The American Veterinary Medical Association (AVMA) functions mostly as a lobby and PR organization for veterinarians. It is a membership organization and, as such, is beholden to whoever its members are, and the organization is very keen to avoid conflict within the profession or any suggestion of forcing vets to do anything in particular. The wild political drama surrounding a simple resolution in the AVMA House of Delegates to acknowledge the demonstrable uselessness of homeopathy demonstrates this quite starkly.
The AVMA does make some attempts to promote standards “within the family,” generally in the form of non-binding position statements. These are often pretty lukewarm compromises between competing interests, but they have some utility. The AVMA also has a Principles of Veterinary Medical Ethics, and the organization is currently asking for comments from members on a proposed Code of Conduct based on these principles.
This document does offer some acknowledgement of the importance of evidence-based medicine for ethical clinical practice, and it seems possible that this could be strengthened somewhat, though I am not extremely optimistic. Nevertheless, I encourage any readers who are AVMA members to participate in this comment period, and anyone else to consider encouraging any members you know to do so.
The commenting period will close at 11:59 p.m. Central Time on March 4, 2024.
Here are the comments I made
Section B subsection 1 paragraph d
“A veterinarian does not have an ethical obligation to deliver care requested by a client that they believe would cause unnecessary pain and suffering for the patient and that is unlikely to be beneficial.”
A veterinarian has an ethical obligation to prioritize offering evidence-based care that is most likely to be beneficial and that maximizes the ratio of likely benefit to potential harms.
Recommendation: I recommend adding the language in bold to this section.
Rationale: The purpose of a code of conduct is to articulate “specific types of behaviors that are either expected or required of members of the veterinary profession,” not merely those behaviors that are not expected. This section indirectly indicates that veterinarians should prioritize care that is likely to be beneficial or with likely benefits that outweigh potential harms, yet it does not clearly articulate a positive expectation for the corresponding behavior. The section should indicate that the ethical behavior is to prioritize and offer only care which is expected to have benefits greater than its risks.
Section B subsection 2 Evidence?based Medicine
“A veterinarian should prioritize the delivery of evidence?based medicine and should inform the client when a therapy does not meet this standard.”
A veterinarian should eschew practices that do not meet a reasonable standard of evidence for safety and efficacy.
Recommendation: I recommend adding the language in bold to this section.
Rationale: The guidelines recognize that there is an ethical obligation to “prioritize evidence-based care” because this is the type of car most likely to benefit patients. If this is true, it is not sufficient to simply inform clients when we are offering care that does not meet this standard and then offer care that is not evidence-based or not likely to be safe and effective anyway. Veterinarians should be expected to eschew practices that are unlikely to have benefits greater than their risks based on a reasonable standard of evidence.
General practice veterinarians (GPs) are often faced with the question of which services they should provide themselves and which should be left to board-certified specialists. The growing availability of specialty care, the expectations of many pet owners for advanced care resembling that which they receive, the expanding availability of new and more technologically sophisticated interventions, and many other factors all add to the pressure to limit services in general practice and refer more patients to specialists.
On the other hand, many pet owners struggle to find and afford veterinary care of any kind, much less the most advanced. The concept of a spectrum of care has gained momentum in veterinary medicine largely in acknowledgment of this and in recognition of the fact that intensive, technologically sophisticated, and expensive healthcare may not always be available and may not even the best option for a given patient and client. I was privileged to be invited to contribute to one of the first attempts to characterize the concept of a spectrum of care in the veterinary literature, and it has gained significant momentum since (e.g. 1, 2)
One element to the spectrum-of-care concept is allowing flexibility in what care is provided and by whom while still providing effective, evidence-based treatment. General practice vets are very experienced at the art of providing care within the many constraints of time, money, and expertise available in private practice.
Unfortunately, sometimes both GPs and specialists, especially some in academic settings, mistake the most intensive and advanced specialty care for the best care, or even for the only acceptable kind of care. This makes it harder for GPs to meet the needs of their patients and clients within the inevitable limitations of the “real world,” that is, practice outside of universities or highly affluent communities.
I have been fortunate enough to work for many years at a practice where I was able to learn and provide advanced care options often considered the exclusive province of specialists, such as endoscopy, chemotherapy, and ultrasound. While some specialists have objected to this, many have understood the importance of avoiding rigid distinctions between primary and specialty care in order to effectively meet the needs of all our patients and clients.
Recently, I have developed the impression that newer veterinary school graduates are more reluctant that earlier generations to provide such advanced care tasks. Whether this is a generational change or a result of the messages they are receiving in school, such a trend could potentially further limit the availability of high-quality care and exacerbate both the shortage of veterinary services and the dissatisfaction driving vets from clinical practice.
I recently wrote an editorial for the Journal of the American Veterinary Medical Association (JAVMA) intended to explore the issue of specialty referral, and to hopefully advance discussions within the profession around this subject. This is based solely on my own experiences in practice, and my understanding of evidence-based medicine and the spectrum of care concept, so it is only my thoughts on the subject, not an objective, data-driven analysis. Nevertheless, I hope this will provide useful context and food for thought to GPs and specialists, and perhaps to pet owners as well.
It’s been ten years since my first post on the use of cannabis in dogs and cats. For a while, I regularly covered new research studies, but the number of those has become great enough that keeping up with individual papers is not feasible. Fortunately, the principles of evidence-based have an answer- literature reviews!
There are two main types of review articles of use to clinicians: narrative reviews and systematic reviews. Narrative reviews are far more common in veterinary medicine. These involve individuals or small groups reviewing the research on a given subject and writing a summary from their perspective. These reviews can be very useful, and I have written several myself. But of course they are subject to significant bias. Authors can choose which studies to include and which to ignore, and they can interpret the results through the lens of their existing beliefs on the subject. This doesn’t mean narrative reviews are not useful, but it is a reason for caution in the level of confidence we place in their conclusions.
