what they ask for even when I know, or ought to know, that they are misinformed about the safety and effectiveness of what they request. CAM providers often complain, quite legitimately, about the misuse of pharmaceuticals. Giving clients an antibiotic for an infection I know is almost certainly viral and not bacterial is not acceptable practice. And referring clients for homeopathy, Chinese Medicine, or other practices that are either clearly not effective or of unknown safety and efficacy is just as inexcusable, even if the clients asks me to do so.

People certainly have a right to choose the therapies they wish, even if they don’t really understand the evidence concerning them. But this freedom does not relieve me of my obligation to understand this evidence and to refuse to provide or recommend therapies that are not in my patients’ best interest. This obligation is perhaps even greater for veterinarians than for physicians since our patients cannot speak for themselves or make their own healthcare choices. We, therefore, must advocate for what we believe to be best for our patients even in those uncomfortable situations in which this runs contrary to what our clients may want.

 

 

Posted in Law, Regulation, and Politics | 7 Comments

American Holistic Veterinary Medical Foundation gives $10,000 to University of Tennessee Veterinary School to Promote Alternative Medicine

Posted on March 18, 2013 by skeptvet

Last fall, I wrote about the American Holistic Veterinary Medical Foundation (AHVMF), an offshoot of the American Holistic Veterinary Medical Association (AHVMA), which is devoted to raising money for the promotion of alternative therapies. The AHVMA is a vigorous advocate of unproven and outright bogus therapies, and I have frequently discussed their activities. From the annual “scientific” meeting that includes promotion of ridiculous pseudoscience on the dime of herb and dietary supplement companies to its vigorous defense of homeopathy, the AHVMA has demonstrated a commitment to the standard of no standards when it comes to veterinary therapies. Despite lip service paid to science and free use of the language of evidence-based medicine, the organization is clearly an advocate for any and all therapies under the broad, essentially ideological label of complementary and alternative veterinary medicine (CAVM).

So while the AHVMF also talks about supporting legitimate scientific research, I have some skepticism about such claims. The parent organization, and many of the individuals involved in the AHVMF, have clearly demonstrate that they are unwilling to reject CAVM therapies even when they are inconsistent with established scientific knowledge or the results of scientific research. My suspicion (and I would certainly be pleased to be wrong here), is that the AHVMF is purely a marketing effort, aimed at promoting what its members already believe rather than finding the truth, and an attempt to create the impression of scientific and institutional legitimacy for therapies that have not been able to achieve these on the strength of the evidence for their effectiveness. A recent article on the AHVMF blog appears to support this interpretation.

The Veterinary School at the University of Tennessee recently received a $10,000 grant from the American Holistic Veterinary Medical Foundation to support “integrative medicine.” The faculty member who runs the Integrative Medicine Center at UT has written a blog post for the AHVMF which illustrates very clearly the goals of this effort.

These goals do not appear to be focused on supporting research to identify which CAVM therapies are actually effective. They appear to be more about pursuing a marketing strategy for bringing CAVM therapies into acceptance within the mainstream by making them more familiar, part of the veterinary curriculum, and something that everyone can see works “with their own eyes,” despite the absence of controlled research support or the existence of negative research data. This is pure proselytizing rather than research. For example:

I remember breaking ground for my own hospital, offering alternative veterinary medicine. It was exciting, but there was something missing.  I was alone in my work so I dreamed I could turn my hospital into a center to bring in other alternative veterinarians to do lectures.  I wanted to share this new knowledge…the clients heard me, but no one else

…My voice was not any louder, when I left my practice, to start an Integrative Medicine service at The University of Tennessee College of Veterinary Medicine.  I worked the service knowing the clients would come, but I would smile quietly when I heard, “Why is Integrative Medicine seeing this case” while my neurologic patient was awaiting an MRI.

[When we achieved full faculty status,] I reached out to tell someone that would understand what this appointment meant and my voice was heard by the AHVM Foundation.  Now it is time for all of us to reach out and be heard; the foundation is our voice.  And for clients who have experienced alternative care, a vested veterinarian, we need to encourage them to support our Foundation

.…as full faculty at a veterinary teaching hospital, we have brought the Foundation here. We have students on our service being exposed to integrative veterinary care. We provide that comprehensive care to many of the faculty’s own furry pets; therefore, we are educating the educators.  We are working to gather funds to launch an Integrative Medicine Fellowship, with the university’s mark and the Foundations support. We have Dean approval and are outlining the Fellowship program for maximum impact; we will need funding to make this happen

.…this is our opportunity to bring into the conventional veterinary medicine forum, another black bag: integrative veterinary medicine.  I am overwhelmed with what the Foundation has done to date and the goals we have outlined going forward.

The article also illustrates how holistic medicine is so often promoted–not on the basis of evidence, of which there is usually little to none, but as a kinder and gentler and more hopeful approach than science-based medicine. Regardless of how one feels about acupuncture, chiropractic, Chinese Medicine, etc., I wonder how conventional veterinarians are expected to feel about this characterization of what holistic medicine is and what, presumably, conventional medicine is not:

I now realize is that what makes holistic and veterinarians different is not just our type of treatment, but how we approach our patient. In the integrative health movement we are constantly seeking therapies and approaches that are outside the box of conventional veterinary medicine. And for various reasons we need access to these therapies as many of our patients have failed to respond to standard approaches. They come to us with hope of finding help not available elsewhere.

…we approach with a lot of thoughtfulness, gentle treatment plans, and a lot of caring.  We are vested in our patients.  And once you become a vested, willing to travel a different path to investigate all the options, there is no turning back.

It’s nice to know that when we emotionally detached doctors who are stuck on the whole science thing have given up on our patients, at least they have someone caring to go to who is willing to try almost anything regardless of the absence of anything as pointless as evidence of safety or efficacy.

The infiltration of unproven, or disproven, alternative therapies into legitimate teaching and research hospitals, largely driven by the irresistible allure of funding for research and faculty contingent on a friendly approach to such therapies, has been dubbed “quackademic medicine,” and it represents a real threat to the well-being of patients.

The diversion of scarce resources to research on implausible or already disproven therapies when this research will never discourage advocates from using them regardless of the results impedes real progress in developing better treatments. The perception that such therapies must be legitimate and demonstrably safe and effective (otherwise, why would universities allow teaching and using them in academic hospitals?) creates a false impression of the evidence concerning these therapies and of their value. And despite claims to the contrary, inadequately tested CAVM therapies can directly harm patients. And the integration of unproven methods with science-based medicine can decrease quality of life and survival for patients with serious illnesses.

