6


EQUINE VETERINARY EDUCATION Equine vet. Educ. (2020) 32 (1) 6-7 doi: 10.1111/eve.13060


Editorial Evaluating evidence for new therapies in equine medicine


“I believe in evidence. I believe in observation, measurement, and reasoning, confirmed by independent observers. I’ll believe anything, no matter how wild and ridiculous, if there is evidence for it. The wilder and more ridiculous something is, however, the firmer and more solid the evidence will have to be.” Isaac Asimov In the 1923, the US Department of Agriculture Special


Report on Diseases of the Horse, A. Liutard M.D.V.M. offered a warning to owners of horses with arthritis, ‘He will do well to be on his guard against the patented “cures” which the travelling horse doctor may urge upon him and withhold his faith from the circular of the agent who will deluge him with references and certificates. It is possible that nostrums may in some exceptional instances prove serviceable, but the greater number of them are capable of producing only injurious effects’. Pursuing novel interventions is fuelled by our desire to improve our patient’s quality of life. Some prove ineffective, some have a small impact and a few have such a large and obvious impact that they may be referred to as parachute treatments. The latter being a tongue in cheek reference to the fact that experimental evidence is not required to prove that parachutes save lives. Few treatments in fact are parachutes with obvious overwhelming benefit. Many that were thought to be have not stood up to scrutiny. Novelty alone is not evidence of efficacy. It is natural to want to be ‘first on the block’, and most practitioners do not want to be the last to adopt a new therapy. We tend to be overly optimistic when assessing new therapies; in fact the novelty bias is well reported. Even in clinical trials a novelty or ‘wish’ bias can overestimate the effectiveness of a new therapy by as much as 27% (Persaud). When rigorously tested, novel therapies demonstrate superiority over standard care only a little more than half the time and only a few new treatments are substantially better than their predecessor (Djulbegovic et al. 2012). In veterinary medicine the criteria for a novel therapy has


been defined as one of the following: a completely original therapy, one that has only been used by a small number of veterinarians, one that has only been applied to a small number of animals of a particular species, a novel combination of previously accepted therapies or utilising an accepted therapy on a condition for which it was not previously indicated (Yeates 2016). This leaves us two significant questions regarding the introduction of novel therapies. What type and quality of evidence is considered adequate to incorporate the novel therapy into practice? Where does the burden of proof for efficacy and safety lie? When considering the quality of therapeutic evidence,


the randomised controlled trial (RCT) remains the gold standard (Cohen 2011). It involves an experimental study where an intervention is compared to a control group, usually a placebo or standard of care. By randomly allocating subjects to one of the two groups and masking both the provider and recipient to which subjects received the intervention, the impact of several biases and potential confounding variables are diminished. Without randomisation and blinding, observed treatment effects could be due to a true causal relationship, confounders or chance. In pre – post


© 2019 EVJ Ltd


treatment studies with no control group, attribution of a treatment effect may be due to regression to the mean, selection bias or simply an animal that was going to improve on its own. The lack of randomised controlled trials in equine medicine has been addressed (Mair and Cohen 2003). Reasons for this may be difficulty in recruiting subjects, overall cost and concerns about equipoise, meaning there is a genuine concern among experts over whether a treatment is effective. Since most equine interventional evidence lacks a control group, relies on subjective or surrogate outcomes, is rarely replicated and is based on small sample sizes, we must accept that our evidence for therapeutic efficacy is weak. If we wish to improve the evidentiary basis for our interventions, we will have to convince members of the equine industry that RCTs are a worthwhile investment that benefits both the horse and the horse owner in the long run. Perhaps pragmatic trials comparing the new therapy to current practice and recruiting subjects from multiple practices can offer an alternative. Outcomes from pragmatic trials are more generalisable and applicable to everyday practice than traditional RCTs. However, they have the potential to suffer from biases introduced due to a lack of randomised allocation and blinding. Routinely collecting and aggregating health data from equine hospitals and primary care facilities have the potential to offer a cost-effective and practical way to assess novel therapies in randomised trials (McCord et al. 2018). Without quality evidence for an intervention, horses serve


as uncontrolled and often poorly monitored experimental subjects. New therapies are based on plausible theoretical evidence that the therapy will improve the condition which it addresses. Excitement and optimism grow, and momentum ensues. Early perceived success and buzz lead to more frequent use of the therapy, the so-called bandwagon effect. This frequently leads to less incentive for further research even as the potential for adverse effects increases. Once adopted and accepted, it takes exceptional evidence or significant adverse effects to reverse course. Significant evidence in human medicine and some in veterinary medicine reveals that even when quality evidence refutes claims, these therapies are not readily abandoned. Some examples in equine medicine would include the use of isoxsuprine for navicular disease, the use of cimetidine (Helle 2012) in the prevention of melanoma and the continued use of nitroglycerin in the treatment of laminitis. Medical reversal occurs when a widely held medical practice is found to have no benefit and possibly causes harm to patients (Prasad et al. 2012). In equine medicine, medical reversal is not well documented since very few, if any, therapies are subjected to large scale clinical trials. Without high quality evidence prior to the introduction of a novel therapy, the likelihood of medical reversal increases. This leads to significant financial waste and sometimes emotional distress. A unique and challenging aspect of equine medicine is the use of unproven therapies in competitive horses. Often the indications for these therapies are short term performance benefits with unknown long-term health consequences. Many of these therapies address orthopaedic issues and fall into the


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76