Conduct, Oversight, and Ethical Considerations of Clinical Trials in Companion Animals with Cancer: Report of a Workshop on Best Practice Recommendations

Abstract

Development of effective and safe treatments for companion animals with cancer requires the collaboration of numerous animal health professionals and the full engagement of animal owners. Establishing ‘Best Practice Recommendations’ for clinical trials in veterinary oncology represents an important step toward meeting the goal of rigorous clinical trial design and conduct that is required to establish valid evidence. Likewise, optimizing patient welfare and owner education and advocacy is crucial to meet the unique ethical obligations to both owners and animals enrolled in these clinical trials and to ensure trust in the team conducting the research. To date, ‘Best Practice Recommendations’ for clinical trial conduct have not been reported for veterinary oncology. This document summarizes the consensus of a workshop held in November, 2014 to identify relevant ethical principles and to ensure responsible conduct of clinical research in companion animals with cancer. It is intended as a working document that will be updated as advances in science and ethical considerations require. To the extent possible, existing guidelines for the conduct and oversight of clinical trials in humans have been adapted for veterinary trials to avoid duplicative effort and to facilitate integration of clinical trials such that translational research with benefits for both companion animals and humans are encouraged.

Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

“…These cases of cancer in dogs themselves require treatment, in addition these spontaneous cancers in dogs represent effective models for the human disease equivalent [ 8 ]. Although developing new treatments in companion animals with naturally occurring disease is less contentious than inducing disease in experimental animals, ethical concerns with regards to the treatment of individuals enrolled on studies and gaining informed consent from owners remain [ 9 ].…”

Companion canines: an under-utilised model to aid in translating anti-metastatics to the clinic

“…phase II) clinical trials also occur in human medicine, however successful phase II human trials more often lead to randomized phase III trials compared to veterinary medicine, where historically such large trials are less common. As a result, there is an increasing awareness of the need to establish rigorous, standardized veterinary clinical trial designs to ensure valid results are obtained, and to this end workshops have been set up to establish 'Best Practice Recommendations' [20]. One example of this increased standardization and rigour is the Comparative Oncology Trials Consortium, which is part of The National Cancer Institute in the USA [21].…”

“…Funding veterinary research for companion animals can be challenging. It is important to appreciate that whilst they are less expensive than human clinical trials, canine oncology clinical trials are significantly more costly than pre-clinical trials in mice [20]. There are also logistical difficulties in collecting 'fresh' versus formalin-fixed canine tumour specimens.…”

Canine cancer immunotherapy studies: linking mouse and human

“…Although conventional therapies are typically offered, and ‘standard of care’ approaches are recommended, owners frequently elect experimental therapies for their dogs (including participation in clinical trials) when there is no current ‘standard of care’ for that tumor type, or for altruistic reasons, or due to financial limitations. In veterinary medicine, financial incentives to participate in clinical trials are not considered to be unethical or coercive, since those clinical trials frequently include ‘standard of care’ human cancer therapies as the backbone of therapy in addition to an investigational agent [65]. …”

“…It is currently estimated that researchers are conducting hundreds of clinical trials on dogs and cats across the world (for all indications), and canine clinical trials are generally viewed as 1 to 2 orders of magnitude less expensive than human trials (but correspondingly 10–100 fold more expensive than rodent experiments) [65, 96]. In addition, as with humans, accrual to trials may be unpredictable, and results especially given the prevalence of trials with non-randomized cohorts may be ambiguous.…”