For all of these reasons, it is unfortunate that the strategy of promoting the integration of unproven or pseudoscientific therapies with legitimate science-based medicine at academic medical centers has reached the veterinary profession. The money this brings to the institutions involved will only harm the profession and our patients if, as seems likely, it is used to promote CAVM rather than conduct legitimate research that will separate the useful from the useless. Such funds would be better spent supporting independent research involving not only dedicated advocates of CAVM but neutral and skeptical researchers with a commitment to rigorous methodological quality and no pre-existing commitment to a particular outcome. Establishing centers to integrate CAVM therapies with conventional medicine when these therapies have not yet demonstrated they are safe and effective is premature and diminishes the integrity of veterinary medicine and is not in the best interests of our clients or our patients.

Posted in General | 15 Comments

Screening Tests and Pre-Anaesthetic Bloodwork in Veterinary Patients: Issues & Evidence

Posted on March 13, 2013 by skeptvet

A perennially hot topic in human medicine is the risks and benefits of screening tests. Blood tests, imaging (like CT scans) and other diagnostic tests are usually seen by the general public as only beneficial. How could it be a bad thing to detect a disease, even before it is causing any symptoms? The reality, of course, is that such tests come with risks as well as benefits, like everything else in medicine.

I’ve written a bit about screening tests before, and I wrote an enthusiastic review of Gilbert Welch’s book Over-Diagnosed, which I believe should be required reading for anyone who is a healthcare provider or patient. The previously underappreciated dangers in inappropriate diagnostic tests have driven significant and sometimes controversial recommendations from the United States Preventative Services Task Force (USPSTF), the federal agency responsible for generating evidence-based guidelines concerning preventative medicine. And a broad coalition of medical specialty groups have formed an organization called Choosing Wisely which is dedicated to promoting sensible use of diagnostic tests by education physicians and the public about the risks and uncertainties, as well as the benefits, of such testing.

In general, the benefits of screening tests involve either allowing a disease to be treated at an earlier stage, even before the patient is aware of having it, and thereby improving the long-term outcome, or detecting risk factors for diseases which can be managed to reduce the chances of those diseases developing at all. For this to work, of course, the tests must screen for something which is treatable or preventable. A test which warns you in high school that you will die of some horrible disease in 30 or 40 years, and that there is nothing you can do about it, isn’t beneficial. In fact, it is more likely to do harm in that it generates anxiety and affects how you live your life in ways that don’t make you any healthier or happier.

Effective screening tests must also be accurate enough that they don’t miss a lot of cases of real disease or indicate disease is present in a lot of people when it really isn’t. No test is perfect, but most medical screening tests can be evaluated in people know to have, or not have, the condition tested for, which can give us an idea how accurate a particular test is. This generates the “sensitivity” and “specificity” numbers often cited to identify how reliable a test is.

For statistical reasons I won’t get into, these numbers can be misleading. Even a test which very rarely misidentifies someone as having a disease they don’t actually have will still misidentify a high proportion of people tested if the disease is really rare. So even the best tests aren’t very useful if we test people who are very unlikely to actually have the disease we are looking for. This is one reason why indiscriminate use of diagnostic tests is a not effective or reliable.

The devil, as always, is in the details, so it is difficult to generalize about when screening tests should or shouldn’t be used. For the most part, the guidelines in humans recommend using most screening tests only when there is some reason to suspect the disease one is looking for is present. If a person has typical symptoms, or is in a demographic group known to be frequently affected by the disease of interest, then a screening test might make sense.

Testing women for prostate cancer with a blood test such as the PSA, for example, is obviously ridiculous. The disease is never going to be present. And even with very good tests, false positives can show up, so what would a doctor do with such a positive test result? Most cases aren’t this clear cut, of course, but the same logic applies for all screening tests. The more likely the disease is to be present, the more reliable a positive test result is. And the less likely the disease is to be present, the more we can trust negative results. So choosing rationally who to test is a very important part of getting reliable results.

So what are the risks of screening test? Well, I’ve already touched on one—the unproductive anxiety associated with being misdiagnosed or with being correctly diagnosed with a disease you don’t have. Many people this hasn’t actually happened to will say they aren’t worried about this and would want to be tested even if this is a possible risk. However, people who have had the experience of a mistaken diagnosis, or a diagnosis they can’t do anything about, describe it as a terrible, life-altering experience. In veterinary medicine, this anxiety is unlikely to affect our patients directly. But there is no question it can profoundly affect their owners, as well as how their owners treat their pets, so this is still a risk to consider.

A more tangible risk of misdiagnosis is the danger and discomfort associated with unnecessary follow-up tests or treatment. Thousands of men have been seriously harmed by unnecessary testing and treatment for prostate cancer that they either never had or that would never have made them ill. This is one of the examples that has driven the more cautious and rational approach to screening tests in humans, and it is relevant to veterinary patients as well. If we diagnose disease that aren’t there, we are inevitably going to harm, and even kill, patients who would have been better off if we had not tested them in the first place. This risk has to be recognized and appropriate steps taken to minimize it, including using tests in a rational, evidence-based way.

And though it seems unpopular in America to acknowledge that it matters, the cost of unnecessary testing is a real issue. In human medicine, healthcare costs are a significant economic burden with widespread harm throughout the economy. And in veterinary medicine, where euthanasia is often chosen when money for further testing or treatment runs out, wasting money on unnecessary tests can easily lead to an inability to provide care that is actually needed.

As usual, the evidence concerning the risks and benefits of screening tests, and the attention given to the issue, are far less in veterinary medicine than in human medicine. However, there is some research evidence looking at screening tests in veterinary patients. Given the aggressive push from the AVMA for more preventative care, which is not a transparent, evidence-based effort and which in some ways appears driven as much by concern about revenue as concern about patient welfare, it is worthwhile to consider the issues involved in recommending screening tests for veterinary patients.

The most common and widely recommended screening tool is the annual physical examination. In human medicine, there is growing doubt about whether physical exams of apparently healthy people is useful or beneficial. There is almost nothing in the way of controlled research on the subject in veterinary medicine.

Certainly, every vet can think of examples of a patient whose owners were not aware of any problem but who turned out, after a good physical exam, to have a serious illness. We are most likely, of course, to remember those examples in which the illness was treatable, since happy endings that make us feel good about the work we do tend to stick in our minds. We may or may not remember cases in which the illness we identified couldn’t be treated or was treated in a way that did little to improve the well-being or longevity of the patient and perhaps even made it worse due to side effects of the treatment. And, of course, we can’t possibly remember those cases in which a client declined to accept the initial test or follow-up investigation and treatment and the disease never materialized. Our memory of individual cases is not, unfortunately, a very reliable way to decide whether physical exams of apparently health pets are beneficial to our patients or not. Availability bias, confirmation bias, cognitive dissonance, and many other cognitive quirks make such anecdotes deeply misleading.

One obvious difference between human and veterinary medicine is that people can tell their doctors about symptoms they experience which might suggest a disease even when there is no outward sign of one. Our pets have a much more limited ability to make known how they feel, and in fact may act8ively hide signs of illness from us. This supports the argument that physical exams, and other diagnostic tests, may be justified in apparently healthy pets even when they aren’t in apparently healthy humans. However, as reasonable as such an argument is, it remains unproven.

