I recently reported on the results of a clinical trial conducted at North Carolin State University on the purported “anti-aging” Leap Years. The study provided no convincing evidence of a beneficial effect, and despite a single statistically significant finding at one time point, the data looked about as clearly negative as a study measuring multiple outcomes like this can.
Despite this, the company and its most prominent figure, Dr. David Sinclair, promoted it heavily as a major advance in canine geroscience. The pushback for these excessive and unsupported claims was surprisingly strong, and Dr. Sinclair had to resign the presidency of a major aging research organization he belongs to. That said. the product is still for sale and the company still makes many unproven claims for it, including some specifically based on this paper.
The original manuscript was released as a preprint, which is not peer reviewed, so when such studies are eventually published (if they are), sometimes the manuscript can change based on reviewers comments. The published version of this paper has now appeared, and there are pretty minimal changes.
As an example, here are the titles and abstracts from the two versions, with the differences bolded-
Preprint- Randomized, Controlled Clinical Trial Demonstrates Improved Cognitive Function in Senior Dogs Supplemented with a Senolytic and NAD+ Precursor Combination
Peer-reviewed- A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination
Preprint- There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p=0.02) with the largest decrease in the full dose group. There were no significant differences between groups in changes in measured activity. However, the proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups. Adverse events occurred equally across groups. All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation. We conclude that LY-D6/2 significantly improves owner-assessed cognitive function and may have broader effects on frailty, activity and happiness as reported by owners.
Peer-reviewed- There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group. No difference was detected between groups using in house cognitive testing. There were no significant differences between groups in changes in measured activity. The proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups, however this difference was not significant. Adverse events occurred equally across groups. All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation. We conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period and may have broader, but more subtle effects on frailty, activity and happiness as reported by owners.
The intention of these small changes seems to be to walk back the level of confidence given for some of the findings and their significance. Similar changes appear in the discussion and elsewhere in the paper, but they don’t fundamentally change the reporting of results. I was a bit surprised that the reviewers did not recommend error bars be added to figure or that these be extended to include the 6-month evaluation. Both of these improvements to the figures emphasize the lack of a consistent and coherent pattern of response that would support meaningful benefits to the subjects.
Dr. Matt Kaeberline, an aging biology expert and strong critic of Dr. Sinclair, has prepared an amended figure based on the data the authors made available. The comparison between that figure and the one in the ;published article emphasizes how easy it is to present the data in one way and see the appearance if a pattern which is much less evident when the same data are presented in a different way.
Figure from paper-
Fire with error bars and 6-month data-
Bottom Line The published paper is very similar to the preprint, which is not surprising since the original study was well-designed and conducted. The best case that can be made is that the supplement might have som effect on cognitive function in older dogs, but the existing evidence is underwhelming and more negative than positive overall. This might be enough to support further testing, but it certainly is not strong or sufficient to justify ongoing use, much less exuberant marketing of the product as an “anti-aging” treatment.
One of my most popular, and controversial, topics to talk about at continuing education meetings is the evidence for abandoning practices that are deeply entrenched in routine veterinary practice. Vets are pretty good at adopting new things when evidence shows these might be worthwhile, often even when the evidence isn’t very good. But giving up things we are used to doing is much harder, even when the evidence is strong. Here are a few things vets might want to think about changing, and you might want to question if they are offered to you.
CHOOSING WISELY: THINGS TO STOP DOING IN YOUR PRACTICE (MAYBE)
THE JOY AND THE PAIN OF EVIDENCE-BASED MEDICINE Veterinary medicine is a science-based profession. The philosophy and principles of science, and the data generated by scientific research, guide our clinical decision-making. The joyful side of this is that we get to watch new tests and treatments emerge during our career, and previously hopeless problems become treatable. The scourge of parvoviral enteritis has been dramatically diminished thanks to the development of a vaccine. The “incurable” malady of feline infectious peritonitis now seems to be beaten, at least in many cases, by new drugs. The first wave of monoclonal antibody therapies is just arriving, offering more treatment options for diverse problems such as osteoarthritis and atopic dermatitis.
The painful side of an evidence-based approach to practice is that we are often wrong. Not only does early and incomplete science sometimes lead us to the wrong conclusions, but as individuals we make even less reliable judgements based on personal experience and anecdote. What is worse, we develop strong emotional and ideological commitments to these judgements. Giving up a therapeutic practice that we believe in, that we were taught as youngsters and that we have since taught to others, that we “have seen work” in our own hands, is deeply unsettling. We don’t like to be wrong, and we don’t like things that challenge our understanding of the world, because that damages our self-image and makes the world seem less predictable and controllable.1,2
But the welfare of our patients is more important than our ego and our sense of security, and we have an obligation as practitioners of a science-based art to follow the evidence where it leads. This will inevitably mean abandoning beliefs and practices that are dear to us repeatedly throughout our careers. So, let’s square our shoulders, raise our chins, and rip off a few of those band aids today!
WHAT IS EVIDENCE? Ok, before we do that, we should take a minute to consider what “evidence” is and how we decide when it is good enough to justify changing our practices.3 You’ve all seen some image like Fig. 1 before. The details are less important than the general point—not all evidence is equally reliable. The bottom of the pyramid contains the most available and accessible evidence– our experiences and opinions and those of others. The top of the pyramid is the smallest because it represents the evidence that’s the hardest to get– consistent findings across multiple, replicated, high-quality controlled research studies. So, we have lots of the least trustworthy evidence and only a little of the best stuff.
Figure 1. Types of evidence categorized by quality and risk of bias.
But the problem is even worse than that! The stuff at the bottom is by far the most psychologically compelling. Our brains are built to understand and trust our own experiences and the stories other people tell us about theirs. Data and numbers from research studies are a lot less satisfying and convincing.4 So we are most confident in the least reliable evidence and least likely to be moved by the evidence that history has shown us, again and again, is most likely to be correct. Bummer!
Science is not, of course, a perfect process. It is simply something humans have developed over a long period of trial and error to compensate for our inherent limitations. Scientific studies can be wrong and misleading, just like anecdotal evidence. Not every study is well-designed, properly conducted and analyzed, and not every study applies to all patient populations. There are a million reasons why scientific research evidence might lead us to the wrong conclusion. But there are ten million reasons why experience and anecdotes will mislead us!
The best we can do is recognize the problem and make an honest effort to remind ourselves often that what feels true may not be if it is based on uncontrolled experience and anecdote. If you find yourself saying, “But, I’ve seen it work!” take a deep breath and try to remind yourself that the proponents of blood-letting, magic healing rituals, and any therapy you believe is useless say exactly the same thing.
USES OF ANTIBIOTICS TO RECONSIDER Treatment of Acute Diarrhea The use of metronidazole as a treatment for acute diarrhea in dogs is a deeply entrenched practice that goes back decades. Various rationales have been proposed to support it, from treatment of potential bacterial causes, such as Clostridium, to anti-inflammatory mechanisms. Few general practice vets have not used this drug for this purpose, and there is abundant anecdotal evidence suggesting it is beneficial.
Unfortunately, there is also a growing body of research evidence showing little to no clinical benefit for most patients and some potential undesirable effects.5 At best, it might shorten the course of diarrhea by about a day. At worst, it can make symptoms worse, disrupt the microbiome in potentially harmful ways, and contribute to antibiotic resistance.
Given that the vast majority of dogs with idiopathic acute diarrhea will get better with time, these risks are hard to justify. Most humans don’t seek medical are or prescription drugs for mild, short-term diarrhea symptoms. The pressure to treat this condition in dogs has more to do with the inconvenience and anxiety it causes owners than the wellbeing of our patients. Although the risks seem small, it is difficult to justify them for a treatment that has mostly psychological benefits for vets and clients rather than medical benefits for patients.
It would be nice to have a clear alternative to offer here, but the reality is no research yet supports any specific treatment for acute, self-limiting diarrhea that is clearly effective and has negligible risks. Probiotics have not entirely lived up to their promise.6 Some evidence supports dietary change and fiber supplementation,7,8 but again most cases are self-limiting and likely to get better without any specific treatment.
Treatment of Upper Respiratory Infections Like acute diarrhea, acute upper respiratory infections (URI) are often self-limiting in dogs and cats, and many have viral etiologies which will not respond to antibiotic treatment. There is limited controlled research comparing antibiotic use to alternatives, such as supportive care alone. Based on the clinical research that we do have, and also the basic science studies providing background on the causes and outcomes of feline and canine upper respiratory disease, expert consensus guidelines generally recommend limiting antibiotic use to cases with significant systemic symptoms (e.g. fever, lethargy) and evidence of bacterial involvement (e.g. mucopurulent discharge), or cases with chronic disease.9
Unfortunately, the lack of evidence for benefits from antibiotic treatment in most cases, and the potential for adverse effects and microbial resistance, vets still seem to often prescribe antibiotics unnecessarily for canine and feline respiratory infections.10,11 There is some indication, however, that awareness of, and adherence to, antibiotic use guidelines may be improving.12
Treatment of Urinary Tract Infections Unlike upper respiratory disease, urinary tract symptoms often are caused by bacterial infection in dogs, and to a lesser extent in cats. These bacterial urinary tract infections (UTI) do sometimes require antibiotic treatment, though common practice in treating UTIs still often does not match current evidence-based guidelines.13
For one thing, just having bacteria in the urine does not a UTI make. Asymptomatic bacteriuria seems to be more common than previously recognized, occurring in from 1% to 13% of healthy dogs and cats, and at much higher rates in animals with immunosuppressive conditions or medications and other risk factors.13 In the absence of clinical symptoms, treatment with antibiotics does not permanently eliminate bacteriuria and appears to have no benefits for the patient. While evidence is somewhat limited in dogs and cats, it is clear that in humans prescribing antibiotics for subclinical bacteriuria raises the risk of adverse drug effects and antibiotic resistance without improving short-term or long-term outcomes for patients. This is true even if there is pyuria!13
Recommended treatment of symptomatic UTI confirmed by urine culture is also different from what many of us were taught long ago. Some of these cases may not require antibiotics at all. Humans with uncomplicated UTI are often treated symptomatically with NSAIDs, and the UTI often resolves by itself. This may be appropriate for veterinary patients too, though we do not yet have studies showing this.