Systematic reviews are more formal projects, with clear and explicit standards to encourage a comprehensive assessment of the research on a given subject and an objective summary of the strength of the evidence. These are less subject to bias, but they have the weaknesses of often being inconclusive. When there are few studies or most research has significant limitations, no confident conclusion is justified, and most systematic reviews end with the conclusion that more research is needed. This is especially the case in veterinary medicine, where having only a few small studies with significant methodological limitations is the rule.
In the case of veterinary cannabis, there are only a few systematic reviews. One has looked specifically at the literature for cannabidiol (CBD) use in dogs with osteoarthritis (OA).
As expected, this review had to rely on only a few studies (five), and “All studies were rated as having a high risk of bias.” The conclusion was that CBD “may reduce pain…but the certainty of evidence was very low.” Fortunately, “CBD is generally considered safe and well-tolerated in the short-run, with few mild adverse events observed, such as vomiting and asymptomatic increase in alkaline phosphatase level.” However, as usual the bottom line is that more and better research is needed to allow any confident conclusions about the utility of CBD in arthritis dogs.
A slightly older review looks at all uses of cannabis in dogs.
Only six studies met the criteria for quality to be included, all in dogs “with osteoarthritis (n = 4), with epilepsy (n = 1), and with behavioral disorders (n = 1)” and all using CBD as the test treatment. All studies showed improvement in the conditions being treated, but “studies were heterogeneous and presented risks of bias that required caution in the interpretation of findings.” As in the more recent study, “CBD was well tolerated with mild adverse effects,” but “More RCTs with high quality of evidence are needed, including greater numbers of animal subjects, additional species, and clear readout measures to confirm these findings.”
A few narrative reviews have also appeared in the last couple of years that provide a good overview of the uses and evidence for cannabis-based remedies in veterinary medicine. The most comprehensive looks at dogs and cats.
One interesting lesson from this review is that despite severely limited evidence and great uncertainty about what cannabis products might be useful for at what doses with what risks, people are using them all the time for everything. The perception appears to be that cannabis is a safe and effective panacea for companion animals, which of course isn’t substantiated by the actual evidence.
“The cannabidiol (CBD) pet market is expected to increase by $3.05 billion during 2021–2025, with a compound annual growth forecast to reach nearly 30%…A survey conducted online in the United States reported that nearly 60% of pet owners give or were giving CBD to their dogs, and 12% to their cats, most commonly for treating conditions like osteoarthritis (OA), seizures, cancer, or anxiety. From these, 64% found it helps with pain reduction, 50% that it aids with sleep, 49% that it reduces anxiety, and 30% that it reduces convulsions.”
The evidence is generally encouraging for some conditions, particularly pain, but it certainly is nowhere near the level needed to justify this kind of confidence among pet owners. Here are some of the main results reviewed for use of cannabis in various conditions.
In canines, recent studies have shown mixed results regarding CBD’s efficacy as an adjunct therapy for managing inflammatory conditions like OA.
Mejia et al. found that CBD administered at 2.5 mg/kg twice daily, either in conjunction with non-steroidal anti-inflammatory drugs or not, did not improve objective measures of pain in client-owned dogs that suffered from OA compared to the placebo. The authors found some improvement in both the placebo and treatment groups, which was attributed to either caregiver’s placebo effect …This was the only study to use objective outcome parameters.
Verrico et al. found a significant reduction in pain (perceived by the owner) combined with increased mobility in large dogs with OA when given CBD for 4 weeks at doses ranging from 0.5 to 1.2 mg/kg.
Similarly, Gamble et al. reported decreased pain and increased activity in client-owned dogs administered 2 mg/kg CBD twice daily for 4 weeks.
Brioschi et al. also found that CBD administered for 12 weeks at 2 mg/kg twice daily significantly reduced the Pain Severity Score in OA dogs when compared to OA dogs not administered CBD. However, all dogs in Brioschi et al.’s study and most dogs in Gamble et al.’s study were administered anti-inflammatory drugs during the clinical trial, indicating a beneficial effect of CBD when combined with anti-inflammatory drugs.
Whether CBD is effective in reducing epileptic episodes in dogs with IE [idiopathic epilepsy] is inconclusive, and to date there are more clinical reports than controlled clinical studies…Two relevant controlled clinical trials explored the effect of CBD in dogs with IE…Additional studies are needed to strengthen the use of CBD or hemp extract in dogs with IE…Despite that, a survey of 297 pet owners with epileptic dogs showed that nearly half of these people were using different supplements to help reduce seizures or control side effects of other medications, and close to 40% of these supplements contained CBD.
A 3-month randomized blinded study found that dogs with IE that received whole hemp extract (THC [tetrahydrocannabinol] < 0.3%) infused hemp oil at 2.5 mg/kg CBD twice daily in conjunction with other epilepsy drugs had a reduction of seizure frequency by 33% compared to the control group. Some study limitations included the small sample size of dogs who completed the trial and the fact that the data could have been analyzed as repeated measures over time to detect individual changes.
Garcia et al. conducted a double-blinded placebo controlled cross-over clinical trial in which dogs with IE received a CBD/CBDA-rich hemp extract at an approximate dose of 2 mg/kg twice a day for 3 months, in addition to 3 other antiepileptic drugs.
Similarly, McGrath et al. found a reduction in the total number of seizures (8.0 ± 4.8 placebo versus 5.0 ± 3.6 CBD/CBDA), as well as seizure days (5.8 ± 3.1 placebo versus 4.1 ± 3.4 CBD/CBDA), when dogs were administered the hemp extract.