The other kind of diagnostic test frequently recommended is bloodwork. There is absolutely no consistency within the profession on what kind of screening blood tests should be done when, how often, and in which patients. It is common to recommend some kind of bloodwork before anaesthesia, and often on some regular basis in older pets, but there are few guidelines, those that do exist are based on opinion and experience rather than high-quality evidence, and individual veterinarians and hospitals vary widely in their recommendations.

There have been a couple of studies looking at how often abnormalities are detected on pre-operative bloodwork, and to a lesser extent whether these abnormalities affected the treatment the patient received. I will discuss a couple of these, which I think fairly represent the state of the evidence at this time.

Alef, M.; Praun, F. von; Oechtering, G. Is routine pre-anaesthetic haematological and biochemical screening justified in dogs? Veterinary Anaesthesia and Analgesia 2008 Vol. 35 No. 2 pp. 132-140

Abstract
Objectives: To determine if routine haematological and biochemical screening is of benefit in dogs requiring anaesthesia and to establish the most useful tests for pre-anaesthetic risk assessment. Animals: One thousand five hundred and thirty-seven client-owned dogs undergoing surgery at the University of Leipzig between January 2003 and April 2004.

Materials and methods: After obtaining a standardized history and a physical examination, all dogs requiring anaesthesia were assigned to an ASA physical status group, their needs for pre-anaesthetic therapy determined and an anaesthetic protocol proposed. Haematological (haematocrit, red blood cell count, white blood cell count, platelet count and haemoglobin concentration) and serum biochemistry tests (plasma urea, creatinine, glucose, total protein, sodium and potassium concentration; serum alanine aminotransferase, alkaline phosphatase and lipase activity) were then performed in all animals. The results of these were then used to: (1) re-define each dog’s ASA physical status; (2) determine any altered requirement for pre-anaesthetic therapy; (3) re-determine the suitability of the dog to undergo surgery; and (4) re-examine the suitability of the original proposed anaesthetic protocol.

Results: The history and clinical examination in 1293 out of 1537 dogs (84.1%) revealed that haematological and biochemical tests would have been considered unnecessary under normal conditions. Of these, 63.9% were categorized as ASA 1, 28.5% as ASA 2, and 7.6% at higher risk. In some dogs, screening tests showed abnormal results: 16.7% of 1293 dogs had abnormal plasma urea levels, with 5.9% of values above the reference range. However, only 104 dogs (8%) would have been re-categorized at a higher physical status category had the laboratory results been available. Additional screening data indicated that surgery would have been postponed in 10 dogs (0.8%) additional pre-anaesthetic therapy would have been provided in 19 animals (1.5%) and the anaesthetic protocol altered in two dogs (0.2%).

Conclusion: The changes revealed by pre-operative screening were usually of little clinical relevance and did not prompt major changes to the anaesthetic technique.

Clinical relevance: In dogs, pre-anaesthetic laboratory examination is unlikely to yield additional important information if no potential problems are identified in the history and on physical examination.

This study fairly clearly shows that only a very small number of dogs presenting for surgery with no reason to suspect illness actually show abnormalities on screening bloodwork, and these abnormalities almost never influence the care these dogs are given. Of course, the question remains open whether testing thousands of dogs to identify relevant problems in maybe 2% is appropriate. Do the benefits for a few individuals (whatever those are, since the study didn’t actually look at the outcome of the procedure) outweigh the costs, the risk of misdiagnosis, harm from unnecessary follow-up testing or unnecessary deferral of needed surgical procedures, and the stress to the owners of dogs who are misdiagnosed?

Another similar study looked at a population for which there is a reasonable rationale to performing pre-operative screening; geriatric dogs.

K E Joubert. Pre-anaesthetic screening of geriatric dogs. J S Afr Vet Assoc. March 2007;78(1):31-5.

Introduction: Pre-anaesthetic screening has been advocated as a valuable tool for improving anaesthetic safety and determining anaesthetic risk. This study was done determine whether pre-anaesthetic screening result in cancellation of anaesthesia and the diagnosis of new clinical conditions in geriatric dogs.

Methods: One hundred and one dogs older than 7 years of age provided informed owner consent were included in the study. Each dog was weighed, and its temperature, pulse and respiration recorded. An abdominal palpation, examination of the mouth, including capillary refill time and mucous membranes, auscultation, body condition and habitus was performed and assessed. A cephalic catheter was placed and blood drawn for pre-anaesthetic testing. A micro-haematocrit tube was filled and the packed cell volume determined. The blood placed was in a test tube, centrifuged and then analysed on an in-house blood analyser. Alkaline phosphatase, alanine transferase, urea, creatinine, glucose and total protein were determined. A urine sample was then obtained by cystocentesis, catheterisation or free-flow for analysis. The urine specific gravity was determined with a refractometer. A small quantity of urine was then placed on a dip stick. Any new diagnoses made during the pre-anaesthetic screening were recorded.

Results: The average age of the dogs was 10.99 +/- 2.44 years and the weight was 19.64 +/- 15.78 kg. There were 13 dogs with pre-existing medical conditions. A total of 30 new diagnoses were made on the basis of the pre-anaesthetic screening. The most common conditions were neoplasia, chronic kidney disease and Cushing’s disease. Of the 30 patients with a new diagnosis, 13 did not undergo anaesthesia as result of the new diagnosis.

Conclusions: From this study it can be concluded that screening of geriatric patients is important and that sub-clinical disease could be present in nearly 30 % of these patients. The value of screening before anaesthesia is perhaps more questionable in terms of anaesthetic practice but it is an appropriate time to perform such an evaluation. The value of pre-anaesthetic screening in veterinary anaesthesia still needs to be evaluated in terms of appropriate outcome variables.

This study appears to find more real and meaningful abnormalities, as one would expect in an older population. However, the details still showed that age did not reliably predict which dogs would have bloodwork abnormalities:

The effect of age and/or breed on the choice of pre-anaesthetic laboratory testing was not fully elucidated in the current study. However, preliminary results show only statistically significant differences (p < 0.05) in platelet count and ALT activity in dogs over 10 years of age. No consistent differences could be found between age groups (<2, 2–7, 7–10 and over 10 years) for the plasma concentrations of glucose, urea and lipase activity. Young dogs (<2 years) showed statistically significant but only slight differences to other age groups in total protein and sodium concentration.

Furthermore, there was no detectable difference in the chances of a pre-operative abnormality in dogs that did or did not have complications during surgery, so it is questionable whether the abnormalities that were found actually helped prevent problems from surgery (though this might have been affected by the deferral of surgery in dogs with some detected abnormalities):

Laboratory test results were within the reference range or interpreted as being clinically irrelevant in 21 of 25 dogs experiencing complications. Relevant laboratory findings were found in only four. The incidence of adverse incidents was 3.8% in dogs with ‘abnormal’ laboratory results and 1.8% in animals with ‘normal’ values. Because of the limited number of complications, no statistical difference could be shown between groups.