Similarly, the recommended duration of treatment is 3-5 days, which is far shorter than the 7-10 day course many of us still prescribe. Even pyelonephritis is typically treated in humans with 7-10 days of antibiotics, and in the absence of better evidence experts currently recommend 10-14 days of treatment in dogs and cats, rather than the 4-6 weeks previously advised.13
One of the most common inappropriate uses of antibiotics for urinary tract signs is for young cats. In cats under about ten years of age hematuria, pollakiuria, and other symptoms of cystitis are far less likely to be caused by UTI (2%-19%) than in cats over 10 years of age (40-45%).14 Feline Interstitial Cystitis (FIC) is the most common cause of lower urinary tract symptoms, and of course antibiotics are not a useful or appropriate treatment for cats with FIC.15
Much of the antibiotic prescribing for urinary tract symptoms, as for gastrointestinal and respiratory symptoms, is driven by psychological factors: owner anxiety and demands for treatment, veterinarian anxiety about negative consequences to undertreating, and simple commission bias (the need to DO SOMETHING rather than wait for self-limiting problems to resolve on their own).4 Given that antibiotics are safe but not entirely benign, and that we are losing some effective treatments for serious infections to antimicrobial resistance, we should do what we can to resist the siren-song of antibiotic prescription above and beyond what is likely needed.
Perioperative Antibiotics Speaking of anxiety, the prospect of a post-operative infection appears to haunt the nightmares of veterinarians, based on the rate at which many of us prescribe antibiotics for our surgical patients.
Available evidence suggests that surgical site infections are uncommon for most clean or clean-contaminated procedures (< 5%), and that giving antibiotics before or after surgery do nothing to prevent these. Even in cases with specific risk factors for infection, the most we should likely do is provide appropriate antibiotic coverage from 30-60 minutes before the procedure until 6 to 24 hours afterwards.16 There is no convincing rationale or evidence, from human or veterinary medicine, to support more extensive antibiotic use to prevent surgical site infections.
Veterinary dentistry is a special case of perioperative antibiotic use.17 Once again, extensive evidence in human medicine shows that bacteremia occurs with chewing, brushing, or flossing just as it does with dental procedures, and that antibiotics are not useful for routine prophylactic procedures. Only people at high risk of infective complications (those with implant foreign bodies, a history of certain cardiac diseases, or those who are immunosuppressed) are likely to benefit from antibiotics when having dental work.
There is a lot less data in veterinary patients, but the expert consensus is that antibiotics are rarely necessary for dentistry patients and are not justified except in those at high risk. Unfortunately, it isn’t clear who those patients are. Infective endocarditis is often suggested as a potential risk from dental procedures, but this appears to be extremely rare in dogs and cats. Overall, antibiotics are very unlikely to benefit the vast majority of veterinary dentistry patients, and their risks likely outweigh their benefits.17
Despite this, it appears that antibiotics are very commonly used in veterinary dentistry. In dogs and cats with established periodontal disease or requiring extractions (which describes most dentistry patients), antibiotic use appears to be very common, though use
varies widely between different veterinary facilities.18 More evidence and clearer guidelines would likely help reduce the overuse of antibiotics in veterinary dentistry.
USES OF ANALGESICS TO RECONSIDER Tramadol If ever there was a cautionary tale veterinarians should heed about an inappropriately used analgesic, it is the story of tramadol. A cheap and widely used opioid and serotonin agonist in human medicine,19 tramadol became a popular pain therapy in veterinary species despite some pretty significant warning signs that our enthusiasm for the drug was premature. Because it is a pro-drug that has to be converted to an active metabolite to have an effect, it should have been a red flag that this conversion is much less efficient in dogs than in humans.20,21
Nevertheless, it became popular for post-operative pain and for dogs with osteoarthritis. The use of tramadol was likely driven by anxiety about NSAIDs, which are the most extensive studies and most clearly effective oral analgesic for dogs and cats. Despite lots of data and a strong overall safety record,22 vets and pet owners seem especially worried about the potential risks of NSIADs and eager to adopt any alternative portrayed as safer, even when the data are scant.
Eventually, clinical studies accumulated showing that tramadol has marginal benefits over placebo for dogs.23 Caregiver placebo effect likely accounted for most of the appearance of benefits. And while tramadol has more of an analgesic effect in cats, due to more efficient conversion to the active metabolite, it also has pretty significant adverse effects in this species.24 Sadly, many dogs undoubtedly experienced inadequately treated acute and chronic pain, and some still do, because of our eagerness to accept a purported NSAID alternative and our willingness to believe anecdotal evidence for what we were hoping and expecting to see.
Gabapentin The authors of the 2022 American Animal Hospital Association pain management guidelines for dogs and cats, at least, are trying to prevent history from repeating itself. They state, “Gabapentin has become the new tramadol, with widespread usage [despite] virtually no supporting data.”25
While there is good evidence in humans to support use of gabapentin for seizures and for some specific types of neuropathic pain (post-herpetic neuralgia and diabetic neuropathy), even most analgesic use in humans is without much supporting research evidence.26 In dogs and cats, there is limited evidence to support using gabapentin to reduce behavioral signs of stress, although it isn’t entirely clear if it reduces anxiety or is primarily a sedative. However, there is little reason to expect it to be of great benefit for acute or chronic pain. While more research needs to be done, it seems likely we have failed to learn our lesson from tramadol and are continuing down a similar road with this drug.
Mixing Lidocaine and Bupivicaine for Local Blocks This is one of those ideas that sounds brilliant but is actually totally wrong!27 Some clinicians mix lidocaine and bupivacaine together with the idea that they will get “the best of both worlds–” the more rapid onset of lidocaine with the longer duration of bupivacaine. What actually happens is that you get the worst of both worlds!
The dilution of each drug leads to a lower concentration gradient, meaning less of both end up getting into the nerves where they act to block pain. The difference in pH also means that mixing them likely slows the uptake of the lidocaine and might make the bupivacaine more likely to precipitate. Clinical studies in actual human and veterinary patients have also shown that this practice does not reduce the time to effect, but it does shorten the duration.
Steroids for Intervertebral Disk Disease (IVDD) Acute medical management of IVDD mostly involves controlling pain and trying to prevent further injury or loss of function. Steroids have long been used for both analgesia and to protect from further deterioration of nerve tissue by reducing inflammation. Unfortunately, it has been difficult to produce research evidence that supports the real-world benefits of this approach. In humans, the use of oral steroids does not appear very beneficial, though it does have a higher incidence of adverse effects than other analgesics. The evidence in veterinary patient is sparse, but the most recent ACVIM consensus statement on the subject indicates that:28
there is limited evidence that corticosteroid use is associated with poorer outcome and decreased quality of lifeas well as a higher rate of recurrence compared to nonsteroidal anti-inflammatory drugs (NSAIDs)
[there is] insufficient evidence to support corticosteroid use for neuroprotective purposes
In a retrospective study, dogs receiving NSAIDs had higher quality of life scores than those receiving corticosteroids
there is not sufficient evidence to support the use of corticosteroids as a protective strategy against the development of progressive myelomalacia
The best we can say is that steroids are probably no better than NSAIDs, and it seems likely they may be worse.
MISCELLANEOUS TREATMENTS TO RECONSIDER ACE Inhibitors for Pre-clinical Mitral Valve Disease Diagnosis and staging of mitral valve disease (MMVD) before dogs are in congestive heart failure (CHF) is now pretty rewarding. The advent of pimobendane has given us an intervention that likely delays the onset of CHF and extend life significantly for dogs with this disease.29 It wasn’t always so.
Back in the Dark Ages that make up most of my career, we used to give these dogs ace inhibitors (ACE-I). There were some sound theoretical arguments to suggest this would slow the progression to CHF. Unfortunately, a few pesky scientists weren’t satisfied with theory, and they did some clinical studies in actual MMVD patients. They found that that we were most likely wasting our time.
As the most recent systematic review puts it, “Administration of angiotensin-converting enzyme inhibitors to dogs with preclinical myxomatous mitral valve disease…results in little to no difference in the risk of the development of congestive heart failure and may result in little to no difference in cardiovascular-related and all-cause mortality.”30
Good thing we’ve all stopped doing this, eh?
Glucosamine for Osteoarthritis (OA) Probably the most popular (and profitable!) supplement in the history of veterinary medicine is glucosamine, alone or mixed with chondroitin or other agents. If everyone has used it forever, it has to work, right?!
Well, it turns out there is some controversy about that. Decades of research, hundreds of studies, are currently summarized in dozens of systematic reviews over the last ten years. For humans, these are often broken down into treatment for OA in specific joints, and there is sometimes analysis of glucosamine alone, in combination with other agents, or in different formulations and dosages. The result is muddled, and no clear, universal conclusions are possible.
About 60% of the reviews conclude there is some benefit to some type of glucosamine-containing product, and the other 40% conclude no meaningful benefit or insufficient evidence to tell. Not exactly a ringing endorsement for one of the most widely used supplements ever. The most recent systematic review for veterinary patients is ambivalent:31
“As we exposed in this review, glucosamine and chondroitin sulfate seems to provide chondroprotective effects and less inflammatory biochemical response in approximately half of the evaluations. However, these effects are inconsistent between the clinical and the preclinical studies… a possible caregiver placebo effect may explain some of the beneficial responses observed in clinical trials with dogs.”
The latest guideline from the American College of Rheumatology and the Arthritis Foundation, “recommends against glucosamine alone or with chondroitin because treatment does not improve knee and hip OA in studies without industry funding.”32 Ouch!
The American Academy of Orthopedic Surgeons say glucosamine “May be helpful in reducing pain and improving function…however, the research is inconsistent/limited.”33
There aren’t official guidelines from specialty groups in veterinary osteoarthritis management, but a recent proposed expert consensus statement highlighted the “lack of evidence” for efficacy needed to draw a firm conclusion.34 Another similar consensus statement indicated that three or four of nine contributing experts recommended offering some form of glucosamine for patients with OA depending on the specific circumstances.35
Despite being widely used for decades, it has proven impossible to clearly demonstrate that glucosamine in some form or combination has meaningful benefits for comfort and function in veterinary patients with OA. It is pretty well demonstrated to be safe, so there is unlikely to be any direct harm from using it. However, if it is ultimately not truly beneficial, what a horrendous waste of money it will have been for owners. And if it is used in place of clearly beneficial treatments (as it likely is, given how phobic people often are about NSAIDs), many OA patients could be suffering unnecessarily.
REFERENCES
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2. Gilovich T. How We Know What Isn’t so: The Fallibility of Human Reason in Everyday Life. 1. Free Press paperback ed. Free Press; 1993.
