The main aim of a phase 3 trial is to provide large-scale data on efficacy of a drug treatment in target populations. They also enable safety data to be collected on a greater number of patients.
Because of the need to include large numbers of patients, phase 3 trials are typically multicentre (recruit at several sites) and often international. The size of a phase 3 trial is determined by statistical calculations of the number of patients who will need to be treated in order to provide statistically significant data on efficacy.
In terms of trial design, phase 3 trials of antibiotics usually involve a comparison between a new drug and a currently recommended treatment. The aim is generally to demonstrate ‘non-inferiority’ – that the efficacy is no lower than that of the currently recommended treatment, within a pre-specified margin (typically 10%).
A further important consideration is the endpoint to be used in a trial – the measure to be used to assess a drug’s efficacy. An endpoint can be clinical (based on a patient’s symptoms and signs) or microbiological (based on the presence or absence of bacteria at a certain point after treatment). Generally, a trial will have a single primary endpoint, relating to efficacy, and several secondary endpoints, which might be other ways of assessing efficacy or relate to safety or tolerability.
It is vital that all aspects of trial design are agreed in advance with regulatory authorities, as data from phase 3 trials will be central to drug-licensing applications.
The larger size of phase 3 studies means that it may also be possible to study a drug’s effect on particular pathogens (such as those with a particular resistance profile) or on different population groups (sub-group analysis). Data analysis plans must be agreed in advance of a study.
Phase 3 trials also provide scope for additional pharmacokinetic/pharmacodynamic (PK/PD) studies so that the metabolism of a drug and its action on pathogens can be better understood.