Certainly, more research is needed on this topic. However, the existing research suggests that routine pre-operative bloodwork is likely to benefit only a very few patients, so the questions about whether this justifies the costs and risks is still not easy to answer.

In human medicine, guidelines for pre-anesthetic screening are more conservative that what is routinely done by veterinarians:

The guidelines from the American Society of Anesthesiology Task Force on Pre-anesthetic Evaluation state the following:

Routine Preoperative Testing
• Preoperative tests should not be ordered routinely.
• Preoperative tests may be ordered, required, or performed on a selective basis for purposes of guiding or optimizing perioperative management.
• The indications for such testing should be documented and based on information obtained from medical records, patient interview, physical examination, and type and invasiveness of the planned procedure.

Preanesthesia Hemoglobin or Hematocrit
• Routine hemoglobin or hematocrit is not indicated.
• Clinical characteristics to consider as indications for hemoglobin or hematocrit include type and invasiveness of procedure, patients with liver disease, extremes of age, and history of anemia, bleeding, and other hematologic disorders.

• Preanesthesia Serum Chemistries (i.e., Potassium, Glucose, Sodium, Renal and Liver Function Studies)

• Clinical characteristics to consider before ordering preanesthesia serum chemistries include likely perioperative therapies, endocrine disorders, risk of renal and liver dysfunction, and use of certain medications or alternative therapies.

• The Task Force recognizes that laboratory values may differ from normal values at extremes of age.

• Preanesthesia Urinalysis • Urinalysis is not indicated except for specific procedures (e.g., prosthesis implantation, urologic procedures) or when urinary tract symptoms are present.

The general policy in humans is to recommend specific tests based on specific indicators of risk for each individual patient, not to routinely screen everybody who is going to undergo anaesthesia.

A recent paper in the Journal of Feline Medicine and Surgery found a relatively high incidence of common problems (dental disease, kidney disease) etc. in cat over 10 years of age, which would support screening for these disorders in this population. However, this was a small study, and the population was different in some significant ways from those in other places (for example having a much higher incidence of FIV infection that is typical in the U.S.), so we must be cautious about generalizing these results.

I think a rational approach in veterinary medicine is to screen those patients which there are reasons to suspect may have relevant abnormalities, such as animals with clinical symptoms, older animals, animals with known pre-existing conditions, etc. In the absence of better evidence, the only firm conclusion we can make is that firm conclusions are probably not justified. Anyone who says that pre-operative screening or annual examinations of young, apparently healthy pets is mandatory and that not doing it is malpractice is expressing only their opinion, not a conclusion based on reliable scientific evidence. And anyone who states that such screening is worthless is also going beyond the evidence.

Decisions about screening tests in veterinary medicine are, like so many decisions in our business, as much about the values and risk tolerance of individual doctors and owners as about what can be demonstrated to be the best practice. The major deficiency at this point seems to me to be a failure of veterinarians to recognize that screening has costs and risks that should be considered as well as benefits. True informed consent requires that we make our clients aware of the concerns that have emerged in human medicine over irrational or indiscriminate use of screening tests, and of the limited evidence to support screening asymptomatic pets. Clients should be helped to make informed decisions which consider both the possible benefits of screening and also the costs and risks for them and their pets.

Posted in General, Science-Based Veterinary Medicine | 19 Comments

Evidence-Based Medicine in Song

Posted on March 12, 2013 by skeptvet

Posted in Humor | Leave a comment

Nativis Voyager–A “Revolutionary” New Cancer Therapy for Dogs?

Posted on March 5, 2013 by skeptvet

The Nobel Disease is a well-known tongue-in-cheek reference to the apparent tendency of Nobel laureates, who have obviously made substantial legitimate contributions to scientific knowledge, to develop strong irrational attachments to questionable theories or outright pseudoscience in their later years. The MD Disease is a variant strain in which ordinary doctors with real medical training and skills become champions of scientifically unsound theories or practices. All of this, of course, is just a way of pointing out why the argument from authority is a fallacy. Smart, educated, well-respected individuals, even with the best of intentions, are not reliably less susceptible to bias, cognitive dissonance, confirmation bias, or any of the mental quirks that lead us to passionately commit to dubious, even ridiculous ideas than the rest of us. The status or personal characteristics of a believer in any given idea is not a useful form of evidence in favor of the truth of that idea.

This phenomenon came to mind earlier this week when I was asked to look into a technique being promoted as a possible veterinary cancer therapy, the Nativis Voyager system, which is apparently the focus of a clinical trial, and some pretty optimistic promotion, by the accomplished and well-respected veterinary oncologist Dr. Greg Ogilvie.

It is difficult to find much information about this product, but it manifests many of the warning signs of pseudoscience. In particular, it is referred to by the company and Dr. Ogilvie as “revolutionary” and “ground breaking,” despite the lack of any substantive evidence to support this claim. And the emphasis of the research seems not so much to find out if the technology works but to find out how well and for which types of cancer: “Voyager is just beginning its voyage as we are beginning the process of identifying the cancers its most effective to treat. It seems to have a broad spectrum of efficacy while being quite safe.”

In a promotional Youtube video for Voyager, anecdotes purportedly showing dramatic improvements are presented, and claims are even made to suggest some patients might have experience complete remissions or a cure. I personally do not feel that contributing to promotional marketing videos for the company while conducting a supposedly objective, scientific clinical trial of that company’s product is appropriate. And the claims made are largely meaningless if they are founded solely on anecdotes, which are an unreliable guide to the safety and effectiveness of medical therapies for many reasons.

The plausibility of this device is not enhanced by the proposed mechanism described in the patent application submitted by Nativis. It is full of pseudoscientific nonsense such as this:

An aqueous anti-tumor composition produced by treating an aqueous medium free of paclitaxel, a paclitaxel analog, or other cancer-cell inhibitory compound with a low-frequency, time-domain signal derived from paclitaxel or an analog thereof, until the aqueous medium acquires a detectable paclitaxel activity, as evidenced by the ability of the composition (i) to inhibit growth of human glioblastoma cells when the composition is added to the cells in culture, over a 24 hour culture period, under standard culture conditions, and/or (si), to inhibit growth of a paclitaxel-responsive tumor when administered to a subject having such a tumor.