3. McKenzie B. Evidence-based veterinary medicine: What is it and why does it matter? Equine Vet Educ. 2014;26(9):451-452. doi:10.1111/eve.12216
4. McKenzie BA. Veterinary clinical decision-making: cognitive biases, external constraints, and strategies for improvement. J Am Vet Med Assoc. 2014;244(3):271-276. doi:10.2460/javma.244.3.271
5. Scahill K, Jessen LR, Prior C, et al. Efficacy of antimicrobial and nutraceutical treatment for canine acute diarrhoea: A systematic review and meta-analysis for European Network for Optimization of Antimicrobial Therapy (ENOVAT) guidelines. Vet J. 2024;303:106054. doi:10.1016/j.tvjl.2023.106054
6. Jensen AP, Bjørnvad CR. Clinical effect of probiotics in prevention or treatment of gastrointestinal disease in dogs: A systematic review. J Vet Intern Med. 2019;33(5):1849-1864. doi:10.1111/jvim.15554
7. Lappin MR, Zug A, Hovenga C, Gagne J, Cross E. Efficacy of feeding a diet containing a high concentration of mixed fiber sources for management of acute large bowel diarrhea in dogs in shelters. J Vet Intern Med. 2022;36(2):488-492. doi:10.1111/jvim.16360
8. Moreno AA, Parker VJ, Winston JA, Rudinsky AJ. Dietary fiber aids in the management of canine and feline gastrointestinal disease. J Am Vet Med Assoc. 2022;260(S3):S33-S45. doi:10.2460/javma.22.08.0351
9. Lappin MR, Blondeau J, Boothe D, et al. Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases. J Vet Intern Med. 2017;31(2):279-294. doi:10.1111/jvim.14627
10. Bollig ER, Granick JL, Webb TL, Ward C, Beaudoin AL. A quarterly survey of antibiotic prescribing in small animal and equine practices—Minnesota and North Dakota, 2020. Zoonoses Public Health. 2022;69(7):864-874. doi:10.1111/zph.12979
11. Robbins SN, Goggs R, Lhermie G, Lalonde-Paul DF, Menard J. Antimicrobial Prescribing Practices in Small Animal Emergency and Critical Care. Front Vet Sci. 2020;7. doi:10.3389/fvets.2020.00110
12. Farrell S, Bagcigil AF, Chaintoutis SC, et al. A multinational survey of companion animal veterinary clinicians: How can antimicrobial stewardship guidelines be optimised for the target stakeholder? Vet J. 2024;303:106045. doi:10.1016/j.tvjl.2023.106045
13. Weese JS, Blondeau J, Boothe D, et al. International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Vet J. 2019;247:8-25. doi:10.1016/j.tvjl.2019.02.008
14. Dorsch R, Teichmann-Knorrn S, Sjetne Lund H. Urinary tract infection and subclinical bacteriuria in cats: A clinical update. J Feline Med Surg. 2019;21(11):1023-1038. doi:10.1177/1098612X19880435
15. He C, Fan K, Hao Z, Tang N, Li G, Wang S. Prevalence, Risk Factors, Pathophysiology, Potential Biomarkers and Management of Feline Idiopathic Cystitis: An Update Review. Front Vet Sci. 2022;9:900847. doi:10.3389/fvets.2022.900847
16. Williams J. Antimicrobial prophylaxis: The why and how of antimicrobial prophylaxis. BSAVA Companion. 2018;2018(11):4-7. doi:10.22233/20412495.1118.4
17. Davis E. The Use of Antibiotics in Veterinary Dentistry. Today’s Veterinary Practice. Published April 14, 2023. Accessed April 3, 2024. https://todaysveterinarypractice.com/dentistry/antibiotics-in-veterinary-dentistry/
18. Weese JS, Battersby I, Morrison J, Spofford N, Soltero-Rivera M. Antimicrobial use practices in canine and feline dental procedures performed in primary care veterinary practices in the United States. PLOS ONE. 2023;18(12):e0295070. doi:10.1371/journal.pone.0295070
19. Subedi M, Bajaj S, Kumar MS, Yc M. An overview of tramadol and its usage in pain management and future perspective. Biomed Pharmacother Biomedecine Pharmacother. 2019;111:443-451. doi:10.1016/j.biopha.2018.12.085
20. Benitez ME, Roush JK, KuKanich B, McMurphy R. Pharmacokinetics of hydrocodone and tramadol administered for control of postoperative pain in dogs following tibial plateau leveling osteotomy. Am J Vet Res. 2015;76(9):763-770. doi:10.2460/ajvr.76.9.763
21. Schütter AF, Tünsmeyer J, Kästner SBR. Influence of tramadol on acute thermal and mechanical cutaneous nociception in dogs. Vet Anaesth Analg. 2017;44(2):309-316. doi:10.1016/j.vaa.2016.02.003
22. Monteiro-Steagall BP, Steagall PVM, Lascelles BDX. Systematic review of nonsteroidal anti-inflammatory drug-induced adverse effects in dogs. J Vet Intern Med. 2013;27(5):1011-1019. doi:10.1111/jvim.12127
23. Donati PA, Tarragona L, Franco JVA, et al. Efficacy of tramadol for postoperative pain management in dogs: systematic review and meta-analysis. Vet Anaesth Analg. 2021;48(3):283-296. doi:10.1016/j.vaa.2021.01.003
24. Guedes AGP, Meadows JM, Pypendop BH, Johnson EG. Evaluation of tramadol for treatment of osteoarthritis in geriatric cats. J Am Vet Med Assoc. 2018;252(5):565-571. doi:10.2460/javma.252.5.565
25. Gruen ME, Lascelles BDX, Colleran E, et al. 2022 AAHA Pain Management Guidelines for Dogs and Cats. J Am Anim Hosp Assoc. 2022;58(2):55-76. doi:10.5326/JAAHA-MS-7292
26. Chincholkar M. Gabapentinoids: pharmacokinetics, pharmacodynamics and considerations for clinical practice. Br J Pain. 2020;14(2):104-114. doi:10.1177/2049463720912496
27. Hoffmeister E. Mixing local anesthetics – yay or nay? North American Veterinary Anesthesia Society. Published September 27, 2019. Accessed April 3, 2024. https://www.mynavas.org/post/mixing-local-anesthetics-yay-or-nay
28. Olby NJ, Moore SA, Brisson B, et al. ACVIM consensus statement on diagnosis and management of acute canine thoracolumbar intervertebral disc extrusion. J Vet Intern Med. 2022;36(5):1570-1596. doi:10.1111/jvim.16480
29. Boswood A, Häggström J, Gordon SG, et al. Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial. J Vet Intern Med. 2016;30(6):1765-1779. doi:10.1111/jvim.14586
30. Angiotensin?converting enzyme inhibitors in preclinical myxomatous mitral valve disease in dogs: systematic review and meta?analysis – Donati – 2022 – Journal of Small Animal Practice – Wiley Online Library. Accessed April 3, 2024. https://onlinelibrary.wiley.com/doi/10.1111/jsap.13461
31. Barbeau-Grégoire M, Otis C, Cournoyer A, Moreau M, Lussier B, Troncy E. A 2022 Systematic Review and Meta-Analysis of Enriched Therapeutic Diets and Nutraceuticals in Canine and Feline Osteoarthritis. Int J Mol Sci. 2022;23(18):10384. doi:10.3390/ijms231810384
32. Kolasinski SL, Neogi T, Hochberg MC, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res. 2020;72(2):149-162. doi:10.1002/acr.24131
33. Brophy RH, Fillingham YA. AAOS Clinical Practice Guideline Summary: Management of Osteoarthritis of the Knee (Nonarthroplasty), Third Edition. JAAOS – J Am Acad Orthop Surg. 2022;30(9):e721. doi:10.5435/JAAOS-D-21-01233
34. Mosley C, Edwards T, Romano L, et al. Proposed Canadian Consensus Guidelines on Osteoarthritis Treatment Based on OA-COAST Stages 1–4. Front Vet Sci. 2022;9. doi:10.3389/fvets.2022.830098
35. Cachon T, Frykman O, Innes JF, et al. COAST Development Group’s international consensus guidelines for the treatment of canine osteoarthritis. Front Vet Sci. 2023;10:1137888. doi:10.3389/fvets.2023.1137888
I am preparing a number of conference presentations for this year, and one of the new ones is on the topic of Spectrum of Care. This is a concept I have been involved this for a while, since participating in a working group organized by a classmate of mine that culminated in a publication kicking off a discussion about balancing the needs of patients and the rising costs of veterinary care.
The core of the Spectrum of Care (SOC) concept is recognizing that the treatment of each patient takes place in a unique context that includes the patient, the client, and the veterinarian.1–3 There is no single, universal “gold standard” that can be automatically applied to every patient. A key role for the practitioner is to identify the best approach for a specific case by integrating-
the needs of the patient
the goals and capacity of the client
the vet’s knowledge and skills
the relevant scientific evidence concerning diagnostic and treatment options
An articulated spectrum of care approach should provide support and guidance to practitioners and ensure consistent and explicit consideration of all relevant information by both vets and clients. Vets provide recommendations for managing the case, always relying on an evidence-based understanding of the needs of the patient and of the risks, benefits, and uncertainties associated with the available interventions. These recommendations are then adapted to the goals and capacity of the owner through an explicit shared decision-making process.
The impact of the approach ultimately chosen on the wellbeing of the patient is then regularly re-assessed, and the plan is adjusted as needed throughout the course of treatment. Such adjustment always involves clear discussion between the vet and the client about all relevant issues, including the apparent benefits and adverse effects on the patient, the caregiver burden, the practical and economic sustainability of treatment, and the ultimate goals as understood by the vet and the owner.
PATIENT FACTORS
The needs and quality of life of the patient are always the central focus of medical care. These should be assessed in as objective and evidence-based a way as possible. The use of clinical metrology instruments, such as pain scales and quality of life tools, can help veterinarians and owners gain a more accurate common understanding of how the patient is doing and what they need.4,5
While veterinary patients cannot intellectually understand their condition and consent to treatment, they do have feelings and reactions to their care that must be taken into account. If a patient has a strong fearful or aggressive reaction to treatment, or if assessment suggests that treatment itself is negatively affective quality of life, alternative approaches should be considered.
Because our goal is to maintain or to reestablish a state of comfortable living in which patients can experience the activities and interactions they enjoy, all possible efforts should be made to ascertain what a good quality of life is for a given patient and to align the veterinarian’s and the clients’ understanding of this to the greatest extent possible. This will help guide the choices both parties make among the spectrum of care options available.
CLIENT FACTORS
The factor vets think about most often when considering the impact of clients on the treatments we can use is money. There is no question that financial constraints very often limit which tests and treatments can be employed, and clinicians must be adept at finding ways to meet the patient’s needs and the clients’ goals while not undermining the financial viability of their own practices.
