The present study represents the continued interest in the conceptual and technical validities of multiple methods for pain assessment in canine OA. The PVF, CSOM, and MA demonstrated convergent results for the detection of diet-induced changes. The PVF exhibited the best technical validity, and the CSOM and MA demonstrated moderate technical validity. However, the CSOM evaluating the dogs’ day-to-day health status was found as related to the PVF and was primarily influenced by MA duration. The differences in the conceptual and technical validities suggested PVF, CSOM, and MA did not provide the same information on OA pain and physical function, but importantly they should be used and interpreted as a whole.
This study demonstrated that the PVF showed responsiveness to a GLM-enriched diet effect on canine OA. The study confirmed that the kinetic force platform gait analysis is a useful outcome because of the relative ease of data acquisition and technical validity
[21, 22, 24, 25, 29–31]. Interestingly, age, sex and radiographically estimated OA severity were not affecting PVF, and the value of PVF representing the most affected limb was an accurate outcome measure for OA. But it might only partially represent the consequences of the entire disease on the physical function in these selected dogs, with regards to the absence of relationship between PVF and MA.
Clinical owner-oriented outcomes would be conceptually preferred, in general, because they are expected to reflect a dog’s quality of life. The questioning of the patient/owner about the quality of life has opened a wider panel of OA physical function and pain assessments. The CSOM is a subjective instrument that satisfied some psychometric qualities in this clinical trial. The owner-described behaviors in the CSOM were similar to previously described behaviors in canine studies of OA symptoms and pain
[7, 19]. These similarities suggest the face validityk of the CSOM, which indicates that this measurement assesses the appropriate outcome
. Reliability testing revealed that the owner’s assessment was not variable over a one-week period. This is suggestive that CSOM scores were stable at the condition the dog’s status did not change between these two successive CSOM assessments (when facing a change, it was expected the owner to alert the investigators). With the conditions of the study, it was not possible to judge on a memory effect (the owner is influenced by the souvenir of the previous scoring) and the potential effect of a random error in CSOM owner assessment. Moreover, regression analyses demonstrated that both CSOM and PVF methods were related, supporting our second hypothesis. But, CSOM measurements were not strictly parallel to PVF (confirming our first hypothesis) as only the PVF detected a strict beneficial effect of the GLM diet. Divergent results between CSOM and PVF for the responsiveness analysis and the criterion validity analysis might be explained by the technical features of the CSOM. Indeed, the quantification scale of the CSOM is limited, likely decreasing its responsiveness. In addition, it was difficult to demonstrate a further decrease in the CSOM beyond D30 suggesting a possible floor effect. The sample size of 23 dogs was based on the power of the trial to detect a specified clinical benefit on the PVF. According to previous work done in similar conditions
, a sample size of 20 dogs ensured a difference of 4.2%BW in the PVF consistent with an effect size of 0.9 could be detected assuming 80% power, a SD of 4.5 and a 5% significance threshold. This sample size might be too weak to fully support GLM diet efficacy using CSOM. This result suggests that the CSOM would decrease the likelihood of false clinical benefits. In contrast, PVF was responsive to GLM effect. Whereas PVF demonstrated significant change between D30 and D90, the primary endpoint CSOM has not demonstrated a statistically significant change for the same interval time. This could look as controversial for the validity of the methods. Therefore, we applied a correction for multiplicity of endpoints that adjusted the Type I error when a significant result was required for more than one but not all multiple primary outcomes after correction of multiplicity
. With the correction for multiplicity, PVF was significantly different between D30 and D90. This method provided stronger evidence to fully characterize the metrological feature of the methods when a small treatment effect is anticipated. In addition, the study suggests the two methods complementary relationship in pain assessment in which the CSOM assessed pain-induced changes in behavior and locomotion, and the PVF analyzed kinetic gait changes.