This appears to be a claim that one can somehow digitally record the curative properties of chemotherapy drugs in solution and then play them back to water, thus transforming the water into a therapeutic substance with none of the unwanted effects of the cancer drugs. Others have investigated such claims from this company and found more direct statements of this highly speculative and implausible idea:

Nativis has developed and patented a breakthrough technology that captures the unique photon field (signal) of active pharmaceutical ingredients (API), or drugs. . .Every drug molecule in a solution is surrounded by a photon field that contains information unique to the molecule. With Nativis’ technology, the photon field, or “drug signal” can be recorded and then replicated for medical treatment. Nativis has proven in preliminary trials that the drug signal – or photonic signature – mimics the original chemical molecule and can unlock the same biological processes as the original to treat diseases, such as brain tumors. With the technology, the drug signal can be reproduced rapidly and flawlessly, each time containing all relevant biochemical information encoded into the new therapeutic signal to drive a biologic reaction. . .

If this sounds vaguely familiar, that’ because it bears an uncanny resemblance to the theories of some homeopaths that the magical healing energy of homeopathic remedies can be digitally recorded and transmitted by telephone or other electronic media. And by an astounding coincidence (or perhaps not?), at least one of the patent holders and key figures at Nativis has previous professional connections with Luc Montagnier and Jacques Benveniste.

Dr. Montagnier is one of the classic examples of Nobel Disease, a co-discoverer of HIV who later became a proponent of homeopathy in both traditional and digital forms. And of course Dr. Benveniste was the author of a famous study in the journal Nature which appeared to show a real biological effect of a homeopathic solution on cells in culture. This effect, however, was later demonstrated to be an illusion due to improper blinding of study personnel, and decades of attempts to replicate it have proven unsuccessful.

Nativis has previously announced a revolutionary new cancer therapy and supporting research evidence which have, in the three years since, not emerged and which are no longer mentioned on the company web site, now devoted to Voyager. A history of claiming revolutionary breakthroughs without published scientific evidence to support them, followed by closing up shop, moving to a new state, and setting up an entirely new product based on almost the same unproven theories, this time for the veterinary rather than human market, is not the behavior of a company I would trust. Certainly, it is not a sound basis for a respected veterinary oncologist to promote the product and make rather strong, optimistic claims about its benefits, raising the hopes of pet owners and using scare resources in the always struggling domain of veterinary oncology research.

Despite his well-earned status in veterinary medicine, Dr. Ogilvie has shown sympathy towards implausible practices in the past. He has been a regular lecturer, and even the Keynote Speaker, at the annual conference of the American Holistic Veterinary Medical Association (AHVMA). This is the same organization that has encouraged and promoted many ridiculous practices at its annual meetings and which recently mounted a major effort to defend homeopathy as a legitimate and scientific therapy. He is also on the advisory board of a “holistic” supplement company along with many of the most prominent spokespeople for homeopathy, so-called Traditional Chinese Medicine, and other alternative veterinary practices. This might explain why, despite his intelligence and unimpeachable credentials as an oncologist, he seems willing to jump on such a ramshackle bandwagon as the Nativis Voyager system.

Of course, the proof of the pudding is in the eating. If convincing and replicable clinical trial evidence eventually emerges showing a significant therapeutic effect for the Voyager, I will be thrilled to have a new and better cancer therapy to offer. If, as I expect is more likely, such evidence never emerges, and this “revolutionary” product goes the way of Dr. Sanden’s Electric Belt, I will be disappointed; both because of the failed promise of a better treatment for my patients and also because of the damage to the credibility of a brilliant veterinarian whose guidance I have often followed in my career.

 

 

 

 

 

 

 

 

 

 

 

 

Posted in Miscellaneous CAVM | 22 Comments

Book Review: Bad Pharma by Dr. Ben Goldacre

Posted on February 20, 2013 by skeptvet

Introduction
Most of the articles I write concern unconventional or alternative therapies. The primary reason for this is that the overwhelming majority of the information available to pet owners about such therapies comes from practitioners and true believers, often with a commercial interest in these therapies. People deserve an independent, skeptical, science-based perspective they can consider when deciding what’s best for their pets, and since there are almost none of these, I have done what I can to provide one.

One of the more superficially reasonable objections to this focus on alternative therapies is that there are many problems with the evidence concerning conventional medicine as well, and there is a need for skeptical and science-based evaluation of all our practices. This is true, and I do engage in such critical appraisal in my daily work, through organizations I belong to, such as the Evidence-Based Veterinary Medicine Association, and sometimes here in this blog. The pharmaceutical reps that come to our practice are no happier to see me than are the chiropractors!

However, the existence of unsolved problems in science-based medicine does not reduce at all the need for critical evaluation of alternative therapies. The limitations of the evidence for conventional practices does not make the implausible plausible, the unproven proven, or the outright ridiculous reasonable. To suggest that no one should critique alternative medicine without giving equal time to criticism of conventional therapies is a fallacy (tu quoque) and a distraction from the weaknesses of the claims made for alternative therapies.

The other problem with the “glass houses” argument is that there is, in fact, much criticism of conventional, science-based medicine coming from within mainstream medicine. Plenty of people are working on identifying and fixing many of the problems with the development and delivery of science-based medical care, and while perfection is nowhere in sight, it is possible to track improvement over time (albeit often frustratingly long periods of time). The folks promoting alternative medicine seem, at least in public, far less willing to criticize their own colleagues or take on the dramatic and egregious problems with claims not based on good evidence within their fields.

A shining example of critics of alternative medicine and proponents of science-based medicine taking on the task of setting our own house in order is the recently published Bad Pharma by Ben Goldacre (recently published here in the U.S., at least, though it’s been out in the U.K. for a while).

Dr. Goldacre, a British academic physician, has been a long-time critic of nonsense of all kinds in all areas of medicine. He is a prominent, articulate skeptic who has given much grief to promoters of homeopathy and other forms of alternative medicine through his well-researched and well-reasoned columns in the Guardian newspaper, collected in his previous book Bad Science. But he has never spared the pharmaceutical industry, government regulators, or his colleagues in journalism and medicine from direct criticism when they fail to meet his standards for a scientific, evidence-based approach to medicine.  

This book provides a set of cogent arguments and a good collection of empirical evidence to illustrate the deep flaws in our system for establishing safety and efficacy of pharmaceutical therapies and for making clinical decisions about the best use of these medicines. It is not without flaws, which I will discuss, but overall it is a readable and important contribution to the betterment of science-based medicine, and I encourage everyone involved in any aspect of medicine, as a researcher, doctor, or as a patient, to read Bad Pharma. And since we are all patients at some point in our lives, that means everyone!

The book has been reviewed in fair detail at Science-Based Medicine, so I will focus on making some general comments about the strengths and weaknesses of the case Dr. Goldacre makes.

Strengths & Weaknesses
Bad Data
The strongest part of the book by far is the analysis of how incomplete and potentially misleading the evidence is from clinical trials sponsored and conducted by the pharmaceutical industry. Dr. Goldacre does a brilliant job of illustrating how a systematic, comprehensive, devastatingly effective system for misleading regulators, doctors, and the public about pharmaceutical therapies can exist without widespread, deliberate lying or an omnipotent conspiracy involving industry, government, and the medical professions. In the sneaky way so common to corporations generally, the pharmaceutical industry manages to rig the game through small, often seemingly innocent steps that aggregate themselves into a deeply flawed system without much if any need for shadowy conspiracies and puppet masters.

