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Clinical trials in dogs
For interventional studies, it is vital importance to have very strict and defined outcome variables. Having diagnostic imaging or laboratory variables as surrogates of genuine clinical success is usually not appropriate, when the aim is to investigate if a certain treatment benefit dogs and cats by improving quality of life and survival. Drug trials are the most challenging types of interventional studies, the reason being that they require many cases included, clear inclusion and exclusion criteria, and well defined end-points (outcome variables). Endpoints in the area of small animal cardiovascular medicine usually includes quality of life variables assessed by attending clinician and owner, duration of pre-clinical period and survival. Drug trials in dogs with pre-clinical myxomatous mitral valve disease (MMVD) are challenging trials. However, due to the lengthy nature of the preclinical period, any therapy effective in prolonging this period could have a major impact on longevity and quality of life of affected dogs. It has therefore been of great interest to find a treatment that has a preventive effect on progression of MMVD, alternatively offers a prolonged preclinical period. The challenges include establishing inclusion and exclusion criteria that leads
to a study population that is representative of the target population (the dogs that will be receiving this particular treatment in the future). Because of the lengthy preclinical period, a clinical trial, aimed at studying progression in treatment groups, must plan for how to handle dogs developing other disease and possibly initiation of medication other than the test substances, and how to handle treatment gaps and dropout of included dogs. Safety is a very important issue in long-term trials in
dogs without clinical signs of disease. The study need to be designed in such manner that potential detrimental effects of the test substance is detected during the study.
Designing studies concerning feline cardiomyopathy
There have been some drug trials conducted in cats with hypertrophic cardiomyopathy (HCM), but few of them have been published, presumably owing to non- significant differences between treatment groups. Feline cardiomyopathy is a group of myocardial diseases where it may be difficult to distinguish one form from the other. Some cats may also share features of all forms. The situation has also been complicated by a lack of robust reference intervals for echocardiographic measurements, which are vital for diagnosing heart disease, HCM
in particular. Fortunately, sometimes help can come
from those who will ultimately benefit from the study, which was the case when new body weight dependent reference ranges were recently published. The reference ranges were based on almost 20 000 echocardiographic screens of pure-bred cats, and the management of the screen reports and entering them all into a database
An Urban Experience
was all done on a voluntary basis for the PawPeds organization. The cost for this study was very low, but demanded a very large amount of voluntary work. These reference intervals will help specialists into better defining disease, and thereby presumably help in establishing better defined study populations in interventional studies.
Concluding remarks
Studies are conducted for many reasons and motifs. Depending on type of study, and quality in design
and performance, they help indirectly by better
disease definitions or better understanding of the pathophysiology, or they can benefit dogs and cats directly. Does it matter? I think it does, but some studies matters more than others.
Selected references
Rishniw M, Ljungvall I, Porciello F, et al. Sleeping respiratory rates in apparently healthy adult dogs. Research in veterinary science 2012;93:965-969.
Ljungvall I, Rishniw M, Porciello F, et al. Sleeping and resting respiratory rates in healthy adult cats and cats with subclinical heart disease. Journal of feline medicine and surgery 2014;16:281-290.
Häggström J, Andersson AO, Falk T, et al. Effect of Body Weight on Echocardiographic Measurements in 19,866 Pure-Bred Cats with or without Heart Disease. J Vet Intern Med 2016;30:1601-1611.
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;30:1765-1779.
Häggström J, Boswood A, O’Grady M, et al. Effect of Pimobendan or Benazepril Hydrochloride on Survival Times in Dogs with Congestive Heart Failure Caused by Naturally Occurring Myxomatous Mitral Valve Disease: The QUEST Study. J Vet Intern Med 2008;22:1124-1135.
Cowie MR, Filippatos GS, Alonso Garcia ML, et al. New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment. Eur J Heart Fail 2017.

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