Objective—To determine the sources and handlingof losses to follow-up (LTF) in parallel-group randomized clinical trials (RCTs).
Sample Population—63 parallel-group RCTs of > 24 hours' duration published from January 2000 through December 2005.
Procedures—Journals were hand searched for eligible reports. Details concerning the presence, cause, and amount of LTF; statistical handlingof data missingbecause of LTF; type of analyses performed; number of animals randomly allocated and analyzed; and the acknowledgement of the potential impact of LTF were recorded.
Results—In 81% (51/63) of trials, LTF were reported. In 80% (41/51) of those studies, losses in the analysis were ignored, and in only 18% (9/51) was the potential impact of LTF on study results acknowledged. Of the 47 studies in which sources of LTF were reported, 72% had loss of subjects because of investigator withdrawals, 30% because of deaths, and 26% because of owner withdrawals. Median loss of subjects for those studies was 12% because of investigator withdrawal (range, 2% to 52%), 8% because of death (1% to 28%), and 4% because of owner withdrawal (2% to 33%).
Conclusions and Clinical Relevance—Most RCTs had LTF, most of which were attributable to investigators removing randomly allocated animals from the study. In most studies, data from animal LTF were ignored and, therefore, only a subgroup of randomly allocated subjects was included in the data analysis. Most reports did not address the potential for a postrandomization selection bias associated with ignoring LTF and did not acknowledge the potential impact of the missingdata on their results.
Objective—To determine how selection bias (allocation bias) was controlled in published clinical trials.
Sample Population—97 parallel-group controlled clinical trials published from January 2000 through December 2005 in 12 peer-reviewed journals.
Procedures—Journals were hand searched to identify eligible reports. Details concerning allocation of animals to study groups, baseline characteristics of the groups, and the number of animals allocated to each group were recorded.
Results—Randomization was the stated method of allocating animals to groups in 87% of the reports, yet in only 11% of reports were both randomization of the group allocation process and concealment of the allocation sequence described. Studies reported as randomized were more likely to report baseline characteristics of the study groups for comparison than studies that did not report randomization (88% vs 54%). Studies in which baseline group characteristics were reported had more subjects allocated to each study group (median, 16) than those that did not (median, 11).
Conclusions and Clinical Relevance—Randomization was reported as the method of allocating study animals to groups in most publications, indicating that the potential power of randomization in controlling selection bias is appreciated by clinical investigators seeking to determine the efficacy of an intervention. However, in most reports, little corroborating information was included to support the claim. The absence of this information makes it difficult for practitioners to critically review the impact of bias on study results and make informed decisions regarding patients.
Objective—To investigate whether an accelerometer-based activity monitor could be used in pet dogs to differentiate among and delineate the amount of time spent in activities of differing intensity.
Procedures—For the first phase of the study, each dog (n = 104) wore an accelerometer-based activity monitor and was led through a series of standard activities (recumbency [sedentary], walking, and trotting). Receiver operating characteristic curves were generated to determine the optimal activity counts for predicting whether a dog was sedentary, walking, or trotting. For the second phase of the study, dogs (n = 99) wore an activity monitor on their collars continuously for 14 days at home; intensity of activity for each dog was classified by use of cut points determined on the basis of results obtained during the first phase of the study.
Results—Analysis of receiver operating characteristic curves indicated that there was 100% specificity and 100% sensitivity in distinguishing sedentary activity from walking activity and 92% specificity and 92% sensitivity in distinguishing trotting activity from walking activity. Analysis of data collected during the 14-day period at home indicated that dogs were sedentary most of the time (median, 87%; range, 65% to 95%).
Conclusions and Clinical Relevance—Counts recorded by an accelerometer-based activity monitor could be used to discriminate effectively among standardized activities in pet dogs. There is potential for use of the method to improve the ability of clinicians and researchers to accurately estimate a pet dog's daily energy requirement.
Objective—To determine the prevalence of exposure to canine influenza virus (CIV) in dogs in a metropolitan animal shelter.
Procedures—Dogs were randomly selected from the canine shelter population. A physical examination was performed, and blood samples were obtained and submitted for serologic testing for the detection of antibodies against CIV. Logistic regression analysis was performed to evaluate the association of factors (body condition score, nasal discharge, coughing, rectal temperature, number of days in the shelter, and relinquished vs stray) with positive results.
