In order to fully understand the benefits and risks of a new medicine a pharmaceutical company must undertake a range of clinical trials as part of its clinical development programme for a new medicine.
Clinical development programmes usually comprise four phases, with each phase conducted consecutively using the information collected in the previous phase. These phases, their primary purpose and typical clinical trial designs are outlined in the table below:
|Clinical development phase||Primary purpose||Typical clinical trial design||Typical number of trial participants|
|Phase I (1)||To test for preliminary safety and establish the optimal dose of the new medicine||Small numbers of healthy volunteers or sometimes patients. Initially low doses of the new medicine are given with doses increased overtime.||20-100|
|Phase II (2)||To test for safety and preliminary effectiveness of the new medicine in patients||All patients given the new medicine at the optimal dose.||100-300|
|Phase III (3)||To establish the safety and efficacy of the new medicine compared with the current medicine normally used in patients.
It is typically expected that there be at least two successful Phase III trials conducted.
|Half of the patients are given the new medicine (investigational group) at the optimal dose, with the other half given placebo and/or the current standard medicine (comparator or control group). Patients are randomly assigned to one of the two treatment arms.
They are commonly known as Randomised controlled trials (RCTs)
Sometimes these trials are ‘blinded’ (meaning that neither the patient nor their doctor knows what medicine each patient is getting), or ‘open-label’ (meaning that both the patient and their doctor know what treatment they are getting). Blinded trials are preferred as they avoid bias in assessing outcomes
|300-3000 or more depending on the disease|
|Phase IV (4)||To monitor for safety concerns in the public after the new medicine has been approved by the regulator for sale||Spontaneous reporting of safety issued by doctors when they use the treatment in any of their patients||NA|
The reliability of the results obtained from clinical trials is highly dependent on their design and conduct. Various aspects of clinical trial design and conduct can have a substantial negative effect on the reliability and relevance of clinical trial results, for example:
- short follow-up of patients
- use of early (so called ‘surrogate’) measures of benefit
- multiple analyses of the same trial
- cross over of patients from the control group to the investigational group
- enrolling patients that are different to those that will be treated in normal practice
- using different doses of the medicine than will be used in practice.
Last updated: 29 March 2016