Animal studies on anxiolytic effects of CBD have shown mixed results. CBD seems to have a bell-shaped curve for managing anxiety, as it seems to be anxiolytic at moderate but not low or high levels…A meta-analysis on human studies concluded that the evidence on cannabis-based products’ effects on anxiolysis is incomplete, because most studies had a small sample size along with some inconsistencies…In dogs, there is no established dose for treating anxiety and fear disorders. The few studies available have focused mainly on the short-term effects of CBD on aggressiveness and fear.
A research study on shelter dogs found that CBD (dose calculated to be ?3.75 mg/kg) administered to dogs for 45 days could reduce aggressiveness toward humans but not behaviors related to stress.
A second study assessed the effect of CBD supplementation on reducing acute fear triggered by fireworks in dogs supplemented with 1.4 mg/kg/day for 7 days and found no effect of CBD alone on reducing fear-induced stress.
Although there is a need for more scientific evidence that CBD is a therapeutic option to treat behavioral problems in dogs, like fearfulness and anxiety, pet owners perceive the calming and antianxiety effects of CBD favorably. Approximately half of pet owners who have given CBD to their dogs to reduce fear or anxiety think it is effective, even though doses given are inconsistent.
No in vivo studies assess the antitumor effects of CBD in either dogs or cats.
Several in vitro studies on canine tumor cell lines have demonstrated cytotoxic effects of CBD on cancer cells. [However, you can run a study showing bleach kills cancer cells in vitro, but that doesn’t make it a safe and effective therapy for cancer patients.]
The authors also touch on one of the persistent problems with veterinary cannabis products– since they are sold over-the-counter with no meaningful regulation (and often with illegal claims), there is poor quality control. “Some reports have noted inconsistencies in pet CBD supplements that are available in the market, such as misleading or untested claims, violations of good manufacturing practices, lower amounts of CBD than what was stated on the label, and/or THC above the allowed limit (0.3%). Unfortunately, many cannabis products are marketed in the United States with unsubstantiated claims of efficacy.”
As with most studies and reviews, the general conclusion is that the safety profile of non-THC cannabis products is pretty good, though adverse effects do occur. In dogs, there is great variability in the absorption and blood levels of CBD and other relevant compounds with different products and forms, so we still have little idea how much of any given product is safe or useful to give. In cats, the research is even sparser, and since cats appear to be more sensitive to the effects of cannabis-derived compounds (as with most other drugs), the safety and effectiveness of existing products in cats is largely unknown.
Both dogs and cats have show gastrointestinal symptoms (e.g. vomiting and diarrhea0 as well as changes in some laboratory values. Lethargy or sedation and behavioral abnormalities can also occur, especially with products containing THC. It is also recognized that CBD and other compound sin cannabis can build up in fat tissues over time, so even when the short-term risks appear to be low, there is no reliable research identifying what risks might occur with long-term use.
Another narrative review from 2023 focuses on the specific use of cannabis-derived chemicals for treatment of pain.
Miranda-Cortés A, Mota-Rojas D, Crosignani-Outeda N, Casas-Alvarado A, Martínez-Burnes J, Olmos-Hernández A, Mora-Medina P, Verduzco-Mendoza A, Hernández-Ávalos I. The role of cannabinoids in pain modulation in companion animals. Front Vet Sci. 2023 Jan 4;9:1050884. doi: 10.3389/fvets.2022.1050884. PMID: 36686189; PMCID: PMC9848446.
This review mostly addresses the underlying biology of cannabinoids and pain. The few clinical studies mentioned are mostly in dogs with arthritis, and the results are mixed, as discussed in more detail in the previous review. The authors conclude there is some evidence to support use of cannabis-derived chemicals for treatment of both acute and chronic pain, but the evidence is largely extrapolation from lab animal studies (especially rodents), and there is little real-world scientific research in dogs and cats to support this.
Bottom Line
Most other reviews have looked at the same limited set of studies and drawn similar conclusions. What we can currently say about the use of CBD (virtually no evidence related to other compounds in cannabis) is this:
It is biologically plausible that CBD may be useful in treating pain, inflammation, epilepsy, and possibly some behavioral problems in dogs and cats.
The existing evidence is extremely weak. We can have a low degree of confidence in the short-term use of CBD for OA pain in dogs. All other uses rely on extremely limited, low-quality, and often conflicting evidence.
The short-term negative effects of CBD, and cannabis generally, appear to be mild. The long-term effects are unknown.
Cannabis is the archetype of a “dirty” drug. It contains hundreds of compounds, most not studied in any depth, and it has effects on many body systems. While this means there is a great potential for cannabis-derived compounds to be useful in many different conditions, it also means the potential for unintended effects and interactions with other drugs is very high unless specific co pounds or subsets of compounds are studied and used individually.
Proponents often talk about the “entourage effect.” This is an idea common in herbal medicine that having multiple compounds in a plant-based remedy is a good thing because they will work in harmony to increase beneficial effects and cancel out each other’s adverse effects. There is no reliable evidence that this phenomenon actually occurs, and it is not very biologically plausible.
The idea originated with the belief that such remedies were purposefully provided to humans by God, and as such were designed to have this benign nature. Only the “unnatural” isolation of individual compounds to use as drugs is responsible for the phenomenon of drug side-effects. This argument is not scientifically credible, and it is far more plausible that mixing multiple compounds leads to more adverse and unintended effects.
Certainly, this is the case with use of cannabis in dogs and cats when THC and CBD are both present in significant amounts. Isolating the CBD reduces these negative effects, so we cannot just assume that using products with multiple compounds and only the THC removed is inherently better than using purified CBD or other cannabis chemicals. Such an entourage effect could occur, but there is not yet compelling evidence for it.