An explicit spectrum of care approach that supports early and open discussion of such issues can help avoid wasting limited resources on tests that will not change the treatment plan or outcome and on treatments that are not effective or sustainable for the client. The sooner and more openly we talk about the availability of multiple paths towards achieving an acceptable outcome for the patient, the more efficiently we will choose and begin following the right path.
Money is not, however, the only client variable that impacts the choice of treatment. There is a growing literature concerning caregiver burden, which includes the physical, social, and emotional impact of caring for a sick pet as well as the financial costs.6,7 There are even instruments for measuring caregiver burden. Expanded development and use of these could be very helpful for vets and clients in understanding the overall constraints on care options and in making more thoughtful and effective choices.
The personal beliefs and values of clients can also affect their care decisions. Clients who have misconceptions or misunderstandings about the safety and effectiveness of medical treatments may need to be educated to inform better choices. And clients who have strong ideological or spiritual beliefs related to healthcare may choose some options and eschew others to stay consistent with these beliefs, regardless of the scientific evidence.
This can be frustrating when the veterinarian has a very different understanding of the situation. Seeing a patient suffering because a client is opposed to potentially beneficial therapies or categorically rejects the option of euthanasia is just as distressing for vets as when a client cannot afford needed care for their pet.
We cannot always achieve what feels like an optimal outcome for our patients in these situations. However, an explicit SOC approach with an emphasis on open communication about such issues and about all the available options may lead to better outcomes for patients than the extremes of an absolutist “my way or the highway” approach or a complete surrender to whatever the client demands.
VETERINARIAN FACTORS
In order to offer a range of diagnostic and treatment options that will effectively address the patient’s needs, vets must be aware of the options available and the risks, benefits, and uncertainties for each. An accurate, evidence-based understanding of these is essential, because offering ineffective treatments or avoiding those that actually work can never benefit patients. Our role in the VCPR is to understand what the patient needs and how we can best achieve this from a science-based perspective that is not directly available to the owner. We then need to advocate for the patient and educate the owner to provide them with the perspective and information necessary for making appropriate care choices.
Just as the client has constraints on their capacity to utilize particular treatments, so vets are constrained by their own knowledge and skills and by the resources available to them. The optimal therapy for a given case may not be available if it involves drugs or equipment the vet doesn’t have, techniques they are not familiar with, or staffing resources that exceed what is available in their practice.
The majority of veterinary assessment and treatment occurs in primary care practices, and this is where the implementation of an SOC approach from the initial encounter is especially needed. Optimal management of a particular patient may be possible in general practice, or it may require some level of specialty consultation or referral.8 One key component of SOC is determining if and when referral may benefit patients and how to achieve the best possible outcome for them when this is not an option. Often, the utility of referral is determined not only by the medical needs of the patient but by the capabilities of the practitioner, the goals and capacity of the owner, and the nature of communication within the VCPR.
COMMUNICATION ABOUT SPECTRUM OF CARE
Veterinarians are essential for effective patient care because we have the medical knowledge to understand the needs of the patient and to offer treatments to meet these. This does not, of course, mean that the client factors already discussed are not critical. The client can often understand the needs of the patient from a perspective not accessible to the veterinarian, and aligning these two perspectives is a key goal of the shared decision-making process. Just as the client cannot make effective decisions without accurate information about their options, the veterinarian cannot offer the most useful guidance if they do not understand and incorporate the clients’ perspective and needs into their recommendations.
To support the best possible care choices, the owner should understand the risks, benefits, and costs of intervention and the expected outcome associated with different approach, as well as the degree of uncertainty involved. The vet should understand the owners’ beliefs, expectations, and limitations well enough to recognize whether recommended interventions can be successfully employed or not. If a particular approach is unlikely to be effective due to client or patient factors, then alternative approaches to obtain an acceptable outcome should be considered and discussed.
Veterinarians are already accustomed to the negotiation and compromises between what they may see as the medically optimal approach and what clients are able or willing to do. However, such compromises are often made in an idiosyncratic manner, according to the particular beliefs, experiences, and habits of the individual clinician. The focus is usually on the financial constraints imposed by the client and how this hampers the “gold standard” care that a vet would like to provide. This process is often framed as a veterinarian recommending the optimal medical treatment and the owner declining, with the vet ultimately agreeing, shamefully or with resignation, to a cheaper and less appropriate treatment approach.
This pejorative view mischaracterizes a necessary process and can leave both clinicians and owners feeling they have failed to provide good care for the patient. It also hampers thoughtful decision making and open communication, which could make the inevitable compromises more rational as well as less unpleasant for everyone.
The concept of a medical “gold standard” is mostly mythical and counterproductive.9 There are no universal treatment approaches that can be automatically applied to every possible case. Veterinary students are still trained predominantly by specialists in tertiary care facilities, often learning their craft from the least representative exemplars of the profession and seeing patients and interventions very different from those common in general practice. This creates a clash of expectations and perspectives that must be resolved once new graduates enter a primary care practice environment.8 One goal of the SOC approach is to legitimize the inevitable differences between these practice contexts and diminish the perception that tertiary care represents to optimal or most appropriate approach while primary care is a lesser, fallback alternative.
Vets need support in developing the communication skills necessary to build effective VCPRs in a diverse client population with varied beliefs, goals, values, and constraints on the care they can provide for their pets. The SOC approach is aimed specifically at providing this support and normalizing the process of developing a management plan within the unique context of each case without the stigma that is currently attached to this process. Official recognition of the value and legitimacy of a SOC approach can also protect veterinarians from the anxiety that they will be punished, legally, financially, or in reputation, for appropriately adapting the available treatment options to the circumstances of each case.
THE ROLE OF EVIDENCE-BASED MEDICINE IN SOC
The lack of a single universal approach which all vets should employ reflexively does not, of course, mean that general principles and guidelines are not useful. These can be extremely helpful to inform decision-making, especially in characterizing the needs of the patient and the risks and benefits of various possible interventions.
Options included within the spectrum of care choices must be effective, and this means not only acceptable to the client and the veterinarian but also with a demonstrably positive balance between risks and benefits. Scientific evidence and the processes of evidence-based medicine are the best tools to identify the patient needs and the strengths and weaknesses of various treatment options.10
The SOC approach also does not render all such options equally appropriate. There are still “wrong” choices, from both a scientific and an ethical perspective. Ineffective treatments, or those which do more harm than good, are no more acceptable within the SOC approach than treatments which the client cannot afford or which the patient cannot tolerate. The discretion of the clinician to adapt general guidelines to the context of a specific case is constrained by scientific truth as well as by the resources or choices of the client.
The development and greater use of evidence-based clinical practice guidelines and tools for assessing quality of life and caregiver burden can facilitate a beneficial SOC practice. More research is also needed to characterize the risks and benefits of alternative treatment approaches for specific conditions. For example, studies comparing patient outcomes between routinely recommended and alternative, less intensive and expensive, treatments for canine parvoviral enteritis and for urinary tract obstruction in cats illustrate how such information can inform discussions between vets and owners about the pros and cons of various treatment options.11,12
Less aggressive treatment may have lower chances of a desired outcome, and clients should know this. However, the chances of a good result are still likely to be greater than when euthanasia is chosen over care that the client cannot afford or the veterinarian cannot provide. And less intensive care may also have fewer adverse effects and a lower caregiver burden, which could provide for better quality of life for the pet even if, in some cases, the length of life might be shorter. Such tradeoffs are inevitable and already commonly made, but vets and clients cannot make them effectively and maximize the potential for acceptable patient outcomes without accurate information indicating the risks and benefits of various approaches.
CONCLUSIONS
Offering a spectrum of care options that meet patient needs and aligns with the goals and capacity of vets and clients is not a revolutionary new idea. Vets have been negotiating the best approach for the unique circumstances of each case forever.
However, SOC is also not the same old thing we have long been doing. The usual negotiations depend very much on the idiosyncratic beliefs, experiences, and personalities of individual veterinarians. What interventions we offer, how we anticipate or respond to constraints imposed by clients, and how we manage the critical communication within the VCPR all depend on ad hoc approaches we each develop individually.
An articulated SOC approach emphasizes an evidence-based understanding of the options available, explicit and open communication about what the patient needs and what the vet and the owner can provide, and shared decision-making for how best to achieve a good outcome for the patient within the inevitable constraints of circumstances. SOC brings structure and transparency to this process and removes the shame created by the myth of a universal “gold standard” for care and the indoctrination in school that tertiary care practices represent the ideal for which all vets should strive.
A concerted effort will be needed, however, to make sure SOC does not just become an empty buzzword. Vets need tools to assess patients, evidence to characterize the pros and cons of various treatment options, training and support in client communication and shared decision-making, and backing from veterinary organizations to support implementing SOC as a routine process.
More evidence also needs to be developed to elucidate the risk and benefits of an SOC approach and determine if this practice really improves greater accessibility and quality of veterinary care for patients. Like all apparently good ideas, the real the value of SOC needs to be demonstrated empirically.
For now, the rationale for the approach, and for building the necessary evidence, tools, and support systems to implement, seems strong, and the potential to improve the experience of all parties in the VCPR seems promising.