Oh, there’s undoubtedly individual malfeasance involved, of course. Much of what we know about how the system works comes from internal documents made available as part of legal cases against the big drug companies. However, the vast majority of individuals working in this industry are smart, well-intentioned, honest people trying to develop new and better medicines. The importance of recognizing this lies in understanding that the way to fix the problems of this industry involve much more than simply finding and cleaning out the bad apples. The system for generating and distributing research information about drugs has to be designed to compensate for the often innocent and unconscious biases that tilt the findings in a direction favorable to the companies even when there is no deliberate program to do so.

Dr. Goldacre does offer some reasonable proposals for achieving this, though he also illustrates how previous reasonable proposals have failed, through lack of enforcement, lack of interest, or unexpected ways the system can adapt to achieve the same misdirection in new ways when some problems are fixed. Overall, Dr. Goldacre does such an effective job illustrating the problem, it is hard to come away with much hope that it can be fixed, despite his assertions that he believes it can. One of the weaknesses of the book is that his efforts at driving home the complexity and severity of the problem are often more successful and convincing than his proposals to solve it.

Drug Approval
Bad Pharma also reviews the process by which drugs are developed and approved for human use. Since this is a lengthy and complex process, Dr. Goldacre necessarily presents a brief, simplified version with a frame intended to illustrate primarily the opportunities for trouble and erroneous or unreliable data. He does not, perhaps, offer an entirely fair view of the difficulties both inherent in the process for biological reasons and imposed by the commercial nature of the endeavor and the often irrational and inconsistent regulatory conditions under which it operates. There are many reasons why developing safe and effective medicines is tremendously challenging apart from the production of misleading and unreliable research data. However, the book was not intended as a “fair and balanced” review of the process but as an expose of its flaws and a call to action. In keeping with Dr. Goldacre’s own suggestion later in the book, it is appropriate to view this section, and the others, with this agenda in mind. The specific points he does make are, as best I can tell, accurate.

Bad Regulation
Dr. Goldacre also spends a fair bit of time discussing the gross inadequacies of the system for regulating the pharmaceutical industry. He presents something of a conflicted view, both making a compelling case for the failure of government regulation and yet repeatedly suggesting regulation as a solution to many of the problems in the industry. I appreciate this conflict as I tend to share it. I have written often about the regulation of medicine in general (e.g. 1,2,3,4) and why I feel it is frequently inadequate at protecting patients from even the most egregious pseudoscience and quackery (e.g. 5).

However, I also believe that consumer choice and market mechanisms cannot do the job, and that the solution to ineffective regulation is more and better regulation properly enforced. Again, I think Dr. Goldacre lays out the problem clearly and effectively, but it does somewhat undermine his own case when he suggests further regulation as an important part of dealing with the problems he identifies. It is important to recognize that the quality of medicine, and the usefulness of research evidence, was far worse in the era of “medical anarchism” before widespread regulation, and it continues to be far worse today in unregulated or under-regulated domains such as dietary supplements and herbal remedies than it is in the domain of pharmaceuticals. The legitimate failings Dr. Goldacre identifies are important and urgent problems, but not a reason to abandon ship or forget the value we get from the regulatory mechanisms we have.

Bad Studies
As an epidemiologist-in-training, one of my favorite parts of the book were the sections dealing with ways in which clinical trials can be designed to generate misleading findings favorable to the sponsor. The whole point of clinical trials, of course, is to compensate for chance, bias, confounding, and sources of error that lead us so easily astray in our day-to-day evaluation of how the world works. The success of science has been due primarily to this ability to compensate for the collective and several weaknesses of individual scientists.

However, the system is not perfect, and there is good reason to believe residual bias and improper design and execution bedevil much medical research. This is part of what makes the processes of evidence-based medicine, which critically evaluate all the research and draw conclusions based on the entire body of evidence in a given area, so crucial.

Dr. Goldacre gives many specific examples of how trial results can be shaped to be misleading, from the selection of unrepresentative patient populations to inappropriate or shifting outcome measures, inappropriate controls, inadequate randomization and blinding, early termination, and dodgy statistics. All of these are flaws which can be easily identified if the full details of the process are publically available from start to finish, which is one of the most important recommendations made in the book for dealing with the problems identified.

Marketing
Finally, Dr. Godlacre addresses the abuses and excesses of the pharmaceutical industry marketing machine, which exists entirely to increase the revenue generated by the industry’s products and yet which masquerades as a system for disseminating useful information to doctors, patients, and politicians. This subject has been covered extensively by others, so there is not much new in this review of the problem.

I also think this section contains some of the weakest parts of Dr. Goldacre’s argument. When he discusses potential conflict of interest, he acknowledges that it is difficult to argue that anyone doesn’t have one. Ideological or philosophical biases and personal relationships can shape our conclusions as much as financial incentives, so no one can claim to have no bias at all. That is, after all, why we need the methodology of science.

But there likely is a reasonable, if somewhat arbitrary point, at which one can distinguish between the ordinary bias that comes from having a point of view and recessive, inappropriate corporate influence on doctors and political decision makers. Dr. Goldacre’s primary suggestion for dealing with conflicts of interests is extreme transparency, suggesting, for example, that any and all affiliations with industry a doctor may have be disclosed in the waiting room of their office or on the Internet. Dr. Goldacre seems to feel that this disclosure will convey the impression to the public of possible conflict of interest and that subsequent public pressure will discourage inappropriate relationships between doctors and industry.

My concern with this line of reasoning is that it feeds all kinds of cognitive bad habits that can lead us to judge people’s claims inaccurately and inappropriately. If any association with industry is seen as suggestive of possible bias, and if almost everyone has some such association, however tenuous, than disclosing these alone will simply convey the impression that all doctors, and medicine as a whole, is merely a tool of the pharmaceutical industry and that recommendations made by our doctors can be dismissed on this basis alone, regardless of the evidence for or against them. I realize, of course, most people are unlikely to be this unreasonable, but unfortunately in the context of this blog I meet a fair number of people who are not and who are looking for any opportunity to play the “pharma shill” card to dismiss science-based medicine in favor of some alternative that is even less evidence-based and reliable.

I do support disclosure of commercial interests that might plausibly introduce bias into research or clinical practice, but I think it would be appropriate to make some reasonable distinctions about what kind of relationships matter or are clearly inappropriate and what kind are less concerning. And ultimately, we cannot eliminate individual bias, so our efforts are likely to be most productive if we focus on ensuring transparent and effective research methods to control for it.

