Designing the Future of Clinical Trials

For the first time in veterinary medicine, a published study proposes a detailed standardization of how a clinical trial’s results are reported, an innovation designed to increase understanding of the effectiveness of treatments and guide potential breakthroughs in medical care.  

Thierry Olivry, professor of immunodermatology at the NC State College of Veterinary Medicine, spearheaded the project and is the lead author of the study published in BMC Veterinary Research. The work offers a detailed core outcome set for clinical trials involving dogs with atopic dermatitis, a common canine allergic skin disease and Olivry’s research focus.

A core outcome set, commonly known as a COS in medical literature, suggests certain criteria a clinical trial should evaluate and the way therapeutic results are reported. A rise in the number of clinical trials conducted in human and animal medicine has resulted in numerous reporting formats and led to increasing calls to harmonize how data is evaluated. At the CVM, there’s an average of 25 trials happening at any given time.

“It’s an attempt to enhance the quality of reporting of clinical trials for a specific disease across the world,” said Olivry.

Olivry’s study suggests three common assessments for atopic dermatitis: veterinarian examination of skin lesions; an owner-reported assessment of behavior such as scratching, licking and biting; and an owner-reported evaluation of treatment effectiveness.

The COS then proposes evaluating each of those assessments on validated numbered scales and streamlines reporting a treatment’s impact. With this new COS, results are reported through percentages, for example, noting that 60 percent of dogs are normal after four weeks of treatment.

Previously, results of AD clinical trials have been reported in many different ways, said Olivry, making analyzing a drug’s overall effectiveness and comparing results with other studies challenging.

“With this COS, we will be able to effectively tell a pet owner that with this drug, 50 percent of dogs will end up normal. We could tell owners the chance of getting your dog better is 90 percent with this treatment,” said Olivry.

Prior to this COS, trial results were typically worded as, for example, 50 percent of dogs improving two grades on an arbitrary 10-grade scale.

Does that help you as a veterinarian?” said Olivry. “Does that help you as a pet owner? What does it mean clinically?

The new COS, strictly a recommendation and designed to evolve over time, was created to help veterinarians and pet owners make more informed treatment decisions through clearer information, Olivry said.

The information may also guide research approaches for future clinical trials, usually the first step to drug development and medical breakthroughs. Standardized clinical trial reporting benefits veterinary students as well, said Olivry. Professors will be able to better explain the comparative potency of treatments to veterinarians in training.

The atopic dermatitis COS was developed over two years and represents a consensus reached between veterinary dermatologists, atopic dog owners worldwide, animal health company representatives, veterinary journal editors and representatives from the largest agencies evaluating clinical trials for drug approval.

This COS — and a push for clinical trial standardization — has been a passion project for Olivry for more than two decades. One of the veterinary scales for rating skin lesions, the Canine Atopic Dermatitis Extent Severity Index, or CADESI, was developed at the CVM under Olivry’s leadership. The fourth version of the CADESI is used in most atopic dermatitis clinical trials today.

While at NC State, Olivry has been dedicated to investigating the mechanisms behind atopic dermatitis and itch, creating innovative approaches to treating a range of animal skin conditions.

One of the first clinical trials led by Olivry led to the approval of cyclosporine in the form of the drug Atopica offered by Elanco for treatment of canine atopic dermatitis. Most recently, Olivry and CVM colleague Bruce Hammerberg, professor of parasitology, pioneered the use of a new NC State-generated biologic targeting the allergic antibody IgE to delay relapses of clinical signs of atopic dermatitis.

Olivry said if researchers chose to follow the new COS, it could quickly shift the way AD clinical trials are reported.

“We are not recommending a small improvement,” said Olivry. “We want to create something that will clinically matter for years, if not decades.”

~Jordan Bartel/NC State Veterinary Medicine