REFERENCES
1. Stull JW, Shelby JA, Bonnett BN, et al. Barriers and next steps to providing a spectrum of effective health care to companion animals. J Am Vet Med Assoc. 2018;253(11):1386-1389. doi:10.2460/javma.253.11.1386
2. Brown CR, Garrett LD, Gilles WK, et al. Spectrum of care: more than treatment options. J Am Vet Med Assoc. 2021;259(7):712-717. doi:10.2460/javma.259.7.712
3. Fingland RB, Stone LR, Read EK, Moore RM. Preparing veterinary students for excellence in general practice: building confidence and competence by focusing on spectrum of care. J Am Vet Med Assoc. 2021;259(5):463-470. doi:10.2460/javma.259.5.463
4. Alves JC, Santos A, Jorge P, Lavrador C, Carreira LM. Evaluation of Four Clinical Metrology Instruments for the Assessment of Osteoarthritis in Dogs. Anim Open Access J MDPI. 2022;12(20):2808. doi:10.3390/ani12202808
5. Schmutz A, Spofford N, Burghardt W, De Meyer G. Development and initial validation of a dog quality of life instrument. Sci Rep. 2022;12(1):12225. doi:10.1038/s41598-022-16315-y
6. Spitznagel MB, Carlson MD. Caregiver Burden and Veterinary Client Well-Being. Vet Clin North Am Small Anim Pract. 2019;49(3):431-444. doi:10.1016/j.cvsm.2019.01.008
7. Silva PTRF, Coura FM, Costa-Val AP. Caregiver Burden in Small Animal Clinics: A Comparative Analysis of Dermatological and Oncological Cases. Anim Open Access J MDPI. 2024;14(2):276. doi:10.3390/ani14020276
8. McKenzie B. Do it yourself or send for help? Considering specialty referral from a general practitioner perspective. J Am Vet Med Assoc. Published online January 3, 2024:1-6. doi:10.2460/javma.23.11.0612
9. Englar RE. The Gold Standard, Standards of Care, and Spectrum of Care. In: Low-Cost Veterinary Clinical Diagnostics. John Wiley & Sons, Ltd; 2023:1-8. doi:10.1002/9781119714521.ch1
10. McKenzie B. Evidence-based veterinary medicine: What is it and why does it matter? Equine Vet Educ. 2014;26(9):451-452. doi:10.1111/eve.12216
11. Cooper ES, Owens TJ, Chew DJ, Tony Buffington CA. A protocol for managing urethral obstruction in male cats without urethral catheterization. J Am Vet Med Assoc. 2010;237(11):1261-1266. doi:10.2460/javma.237.11.1261
12. Venn EC, Preisner K, Boscan PL, Twedt DC, Sullivan LA. Evaluation of an outpatient protocol in the treatment of canine parvoviral enteritis. J Vet Emerg Crit Care San Antonio Tex 2001. 2017;27(1):52-65. doi:10.1111/vec.12561
In the endless debates about the health effects of various approach to feeding our canine and feline companions, the subject of “processed foods” or “ultra-processed foods” comes up often. Generally, the argument is made that traditional commercial pet foods, including canned but most especially extruded dry foods (aka kibble), are “ultra-processed” and are functionally equivalent to potato chips and sliced lunch meat. Since the evidence is pretty consistent that convenience foods, packaged snack foods, and most “fast-foods” are associated with increased health risks in humans, the conclusion is that these traditional commercial foods must be unhealthy for our pets.
This is a superficially logical argument, but it is also convenient for proponents of various unscientific approaches to animal health because it fits nicely with the “appeal to nature fallacy” many of them are committed to. That is the idea that something which appears “natural” to them is healthier than something which seems artificial or unnatural.
This is, of course, an arbitrary and nearly meaningless aesthetic judgment, not a rational or scientific categorization. However, since the health risks of ultra-processed foods for humans, and the apparent equivalence of traditional pet diets with such foods, reinforce an existing bias, this is taken as a strong argument for alternative diets that present the appearance of being more “natural: and more like the less processed “whole foods” widely recommended for humans.
In these discussions, I have tried many times to point out a clear and gaping hole in this reasoning—just because commercial pet foods come in a bag or a can, doesn’t mean they are all the same or that they are equivalent to human snack foods. Potato chips, lunch meats, and fast foods are intentionally designed to be appealing, in terms of appearance, taste, sensory experience (e.g. mouth feel and smell), and low cost. They are not meant to be nutritionally substantive or “healthy” in any way.
This is quite different from pet foods, which are deliberately formulated to be nutritionally appropriate and to support long-term health. The “processing” is not the real problem with “processed foods,” it is the excesses of salt, calories, and harmful fats and the absence of micronutrients, fiber, and other dietary components that make such foods a health risk.
This study evaluated diet and health outcomes in tens of thousands of North American healthcare workers followed for over thirty years. Here are some key findings:
People with consumption of ultra-processed foods (UPF) in the highest 25% had an increase in all-cause mortality of 4% compared with people in the lowest 25% of UPF consumption. This is an absolute difference of 64 deaths per 100,000 person years (1472 compared with 1536 deaths per 100,000 person years).The worst diet led to a real, but very small difference in mortality rate compared to the best diet.
This difference was a little larger when considering non-cancer and non-cardiovascular causes of death specifically: 9%
There was no difference in the risk of death from cancer or cardiovascular disease between the highest and lowest consumption of UPF.
All of this supports the existing evidence that UPF represent a health risk, but it also puts this in perspective. The risk is relatively small, much smaller than other known risk factors such as smoking, drinking excessively, or driving without a seat belt.
Even more telling, “this association was no longer apparent after overall diet quality was taken into account.” This means that there was no detectable difference between those who ate a lot or only a little UPF when the overall quality of the diet was accounted for. Again, the problem with UPF is not the “processing” but the unhealthy nutritional composition, and people who ate a generally healthy diet did not significantly increased their risk of dying if they included some UPF.
This point is further reinforced by the finding that the mortality risk difference was greater when alcohol was included as a UPF, and it was less when whole-grain bread products were included as a UPF. The health risks were affected by the nutritional quality and the other risk factors associated with a food (such as the toxic nature of ethyl alcohol) regardless of whether both items were equally “highly processed.”
The specific types of food most closely associated with increased mortality risks were meat products and sweetened beverages (though, interestingly, drinks sweetened with sugar had a slightly stronger negative effect that artificially sweetened, again undermining the “natural is better” argument).
The authors state their conclusion based quite clearly, and it reflects the point I have been making for years now:
Our data together suggest that dietary quality has a predominant influence on long term health, whereas the additional effect of food processing is likely to be limited.
Because the nutritional composition and overall diet quality is what matters, not the level of processing, the implications of this for diet recommendations is clear:
Limiting total ultra-processed food consumption may not have a substantial influence on premature death, whereas reducing consumption of certain ultra-processed food subgroups (for example, processed meat) can be beneficial.
The accompanying editorial expand son this point:
Not all ultra-processed food needs to be universally restricted and…careful deliberation is needed when considering whether to include recommendations about ultra-processed food in dietary guidelines. In countries where affordable, mass produced packaged wholegrain products such as breads are a recommended dietary staple and a major source of fibre, adding a sweeping statement in dietary guidelines about avoiding ultra-processed foods is not helpful.
As veterinary professionals and pet owners, these results reinforce the point that we should not obsess about the “processing” involved in the making of the pet foods we use. While inclusion of some fresh or whole foods may well turn out to have some health benefits, it is far more important that making sure our pets are eating complete and balanced diets that meet their nutritional needs, regardless of the form they take.
Over the years, I have reviewed the general evidence and some specific studies concerning vegetarian and vegan diets for dogs and cats. Despite the aggressive claims of some advocates for such diets (including some egregiously unscrupulous individuals), the actual evidence has not been extensive or definitive. My conclusions in previous posts have been that there is no clear evidence vegetarian or vegan diets have benefits for dogs and cats, and there is some real potential for harm, especially in cats:
There is no evidence that vegetarian diets have health benefits for dogs and cats, and no real reason to believe they should be, based on the physiology and nutritional requirements of these species.
Dogs are omnivores shaped by domestication to be able to eat both plant and animal foods, and in theory they should be able to thrive on vegetarian or vegan diets. However, these diets must be carefully formulated, and many commercial vegetarian dog foods do not appear to be nutritionally adequate. There is also little reliable research evidence showing that dogs can remain healthy fed only a vegan diet.
Cats are clearly obligate carnivores with nutritional requirements that are unlikely to be effectively met by vegan diets. Such diets offer only risks and no benefits for cats and should be avoided.
This study didn’t actually evaluate the effect of plant-based vs. meat-based diets on health or longevity in cats. What the study evaluated was the perceptions of owners about their cats’ diet and health. The difference is crucial.
All we can say is that owners who choose to feed a plant-based diet believe their cats are a healthier weight than owners who feed meat-based diets. Since plant-based diets are fed to a small minority of cats, the people who feed these diets must choose to do so based on pre-existing beliefs about their health value. Such individuals already believe these diets are healthier, and they are likely to see and report what is consistent with these beliefs, whether or not it is the reality of their cats’ condition.
Prospective, blinded, randomized feeding studies would be needed to allow any strong conclusions about whether or not plant-based diets are safe and healthy for cats.
The particular population of pet owners surveyed believes that feeding raw and plant-based diets are associated with better health in their pets. They also believe that their veterinarians think their pets are healthier (though whether these vets actually believe this is unknown)…Like previous studies relying on owner surveys and both conducted and funded by folks with strong a priori opinions about diet and health, this is a useful insight into such beliefs. It is not compelling or probative evidence for actual health effects of different feeding strategies.
Controlled studies with objective measures of outcome and more defined and verified feeding practices are required to draw any meaningful, actionable conclusions about the healthiest feeding strategy for our pets.
I am neither for nor against vegan diets for dogs, and I am even open to reversing my objection to feeding vegan to cats or raw diets to cats or dogs if strong evidence is generated that these are safe or beneficial practices.
I recently came across a systematic review of the literature that summarizes and assesses the available evidence concerning vegan diets for dogs and cats.
The data from review largely support my concerns about the lack of evidence, though the authors draw a somewhat more optimistic conclusion than I would:
In this review, we conducted a formal assessment of the evidence in the form of a systematic review. We found that there has been limited scientific study on the impact of vegan diets on cat and dog health. In addition, the studies that have been conducted tended to employ small sample sizes, with study designs which are considered less reliable in evidence-based practice. Whilst there have been several survey studies with larger sample sizes, these types of studies can be subject to selection bias based on the disposition of the respondents towards alternative diets, or since answers may relate to subjective concepts such as body condition. However, there is little evidence of adverse effects arising in dogs and cats on vegan diets. In addition, some of the evidence on adverse health impacts is contradicted in other studies. Additionally, there is some evidence of benefits, particularly arising from guardians’ perceptions of the diets. Given the lack of large population-based studies, a cautious approach is recommended.
The short version of this is that there aren’t many studies, and most have serious flaws or limitations, so strong conclusions either way aren’t justified.
No obviously horrible risks have shown up, but given that the studies which looked at actual health outcomes were few, short-term, and involved small numbers of animals on several very different diets, it would be a mistake to draw the general conclusion that vegan diets are safe.
Similarly, a few studies claim to show health benefits, but these are all based on owner surveys with groups of owners self-selected to include people already convinced that vegan diets are healthier. This kind of evidence, also frequently cited to support health claims for raw diets, is highly biased and tells us more about what believers in such diets expect to see than about the actual health effects on their pets.
Finally, some nutritionists have pointed out a significant problem with this kind of review– the idea that broad categories of diets (e.g. canned, kibble, raw, fresh, vegan, etc.) can be identified as beneficial or harmful doesn’t really make sense. The health impact of a diet depends on the specific composition, the ratio and availability of nutrients in the diet, and the nutritional needs of each individual. Vague generalizations, such as “vegan diets are healthy” or “kibble is unhealthy” are so broad as to be pretty meaningless, and they don’t help us decide what the best diet is for our specific pets. While some level of generalization is, of course, necessary and useful, these characterizations go too far to be accurate or helpful.
