**5.1. First in human studies**

The main purpose of the first in human clinical study (FIH) for a drug is to test that it is safe, meaning that subjects are monitored for signs of toxicity, especially those indicating risk of mortality or morbidity. Tolerability, the ability of a patient to use the drug for its intended indication, without unacceptable, non-life-threatening adverse events that would require discontinuation of treatment, is also an important consideration. Risk-to-benefit ratios are considered when determining the required tolerability and risks of toxicity; a drug for a life-saving, unmet clinical need, such as cancer, would be considered for approval even if it carries more risk than a drug for a self-limiting or non-life-threatening disease, such as the common cold. From the animal data discussed above, researchers have a good idea of the types of toxicity and at what exposures they may occur for a given drug, yet the first human study is critical in confirming the drug's potential for toxicity in a human. PK in a FIH is therefore very informative, telling us not just if toxicity occurs, but at what exposure that toxicity correlates with.