The other important lesson to draw from these recent reviews is that the popularity of cannabis products for dogs and cats is not based on real scientific evidence showing these are safe and effective. This is a fad derived from the popularity of cannabis use in humans, which has origins in ideologies around “natural” medicine, reactions against excessive and largely irrational government prohibitions of cannabis, and factors that have little to do with the actual merits of cannabis as a medicine.
Hopefully, the high level of interest will drive more research, and we will find out what uses it has. I am concerned, however, that the great confidence pet owners already have in cannabis will mean it continues to be profitable to make and sell unregulated and untested products without any motivation for companies doing so to produce meaningful scientific research evidence. Like glucosamine, which has generated billions of dollars for decades despite being almost certainly useless, the cannabis-based supplement market may be just another example of companies seeking profit and consumers seeking panaceas with neither bothering to put in the effort needed to determine what is actually safe and effective treatment for our pets.
The evidence has certainly grown in the ten years since I began discussing the issue. Unfortunately, it is still weak and limited, and the enthusiasm for cannabis has grown much faster than the scientific evidence.
Well, that could easily be the shortest SkeptVet blog post ever, but I guess I can’t really leave it there. For one thing, the answer should really be, “Almost certainly no,” since my level of confidence is high but not absolute. Secondly, it’s the wrong question to be asking, and not one in which I have any interest.
The subject has come up because of some recent publicity around my work with Loyal, a biotechnology company working towards FDA approval for drugs to extend lifespan (the number of years lived) and, more importantly, healthspan (the time lived in good health) in dogs. We recently achieved a pretty exciting milestone on this path, and this has generated a lot of media coverage.
Unfortunately, media coverage of science generally, and veterinary medicine in particular, is often fluffy and ebullient but short on details and nuance. I think a lot of folks may be coming away with the wrong impression about our goals and our work at the company and about what this recent announcement really means. Since SkeptVet readers are hardy enough to tolerate more detailed content, I thought I’d try to set the record a bit straighter here. [Here I will insert the necessary disclaimer that what follows is my understanding and opinion, not the official position of the company I work for.]
I’ve written about aging quite a bit here and in the scientific literature, as well as talking about it for several years at veterinary continuing education meetings (you can check my latest CV for list). My claims about it are simple and, I believe, pretty scientifically sound-
Aging is not a mysterious inevitability built into the universe–it is just biology. Complex biology, but nevertheless a process composed of elements we can understand through scientific investigation.
With that understanding comes the potential to influence the process in beneficial ways, as we do many other pathophysiologic processes in medicine.
Aging may be most usefully thought of as a modifiable risk factor for the negative health outcomes often associated with being aged- disability, disease, and death.
Basic science and pre-clinical animal model research, including a very little bit in dogs, supports these claims. The next logical step is to turn this knowledge into practical preventative healthcare interventions.
So far, I think, so reasonable. Where thinks get dicey, as always, is what some folks claim is the potential of such interventions, and the extent to which specific approaches are or are not yet “proven” to affect aging and health. Again, my claims here are pretty simple, and I think reasonable-
We will likely be able to extend lifespan and significantly delay or reduce age-associated disability, disease, and death in pets and in humans.
The extent of our ability to accomplish this cannot be accurately predicted at this point. It will likely be enough to matter, to be meaningful in real-world terms. It will likely not be anything even remotely approaching “immortality,” at least in the foreseeable future.
There are, as of now, no properly validated or “proven” interventions to significantly extend lifespan and healthspan in dogs and cats by directly targeting aging. The closest we have is the pretty good evidence for the health and lifespan benefits of
Some elements of regular preventative veterinary care (e.g.)
Even these require further research to validate and clarify the specific approaches and the effects on lifespan and aging-associated health problems.
With that as the context, what have we achieved at Loyal and what does it really mean?
We have chosen to pursue FDA approval for prescription medications, rather than whipping up an “anti-aging” supplement to sell with minimal oversight and evidence, because we believe this process better ensures the final product is safe and effective. FDA approval is a pretty high bar, but it is by no means requires the highest possible level of evidence. As a refresher, here is the pyramid of evidence I have harped on for years-
The best evidence for any medical intervention is ultimately a solid foundation in well-understood basic science (i.e. biologic plausibility) combined with multiple high-quality clinical trials conducted by multiple investigators with different biases and agendas. This, sadly, is a level of evidence virtually never available in veterinary medicine due to the time, expense, and logistically challenges in producing it.
The best we can usually hope for is biologic plausibility demonstrated by decent pre-clinical evidence and then one or two moderate-quality clinical trials with decent bias-control mechanisms. Even this is more than the vast majority of therapies in current use in veterinary medicine have, but if we sit on our hands and wait for perfect evidence, we won’t have any tools to help our patients.
I have always said that we should choose the best therapy we can based on the best available evidence. That may be no more than a handful of anecdotes (sadly), but that can be appropriate if the need is great enough, we give the client sufficient honest information to understand the risks and uncertainties, and we proportion our confidence in the treatment to the level of evidence so that we can abandon treatments that are unsafe or ineffective when new evidence comes along.
In the case of regular FDA approval, there is a requirement for strong evidence to support biologic plausibility (a plausible mechanism of action, research evidence showing the drug is present in the body and acting on the physiologic pathways it is supposed to act on, etc.), safety (including testing in individuals of the species the drug will be used on at multiple doses, including some that are higher than the actually intended clinical dose), appropriate manufacturing methods, and no significant negative impact on the environment or human food safety.