Bottom Line There is very little research examining the health effects of vegetarian or vegan diets in dogs and cats. The existing evidence has significant limitations, which makes any firm conclusions impossible.
General theoretical arguments for why such diets should be healthy are not especially plausible nor convincing. It is likely that a properly formulated vegan diet could be adequate for many dogs, and possible for cats as well, but whether there are any benefits to feeding such diets, and whether these might outweigh potential risks, is not yet known.
Given this uncertainty, and the much better evidence for the appropriateness of cooked, meat-based diets, feeding dogs and cats a specific vegan diet is essentially a haphazard experiment, with as much or more potential for harm as for benefit.
Back in 2011, I first wrote about the issue of concerning whether dogs with cranial cruciate ligament (CCL) ruptures did better with surgery or with non-surgical management. My conclusion at that time was:
For most dogs under 15kg, conservative management (primarily restricted activity for 3-6 weeks, achieving and maintaining and appropriate body weight, and possibly physical therapy and pain medication) can achieve acceptable comfort and function. In larger dogs, significant arthritis is inevitable and dysfunction is extremely likely without surgical treatment.
This study does provide some support for the contention that overweight, large-breed or giant-breed dogs have better long-term outcomes when treated with both surgery and non-surgical therapy rather than with non-surgical therapy alone. However, the limitations in these data are great enough that the case for preferring surgical intervention is not strong
Since that time, there has been some further research, but there has not been one single, definitive clinical study comparing surgery with other approaches for managing CCL disease. This is partly for ethical reasons. Since most vets believe surgery produces a better outcome, it is considered unethical to randomly assign dogs with CCL disease to getting surgery or getting a potentially inferior treatment.
A new study has attempted to use existing data on a large number of dogs, and some complex analytic techniques, to mimic such a study.
I don’t have the expertise to evaluate the analytic approach in this study. The authors acknowledge many of the usual limitations to large retrospective analyses, but despite these issues, such studies are valuable, especially I the evidence-poor environment of veterinary medicine.
The results are pretty consistent in showing better outcomes in dogs treated surgically:
The current study shows that on average, surgical management leads to reduced lameness and analgesic prescription outcomes compared with non-surgical management.
Interestingly, the study did not find any difference between large and small dogs. Both groups seemed to do better with surgery, which is a different finding than some previous research. The authors suggest this may be related to limited numbers of small dogs being treated, since they are less likely to develop CCL disease, so further work is needed to clarify the impact of size on the choice of treatment.
While there are always individual factors to integrate into any decision about the best management for a specific patient, this additional evidence tends to support the existing view that surgery probably produces better outcomes for dogs with CCL disease. While this is not the perfect definitive clinical trial, such a study is unlikely to occur. The evidence that we do have is pretty consistent, and it supports at least a moderate degree of confidence in recommending surgery for those patients in whom it is an option and who have no specific reasons to avoid surgical treatment.
One of the goals of this blog has always been to warn pet owners about dangers to their animals: dangerously unreliable ideas and ways of thinking about science and medicine, dangerous therapies (or at least those not yet proven to be safe or effective), and dangerous individuals who promote both unscientific approaches and unproven or unsafe treatments. There is remarkably little effective regulation and oversight of pet healthcare products, apart from prescription medications. Unscrupulous sellers of snake oil, including vets, can often get away with egregiously illegal and dangerous claims and practices.
Despite this, a few of the individuals I have warned pet owners about over the years have faced at least some legal or regulatory sanctions, though the process has been slow and has often not impeded their ability to sell their nonsense. Recently, one particularly bizarre example, Jonathan Nyce, has finally been sentenced to prison for selling fake cancer treatments for dogs, a decade after I started warning people about him.
This belated but positive outcome seemed like a good prompt for me to revisit some of the folks I have been writing about for some time who have faced official sanction for their abuse of science and the public’s trust. While the outcome in Mr. Nyce’s case is positive, the balance of these cases have not resulted in effective protection of the public and our pets.
Jonathan Nyce My first post about Mr. Nyce was in 2014. In it, I looked at his claims for his supposed miracle cancer cure Tumexal (later renamed Naturasone). The product and the marketing had many of the hallmarks of quackery, from secret ingredients to use of testimonials and unpublished, potentially fabricated, test results. Mr. Nyce had a worrisome background, including previously questionable and unsuccessful attempts to market a drug for humans and a criminal conviction for murder, though I made a point of not making my critique of the product or the claims for it a personal critique of Mr. Nyce, since that is not a reliable way to judge such claims.
In 2020, I briefly reported on the criminal charges filed against Mr. Nyce for his illegal marketing of a fake cancer treatment. Finally, last month, Mr. Nyce was sentenced to 97 months in prison for his activities, which included bilking over 900 dog owners of nearly $1,000,000. Who knows how much harm his deception of well-meaning owners did to the patients themselves? As tempting as it is to rejoice at a well-deserved sentence, the more important question is whether this conviction will do anything to stop others from marketing bogus treatments. I have to admit to not being very optimistic on this point, for reasons which may be clearer as I review some other examples.
Gloria Dodd Even before covering Jonathan Nyce’s misdeeds, I wrote about veterinarian Gloria Dodd in 2011 (not to be confused with Jean Dodds, about whom more later….). Dr. Dodd was a proponent of a broad array of pseudoscientific nonsense, from auras and homeopathy to crystal healing and dowsing. She was also a seller of many alternative remedies that were either entirely useless (e.g. homeopathic) or untested and based on unscientific principles.
Her practices were determined to cross legal lines more than once. In 2004, the FDA sent her a warning letter for selling a fake “homeopathic vaccine” for West Nile virus. That product was still available when I wrote about her in 2011.
She was also disciplined by the California Veterinary Medical Board for practices that were blatantly unscientific, “a smoke and mirror power of magic type of practice,” in the words of the VMB. Her license was suspended for prescribing treatments for patients she had never seen in person. However, the courts effectively overturned this ruling, and Dr. Dodds continued to practice her “magic” for years to come.
Dr. Dodd passed away in 2013, but her company continued to promote her ideas and products for several more years. Regardless of how kind and genuine a person Dr. Dodd may have been, it is tragic that she was able to mislead pet owners about health and veterinary medicine for decades and sell products that could not have been beneficial and may well have harmed patients, either directly or by replacing other, truly effective remedies. The failure of the legal and regulatory system to protect the public from such practices is disappointing, though not unusual.
Al Plechner Dr. Plechner was another California veterinarian with deeply unscientific ideas about science and medicine. For decades, he treated patients for the mythical entity of “Plechner Syndrome” with high doses of steroids, thyroid hormones, Montmorillonite clay, and a variety of other nonsensical nostrums. While he claimed to have “research” to back his theories, he never published anything, and his descriptions sounded like nothing more than anecdotal case reports. Certainly, he never produced any evidence that convinced actual exerts in veterinary endocrinology that Plechner syndrome existed or had the causes and treatments he championed.
Like most purveyors of pseudoscience, Dr. Plechner did have dedicated supporters, who came out enthusiastically to “correct” me after my first post discussing his methods. His detractors, sadly, were less willing to go public. The private veterinary discussion boards on the Veterinary Information Network (VIN) contain many complaints and laments about Dr. Plechner’s ridiculous ideas, and about patients inappropriately treated with unsafe methods, but these never reached the public.
In 2015, I was contacted by an individual whose cat had been treated by Dr. Plechner with blatantly inappropriate doses of steroids. The cate suffered skin fragility syndrome (similar to this case) and faced surgery and a prolonged recovery from the effects of the drugs. Though several vets saw this cat and explained that the drugs were the cause of the problem, the owner had difficulty getting someone to support her complaint against Dr. Plechner, due to a combination of personal relationships between him and some of the vets and the general reluctance of veterinarians to call out even grossly inappropriate behavior by their colleagues.
The owner was able to find an internal medicine specialist to support her complaint to the VMB. Unfortunately, the wheels of justice ground slowly and started turning too late. Dr. Plechner retired and gave up his license in 2016. This did not automatically stop the VMB investigation, but Dr. Plechner then passed away in 2017, and no findings were ever released. However, his website is still active, his books are still for sale, and other vets (themselves with legal troubles) continue to promote his approach.
Most recently, in 2021 I briefly discussed the citation against Dr. Dodds from the California Veterinary Medical Boardfor practicing medicine without a license, as she has done for many years. The citations was “satisfied” in August, 2023, presumably meaning she paid the fine and promised not to practice medicine (though I have not been able to find any no public record of how this was resolved). Despite this, Dr. Dodds profile, and the activity of her company, Hemopet (which itself has been fighting with the state over tax obligations) continue to operate openly and freely. The fact that her medical practice has been illegal for years does not seem to have lessened her influence or her business activities in any meaningful way.
Andrew Jones
Dr. Jones did not initially get his own post, but he popped up in passing in another article I wrote in 2010 as an example of the mania for magical “secrets” that alternative medicine proponents often claim to have for treating health problems that science-based medicine can’t cure. Later that year, Dr. Jones chose to give up his veterinary license rather than stop defaming veterinarians who practice mainstream medicine as a way of promoting his own alternative approach. It turned out Dr. Jones’ followers were even more aggressively supportive of their angry saint than those of Dr. Plechner, and when he rallied them, they went on the attack against me in all sorts of corners of the Internet. Several years later, Dr. jones was still perturbed by my criticism, and his supporters continue to leave comments on the blog more than ten years after my first article about him.
Of course, the reason for that is that losing his medical license has done nothing to deter Dr. Jones from selling his bogus “secrets,” and all sorts of products, online. The snake oil business is still booming, and many of his customers see him as a martyr rather than someone who couldn’t keep his medical practice consistent with science and the law. He proudly promotes his book, “From the #1 bestselling author and former practicing veterinarian,Andrew Jones DVM.” Bizarre! And while some do continue to push back against his pseudoscientific claims, Dr. Jones has a thriving career selling nonsense and lies despite no longer being licensed to practice medicine.
In 2018, he signed a stipulation from the Minnesota State Dept. of Public Health admitting to unlicensed practice of alternative medicine and misrepresenting his credentials and promising not to do it again. He also paid a $263 fine. In the most bizarre legal resolution to any of these cases I have yet seen, doing this apparently allows Mr. Weisman to do whatever bizarre voodoo he likes with the permission of the Minnesota state government:
Apparently, claiming to be able to treat serious life-threatening illnesses, interpret clinical lab tests and MRI images, and discouraging patients from seeing legitimate, science-based medical practitioners is now A-OK in Minnesota! Yet another quack thriving by deceiving the public.
Leap Years is similar to most veterinary supplements on the market: It is based on some plausible ideas with limited supporting evidence, and it is marketed with claims that go well beyond anything scientifically proven or reasonable.
