The Golden Retr iever Lifetime Study: Assessing factors associated with owner compliance after the first year of enrollment

Abstract Background The Golden Retriever Lifetime Study (GRLS) is one of the largest canine cohort studies undertaken in the United States to date. This study design allows for evaluation of multiple exposures and outcomes throughout the lifetime of each dog, but relies on participants to comply with study requirements over a long period of time. Failure to do so can lead to biased reporting of results. Objectives To examine factors associated with dog owner compliance for GRLS. Animals Golden Retrievers (n = 3044) whose owners elected to participate in GRLS. Methods Prospective, cohort study. A logistic regression model was constructed to examine associations between data collected at the time of initial enrollment in GRLS and the outcome of failure to fulfill all study obligations at the end of the first year after enrollment in GRLS. Results There were 192 (6.3%) owners who did not comply with study requirements 1 year after enrollment. Owners of dogs without a record of vaccination had nearly 4 times higher odds (adjusted OR: 3.7, 95% CI: 1.5, 9.2) of being noncompliant than owners of vaccinated dogs and owners of dogs that slept in the garage had nearly 6 times higher odds (adjusted OR: 5.7, 95% CI: 1.9, 17.0) of being noncompliant than owners of dogs that slept in their bedroom. Conclusions and Clinical Importance Survey questions about a dog's sleeping location at night and vaccination status are important indicators of an owner's odds of compliance in a prospective study. Use of similar questions during enrollment in cohort studies might help to predict owner compliance that can aid in subject selection.


| INTRODUCTION
Prospective cohort studies like the Framingham Heart Study and the Nurses' Health Study have proven to be valuable for collecting a large amount of epidemiological data about human populations over an extended period of time. [1][2][3] Longitudinal cohort studies are less commonly utilized in veterinary medicine than in human medicine, but the use of this type of study can be valuable for investigating the complicated relationships between genetic and environmental exposures and disease outcomes within a dog population. In fact, genetic variation is reduced within dog breeds, making disease mapping within a single dog breed more efficient as compared to the use of the same technique in humans. [4][5][6] Furthermore, the canine spontaneous tumor model is ideal for furthering human cancer research because (a) dogs spontaneously develop tumors, which are similar to human tumors; (b) more dogs than people are diagnosed with cancer each year; and (c) dogs age more quickly than people and therefore have an accelerated rate of disease progression. 4,5 The Golden Retriever Lifetime Study (GRLS), predicted to be a 15-year cohort study of more than 3000 Golden Retrievers, is currently being conducted by Morris Animal Foundation. 7 The primary aim of GRLS is to identify risk factors for, and incidence of, common cancers in Golden Retrievers, but information about many other aspects of health and lifestyle can be evaluated within the framework of GRLS. Similarly, a large amount of health and lifestyle of dogs' data are being collected about Labrador Retrievers in the United Kingdom through Dogslife, a web-based longitudinal study. 8 Another largescale project currently enrolling participants is the Dog Aging Project, which is collecting health and lifestyle data about dogs of all breeds in the United States. 9 Studies such as these involve a large investment of resources, so efforts must be implemented to achieve the greatest success possible by recruiting a large subject pool with owners likely to comply with study protocols throughout their dog's lifetime.
Recruitment, retention, and compliance, especially with regard to adherence to timelines, have all been challenges for Dogslife. 10 Without past research on strategies for owner recruitment and selection for large longitudinal studies involving dogs and their owners, it is important to gain a better understanding of what factors affect owner compliance as maximizing compliance will improve both the economics of study resource use and the likelihood of study success through efficient data generation. Therefore, the purpose of this study was to examine factors associated with dog owner compliance at their second study visit (1 year after enrollment in GRLS).

| Overview
All 3044 dogs enrolled in GRLS were included in this study. A logistic regression model was constructed with the primary endpoint being failure to fulfill research obligations at the end of the first year after enrollment in GRLS. Data collected from the owner at the time of enrollment in GRLS were used to examine associations with the outcome of non-compliance.

| Study design and compliance
Enrollment into GRLS was an owner-driven process that has been described previously. 7 Briefly, owners of Golden retriever dogs less than 2 years of age with at least a 2 generation purebred pedigree who were free from known chronic diseases living in the continental United States were recruited through the Morris Animal Foundation website, social media, and word of mouth. Owners were asked to complete a survey and take their dog to a veterinarian at the time of enrollment and each year after enrollment throughout the dog's lifetime. Contact information collected from the owners included their email and mailing addresses as well as their phone number. No direct questions about the owner were included in the survey, rather the survey contained questions about their dog's health and lifestyle (activity level, sleeping habits, etc.). Additionally, veterinarians were asked to complete an annual survey after each routine visit and submit samples collected at the time of the visit, including blood, urine, hair, toenail clippings, and feces to a biorepository for long-term storage. 7 Owners could begin the annual study processes 90 days before their enrollment anniversary date and had about 6 months after that date to fully complete the requirements. A time-structured reminder protocol that utilized email, phone, and postcard reminders was

| Data collection and analysis
Data collected at the time of enrollment in GRLS were used for this study. Most variables were analyzed based on individual survey questions (eg, sex, age), but individual behavior-related questions were combined to form composite scores for behavior variables (eg, ownerdirected aggression). Composite scores were calculated using a method outlined in the Canine Behavioral Assessment and Research Questionnaire (C-BARQ). [11][12][13] Lower composite scores were favorable for all behavior variables except trainability. Categorical variables were collapsed to facilitate analysis. Composite behavior scores, activity level, walk frequency, and aerobic activity frequency were dichotomized and sleeping location was categorized (Table 1).
Variables included in the modeling approach for owner noncompliance were the dog's sex and age at enrollment, geographi-

| Description of population
The initial GRLS population consisted of 3044 dogs. Nine dogs died during year 1 and were removed from the data set. Thus, there were 3035 dog owners included in this study (Table 1). Of these owners,

| Logistic regression model
Of the 36 variables analyzed using univariable logistic regression models, 20 exposure variables were included in the initial Although Oversampling owners predicted to be noncompliant would potentially avoid bias that would be introduced by simply excluding potentially noncompliant owners altogether.
Another strategy that could increase owner compliance is the use of incentives, such as rewards or gifts, being given at the completion of the annual survey and veterinary visit or prepaid cash incentives sent with the reminder in advance of the due date for the annual survey. However, the use of such incentives in longitudinal studies has been shown to be variably effective and can disproportionately attract different types of respondents. 14,15 In addition, the use of incentives with large study populations can be cost prohibitive.

CONFLICT OF INTEREST DECLARATION
Authors declare no conflict of interest.

OFF-LABEL ANTIMICROBIAL DECLARATION
Authors declare no off-label use of antimicrobials.

INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) OR OTHER APPROVAL DECLARATION
Authors declare no IACUC or other approval was needed.

HUMAN ETHICS APPROVAL DECLARATION
Authors declare human ethics approval was not needed for this study.