There is also a requirement to prove clinical effectiveness– that the drug actually does what it is meant to do in animal patients. This last criterion usually requires a well-designed and properly conducted field trial, meaning a clinical trial in real-world patients. While this is, again, not the best evidence one could possibly ask for, it is strong evidence and far better than most veterinary therapies ever achieve.
The FDA also allows a slightly different pathway for what is called “conditional approval.” In situations where there is a serious health problem for which no proven effective treatment exists, a new treatment can sometimes be conditionally approved to be used in patients before completion of this field trial. All of the other criteria must still be met as usual, including demonstration of safety, but effectiveness can be substantiated by showing “reasonable expectations of effectiveness” through evidence other than a full clinical field trial. Even this is only allowed if conducting a field trial would be so complex and time-consuming that it would significantly delay the availability of the drug to patients who, again, have a serious health problem with no currently available approved treatments.
The field trial must still be done, but the drug can be made available temporarily (for one year at a time up to a total of five years). This is intended as a compromise between the need for strong evidence to support efficacy and the need for new treatments to be made available to patients with serious health problems as quickly as possible.
There are several conditionally approved therapies on the market now, including-
Varenzin for cats with anemia due to kidney disease
So what does all of this have to do with our work at Loyal? Well, we recently received a notice from the FDA indicating that the agency accepted the evidence we submitted for one of our products, called LOY-001, as sufficient to meet the standard for a reasonable expectation of efficacy. Let’s start with what this doesn’t mean-
We are not marketing a drug for aging. LOY-001 hasn’t completed the other steps in the conditional approval process and is not available for use. If all goes well, we may finish this process in 2026, but that is only a goal, not a prediction.
We are not claiming this or any other product extends lifespan or slows aging. The whole point of pursuing FDA approval is that we can’t and won’t make any claims about any of our drugs until the FDA says the evidence is sufficient to support those claims and grants approval.
We are still planning on completing the full approval process for any drug we market, so even if we achieve conditional approval for this or another product, that doesn’t mean we accept reasonable expectation of efficacy as the final standard of evidence.
We’re not claiming, and will never claim, that any drug makes dogs live forever. The obsession with immortality is a distraction from the more realistic and meaningful work of prolonging healthspan and reducing the suffering associated with aging.
With that clarification, I will address some of the questions and concerns I have heard since the announcement.
To begin with, some folks feel that the conditional approval pathway is insufficient to demonstrate effectiveness and that no drug should be used until it achieves full approval after a field trial. That’s a perfectly reasonable position, and I won’t try to argue anyone out of it. I will point out, though, that the purpose of having a conditional approval process is to acknowledge that delaying the availability of new treatments while a field trial is completed, especially one that will take a long time, does have a cost as well as a benefit. While the final evidence is stronger, and while we may be glad we waited if the field trial doesn’t confirm the expectation of effectiveness, patients are going without treatment while we wait.
Aging is arguably responsible for the vast majority of the disability, disease, and death we see in senior dogs, and there are no approved or well-validated treatments currently available to target this major cause of suffering, so it certainly represents an unmet need. The fact that we have always accepted it as inevitable and immutable doesn’t mean there is no urgency to developing treatments for it, only that we aren’t yet accustomed to thinking about the harms of aging the way we think about the harms from cancer, chronic kidney disease, or other health problems in our pets and patients.
Obviously, any clinical trial evaluating the effect of a drug on lifespan is going to be complex and take a long time. We are planning several such trials. The first, for a different product, is starting this month and will involve 1,000 dogs studied over 4-5 years. This is probably the largest clinical trial ever done in veterinary medicine, so it certainly counts as complex and prolonged. A field trial of LOY-001 would likely be very similar.
If LOY-001, or any other drug targeting aging, achieves conditional approval, it will have met the same standards of evidence for safety as any fully approved drug. Vets and dog owners will then have to decide whether the potential benefits outweigh the uncertainties inherent in the reasonable expectation of effectiveness standard and whether they want to use the drug right away, wait until a field trial is complete and it is fully approved, wait until the drug has been in use for some period of time after approval, or whatever other standard of evidence they feel is appropriate. That is the same decision we all must make for any new treatment that becomes available, and there is no absolute or universally “right” or “wrong” choice.
Some readers have expressed concern that I am helping to work towards conditional approval for this drug while having been critical of other treatments, both conventional and alternative, based on claims or uses for these without sufficient evidence. This seems inconsistent to some folks. I don’t believe that is the case, and I think a close reading of my critiques of many different therapies will show that I do not argue absolutely against the use of anything unless there is either clear evidence that the risk outweighs the benefits. I frequently point out that using even therapies with minimal supporting evidence is fair if, as I said earlier, the need is sufficient, there is informed consent, and we don’t make claims with unjustifiable confidence.
In the case of any conditionally approved product, including those that may become available from Loyal, I believe the risks and benefits of their use should be weighed in the context of the uncertainty and claims should be proportional to the strength of the evidence. If LOY-001 or another Loyal product becomes available under the conditional approval pathway, I will apply this same standard. As of now, I am not making any claims since there is no approved product to make them for.
I have also been asked why, if there is no drug actually available, this milestone matters at all. The answer to that has to do with the issue of how aging is approached in veterinary and human medicine.
We have traditionally played a game of whack-a-mole with age-associated health problems—waiting for them to appear and then treating them as best we can. Since aging has been considered inevitable and just a fact of the universe, we haven’t thought much about it in terms of prevention or of treating the underlying causal mechanisms of age-associated disease. This has included a reluctance to consider aging a treatable problem for which drugs could be developed and approved. The FDA acceptance of our evidence for reasonable expectations of effectiveness is the first time, as far as we can tell, that the FDA or any other health regulator has accepted the idea that a treatment could be approved for extending lifespan or mitigating the consequences of aging by targeting the mechanisms of aging directly.