In any case, there is no question that the shift in public political values and priorities, especially in the U.S., has led to a situation in which the lion’s share of medical research is supported by commercial interests rather than government. This has had the consequence of raising the threat financial bias poses to the integrity of research data. And the marketing mechanisms employed by the pharmaceutical industry are often a paragon of cynical, blindly self-interested manipulation of opinion not conducive to the best interests of patients.

Bottom Line
Bad Pharma is a compelling and important exposé of the well-known but still unresolved problems with the influence of pharmaceutical companies on the generation and distribution of research evidence concerning drug therapies. It skillfully and convincingly identifies many specific problems. It also offers many reasonable and practical suggestions for improving the situation, though the strength of the solutions offered is noticeably weaker than the strength of the case made for the problems themselves, leaving one struggling with a bit of pessimism about the chances of reforming the system in significant and effective ways.

In addition to illustrating the problem and discussing solutions, Dr. Goldacre has partnered with the British Medical Journal, The Centre for Evidence-Based Medicine, Sense About Science, and the James Lind Initiative to form the All Trials Campaign. This effort is focused primarily on pressure the pharmaceutical industry, governments, medical professionals, researchers, and patient organizations to take steps to ensure all research data related to pharmaceuticals is freely, efficiently and widely available so that the evidence-based analysis necessary to guide medical practice has access to the evidence it needs to draw correct conclusions. I encourage everyone interested in improving the state of medical science and healthcare to support this initiative and to read Dr. Goldacre’s book.

Posted in Book Reviews | 3 Comments

Benefits and Risks of Neutering, an Evidence Update: Study Investigates Effects of Neutering in Golden Retreivers

Posted on February 17, 2013 by skeptvet

Given that I recently presented a couple of evidence-updates on the subject the health effects of neutering, the timing was excellent for the release last week of a new research study looking at the same issue.

Torres de la Riva G, Hart BL, Farver TB, Oberbauer AM, Messam LLM, et al. (2013) Neutering Dogs: Effects on Joint Disorders and Cancers in Golden Retrievers. PLoS ONE 8(2): e55937. doi:10.1371/journal.pone.0055937

This was a retrospective cohort study in which records were searched to identify Golden Retrievers who had been patients at the UC Davis veterinary school, were between 12 months and 8 years of age, and who could be classified as having been neutered “early” (before 12 months of age), “late” (after 12 months of age), or not at all. The occurrence of a number of diseases common in Golden Retrievers was then evaluated to see if it differed between dogs in these three categories. There are several reasons to be cautious in how we interpret the results of this study, but let’s start by looking at what those results were.

The authors looked at the occurrence of hip dysplasia (HD), elbow dysplasia (ED), cranial cruciate ligament rupture (CCL), and a number of cancers com including lymphosarcoma (LSA), hemangiosarcoma (HSA), mast cell tumor (MCT), osteosarcoma (OSA) and mammary cancer (MC). The figures below illustrate the relative occurrence of some of these diseases in males and females by neuter status (the diseases not shown did not occur often enough to be included in the analyses).

 ucdstudygoldensneuteringfig1

 

Figure 1. Percentages and number of cases over the total sample size for each neutering status group; intact and neutered early or late for male Golden Retrievers (1–8 years old) diagnosed with hip dysplasia (HD), cranial cruciate ligament tear (CCL), lymphosarcoma (LSA), hemangiosarcoma (HSA), and/or mast cell tumor (MCT) at the Veterinary Medical Teaching Hospital of the University of California, Davis, from 2000–2009.

For HD and LSA, the differences between early-neutered and intact or late-neutered groups were statistically significant (K-M), as were differences for CCL between intact and early-neutered groups.

ucdstudygoldensneuteringfig2

 

Figure 2. Percentages and number of cases over the total sample size for each neutering status group; intact and neutered early or late for female Golden Retrievers (1–8 years old) diagnosed with hip dysplasia (HD), cranial cruciate ligament tear (CCL), lymphosarcoma (LSA), hemangiosarcoma (HSA), and/or mast cell tumor (MCT) at the Veterinary Medical Teaching Hospital of the University of California, Davis, from 2000–2009.

For CCL the difference between intact and early-neutered was statistically significant (K-M). For HSA, the differences between early and late-neutered and intact and late-neutered groups were statistically significant (RR), as were differences for MCT between early and late-neutered groups. A similar statistical comparison for late neutering and intact groups was not possible for MCT because there were 0 cases in the intact group.

doi:10.1371/journal.pone.0055937.g002

These results suggest that there is a complex and inconsistent pattern of associations between neuter status and these diseases. In general, there was a tendency for neutered animals to have higher rates of these diseases than intact animals and for early neutered animals to have higher rates than late neutered animals. However, there are many cases in which differences were not statistically significant or the difference was significant in one sex but not the other, and a few in which the direction of the difference was opposite that expected (for example with HAS occurring more often in late-neutered females than either intact or early neutered females).

The difficulty lies in knowing what these results mean in terms of predicting the risks for individual pets and making decisions about neutering in general. The natural tendency will be to look at these data and conclude that not neutering, or neutering after 12 months of age, is safer than the common current practice of neutering most animals before 12 months. However, this is not a conclusion we can reliably draw from these data.

To begin with, this is a group of dogs that are, in many ways, very different from most dogs neutered by veterinarians. Apart from only representing one breed, and a breed known to have higher rates of the diseases studied than most other breeds, the subjects were patients at a university veterinary hospital. In general, only the sickest animals with the most unusual or serious diseases are seen at universities. Most healthy animals or those with typical illness are seen at general veterinary practices. So it is uncertain if neutering will have the same effects as in this study on dogs of other breeds or those healthy enough to have never seen the inside of a university hospital.

The population also contained small numbers of intact and “late” neutered dogs. This makes it more likely that small, random differences in the health of individual dogs in the study group could alter the apparent effects of neutering on health.  And the authors chose to limit the study population to dogs between 12 months and 8 years of age. Quite a few Golden Retrievers live past 8 years, and the rates of cancer generally go up dramatically with age. If the proportion of these diseases among intact and neutered animals over 8 years old are at all different from those in dogs under 8, then the direction and statistical significance of the differences between groups seen in this study could easily be altered.

And it’s important to consider the absolute risk and benefit numbers when making decisions about whether to neuter. If, in fact, neutering is strongly protective against a common cancer (as it is thought to be for mammary cancer) but also slightly increases the risk of a rare cancer, it may still make sense to neuter early depending on the unique situation of an individual patient.

Finally, two of the major diseases against which neutering is thought to be protective in females, uterine infection and mammary cancer, did not occur often enough to be included in the analysis. This may be because relatively few of the dogs were intact or because of the age cutoff. Obviously, if there really is a protective effect of neutering on these diseases that didn’t show up in this study, that might influence the interpretation of the results.