Previous studies have not indicated the details of the construction of the CSOM
. As previously noted, owners easily report on their dog’s activities, but the number (from 5 to 3 activities) and the nature of the selected activities in the CSOM differed between users
[19, 34]. This result suggests that OA has a variable impact on the daily life of dogs or that some owners missed behavioral changes that are caused by chronic pain
. In this study, an analysis of the influence of each activity revealed that the ranking of activity was neither valid nor informative. However, the categorization of the activities demonstrated significant behavioral changes. The owners detected higher limitations in activity in their dogs after exercise (Ctg(2)) or after a certain period of inactivity, including stiffness at night/after activity/in the morning (Ctg(4)). These behaviors are events that concur with suggestions of pain signs in previous studies. Hence, the selection of the same number of activities (we suggest 2 to 3 activities) that are worded by the owner but selected from the present categories would allow more precise and sensitive comparisons between dogs in future studies.
Our findings reported a significant difference in MA from P1 to P6 (Figure
2). However, the graph clearly suggests the possibility to detect more frequent differences while taking account individual variability of these data (cf. the actual difference with age on this limited sample) and required sample size to avoid Type II error. In addition, according to the small sample inference of the linear mixed model
, our result needs to be verified on larger sample size. Despite limitation about the statistical inference, the present result about MA opens new insight in the field of pain evaluation for osteoarthritic dogs. Interestingly, MA did not significantly rely on PVF but to CSOM. These results emphasized that MA provided an aspect of spontaneous physical activity that was not detected by the conditioned gait evaluation, i.e. PVF. In addition, MA may be influenced by the proper ability of the dog to move freely and reflect its quality of life as defined by CSOM. Therefore, MA and CSOM are attractive outcome measures of pain and physical function in OA dogs because they are interrelated but different; one measurement is objective and the other is subjective.
The observed divergence in the results of the constitutive MFQ subscales (e.g., MFQ-NRS and MFQ-S from D0 to D30), the lack of responsiveness (for MFQ-RTx and MFQ-D) and the weak internal consistency (particularly for MFQ-S) lead to poor technical validity and question the construct validityl of this method. Although the CSOM and the MFQ were designed for clinical use to evaluate similar aspects of OA, the current results suggest that both pain scales partially reflect the same construct or that the MFQ did not satisfy adequate psychometric features. The standardized MFQ scale looked less potent to reflect the variability in limb impairment, activity limitations and other pain syndromes in canine OA.
The EDA measurement did not provide conclusive results in this clinical study. Invalidated outcome measures were observed in experimental conditions in rodents with a higher sympathetic tonus
, but our own group has reported positive results with its use in the experimental (Pond-Nuki) canine OA model
The GLM-enriched diet and the GLM extracts although not a reference treatment for OA were shown to exert a positive therapeutic effect on the clinical signs of dog OA
[14, 38]. Although a placebo-controlled trial would have been favored, ethical issues precluded a parallel comparison over 60 days between GLM- and placebo-treated dogs. Therefore, only a longitudinal one-way crossover design was included in the experimental design using the dogs as their own control. The anticipated effect of the GLM-diet was weak
[14, 38]. We did not know how much difference should be seen after two months of giving GLM. In addition, we observed slight improvement from D0 to D30 for CSOM, and MA seemed to be better during P2 (D16 to D29) two weeks after changing the home food for the control diet. Previous studies reported better owner-assessed pain in OA dogs with diet change
[39, 40]. Altogether, it is possible that the changes were not resulting from the GLM-diet but might be representing a trend over time caused by the diet changes
. Some might argue that PVF was not a good indicator of pain (or, at least claim that PVF is less sensitive than vertical impulse for hip dysplasia condition). As other critic in the present study, we could mention the fact that the other methods, i.e. MFQ and EDA, did not detect any treatment effect over the GLM-diet period. However, the sensitivity of MFQ and EDA was not previously investigated in other OA related-pain study in clinical condition, whereas the vertical ground reaction forces, such as PVF, have already proven their ability to detect change with NSAIDs treatment