Large animal models: non-human primates
Prior to clinical trials, candidate products are assessed in “Pre-clinical trials”. This phrase is used to describe both the in vitro and in vivo assessment of the compound prior to use in humans.
In vivo assessment is performed to assess the relative safety and toxicology of the product in target organs as well as determining appropriate doses for use in humans. This assessment is performed in a rodent species and at least one non-rodent species, typically dogs, pigs or nonhuman primates. The latter is more commonly used when the immunological response is important e.g. in vaccine and infectious disease studies.
Successful compounds will then be assessed in human clinical trials. There are four phases of clinical trial; Phases I to IV. Phase I determines the safety of the compound in a small number of healthy humans; Phase II primarily determines the safety in several hundred afflicted humans; Phase III assesses the safety, efficacy and effectiveness in several thousand patients; and Phase IV assesses the safety post-market.
- For rare diseases, or diseases where outbreaks are sporadic or unpredictable, or in cases where the route of infection is not the naturally occurring route of the infection, Phase III trials are difficult to undertake in a time appropriate manner.
- In the UK, NHP models are only available for Ebola, Marburg, Plague and Q Fever. They exist, but are not available in the UK, for: Chikungunya, CCHF, Dengue, Hantavirus, Lassa, MERS, Nipah and Rift Valley Fever.
Re: Phase III trials bottleneck: The FDA has developed new guidelines to facilitate the use of well-characterised, appropriate animal models to replace Phase III clinical trials. The EMA are following a similar trajectory. To date, nonhuman primate efficacy data has been pivotal in the licensure of all seven of the products through the FDA’s “animal rule”.