In that review, I pointed out that one piece of evidence the manufacturer cited to support their claims was an unpublished clinical study conducted at the veterinary school at North Carolina State University (NCSU). That study is still has not been published in a peer-reviewed journal, but the company has recently released a report on the preprint service Bioarxiv.
This is an increasingly common practice which is supposedly intended to make important information available more quickly, but which in most cases has more public relations value than scientific value. Until a paper is put through peer-review, it has only been critically evaluated by the authors or people they have chosen, which leaves lots of opportunity for bias. Such preprints may change significantly before publication or even never be peer-reviewed and published at all.
Preprints are clearly a lower level of evidence than full published research reports, but they do at least provide more detail for anyone interested in evaluating the research and claims made using it. As you have probably already guessed, that’s what I intend to do here!
The Study The study was a blinded, randomized, placebo-controlled clinical trial conducted in accordance with appropriate methodological guidelines, which is always nice to see. The authors do a good job of describing the methods, including the bias-control practices, progress of subjects through the trial, and the potential limitations. The one critical piece of information missing is the actual chemical compounds used in the supplement.
As discussed in my previous review, Leap Years supposedly contains an NAD+ booster, which the company states is not NMN but otherwise does not identify. This was given daily for the duration of the 6-month study period. The supplement is also claimed to contain a senolytic, which is also not identified and which was given on two consecutive days each month during the study.
The FDA is pretty clear that veterinary supplements are not covered under the limited regulatory rules for human supplements (the Dietary Supplement Health and Education Act or DSHEA). Anything marketed for animals must either be a food or a drug. Leap Years is clearly not a food, and the claims made for it very much sound like treatment claims for a veterinary drugs:
[Leap years] significantly improves owner-assessed cognitive function and may have broader effects on frailty, activity and happiness as reported by owners.
That would make it seem like the company is marketing an unlicensed veterinary drug without first demonstrating safety and efficacy, as is required. However, the FDA does not seem to have the resources or political backing to effectively enforce these rules, and the same is true for many other veterinary supplements. Legal or not, it seems to me unethical (if not unusual) to market a supplement with undisclosed ingredients and claim that it prevents or treats serious health problems in dogs. This study does nothing to address that concern.
The trial started with 67 dogs randomized to placebo, low-dose supplement, and high-dose supplement (though the authors refer to these as “low-dose” and “full-dose,” which seems an obvious attempt to avoid the potential negative connotations and anxiety that might come with claiming to provide a “high” dose of whatever the undisclosed ingredients are). Subjects dropped out at various stages of the study for a variety of reasons. The total dropout rate was a bit high (19-26% from baseline to final analysis of the data), as is to be expected with an already old population. However, the dropouts seemed roughly balanced across groups, so while this might have affected the statistical power of the study, it probably didn’t bias the results for or against any of the treatments.
The dogs were included in the study if they were at least 10 years old and had mild or moderate cognitive dysfunction as assessed by a validated tool (CADES). They also had to be cooperative for behavioral testing and not so sick or debilitated that they couldn’t complete the various evaluations of the length of the study. All of these are reasonable inclusion criteria.
There were quite a few outcomes measured, though at least these were appropriately identified as a primary outcome (which is all that is supposed to matter when one critically evaluates a study like this) and secondary outcomes (which are supposed to be viewed as potentially interesting but not probative).
The primary outcome was the change at 3 months in a validated measure of canine cognitive dysfunction (CCDR, not the same as used to test dogs for inclusion in the study). As the figure below shows, all groups improved, including those taking a placebo, which is a classic finding for non-specific effects of participating in a clinical study. Patients tend to get better due, most likely, to the increased care, attention, and monitoring they get as study subjects, even if the treatment doesn’t do anything (which is part of why having a placebo group is so important).
At 3 months, the placebo group looks better than the low-dose group, and the high-dose group looks better than both, and the authors report, “There was a significant difference between treatment groups over the three-month period (p=0.02).” However, differences in “successes” and “failures” (improvement or worsening of CCDR scores) between groups were not significant at 3 months.
More importantly, it’s not clear if these differences would be meaningful in terms of function or quality of life even if they were statistically significant. It is not even clear that these differences are real since they are variable across time periods and do not show the expected relationship between dose and response (the placebo group should stay the same or get worse, the low-dose group should get a little better, and the full-dose group should improve more than the low-dose group).
Expanding the chart to include the data from the 6-month timepoints (reported in the supplement to the preprint) shows the lack of these relationships and suggests that there is not clear and meaningful improvement with the supplement. Even though the 3-month timepoints was reported as a prespecified endpoint, it is interesting that it is the only timepoints that seems to show a significant improvement in a treated group and not the placebo group. Despite the statistical difference reported, it is pretty clear that the primary endpoint did not show the treatment to be effective.
The secondary outcomes also failed to show any clear evidence of a beneficial effect:
The CCDR was measured again at 6 months, and there were not changes nor differences within or between the groups
There was no change within groups nor differences between them in activity level determined by an objective monitoring device
There were no significant differences between the groups in the number of dogs reported to have maintained the same level of activity. The results also don’t show the kind of progressive effect with increasing dose that would be expected if there was actually a real treatment effect: placebo 55% unchanged low dose 62% unchanged high dose 44% unchanged
Similarly, no significant differences or dose response was seen in the percentage of dogs reported to have increased their activity level: placebo 20% increased low dose 10% increased high dose 39% increased
There were no statistically significant differences or dose response seen in the proportion of dogs with stable or improved frailty scores: placebo 55% stable or improved low dose 76.2% stable or improved high dose 72.2% stable or improved
A variety of cognitive function tests were run on the study dogs. These haven’t been validated to show changes over time or drug treatment effects, though they could potentially be useful for doing so. There were no significant differences and no clear sign of a dose response for these tests.
Cylinder test- all groups improved with no differences between them
Detour test- there was a slight decline in the full-dose group, a slight improvement in the other groups, and none of these differences were significant
Sustained gaze test- all groups improved with no differences between them
Gait speed- there were no changes nor differences between groups
Only a limited subset of the results was reported for owner-reported happiness in the paper, and I have not dug through the full data spreadsheet to find the rest, but the most hopeful subset reported by the authors still does not show a clear effect.
At 6 months, there were some differences in the proportion of dogs reported to get better on this measure, but these were not statistically significant, and again they don’t show a logical dose response: placebo 24% better low dose 47% better high dose 35% better
At 3 months, there were some differences in the proportion of dogs reported to get worse on this measure, but these were not statistically significant: placebo 15% worse low dose 10% worse high dose 0% worse
The authors also monitored for adverse effects and classified these according to appropriate standards. There were few serious adverse effects observed, and these were evenly distributed between the groups and did not suggest any dramatic safety problems with the product.
Bottom Line This report does not count as a peer-reviewed publication, and it adds only a little to the evidence already discussed a year ago to support the product claims. However, the report is useful in that it provides more detail about how the study was conducted and what the results were. Generally, the study was designed and reported appropriately, and the level of control, for bias was pretty good. Unfortunately for the company, the results failed to show statistically significant or clearly meaningful benefits for treated dogs.
The discussion and the company website, of course, try to present the findings in at least a slightly positive light, but the final statement that the product, “can be used safely to mitigate cognitive decline in senior dogs and might have broader effects on dog health manifesting as improved happiness and reduced frailty” is certainly not supported by the actual results reported here. The best we can say is that there were no apparent signs of significant risk and there were a few non-significant findings that might turn out to be mildly beneficial at a low but significant level in a larger study or with different outcome measures.
This level of evidence is never the definitive word for or against a treatment, but that this is the best the company can come up with after over a year on the market is not encouraging. The company makes claims which seem likely to be prohibited for a veterinary supplement, and they rely on anecdote and questionable extrapolation from theoretical science and results in other species to market the product, and the release of this study does nothing to strengthen their case.
March 12, 2024- Addendum Today Dr. Nir Barzilai announced that Dr. Sinclair was resigning from the presidency of the Academy for Health and Lifespan Research. It is nice to see some consequences for such clear, commercially motivated misuse of science. Hopefully, this will encourage Dr. Sinclair to focus more on research and less on selling unproven supplements, for dogs or humans!
As I’ve mentioned previously, in the last four years I have continued my clinical practice while also working for Loyal, a biotechnology company pursuing FDA approval of drugs to extend health lifespan in dogs. There is little overlap between my SkeptVet activities and my work at Loyal, and of course my writing here doesn’t represent the official position of the company on anything. But I do like to share here some of the science and publications on aging that I work on at the company. Sadly, that tends to draw the attention of those irritated by my advocacy for science-based veterinary medicine.
Recently, there was a large amount of publicity surrounding a milestone on the road to potentially getting our first drug approved at Loyal. While this drew mostly positive interest, I was accosted on the SkeptVet Facebook page by a follower of the “holistic veterinarian” Dr. Judy Morgan. Dr. Morgan’s fan asked me to respond to a FB Live video briefly discussing (or “ranting about,” in Dr. Morgan’s own characterization) the press coverage of Loyal’s work.
I eventually had to block this fan’s account for personal abuse, and I don’t generally bother to respond to trolls since their comments are typically ignorant and disingenuous, and their minds are firmly closed. Dr. Morgan’s fan wanted to set up a “debate” between us, a common tactic among alternative medicine advocates that mistakes theatrical performance for substantive exploration of evidence-based science. As I explained to her on FB, “science isn’t about public debate or performance, its about evidence. [Dr. Morgan] can say what she likes, and support it with whatever evidence she has, and I can do the same, and everyone can evaluate her claims and support for themselves…How we sound or look on video talking to each other isn’t useful or relevant, it’s just theater.”
However, there are some pretty significant misconceptions and misrepresentations of science and the drug approval process generally in Dr. Morgan’s video, and I thought it might be useful to take the opportunity to respond to those and, hopefully, give everyone a clearer picture of how those processes work and how science gives us the best chance at finding therapies that provide meaningful, beneficial impact on the health and wellbeing of our pets.
What Was the Fuss About? The announcement and associated publicity concerned something called Reasonable Expectation of Efficacy (RXE). This is a standard for supporting evidence that the FDA sets for veterinary drugs as part of the process of pursuing conditional approval. Since the regulatory system is complex and not something vets or pet owners often know much about (I certainly didn’t before becoming involved in this project!), I thought I’d start with a brief outline of how it works. The official explanation and detains can be found on the FDA web site.