This opens up the possibility of an entire new field of medicine and a proactive, preventative approach to aging. Whether or not LOY-001 or any other specific drug achieves approval, this is a significant milestone in the effort to change how we approach aging and age-associated health problems. For once, veterinary medicine is leading rather than following human medicine!
Finally, there is the question of my own bias with regard to this and other products produced by Loyal because I am an employee of the company. The question is not whether or not I have a bias, because of course I do! I have a financial interest in the success of the company, and while I believe my ethics would prevent me from saying anything misleading or untruthful about the company or our products, financial bias is a reality, and it is fair to acknowledge the potential subtle and unconscious influences this may have on anyone.
As I have explained many times before, though, I think the more interesting and important source of bias is ideological and institutional. I wouldn’t work for Loyal if I didn’t feel like the values and goals and scientific work being done there didn’t already align with my own views and values. I tend to agree with the approach to aging and the way we are going about our work not because I get paid by the company but because I chose to work for them in the first place because of this alignment!
Does that mean anything I say about the company or our products is meaningless or should be dismissed due to my bias? Well, that’s up to each reader to decide for themselves. What I will say is that, in an ideal world, no claim about a medical intervention should ever be accepted entirely on the basis of the opinions of any individual, including me. We should all review the objective evidence critically and make our own decisions. If our products achieve conditional or full approval, the evidence will all be publicly available for people to use in making up their own minds.
That said, we can’t all be experts on every subject, and we don’t always have the time or skills to evaluate every claim effectively on our own. When I have questions about infectious diseases, I give great weight to the opinions of trusted experts who I know have an evidence-based approach and the expertise to make critical judgement about this area (e.g. Dr. Weese). I do the same in other areas, relying on the expertise of nutritionists (e.g. Dr. Larsen, Dr. Weeth, Dr. Villaverde), cardiologists (e.g. Dr. Rishniw), and so on. I balance independent critical thinking with a recognition of the inevitable limitations of my own knowledge and capacity, and I rely on others to help inform my understanding of specific topics.
We all have to do this since we cannot know everything about everything. The biggest challenge is identifying reliable sources and striking a balance that doesn’t fall into the traps of overconfident independence on one end or blind following of equally imperfect humans on the other. How people choose to regard my opinions and evaluation of any subject, including aging therapies, will be a decision of this sort.
I first began writing about potential medical uses for cannabis products in pets ten years ago. AT the time, there was weak evidence for a few uses in humans, and almost no research evidence in dogs or cats. Since then, I have covered the topic frequently, and new evidence has appeared regularly. This evidence has been mixed, with some studies suggesting benefits and others not. Generally, the safety data has suggested minimal risk, though a recent recommendation to lower the maximum daily dose of CBD in humans reflects the fact that there is much we still don’t know about the potential consequences of long-term use of cannabis-based compounds.
It is currently vogue to use CBD for a wide-range of problems in dogs and cats, and there is little to no evidence to support most of these uses. The most common use, and that with the best evidence, is for pain. However, even in humans there is controversy about how effective CBD and other cannabis-based compounds are for pain. A recent systematic review found that,
“Studies in this field have unclear or high risk of bias, and outcomes had GRADE rating of low- or very low-quality evidence. We have little confidence in the estimates of effect. The evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or CBM in the management of pain.”
A similar systematic review was recently published for the use of CBD in treatment of arthritis in dogs.
As a refresher, a systematic review is the highest level of research evidence available for most questions. It involves the explicit and formal finding and analysis of controlled research studies on a given topic. Such reviews are not perfect nor free from bias, and they are less useful the less roust the primary research evidence is, but they give the best overview of an issue based on the highest quality evidence currently available.
The conclusion of this review is typical of many in veterinary medicine:
“Five articles were included, which investigated the effects of CBD in 117 dogs with OA. All studies were rated as having a high risk of bias.
CBD is considered safe for treating canine OA. CBD may reduce pain scores, but the evidence is very uncertain to conclude its clinical efficacy. High-quality clinical trials are needed to further evaluate the roles of CBD in canine OA.”
There have been relatively few studies involving few patients and all with significant methodological risk of bias. From this kind of evidence base, the best we can safely conclude is that CBD might have some benefits for dogs in pain and probably doesn’t have any acute risks.
That is sufficient to consider adding it in as a treatment for dogs with arthritis not sufficiently controlled by other treatments, but NOT to use it as a first-line treatment or a substitute for treatments with better evidence for efficacy (such as non-steroidal anti-inflammatory drugs).
The general trend for life expectancy in humans has been upward for a long time. Improvements in nutrition, sanitation, and both therapeutic and preventative medical care have led to humans today living longer and healthier lives than at any time in history.
The impression most veterinarians have is that the same is true for our pets. Nutrition and healthcare have improved for dogs and cats, as they have for humans, and owned pets who are well cared for are clearly healthier than free-roaming, unowned individuals. However, not nearly as much data is collected on lifespan and mortality patterns in companion animals, so it is difficult to prove that life expectancy is increasing.
I have written about this topic previously here and elsewhere. My conclusions based on the data available then were that it seemed likely dogs, at least, were living longer, but it couldn’t be stated with any confidence. Now, however, there is a bit more data which strengthens the case a bit.
This study looked retrospectively (backwards in time) at the huge patient data set collected by the Banfield Pet Hospital group. While there are challenges and limitations in this kind of data set and analysis, it provides a useful source of data for many types of research.
In this case, the authors looked at mortality data and constructed a set of life tables, to get a sense of how long dogs and cats in this population lived and what factors were associated with this. With all of the necessary caveats (discussed in the original paper), the general trend was consistent with most of the previous data; life expectancy seems to be increasing for our pets.
