by Dale M. Cooper, DVM, MS, DACLAM
When people are suffering or dying from disease, there’s a powerful incentive to move new treatments through the pipeline as quickly as possible. But while speed is important, it cannot come at the expense of quality and compliance. The care of animals involved in preclinical safety studies is a compliance expectation by several regulatory bodies, and because the animal is the test system, good animal welfare is also good science.
Establishing humane endpoints before a study begins is the right thing to do. It is an ethical expectation of the public, and it makes good business sense; humane endpoints can reveal crucial insights on a drug candidate’s mechanism of action and strengthen the rationale for a go/no-go decision.
Identifying humane endpoints and including them in a study design can be a challenge. The goal is to set criteria that meet study objectives while ending the study as early as possible to avoid or stop unrelieved pain or distress in an animal. That goal aligns with guidance from the National Institute of Health (NIH) Office of Animal Welfare.1 A study that carries on past those criteria is neither humane nor scientifically justified.
To ensure a study is designed with humane endpoints in mind, here are six steps to consider when working with a CRO:
- Make sure the toxicologist understands the drug candidate’s mechanism of action, class effects, and/or intended therapeutic use.
- Partner with the toxicologist involved in the study to review the literature and other data on mortality, clinical signs, clinical pathology, or histological changes. Together you may be able to identify a biomarker of toxicity and efficacy.
- Get insight and advice from a laboratory animal veterinarian on how a given species may respond to a drug candidate based on mechanism of action, clinical signs, and interim diagnostics. With this input, you may be able to design a better study.
- Consult with a pathologist to learn how to better detect significant toxicity, use other data to identify the maximum tolerated dose, and minimize adverse clinical signs.
- Connect with the Institutional Animal Care and Use Committee (IACUC)—which may be a separate conversation from that with the veterinarian—to make sure you are clear on the expected endpoints and what actions to take if adverse effects occur.
- Talk with the approving agency and the clinicians who will conduct future human trials on the drug candidate so everyone is aware of the critical factors of success (or failure).
Humane endpoints are usually unique from study to study. Establishing them takes time and careful effort—more collaboration, more pre-trial analysis, and more monitoring and use of technology. But the outcome is worthwhile in terms of better data, better decisions, and better treatment of study animals.
Dale M. Cooper, DVM, MS, DCLAM, is Director of Clinical Medicine and Attending Veterinarian at MPI Research. Learn more about how MPI Research is commitment to animal welfare and humane endpoints in preclinical development by contacting us at firstname.lastname@example.org.
1 OLAW/ARENA (Office of Laboratory Animal Welfare/Applied Research Ethics National Association) Institutional Animal Care and Use Committee Guidebook. 2nd ed. Bethesda: National Institutes of Health; 2002