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

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

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

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

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

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

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

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

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

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

As part of my ongoing coverage of the risks and benefits associated with neutering, I wanted to review a recent article on the subject, this one looking specifically at cancer risk and behavioral problems in Vizslas.

Zink, MC. Farhoodly, P. Elser, SE. Ruffini, LD. Gibbons, TA. Riegr, RH. Evaluation of the risk and age of onset of cancer and behavioral disorders in gonadectomized Vizslas. J. Amer Vet Med Assoc. 2014;244(3):309-319.

The Study
This study involved  an analysis of data collected in 2008 through an online survey of owners of Vizslas in the U.S. and other countries (U.S. owners made up about 87% of the responses, with almost all the others coming from the UK, Australia, and Canada). Information was collected on about 2,500 dogs, and both cancer and behavioral problems were reported in about 25% of these.

The authors looked at the cancers and behavioral problems reported by owners as well as the age when individuals were neutered, if they were, the sex, and the age at which the medical problems examined were reported (though this last figure often had to be guessed at). The authors specifically excluded many conditions from the analysis, including some previously reported to be associated with neuter status. They did not, for example, consider orthopedic diseases because these were uncommon (~9% of the dogs). Oddly, they did not consider skin conditions either, though these were reported in about 20% of the dogs.

The reported results cover several cancers that are especially common in Vizslas, including Mast Cell Tumors (MCT), Hemangiosarcoma (HAS), and Lymphoma (LSA), as well as behavioral problems (noise phobias, separation anxiety, and various forms of aggression). The general results, broken down by age of neutering, are reported in the tables below.

The odds of MCT and LSA were higher for neutered than intact animals. The odds of HSA was higher for neutered females than for intact females, but there was no relationship between neutering and HSA risk for males. The odds of cancers other than these three were also higher for neutered than for intact animals. For all of these cancers, the odds were higher in those neutered after 12 months of age than in those neutered earlier.

For behavioral problems evaluated, the odds of having such a problem were higher in dogs neutered before 6 months of age than in intact dogs. There were no differences in the odds of behavior problems between intact dogs and those neutered after 6 months of age with the exception of storm phobia which was more common in neutered animals overall than in intact animals.

There was no difference in the age at death or the longevity of neutered dogs compared with intact dogs.

Limitations of the Study
The first potential limitation of this study is that the population of dogs included are potentially not representative of the general pet dog population. Only one breed was included, and only 60% were reportedly kept as “primarily a family pet,” with most of the others being used for show or hunting activities. About 23% were reported to have had offspring and almost half (43%) of the dogs were intact, whereas surveys suggest over 80% of the overall owned dog population is neutered. The average age at death was also reported to be 9 years, which seems quite young compared to many other breeds and mixed-breed dogs of similar size. Since there are genetic factors involved in many health conditions, and potentially developmental and environmental factors associated with how dogs are kept, caution must be used in extrapolating results from one population to another.

Another significant limitation of this study is the method of data collection. All data was collected by anonymous online questionnaire, with no attempt to verify the accuracy or validity of these data. Diagnoses of cancer and behavioral problems and assessment of age at neutering were based entirely on reports of owners, sometimes many years after the fact.

This raises a host of concerns. Owners may have reported diagnoses incorrectly, such as misidentifying cancers or reporting benign tumors as “cancer.” Owners may have been more likely to report cancer and/or neutering information if they believed there to be a relationship between the two or if they knew one purpose of the study was to examine such a relationship. Owners also identified cancer and skin conditions as top health concerns, suggesting a population of respondents particularly interested in these conditions, which might have affected their rate of reporting them.

There is also no way to identify what if any differences there were between people who participated in the survey and people who did not, or between the dogs owned by these different groups. It is likely that people who were aware of the survey and motivated to complete it differed in numerous ways from other Vizsla owners and owners of other kinds of dogs, and this again could affect the health conditions reported and the risk factors affecting them.

Another issue is that this study looked at potential risks posed by neutering, but it did not include assessment of most of the potential benefits of this procedure in this population. For females, for ecample, neutering is believed to be protective against mammary cancer (though the evidence is not as strong as commonly supposed), which in some populations is a very common and frequently malignant type of cancer. In this population, mammary cancer was reported in less than 1% of the females in the study, a rate dramatically less than in other populations studied. This suggests either that this population is a much lower risk of mammary cancer than others, in which case the protective effect of neutering might not be meaningful, or that the incidence of this disease was underreported.

Similarly, uterine infections (pyometra) are a common and serious disease in intact females, and these can be completely prevented by neutering. Yet the rate reported in this study was quite low. 22 cases were reported, which would be a rate of about 4% of the ~535 intact females included. Other studies have reported rates of 10-50% depending on age, so either this population has an unusually low rate of this disease, or the incidence was not accurately reported.

Health problems and cost or disruption for owners associated with estrus, reproductive behaviors, or actual reproduction were also not evaluated in this study.

Overall, the study found no difference in the longevity or overall mortality of neutered versus intact dogs. This is in contrast to other studies which suggest neutered animals may live longer on average than intact animals. More importantly, it calls into question the significance of the reported increase in cancer risk in neutered dogs. If neutered dogs are truly at significantly higher risk of often fatal diseases like HAS and LSA, one might expect intact animals to live longer as a results of being less likely to experience these diseases. And if the two groups have roughly the same life expectancy, perhaps there are benefits to neutering not reported here that counterbalance the risks discussed?

Bottom Line
This study contributes useful new information to the ongoing process of evaluating the risks and benefits of neutering. It supports information from other studies, in Rottweilers and Golden Retrievers, that suggest neutering may increase the risk of some cancers, such as hemangiosarcoma and lymphosarcoma, in breeds predisposed to develop these diseases.

The study also has a number of significant limitations. The dogs in the study were all of one breed, and they differed in a number of ways from the general pet dog population, so findings in this group may not be applicable to other populations.  The data was collected though anonymous questionnaires completed by owners, often years after the events being asked about, and there was no way to confirm the accuracy or validity of these reports. There is also a high risk that the people who chose to participate in the survey, and the dogs they own, are quite different from the general pet owning population and their pets, in their concerns, knowledge, and pet care practices.

The study did not examine many of the risks posed by being intact, which have to be considered in weighing the overall risks and benefits of neutering. Rates of pyometra and mammary cancer, common and serious medical problems prevented by neutering females, were far lower in this study than generally reported elsewhere, suggesting either that the study population was quite different from other dog populations or that the rates of these diseases were not accurately reported.

And it is unclear how significant the reported increase in the risk of cancers in neutered animals really is since there was no overall difference in the longevity of neutered and intact animals. If neutered animals are much more likely to get cancer, it is surprising that they tended on average to live just as long as intact dogs.

Overall, this study supports the current trend towards questioning the dogma of routine neutering for all dogs. The risks and benefits are likely to vary according to breed, age, and many other variables, and a one-size-fits-all approach is not ideal. Unfortunately, a great deal of additional research will need to be done for dog owners and veterinarians to have confidence in specific recommendations for individual dogs.

I was recently interviewed for an article on the nature of evidence in veterinary medicine, and why pet owners should be concerned about the evidence their veterinarian uses to support his or her recommendations. If clients demand the therapies given to their pets be based on good science, veterinarians will make this happen. If pet owners simply accept personal experience of anecdote as the reason for using a particular treatment, they won’t be providing their animal companions with the best possible care.