Risk Management in Phase I Clinical Trials

Jorg Taubel
Richmond Research Institute

Introduction/Background & aims Phase I clinical trials, and particularly first-time-in-human (FTIH) trials are a key part of the drug development process. Phase I trials are the first instance at which a new medicinal product is administered to humans and involves a small group of patients or healthy volunteers. The purpose of a phase I trial is purely to assess the safety of a new product. This is in contrast with a phase II trial, which involves larger numbers of people, and seeks to establish the effectiveness of a new product.

Method/Summary of work Phase I clinical trials necessarily come with a significant risk. As this is the first time at which a product is used in humans, the precise on- and off-target effects of the product are not entirely predictable. In order to mitigate and minimise risk, the total amount of research on a given drug must be adequately and thoroughly considered before commencing a Phase I trial. This research will involve in vitro testing to establish effectiveness and proof of concept, followed by animal testing in order to examine effectiveness and safety. When producing a Phase I Clinical Trial protocol, researchers must consider data from in vitro testing, animal testing, and comparison to existing, similar products (such as drug compounds of the same chemical class).

Results/Discussion Often, Phase I Clinical Trials are designed by researchers who are more familiar with later phase clinical trials, in which safety profiles are better known, and risks are comparatively lower. This can be dangerous, particularly when the Phase I cohort is one with a particular disease, rather than being healthy individuals. Here we present a case study of a Phase I clinical trial of a gene editing therapy in a patient cohort. The trial had entirely predictable side effects related to clotting based on animal trial data, yet the protocol did not include risk management strategies to anticipate these side effects in a potentially fragile group of patients

Conclusion(s) To conclude, when phase I clinical trials are conducted in patient cohorts, risk management strategies should always consider all available pre-clinical data, and should include risk management strategies that equal or exceed similar studies in healthy volunteer cohorts.