Results—31 of 74 (42%) dogs were seropositive for antibodies against CIV. Positive serologic test results were detected for 6 of 39 (15%) dogs housed in the shelter for ≤ 7 days and for 25 of 35 (71%) dogs housed in the shelter for ≥ 8 days. Number of days in the shelter was the only factor significantly associated with positive serologic test results. For every 3 days in the shelter, the odds of a positive serologic test result increased significantly by 2.2 (95% confidence interval, 1.5 to 3.4).
Conclusions and Clinical Relevance—Analysis of the results suggested that more dogs were exposed to CIV in the shelter than were exposed in the urban environment. This has serious implications for design and management of animal shelters.
Objective—To determine whether an activity monitor (AM) could be used to detect changes in activity in dogs with osteoarthritis treated with carprofen or a placebo.
Design—Randomized controlled trial.
Animals—70 dogs with no clinically important abnormalities other than osteoarthritis for which they were not currently being treated.
Procedures—Dogs wore an AM continuously for 21 days. On days 8 through 21, the dogs were treated with carprofen (n = 35) or a placebo (35). Total activity counts for days 1 through 7 (baseline) were compared with total activity counts for days 15 through 21 (endpoint). The change in total activity count from baseline to endpoint was assessed within each treatment group as well as between groups. Linear regression analysis was performed to test for an association between treatment and percentage change in activity counts while controlling for other variables.
Results—For placebo-treated dogs, median baseline total activity count was not significantly different from median endpoint total activity count (1,378,408 vs 1,310,112, respectively). For dogs receiving carprofen, there was a significant increase in median activity count from baseline to endpoint (1,276,427 vs 1,374,133). When age and baseline activity counts were controlled for, dogs in the carpofen-treated group had a 20% increase in activity counts, compared with placebo-treated dogs (95% confidence interval, 10% to 26%).
Conclusions and Clinical Relevance—Results suggested that the AM used in the present study may be a valid outcome assessment tool for documenting improved activity associated with treatment in dogs with osteoarthritis.
Objective—To determine the optimal method for use of the Canine Brief Pain Inventory (CBPI) to quantitate responses of dogs with osteoarthritis to treatment with carprofen or placebo.
Animals—150 dogs with osteoarthritis.
Procedures—Data were analyzed from 2 studies with identical protocols in which owner-completed CBPIs were used. Treatment for each dog was classified as a success or failure by comparing the pain severity score (PSS) and pain interference score (PIS) on day 0 (baseline) with those on day 14. Treatment success or failure was defined on the basis of various combinations of reduction in the 2 scores when inclusion criteria were set as a PSS and PIS ≥ 1, 2, or 3 at baseline. Statistical analyses were performed to select the definition of treatment success that had the greatest statistical power to detect differences between carprofen and placebo treatments.
Results—Defining treatment success as a reduction of ≥ 1 in PSS and ≥ 2 in PIS in each dog had consistently robust power. Power was 62.8% in the population that included only dogs with baseline scores ≥ 2 and 64.7% in the population that included only dogs with baseline scores ≥ 3.
Conclusions and Clinical Relevance—The CBPI had robust statistical power to evaluate the treatment effect of carprofen in dogs with osteoarthritis when protocol success criteria were predefined as a reduction ≥ 1 in PIS and ≥ 2 in PSS. Results indicated the CBPI can be used as an outcome measure in clinical trials to evaluate new pain treatments when it is desirable to evaluate success in individual dogs rather than overall mean or median scores in a test population.
Objective—To evaluate the effect of signalment and body conformation on activity monitoring in companion dogs.
Animals—104 companion dogs.
Procedures—While wearing an activity monitor, each dog was led through a series of standard activities: lying down, walking laps, trotting laps, and trotting up and down stairs. Linear regression analysis was used to determine which signalment and body conformation factors were associated with activity counts.
Results—There was no significant effect of signalment or body conformation on activity counts when dogs were lying down, walking laps, and trotting laps. However, when dogs were trotting up and down stairs, there was a significant effect of age and body weight such that, for every 1-kg increase in body weight, there was a 1.7% (95% confidence interval, 1.1% to 2.4%) decrease in activity counts and for every 1-year increase in age, there was a 4.2% (95% confidence interval, 1.4% to 6.9%) decrease in activity counts.
Conclusions and Clinical Relevance—When activity was well controlled, there was no significant effect of signalment or body conformation on activity counts recorded by the activity monitor. However, when activity was less controlled, older dogs and larger dogs had lower activity counts than younger and smaller dogs. The wide range in body conformation (eg, limb or body length) among dogs did not appear to significantly impact the activity counts recorded by the monitor, but age and body weight did and must be considered in analysis of data collected from the monitors.