Any medicine intended to treat disease in animals must be approved by the FDA. This is to ensure that these medicines are both safe and effective. Of course, as I’ve said many, many times, nothing is ever perfectly safe or always effective, and medicine is about balancing the benefits of a treatment against the potential risks, all in the light of the available scientific evidence and the frustrating, but inevitable, uncertainty about these. Having FDA approval means that a significant degree of scientific evidence at multiple levels is available to support the specific claims of safety and efficacy made for a prescription drug. This is not perfect, but it’s a great deal better than what is available for treatments that don’t go through this process (including supplements and nearly all forms of “alternative” medical treatments).
In the case of the typical FDA approval process, the agency requires several types of supporting evidence for safety and effectiveness. This includes pre-clinical research, that is studies done in test tubes or lab animals showing how a drug works and what biological effects it has. Such studies are an important part of demonstrating what we call “biologic plausibility,” the existence of an explanation for how something works that is consistent with established scientific knowledge.
Therapies such as homeopathy or “energy medicine” (such as Reiki) lack biologic plausibility because there is no scientific rationale for how they might work; they can only work if much of what we know about basic physical, chemistry, and biology is wrong. While scientific knowledge isn’t always completely correct, the basic knowledge that is the foundation for most of the successful medicine and technology in use today is pretty unlikely to be completely wrong. Clinical studies of these implausible therapies don’t make much sense and are often misleading.
Once there is good evidence for the underlying biology of how a drug might work, then a company seeking approval has to test it directly in the species it is intended for. If the drug is being developed for dogs, then studies must be done in dogs to understand how the drug works and what risks it may have. Sometimes this involves studies in laboratory dogs, often beagles, but it may also involve research in companion dogs. These studies have to comply with rigorous guidelines for methodology and to control various types of bias and error, so they are usually stronger evidence than studies not performed under such guidelines.
Finally, if the evidence to this point shows the drug is likely to be safe and effective for its intended purpose, a clinical trial is performed. This is the “randomized controlled trial” or RCT that people most often associate with medical science, even though it is only one part of a much more comprehensive testing process. In an RCT, ideally some dogs are given the new drug and others are given a placebo (a “fake” drug which does nothing at all), and everyone involved is “blinded” so they don’t know which is which. The details vary with the specific drug being tested, but again the standards for how these RCTs must be conducted to gain FDA approval are very specific and quite high, so the results are pretty good quality evidence.
This process often takes many years and is very expensive to complete. This is a problem because it makes it harder for veterinarians to get new and properly tested therapies. The system in most countries, and certainly in the U.S., is set up so that private companies are responsible for paying the costs of developing and testing new drugs, and so they aren’t likely to do so unless they think they can make back the money invested in this. Lots of interesting political debates could be had over whether a different system would be better, but that’s beyond the scope of this blog, and frankly nothing about this is likely to change here any time soon.
The FDA recognizes that vets can’t get many treatments that have met the high standards of the typical approval process, and so it allows some compromises to make useful therapies available to vets and their patients. We are, for example, allowed to use drugs approved for humans “off-label,” meaning in ways they were not tested and approved for. Many of the treatments vets use have been tested thoroughly for safety and efficacy in humans but not in dogs or cats. While this increases the potential risks when we use them in these species, often this is still better than the alternative of having no treatment for a given problem, or having treatments that haven’t even been scientifically validated in any species.
The FDA also doesn’t regulate some treatments much at all. The rules governing dietary supplements are especially lax (and violated all the time with little consequence), so it is much faster and more profitable for companies to make supplements than develop prescription drugs. Sadly, this has led to a booming and lucrative industry (highly favored by alternative medicine advocates like Dr. Morgan) selling products that may be claimed to be safe or effective even when there is little to no real evidence that these claims are true.
A more recent change in the FDA approval system has been the pathway of conditional approval. Under this approach, new drugs must meet all the same requirements for proving safety, manufacturing quality, environmental impacts, and so on as under full approval. However, if a product is targeting a serious health problem with no existing effective treatments (which is clearly the case for aging), and if the RCT needed for full approval is complex and likely to take a long time (again, this is clearly true for drugs intended to extend healthy lifespan), then a drug can be made available to vets for use while that RCT is being conducted.
In order to do this, the company must provide sufficient evidence that the product is likely to be effective (aka reasonable expectation of efficacy or RXE) along with the usual evidence for safety and other components of approval. Several products have been made available to vets under this pathway, including medications for heart disease, pancreatitis,anemia, and epilepsy.
The big news in the press that prompted Dr. Morgan’s “rant” on FB was that the FDA granted this RXE approval for one of Loyal’s products. The support for this approval included four years of pre-clinical research and 2,300 pages of data and documentation, so it is a pretty robust standard even prior to the completion of the final RCT. The product has not yet been approved, and it is not expected to be available for at least another year even if it eventually achieves this approval. However, the milestone was pretty significant since the FDA has never before granted RXE status (or approval of any kind) for a drug intended to treat the mechanisms and consequences of aging. Ultimately, this has the potential to open up an entire new area of preventative medicine, though there is a long way yet to go towards this goal.
Who is Judy Morgan? Dr. Morgan is a self-described “holistic” veterinarian. She was in clinical practice for many years, and since retiring she has focused exclusively on selling products, books, and educational courses on her web site as well as a variety of other educational and advocacy activities. She is quite typical of the alternative medicine advocates I have written about many times. She promotes Traditional Chinese Veterinary Medicine (TCVM), homeopathy, raw diets, innumerable untested supplements, and a wide range of dubious or disproven tests and treatments. She is also deeply suspicious of science-based veterinary medicine, condemning conventional diets and ranting about the dangers of conventional drugs, vaccines, parasite preventatives, and other mainstream medical tools.
Her educational courses often touch on longevity and geriatrics, and she clearly has an interest in these areas. However, her advice is largely unscientific, and she makes numerous false claims about the “proven” benefits of raw diets, TCVM, supplements, and so on. Anyone who suggests vets should choose supplements and foods for maintaining health or treating disease based on supporting “elements” such as Fire, Wood, and Water, or on “balancing” mystical energies like Yin and Yang, cannot be taken very seriously when commenting on science and scientific medicine.
What’s the “Rant” About? Most of Dr. Morgan’s video has nothing to do with Loyal’s products or the related media coverage. She spends much of her time talking about the work of a Japanese scientist on apoptosis inhibitor of macrophages (AIM), a protein supposedly being developed into a dietary supplement or injectable medicine to prevent or treat kidney disease and extend lifespan in cats (a set of claims that are themselves pretty dubious, and which I will try to find the time to talk about someday).
Unfortunately, she doesn’t make the transition very clear when she switches from talking about the Loyal RXE coverage and other subjects, and she repeatedly talks about a “vaccine” for aging, although neither Loyal nor the Japanese scientist she discusses are developing a vaccine. This may just be a sloppy shorthand for anything injectable, or a superficial reading of the media coverage (one web site does describe the AIM product as a “vaccine,” though the actual company web site makes it clear that is not what is being developed.) However, since she does spend a fair bit of her time talking about the dangers of vaccines (while still claiming to support them), I think this is part of the obvious effort she is making with this video to cast these products in a suspicious light for her viewers, many of whom are likely as distrustful of vaccines as she is.
Dr. Morgan begins the video by suggesting that she isn’t impressed by the RXE approval and she is “gonna wait ten years and see what the reports are” before even considering using this or any other drug treatment for aging. This is part of a consistent theme throughout the video– suspicion of scientific evidence and a preference for anecdotes to evaluate medical treatments. At one point, she actually says, “one of the great ways to find out what side-effects can be seen is social media.” ???? In her view, “if people are reporting the same side-effect time after time after time” then this is a reliable indicator of the safety of a drug. This ignores the well-established unreliability of anecdotal evidence (as the saying goes, the plural of ‘anecdote’ is not ‘data’).
She clearly doesn’t understand the role of pre-clinical evidence, not only because she recommends therapies that fail to show basic biologic plausibility, but because she acts as if any use of a drug without a comprehensive RCT is a dangerous experiment. With regard to conditionally approved drugs, she says, “When you go to your vet the day this thing hits the market, your dog is part of that clinical trial, you are saying, Yes, I am going to let my dog be part of that science experiment…it might have some serious side-effects that we don’t know about.”
One could claim that she is simply demanding the highest form of evidence for medical treatments, except that clearly she is comfortable using supplements, diets, and alternative therapies that have never been shown to be safe or effective through clinical trials. What is more, she explicitly admits she would never participate in a clinical trial because she thinks they are too dangerous: “I will not sign my dogs up for clinical trials. I know somebody has to somewhere but it’s not gonna be me.” Instead, she has the bizarre but common belief that scientific evidence is unreliable but if we have enough anecdotes then we can know what therapies are safe or effective. That is the sort of fundamental misunderstanding underlies so much of alternative medicine, and it makes her judgements on specific interventions unreliable.
Consistent with this approach, she often makes false claims about the risks of lack of efficacy of treatments based on anecdotal reports collected online. For example, she claims that isoxzoline parasite preventatives “have killed hundreds of thousands of animals” based on such reports, which is a demonstrably untrue exaggeration (e.g. 1, 2, 3). She also argues that the allergy treatment lokivetmab (a.k.a. Cytopoint) commonly ceases to work because of anti-drug antibody formation (for which there is no substantive evidence) and that there are “tons of side-effects” but the company “[doesn’t] have to report the side-effects that are seen once the drug is used widely,” which is again completely untrue.
Bottom Line None of the drugs Loyal is developing have been approved for use by the FDA, so of course no one is claiming they have been proven to be safe and effective yet. Having strong scientific evidence at all levels is the whole purpose of going through the prescription drug approval process rather than just launching a longevity supplement, which is a much faster and easier way to get a product to market with minimal scientific evidence. More evidence is needed, and it is being generated.
However, it is clear that better scientific evidence is not really what Dr. Morgan is concerned about. She already believes she can extend lifespan and healthspan with therapies that don’t have any meaningful scientific support, such as raw diets, supplements, and TCVM. And she repeatedly rejects the evidence when it is favorable to treatments she believes are dangerous base don anecdote or just simple prejudice against “injections” and “chemicals” and so on.
Hopefully, veterinarians and dog owners with a genuine interest in aging and in prolonging healthy lifespan will be interested in any new tools that are developed to achieve this. Hopefully they will critically evaluate the strengths and limitations of the scientific evidence as we all should for all of the therapies we use. However some, and I suspect Dr. Morgan will be one, will automatically reject any pharmaceutical as a safe and effective way of extending healthspan regardless of the evidence because it doesn’t fit their fundamentally unscientific philosophy. That’s fair enough, of course, but those folks shouldn’t try to claim that this rejection is really about holding out for more and better evidence if this is obviously inconsistent with their other claims and practices.
