Re-evaluating the placebo response in recent canine dietary epilepsy trials

Schmidt, T; Meyerhoff, N; Meller, S; Twele, F; Charalambous, M; Berk, BA; Law, TH; Packer, RMA; Zanghi, B; Pan, YL; Fischer, A; Volk, HA

Abstract

The placebo response is a common phenomenon. Limited evidence is available about its magnitude in canine epilepsy trials, even though it can significantly influence the efficacy evaluation of new treatments. It was hypothesised that the placebo response is diminished when epilepsy trials are conducted in a prospective crossover design. Seizure data spanning six months from three previous multicenter epilepsy studies were analysed. The monthly seizure frequency of 60 dogs diagnosed with idiopathic epilepsy was calculated, comparing baseline data with placebo treatment. Furthermore, differentiation was made between dogs randomised to the placebo group early (Phase 1: first 3 months) or later during the study (Phase 2: second 3 months).The analysis did not reveal any placebo response in terms of monthly seizure frequency. Instead, an increase was noted during the placebo treatment period, with a mean of 2.95 seizures per month compared to 2.30 seizures per month before study entry (p = 0.0378). Additionally, a notable phase effect was observed. Dogs receiving the placebo in the second study phase exhibited a significant increase in monthly seizure frequency compared to baseline (p = 0.0036). Conversely, no significant difference from baseline was observed for dogs receiving the placebo in the first study phase. These findings underscore the considerable variability in placebo responses observed in trials for canine epilepsy, contrasting with previous limited data. The identified phase effect should be carefully considered in the design and evaluation of canine epilepsy trials to ensure a more accurate assessment of efficacy for new treatments.

Citation

Schmidt, T., Meyerhoff, N., Meller, S., Twele, F., Charalambous, M., Berk, B., Law, T., Packer, R., Zanghi, B., Pan, Y., Fischer, A., & Volk, H. (2024). Re-evaluating the placebo response in recent canine dietary epilepsy trials. BMC Veterinary Research, 20(1), https://doi.org/10.1186/s12917-024-04066-z

• Journal Article Type: Article
• Acceptance Date: May 7, 2024
• Online Publication Date: May 24, 2024
• Publication Date: 2024
• Deposit Date: Jun 3, 2024
• Publicly Available Date: Jun 3, 2024
• Print ISSN: 1746-6148
• Electronic ISSN: 1746-6148
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 20
• Issue: 1
• DOI: https://doi.org/10.1186/s12917-024-04066-z
• Keywords: Placebo response; Placebo effect; Honeymoon effect; Crossover trials; Epilepsy; Dogs; PARTIAL-ONSET SEIZURES; DRUG-RESISTANT; EFFICACY; BLIND; DOGS