Overall, this is a useful piece of research adding to the information we have about the pros and cons of neutering and the possible role of age in the effect of neutering on disease. It should be over-interpreted as the final word by itself, but it should be incorporated into a broad analysis of all the available evidence.

As it stands, there is reason to believe early neutering has significant benefits in females, though as the recent systematic reviews pointed out the evidence behind this belief is not strong. There is also reason to be concerned about possible risks, though the evidence for this is also not robust yet. On balance, one can make a reasonable case on both sides, and the risk profile for individual dogs, as well as larger issues such as the problems associated with unwanted reproduction. Anyone who says there is an absolute and universal right answer concerning if and when to neuter female dogs is exaggerating by quite a bit.

For males, I believe the evidence of benefits from neutering, especially before 12 months of age, is not compelling, and I don’t see a strong reason to neuter earlier in the case of owned dogs with owners willing to commit to preventing roaming and unwanted reproduction and in the absence of intolerable interdog aggression. For large breeds in particular, delaying neutering of males seems reasonable, though we very much need better evidence to have confidence in such a recommendation. It is encouraging that more attention is now being paid to the complexities of neutering and the risks and benefits associated with it, and I am optimistic that this will lead us to more reliable guidelines in the future.

 

Posted in Science-Based Veterinary Medicine | 12 Comments

The Myth of Antioxidants?

Posted on February 12, 2013 by skeptvet

I have written often about the popular notion that vitamins, dietary supplements, herbs, and other things which can be identified as “antioxidants” based on in vitro laboratory studies must automatically be good for our pets. This sort of simplistic reasoning is rarely justified in biology, and there is ample reason to doubt the hype that free radicals and oxidation are always bad and that antioxidants are always good.

In terms of specific supplements, there is large-scale clinical research evidence showing that even essential antioxidant vitamins, such as Vitamin E and Vitamin C, are not only not beneficial in excess but can increase the risk of cancer, heart disease, and other serious ailments and interfere with some medical treatments, such as chemotherapy. The common alternative medicine mantra that such supplements prevent cancer and other diseases, or help “boosting the immune system” in patients with serious illness, is inaccurate and potentially dangerous.

A recent review in Scientific American magazine does a nice job of summarizing the growing research evidence of the last decade showing that the theory of oxidative damage as a primary driver of aging and disease is deeply flawed, and that antioxidant supplements (as opposed to fruits and vegetables in their whole form) can often do more harm than good.

Moyer, M.W. The Myth of antioxidants: The hallowed notion that oxidative damage causes aging and that vitamins might preserve our youth is now in doubt. Scientific American. February, 2013. 64-67.

Though intended for the general public, and thus not a systematic review, this article does a good job of identifying several areas in which theories about the role of free radicals and antioxidant appears to have failed to hold up. The first is the notion that oxidative damage is a key component of aging and that reducing oxidation and supplementing antioxidant should lengthen life. The article cites a number of laboratory studies in invertebrates and mammals showing that animals genetically engineered to have reduced activity of natural antioxidant systems do, in fact, have increases in free radicals. However, these animals live longer than animals with better antioxidant function! And supplementing these subjects with antioxidants reduces their life expectancy to that of animals with normal anti-oxidative functions.

The author also reviews some of the early studies produced by the first proponents of the oxidative damage theory, and points out that attempts to replicate these have usually failed. There are even studies showing that application of an herbicide which increases free radical production can increase lifespan in some laboratory species, and again antioxidant supplementation eliminates this increase in life expectancy.

More nuanced theories suggest that, as is usually the case, the truth is complex and depends on context and many factors. There are undoubtedly situations in which free radicals and oxidative damage are harmful. But there may also be situations in which increases in free radicals may be beneficial. Such oxidative compounds increase as a consequence of exercise, for example, and antioxidant vitamins appear in some research to attenuate the benefits of exercise. And oxidative damage is one mechanism by which the immune system and some medicines destroy infectious organisms and cancer cells. Antioxidant that interfere with these beneficial activities can actually cause harm.

There is much work yet to be done to refine our understanding of the positive and negative effects of oxidation and antioxidants, but one thing is clear. Simplistic notions of antioxidant supplements as automatically beneficial are nonsense and not a sound basis on which to recommend supplements, herbal remedies, or other preventative or therapeutic products.

Posted in Herbs and Supplements, Science-Based Veterinary Medicine | 10 Comments

Benefits and Risks of Neutering, an Evidence Update: Neutering and Mammary Cancer in Female Dogs

Posted on February 8, 2013 by skeptvet

This is another in my series of evidence updates on the risks and benefits of neutering in dogs and cats. I will be updating the evidence and conclusions of my original 2010 review based on a series of systematic reviews being produced by a research group in the UK. The first such update concerned the effect of neutering and age at neutering on urinary incontinence in female dogs. This update concerns one of the most important reasons to considering neutering female dogs: mammary cancer.

Beauvais W, Cardwell JM, Brodbelt DC. The effect of neutering on the risk of mammary tumours in dogs–a systematic review.J Small Anim Pract. 2012 Jun;53(6):314-22.

In my 2010 review, I found evidence suggesting that mammary cancer is very common in intact female dogs, that it is malignant about half the time, and that neutering dramatically reduces the risk of this disease. I also found evidence suggesting that neutering is most effective in preventing mammary cancer if performed before the first heat, and that the benefit disappears after the third estrus cycle. This is a major reason why I still recommend neutering young female dogs.

The UK group found only 4 research reports that addressed the question of the impact of neutering on mammary cancer risk and that met the minimum quality criteria for review. One of these also addressed the issue of whether age at neutering was associated with mammary cancer risk. They reported the following results: 

  1. All studies had significant methodological flaws, and none provided information that could be confidently generalized to the general dog population.
  2. One study found a strong protective effect of neutering. Another found some protective effects but these were inconsistent. The remaining two studies found no association between neutering and mammary cancer risk.
  3. The one study that evaluate age at neutering found a significant decrease in the protective benefits of neutering with each of the first three heats, and no benefit after the third heat.

Once again, the general conclusions are consistent with the current consensus, that neutering young female dogs likely has a meaningful beneficial effect on reducing the risk of mammary cancer later in life. However, the existing evidence is extremely weak, and this conclusion has to be viewed as tentative. While current evidence does not justify a change in the common practice of recommending neutering to prevent mammary cancer, we cannot view our current conclusion with any great confidence, and we desperately need more and better quality research to determine if the current evidence is correct or if a significant change in our recommendations is called for.

As always, the decision to neuter must be based on the entirety of the known risks and benefits, with a clear understanding of the uncertainty involved, as well as on the unique circumstances of each individual. The value of this review is not so much in answering our questions about the subject, which it cannot do, but in making it clear what the strengths and weaknesses are in the evidence behind our current recommendations and in guiding us in the development of better evidence that will permit more confident conclusions.

 

 

Posted in Science-Based Veterinary Medicine | 11 Comments