Objective—To determine by use of an accelerometer the sampling interval that has the least variable total activity counts from one week to the next in companion (ie, nonlaboratory) dogs.
Procedures—Dogs wore an accelerometer continuously for 2 weeks. Between-dog and within-dog day-to-day variability in total activity counts were evaluated. The changes in counts between week 1 and week 2 were compared for weekdays, weekends, and full weeks.
Results—Significant between-dog variability in total activity counts was detected. Within dogs, there was significant day-to-day variability, with highest counts recorded on weekends. In comparison of data from the first week with data from the second week, the greatest differences were in weekend counts (median difference, 21%; range, 0% to 154%) and the smallest differences were in full 7-day counts (median difference, 10%; range, 0% to 74%). Comparison of weekday counts revealed a median change of 12% (range, 0% to 104%).
Conclusions and Clinical Relevance—Significant between-dog variability in total daily activity counts was detected. Within dogs, a full 7-day comparison of total activity counts from one week to the next provided the least variable estimate of the dogs' activity. For dogs in their home environment, the activity monitor may be most useful in following changes in activity over time. For dogs that have no change in routine according to the owner's report, the least variable estimates of activity can be collected by comparing activity in 7-day intervals.
OBJECTIVE To describe development and initial psychometric testing of the Canine Symptom Assessment Scale (CSAS), a multidimensional owner-reported questionnaire instrument, in a population of dogs with solid tumors enrolled in clinical trials.
DESIGN Questionnaire development and validation study.
ANIMALS 238 client-owned dogs with solid tumors.
PROCEDURES A 14-symptom questionnaire was developed. Symptoms were defined as subjective physical disturbances dogs experienced during the course of daily living as assessed through proxy reports of pet owners. For each symptom, owners reported frequency and severity of the symptom and extent of distress caused by the symptom for the dog and the owner. Questionnaire content, symptom prevalence and dimensionality, internal consistency, and factor structure were examined. Construct and criterion validity were examined via comparison with the Canine Brief Pain Inventory (CBPI).
RESULTS Symptom prevalence was high, with pain and lack of energy reported in most dogs. Severity, versus frequency, was most highly correlated with both dog and owner distress. Two symptoms were removed from consideration because of poor performance. Analysis of the remaining 12 symptoms revealed that they could be grouped into 3 factors: malaise, anxiety, and digestive upset. The CSAS factor and total scores demonstrated predictable relationships with quality of life and pain scores as measured by the CBPI, including a significant association between increasing symptom burden and decreasing quality of life. The Cronbach α for the CSAS was 0.77.
CONCLUSIONS AND CLINICAL RELEVANCE The 12-item CSAS was a psychometrically sound owner-reported instrument for assessment of symptom frequency and characteristics in client-owned dogs with solid tumors. Potential applications include clinical research and practice settings.
OBJECTIVE To describe the learning curve for veterinary surgery residents performing hemilaminectomy surgeries in dogs.
DESIGN Retrospective case review and learning curve evaluation.
SAMPLE 13 individuals who completed a 3-year surgery residency program at a university teaching hospital and who had no prior experience performing hemilaminectomies.
PROCEDURES The 13 residents performed hemilaminectomies on 399 dogs between July 2006 and July 2013. Medical records were reviewed, and operative time was recorded. Data were examined with a linear mixed-effects model to quantify fixed and random effects, a curve-fitting technique to find the best-fit curve, and a segmented 2-phase linear model to describe the domains and learning rates for 2 phases of learning.
RESULTS The linear mixed-effects model indicated that increasing patient body weight and increasing surgical complexity (graded on the basis of number and contiguity of hemilaminectomy sites) were associated with longer operative times and that increasing exposure number was associated with shorter operative times. The monoexponential and biexponential parametric curves were of similar quality in modeling the data. The segmented 2-phase linear model showed an early phase of learning during which operative time decreased rapidly and a late phase when operative time decreased more gradually.
CONCLUSIONS AND CLINICAL RELEVANCE The learning curve for the residents suggested that for early exposures, instruction in the form of direct supervision provided substantial benefit. By the tenth exposure, the benefit of instruction diminished and ongoing improvement was primarily a result of refinement. If validated by further study, this understanding of a 2-phase learning curve may inform the design of training programs in veterinary surgery.