Phase I

This phase involves a trial of the drug in a small group of people, who are usually healthy volunteers. The main objectives of this stage are to discover a safe dose of the drug and understand how it affects the human body, including any side effects.

The researchers will also consider the best means of administering the drug. For example, by pill or through an injection, and how frequently doses should be administered.

Phase II

If Phase I is successful, researchers can conduct a Phase II trial that involves a larger cohort of people. These people will usually have the medical condition that the drug is targeted at. Again, researchers are concerned with how the drug affects the body. With a larger sample size, differences based on people’s characteristics may start to become apparent. For example, age, gender, or ethnicity may influence the likelihood of experiencing side effects, as may lifestyle factors such as whether a person is overweight, a smoker, or regularly drinks alcohol.

The researchers will need to show that the drug has a positive effect on the medical condition, and gather data on how much of the drug needs to be given to achieve this improvement, in addition to adverse reactions.

Phase III

If Phase II is successful, researchers can conduct a much larger trial involving hundreds or even thousands of participants. The potential benefit of the new drug is measured using a control drug, such as an existing licensed treatment for the medical condition or a placebo.

The participants will not know whether they have received the new drug or the control drug, this is known as ‘blinding’. This is done to prevent the placebo effect and bias that might otherwise skew the data. Sometimes trials are ‘double-blinded’ which means that the researchers do not know whether the new drug or a control drug, is being used in a particular patient,  until after the data has been gathered and analysed.

If a Phase III trial is successful, an application for MA can be made.

Phase IV

If the MHRA gives the MA and the medicinal product is brought to market, Phase IV can begin. This stage of the research is focussed on developing knowledge about the effects of the drug on different types of people. It can be difficult to build a full picture of how it will affect an entire population in the preceding trials because, even if a few thousand people take part, the representation of specific groups might not be sufficiently high to flag issues. This is especially true where a combination of characteristics and lifestyle factors need to be considered in order to understand the risk of experiencing side effects.

Phase IV also looks at the long-term effects of using the drug, for example, whether it becomes less effective over time, whether it causes undocumented side effects, and whether the risk of known side effects increases.

Can the Phases Run Concurrently?

Reports on the different COVID-19 vaccines have attributed their fast development to the speeding up of the usual regulatory process, as well as other factors. Does this mean that the Phases I-IV were run concurrently? Or that any were skipped?

No, the speeding up that these reports refer to is about the examination of the resultant data and the applications themselves being fast-tracked. For example, Phase III data was passed to regulators for them to begin assessing before the trial was fully complete. This sped up the appraisal process, but the standards for declaring the vaccines safe and effectiveness remained the same.

© Life Science Law March 2021.