title: Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis.
abstract: BACKGROUND
  Pain and impaired mobility because of osteoarthritis (OA) is common in dogs and humans. Efficacy studies of analgesic drug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 - transient receptor potential vanilloid 1 (TRPV1) antagonist, Carprofen - non-steroidal anti-inflammatory drug (NSAID), Tramadol - synthetic opiate, or Placebo) for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication.
  
  
  RESULTS
  Acute hyperthermia developed after ABT-116 treatment (P < 0.001). Treatment with carprofen (P ≤ 0.01) and tramadol (P ≤ 0.001) led to improved mobility assessed by owner questionnaire. Nighttime activity was increased after ABT-116 treatment (P = 0.01). Kinetic gait analysis did not reveal significant treatment effects. Use of rescue treatment decreased with treatment in the ABT-116 and Carprofen groups (P < 0.001). Questionnaire score and activity count at the end of treatment were correlated with age, clinical severity at trial entry, and outcome measure baseline status (SR ≥ ±0.40, P ≤ 0.005). Placebo treatment effects were evident with all variables studied.
  
  
  CONCLUSIONS
  Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying analgesic treatment of canine OA. Our results suggest that analgesic treatment with ABT-116 is not as effective as carprofen or tramadol for treatment of hip arthritis pain in client-owned dogs.
authors.affiliation: Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Malek
authors.forename: Susannah J
authors.initials: SJ
authors.lastname: Sample
authors.forename: Zeev
authors.initials: Z
authors.lastname: Schwartz
authors.forename: Brett
authors.initials: B
authors.lastname: Nemke
authors.forename: Peer B
authors.initials: PB
authors.lastname: Jacobson
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Cozzi
authors.forename: Susan L
authors.initials: SL
authors.lastname: Schaefer
authors.forename: Jason A
authors.initials: JA
authors.lastname: Bleedorn
authors.forename: Gerianne
authors.initials: G
authors.lastname: Holzman
authors.forename: Peter
authors.initials: P
authors.lastname: Muir
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D001831:Body Temperature / Q000187:drug effects; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004311:Double-Blind Method; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007794:Lameness, Animal / Q000188:drug therapy; D008297:Male; D015207:Osteoarthritis, Hip / Q000188:drug therapy / Q000662:veterinary*; D010146:Pain / Q000188:drug therapy / Q000662:veterinary; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D015990:Placebo Effect; D012119:Respiration / Q000187:drug effects; D014147:Tramadol / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: C551310:ABT 116; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D007191:Indazoles; D010671:Phenylurea Compounds; D014147:Tramadol; C007005:carprofen