Quantifying placebo and trial participation effects on cognitive outcome measures in aging dogs

The placebo effect, or the positive effects observed after an inert treatment which result from patients' expectations for the therapy, is well documented in human medicine. However, in veterinary medicine, where owner's expectations serve as a proxy for their pets, it remains underexplored, particularly for elderly dogs with cognitive decline. To address this gap, we examined 21 dogs (mean age: 12.85 years, SD: 1.46) from a placebo group in a randomized controlled trial (RCT) and compared their results to 17 dogs (mean age: 13.24 years, SD:1.56) from an observational, longitudinal study to distinguish placebo effect from trial participation effect. Both populations had statistically comparable baseline data. Cognitive changes were evaluated with two remotely administered owner questionnaires (Canine Cognitive Dysfunction Scale (CCDR) and Canine Dementia Scale (CADES)) and three in-house cognitive assessments (Cylinder Task, Detour and Sustained Gaze). We hypothesized that placebo effect would be greater than trial participation effect, particularly in owner-reported measures. Matched pairs T-tests and effect size calculations (Hedge's g) were used to calculate changes across 6 months. A strong (g = 0.76), significant (p = 0.021) improvement in CADES was observed in the placebo cohort after 6 months, while no changes were detected with CCDR. Conversely, the observational cohort showed a small (g = 0.35) and significant (p = 0.03) deterioration on CCDR, and no change in CADES. No significant changes were noted on the in-house cognitive assessments in either cohort. We conclude that study context influences remotely delivered owner assessments and CCDR is more robust against caregiver placebo effect in RCTs than CADES.