Real World Evidence in Veterinary Medicine: the Golden Retriever Lifetime Study

In veterinary cancer care, it’s common to come across tough clinical questions where there is no known right answer.

There has been a growing focus on analyzing data gathered from routine care, leading to a new field called real world evidence (RWE). The RWE approaches being used in human oncology can also be applied in the veterinary space.

Morris Animal Foundation’s Golden Retriever Lifetime Study is the most extensive investigation ever undertaken in veterinary medicine. With data on more than 3,000 Golden Retrievers throughout their lives, the study is identifying nutritional, genetic, and environmental risk factors for cancer and other important diseases in dogs. The results will provide comprehensive data on diseases and other health challenges in veterinary medicine.

Dr. Page is a Professor & Director at Flint Animal Cancer Center and Principal Investigator for the Golden Retriever Lifetime Study. Dr. Kiehl is the Senior Director of Science and Communications for Morris Animal Foundation.  

How and why did the Golden Retriever Lifetime Study (GRLS) come into being?

Twelve years ago, we realized a significant paradigm shift needed to happen if the veterinary community was going to address early detection of canine cancer.

Determining research methods, such as sample size, methodology, etc. took about four years, and enrollment began in 2012.

Social media networks helped us realize a robust enrollment -- leading to an enrollment of up to 50-100 Goldens a month. Being able to get the word out for studies like this is key!

Golden Retriever owners are extremely passionate about their dogs.

What are the mechanics of this study?

The study aimed to quantify fully, for the first time, the incidence of certain kinds of diseases (specifically cancers) in Golden Retrievers. Most registries don’t have the advantage of having a common denominator.

Total enrollment was 3,044 dogs, with 100 withdrawn and 221 deceased.

The study focuses on four cancers:

• Lymphoma
• Osteosarcoma
• Hemangiosarcoma
• High-grade mast cell tumors

The study subsidized biopsies to make as much information as possible available. Biopsy samples are saved, stored, and rechecked/adjudicated for accuracy.

Dogs had to fulfill certain criteria: a traceable pedigree, age between 18-24 months, owner and veterinarian check-in questionnaires, available samples if cancer was detected.

These questionnaires are exceptionally detailed, showing tons of info about the environments, histories, and lifestyles of the dogs. They took several years to develop, resulting in an estimated 5 million data points.

Primary endpoints were diagnoses of the four cancers mentioned above. Secondary endpoints were recurrence of cancer, mortality, hypothyroidism, allergies, heart failure, epilepsy, hip dysplasia, renal failure, any other condition with 4% or greater incidence. We extrapolated expectations from a 1998 Golden Retriever study.

What did you find in regards to cancer diagnoses? Any interesting trends?

Cancer outcomes:

• 56 lymphoma, 45 deaths
• 5 MCT, 3 deaths
• 57 hemangiosarcoma, 46 deaths
• 5 osteosarcoma, 1 death

About 50-60% of deaths in the study were due to cancer. It’s important to note that they were generally young dogs.

We predict that out of an anticipated 500 lifetime diagnoses, about 50% will be hemangiosarcoma.

What’s the percentage of people who seek out oncologic care?

It’s important to acknowledge that the owners of the Goldens Retrievers enrolled in this study are by and large well-to-do and extremely invested, both emotionally and financially, in the well-being of their pets.

There isn’t data for this question on the whole - but it’s an interesting question to approach in the future, especially to help figure out how to talk to pet parents about their dog’s treatment. It would also be interesting to see how parents with pet insurance vs. those without treat their pets.

Many parents don’t see specialists when maybe they should. Many general practitioners are comfortable quickly diagnosing things like lymphoma and performing CHOP. To this today, there’s not a lot of information circulating on the importance of seeing specialists.

Can you tell us a little about projects currently in progress using study samples and data?

We have several nested studies in progress. One nested study includes heart disease and taurine deficiency. Another looks at potential genetic links to obesity in Golden Retrievers, similar to how Labrador Retrievers tend towards obesity. There is also a study for gut microbiome differences between lean and obese dogs,

It’s a rolling process to submit requests. We have a lot of data and we’d love to use it. There are so many other questions that we could be looking at. If people have something they’d like to investigate, we are happy to entertain ideas.

How do people get in touch with you for future projects?

• Apply for a Grant: to find all the information specifically related to the GRLS call including, Guidelines, Rubric, Sample Infographic, etc.
• GRLS Project Inquiry Form: to first submit a project inquiry to be considered for an invitation to submit a full proposal.
• Data Commons: While Data Commons is separate from the rolling call itself, it is a great resource for GRLS applicants.

Q&A

How much longer is the study funded?

The hope is for it to go on another 5-8 years.

We would like to collect data on the surviving dogs, genotyping every dog in the study with low and high density sequencing - well-phenotyped patients, along with susceptibility markers or abnormalities in genomic DNA.

This data will be available via open access.

What would be the next breed that you would study if you could fund another lifetime study?

It depends on what we want to look at. If it’s valve disease, it would be small dogs.

There are significant costs involved. As we learn how to handle this data, we are figuring out new ways to collect big data sets more efficiently.

The study will cost $32 million by the time it is done. Around $24 million has been raised, with ~$18-19 million raised by donations There’s been institutional partnerships that have been invaluable.

Who is typically more compliant with data entry? Clinicians or owners?

Owners! Owners are vastly more interested in what their dogs are doing and they get it done right away.

Our compliance number is around 83-84%, which include both clinicians and owners.

We have 2,000 veterinarians and 3,000 dogs in the study. Many of them have multiple dogs. One veterinarian has 18 dogs for the study.  

Please visit the Morris Animal Foundation website for more information about the Golden Retriever Lifetime Study.