Confidence in this result is increased by the consistency of other findings in the study. For example, overweight dogs tended to have shorter lives, as other studies have shown and as we would expect from much more robust evidence in humans. This relationship, interestingly, was not as clear in cats, and other research has also shown that the relationship between body weight and lifespan in cats is much more complex than typically seen in humans and dogs.
While we are always forced to cope with more limited data in veterinary medicine than our human healthcare colleagues have available, we must make decisions based on the most plausible arguments and highest-quality data we do have. Contemporary nutrition and healthcare for our animal companions are better than in the past, and this appears to be extending their lives as it does ours.
For many years now, I have fought against the encroachment of anti-vaccine misinformation and fears into veterinary medicine. I have written blog posts and journal articles on the subject, and I’ve discussed vaccine hesitancy in podcasts, on YouTube, and at veterinary conferences.
It has long been clear that some pet owners have been frightened by proponents of unscientific anti-vaccine ideas. They are exposed, like all of us, to misinformation from activists opposing vaccines for human use, such as disgraced former doctor Andrew Wakefield and the Disinformation Dozen, well-known sources of bad information such as Mercola, RFK Jr., and the Bollingers. Unfortunately, there is also no shortage of vets and others in the animal health world also contributing to excessive and harmful anxiety about vaccines in pets. Anecdotally, many vets feel that pet owners have become more hesitant about appropriate vaccination of their dogs and cats.
Now, we have a bit of research data that, unfortunately, reinforces this concern.
This study surveyed 2,200 adults in the U.S. and evaluated the presence of Canine Vaccine Hesitancy (CVH), defined as, “dog owners’ skepticism about the safety and efficacy of administering routine vaccinations to their dogs.” The findings were a clear warning to vets and other animal lovers about the danger of anti-vaccine misinformation and the importance of speaking up and providing the public with honest, reliable, fact-based information about vaccination.
As the authors state, “a large minority of dog owners consider vaccines administered to dogs to be unsafe (37%), ineffective (22%), and/or unnecessary (30%). A slight majority of dog owners (53%) endorse at least one of these three positions.”
Also worrisome was the finding that 48% of dog owners opposed mandatory rabies vaccination and agreed with the statement, “The decision to vaccinate dogs that are kept as pets should be left up to individual pet owners.” This echoes powerfully the kind of anti-public health position that emerged to oppose vaccination for SARS-CoV-2, and which led to hundreds of thousands of unnecessary deaths from COVID-19 in the U.S. alone.
The study also looked at factors that might be associated with CVH. Endorsement of misinformation about human vaccines was a predictor of CVH, whereas a college education was associated with a lower risk of hesitancy about canine vaccination.
These results, while depressing, are not surprising. We are in a period of significant mistrust and misinformation about science generally, and there is no reason to expect pet owners or veterinary medicine would be exempt from this problem. The study is also just a preliminary effort at assessing a complex and multifactorial problem. However, this first step at gathering real data about the issue of veterinary vaccine hesitancy is an important one. It should serve as a powerful warning to veterinarians and others who value animal welfare that we cannot afford to be complacent nor quiet.
For pet owners who are concerned about the safety and effectiveness of vaccines for dogs and cats, here are some resources with reliable, science-based information to help you. You also deserve an open, honest conversation with your vet based on scientific evidence, and I encourage everyone to ask their pets’ healthcare providers to address your concerns and helpo you choose the best care for your pets.
One of the least reliable sources of veterinary information the internet, Dr. Karen Becker, is at it again.
In a recent FB post, she implies that my criticism of her anti-science claims, her promotion of unscientific, unproven, and ineffective therapies, and her spreading myths about mainstream, science-based veterinary medicine, are “attacks” equivalent to the activity of “hate groups.” Along with this comment, she reposts the absurd video produced by Rodney Habib suggesting that my work promoting science-based pet health is contributing to the problem of suicide in the veterinary profession.
There is tremendous (unrecognized) irony in this comment. Proponents of alternative therapies base much of their argument on the idea that conventional, scientific medicine is unsafe or ineffective, and this is a standard approach for Dr. Becker (e.g. 1, 2, 3). Claiming that vaccines and drugs are harmful and that scientific medicine treats only symptoms and ignores the “root”real” causes of disease is commonplace. And while she doesn’t usually go as far as her sponsor Joseph Mercola, perhaps the most prominent and aggressive anti-science disinformation providers on the planet, her long association with him shows how comfortable she is with these sorts of attacks on mainstreams science and medicine, and those of us who provide it.
Her plea for “inclusion, acceptance, or tolerance” is simply a way of saying that when she makes claims like these, or tells pet owners to use useless therapies like homeopathy or unproven, potentially harmful treatment such as Chinese herbal remedies, the rest of the profession should let her do so freely, without criticism or challenge. Want she wants is the freedom to say and do what she believes in, whether it is actually true or really helps pets or not, and not be criticized for it. Her attacks on scientific medicine are, apparently, fair play, but pushing back against her claims with logic and evidence are being mean. This is a typical double standard employed by the CAVM community (e.g. 1, 2)
Refraining from warning pet owners about the unproven and potentially dangerous nature of Dr. Becker’s approach is not being “nice” or inclusive. This is simply ignoring misinformation even when it does harm. I believe people should be treated kindly, but ideas deserve no respect other than what they earn through their logical foundations and supporting evidence.
