Different treatments for canine hip dysplasia (CHD) have been described, with variable success. suggested that the implantation of gold beads at specific acupuncture points in dogs with chronic pain due to hip dysplasia seemed promising.
During the planning of a clinical therapy trial with implantation of gold beads in CHD, no information on the most suitable stratification factors could be found in the published literature. While CHD is a very common disorder in dogs and a large number of publications exists on its etiology, risk factors for development, breed prevalence, diagnostic methods, importance of prognostic factors for the development of coxarthrosis, and different therapeutic methods, good methodological studies of factors influencing treatment outcome are lacking.
During statistical analysis of treatment results, it is highly desirable to have as equal groups as possible regarding both the patient characteristics and diagnosis of disease. Although methods of statistical analysis exist to compensate for unequal treatment groups, it is more convincing to present data from equivalent groups, and stratification is a method for equalizing treatment groups [19, 25]. If we know the factors that may influence the outcome of a specific treatment, we may need to stratify for those factors. Sometimes the same factor that causes a disease may influence the outcome of treatment. However, the etiological factors are often different from the stratification factors that affect the results of treatment. In CHD, heredity is an important etiologic factor, but is not necessarily a factor that affects the outcome of a hip dysplasia treatment. When comparing small treatment groups of up to 50 dogs, it is important to eliminate or balance the factors that influence the outcome [23, 19].
How can stratification factors be identified? In smaller studies, this can be done by surmising all factors that could possibly influence the outcome of the treatment. The number of such factors may be large and the choice may be difficult. To stratify the animals on too many factors will result in many groups with few cases each. Consideration of earlier published trials or related experiments may also indicate one or more factors that may affect treatment outcome. Former treatment trials of CHD with published stratification factors were not found, although a related study of risk factors for degenerative joint disease associated with hip dysplasia found that body weight and hip joint laxity were such risk factors . It may be of psychological benefit if the person reporting the treatment effect knows that the animal is receiving a new treatment. In contrast, owners that know their animal is on a standard treatment may react unfavorably if they are made aware that other patients are "privileged" by receiving a new therapy. Such attitudes towards the given therapy may affect the owner's co-operation in a study, and may also influence the reported efficacy of the given treatment and any comparison of treatments in a controlled clinical trial (CCT) in animals, or may be distorted if the patient or animal owner, or those responsible for treatment and evaluation, know which treatment is being used. This problem can be avoided by performing a double blind trial, in which neither patient or owner nor physician or veterinarian are aware of which treatment the patient or animal is receiving. The first study to include blinding in CCT seems to have been published in 1927, and concerned vaccines for the common cold . In the first reported experiments with control groups [9, 17], the allocation to treatment was arbitrary or simply decided by the investigator.
Any blinded and balanced CCT should include an investigation of a possible placebo effect. A placebo effect is any medical intervention that has a favorable, non-specific, psychological, or psycho-physiological therapeutic effect, but without specific activity for the condition being treated. This non-specific effect may also be negative, that is, unfavorable , in which case it is called a nocebo effect. To the best of the authors' knowledge,  performed the first placebo CCT in 1799 and described the placebo effect for the first time. Placebo effects are commonly reported in CCT studies where humans are involved. In addition to Pavlov's morphine experiments on dogs , one of the first to describe this effect in animals was , who injected scopolamine hydrobromide to laboratory rats and demonstrated that saline injections to some extent imitated the effect of the drug. Other studies of conditioning placebo responses have been performed in animals [20, 26].
However, the prime reason for introducing placebo controls is to distinguish between the effect caused by an active treatment, and other effects due to reasons not related to the active treatment. A possible placebo effect was discussed in a study of gold wire implants in CHD where an equal improvement in locomotion and pain as evaluated by owners was found in both the placebo and treatment groups . A placebo effect in companion animals that resembles those reported in human CCTs, where treatment efficacy is assessed by the dog owner several months after the treatment had been given to the dog, seems not to have been shown in veterinary clinical studies.
The aim of this methodology study was to examine the need for and choice of stratification factors in the treatment of canine hip dysplasia, and to investigate the effect of blinding and placebo in a controlled clinical trial of pain treatment in CHD.