Drug development process
Discovery
Many thousands of new chemical compounds will be created and tested to identify those that have potential. These go into a pre-clinical phase of laboratory and animal testing before being given a clinical trials authorisation that allows them to be tested in humans. There is a very high drop out rate at this stage; fewer than 1% of all the compounds that are made ever progress to testing in humans.
Once permission has been given for a compound to be tested in humans, it goes through three different clinical testing phases.
Phase I
The first step in testing a new drug is to determine its safety in a small number of healthy volunteers. This stage helps researchers understand some aspects of how it works and establishes the likely dose required.
Phase II
If the treatment proves to be safe, studies begin to determine the effectiveness of the drug in people with the condition to be treated. These studies may last several months or years and involve larger numbers of people, perhaps one or two hundred. The study is 'controlled' – that is the drug is compared with the standard treatment or placebo (dummy treatment), 'double-blind' – that is neither the investigators nor the participants know which treatment they are receiving, and 'randomised' – that is participants will be randomly allocated to receive active treatment or placebo.
Phase III
If a drug shows effectiveness, a larger study is conducted in hundreds of people. These clinical trials take place at different locations (multi-centre) and across several countries and may last several years. These studies allow researchers to more accurately assess the potential of the new drug in a wider range of people and compare it to existing treatments.
Regulation of new drugs
Data from all of these three phases is presented to the regulatory authorities (in the UK this is the MHRA - Medicines and Healthcare products Regulatory Agency or the EMEA - European Medicines Agency). If the authorities are satisfied that the new medicine is effective, safe and meets manufacturing quality standards, a marketing authorisation or licence is issued.
Once a new medicine has been licensed, there may still be one final hurdle. Set up to help eliminate post code lottery prescribing, NICE (National Institute for Health and Clinical Excellence) for England and Wales and the SMC (Scottish Medicines Consortium) for Scotland appraise certain new medicines and will look at issues such as cost effectiveness of the new treatment. The NHS is legally obliged to fund medicines recommended by NICE or SMC. The reverse also holds true - if NICE or SMC do not approve a new medicine, then primary care trusts are not required to provide funding for it.
Phase IV
Phase IV trials are carried out after a medicine has been granted a licence. These trials aim to:
- find new treatment uses
- compare the new medicine with other treatments
- determine effectiveness in a much wider range of patients
- assess long term benefits and safety
Yellow card scheme
The newly-licensed medicine will be carefully monitored for safety. All medicines have a patient information leaflet (PIL), which gives instructions on how the medicine should be used, and on its side effects. Rare side effects, for example those occurring in 1 in 10,000, may only become apparent once a medicine is in general use. In the UK, the Yellow Card Scheme is used by doctors and members of the public to report unwanted side effects of a medicine to the MHRA. If a suspected side effect is confirmed, depending on its severity, the PIL may be amended, extra warnings may be issued or the medicine may be withdrawn.
New uses of a medicine
A licence is granted for a specific use and in a particular group of people. However, once a medicine has been approved for one purpose, doctors are free to prescribe it for any other purpose that in their professional judgment is both safe and effective - this is described as off-label use. In general use, new treatment areas may emerge or different categories of patients may be defined. In order to promote these new treatment areas, a pharmaceutical company will need to conduct further clinical trials and present new data to the regulatory authorities in order to extend the current licence.