I will say of Dr. Becker, as I say of most of the proponents of pseudoscience and anti-science misinformation, that I have little doubt she is sincere and has the best interests of her patients at heart. I also believe she is very often wrong, and her approach is dangerous and misguided. As I too have the best interests of veterinary patients at heart, I have just as much responsibility to push back against her claims as she feels she has to challenge the practices of scientific medicine. Neither of us is obliged to ignore what we see as false or dangerous claims and practices, and the standards of civility, just like the standards of evidence, should be the same for both of our positions.
I can, of course, sympathize with how frustrating and demoralizing it can be to be attacked publicly. I have no doubt the personal attacks I receive, including Mr. Habib’s ridiculous video, are as numerous and at least as harsh as any Dr. Becker experiences. My chronicles of the hate mail I receive are evidence of this. I don’t see Dr. Becker expressing any sympathy or compassion for skeptics who are attacked in this way, even when it is done in her name or defense:
This article made my blood boil because Dr.Karen Becker has more balls than any of you tiny brainwashed humans coming out of vetschool… if your veterinarian is anything like this quak continue searching for another…I LEGIT HATE u whoever u are.
I have made great efforts to focus my criticism on ideas rather than persons, and while I admit that I can understand why referring to Dr. Becker as a proponent of misinformation and anti-science nonsense might be upsetting to her, these are descriptions of her behavior supported by a great deal of evidence, not attacks on her person. That she expresses her objection to this by reposting a video that literally demonizes me through visual and audio effects and accuses me of contributing to the suicide of fellow veterinarians is pretty stark hypocrisy.
I’m sure Dr. Becker and I would agree on some things, including the tremendous challenges vets face, financially and psychologically, and the real harm of personal online attacks. However, these serious issues should not be used as an excuse to claim an exemption from criticism, or as a distraction from the equally real danger of misinformation and anti-science ideas to veterinary and human patients.
There are undoubtedly some risks to this product, and it is possible that they are greater than has so far appeared in the scientific literature. The research done on this product has mostly come from companies and investigators with a financial interest in it, and that always raises some concern about the potential for bias in the data. On the other hand, such concern doesn’t somehow make collections of unsubstantiated anecdotes a reliable source of data…. Unfortunately, rigorous scientific investigation takes time; a lot more time and work that sensationalist medial reporting. My hope is that reasonable people will respond to this latest example of poor-quality reporting in a reasonable way. We likely should take a careful, objective look at the safety data for this product, and perhaps conduct further research if warranted.
The EPA responded to the concerns raised about this product by requiring more extensive monitoring of reported problems and then analyzing the relevant evidence. This included controlled scientific research already available as well as the flood of reports from owners that always comes when the media raises the alarm about a pet healthcare product.
As I discussed in my previous post, simply having a bunch of such reports doesn’t tell us if a product is actually safe or not. The number of reported problems has as much or more to do with public awareness and anxiety about a product as about its actual biological effects. The EPA attempted to control for this by comparing reports regarding Seresto to those for other similar products and for alternatives, such as spot-on flea control products. The agency has produced a report which, in true government agency fashion, is a compromise unlikely to satisfy anyone but easily claimed as vindication by both camps.
The bottom line is that the EPA found mild adverse events consistent with those reported in controlled studies were most common- itching and hair loss. A small proportion of dogs (about 10%) were reported to get lethargic with use of the product. More serious events were rare and could not be clearly linked to the ingredients in the product, which previous research has shown to be generally quite safe.
The rate of these kinds of adverse effects was not significantly different from those reported for other similar collars. For mild events, there was also no difference between Seresto and spot-on products, but there were more repost of “moderate” events with Seresto than with the spot-ons.
It was generally impossible to show that any of the uncommon serious adverse events were actually caused by the collar, and many of these cases had other factors that could just as easily have been the cause, such as existing illness or other medications. The agency could not show a high level of confidence that Seresto was responsible for any of the serious adverse events with one exception- 4 dogs and 9 cats died as a likely result of being strangled by the collars when they failed to release appropriately under tension.
The manufacturer claims the report supports the safety of the product. This is largely true, but being unable to determine if many of the negative events reported were or were not related to the collar due to lack of adequate information isn’t a ringing endorsement. Information suggesting the ingredients are probably safe already existed, but this report doesn’t add much confidence to that conclusion.
Critics of the collar also claim victory, even though the agency didn’t revoke the product approval as they wanted. They base this not on the finding of actual evidence of harm, because there wasn’t any, but on the actions the agency took in response to the review. These actions were reasonable but largely aimed at getting additional information and making the agency look like it is taking the public concerns seriously even though the existing evidence isn’t particularly strong. So what did the EPA actually do?
The collar is approved for only 5 years, instead of the usual 15, and additional reviews will need to be done
The company must collect and submit additional, more detailed information about possible adverse events associated with the collar
The company must develop and distribute educational materials for vets and owners discussing possible safety concerns and adverse reactions to the product
The company must add a warning label to the product information identifying possible adverse reactions that have been reported
The company must study the release mechanism and report on this to the agency
At this point, the report doesn’t do a lot to change the state of evidence regarding this product. There is reason to believe the ingredients are pretty safe; there have been a lot of reported adverse events; most of these are minor and it isn’t clear that there are proportionally more than for other pest-control products; more information is needed to determine if the benefits of the product in preventing parasites and parasite-transmitted diseases outweigh the risks.
None of this is likely to satisfy critics of the product, but the state of the evidence is evolving, as it does, and we always have to make the best decisions we can based on the evidence available now, not the perfect evidence we would like to have. As I said previously, I don’t actually prescribe this product in my area, but I also don’t discourage owners from using it, though I do discuss the concerns and uncertainties with any who express and interest or who are using it already. This is, I believe, a reasonable compromise as we, hopefully, gather more evidence to strengthen our understanding of the risks and benefits of the Seresto collar.
