In the early stages of research, we investigate thousands of compounds for their potential to become a new medicine. Only a small number succeed because of the demanding selection process, which centres on safety and how well the medicine works.
When we identify a potential new medicine we conduct a range of pre-clinical studies, including animal research, to gain essential information about how it might work to treat the disease, how it might be distributed and metabolised in the body, and what possible side effects it may have. We aim to eliminate, as early as possible in the process, candidate drugs with unacceptable benefit/risk profiles. In addition, safety data from animal studies are required by regulatory authorities around the world before the required permission is granted to begin testing in humans (clinical trials).
Safety data are then collected and evaluated continuously throughout a candidate drug’s clinical development. For some studies, in addition to our own internal resources, we also use independent external safety data monitoring boards to further strengthen the safety evaluation process.
Once we have satisfied ourselves that a new medicine has an acceptable benefit/risk profile, we submit comprehensive information, including clinical trial data, to the regulatory authorities responsible for approving medicines in each country or region in which we want to launch the product.
Regulatory approval to market a medicine will only be given if, after rigorous review of our submissions, the authorities decide that the medicine’s benefits in treating a particular disease outweigh its risks.
What happens after you have launched a new medicine?
After launch, we continue to monitor the use of all our medicines for any side effects not identified during the development process. This is known as pharmacovigilance and is core to our ongoing responsibility to patients.
Though extensive, clinical trials cannot replicate the complete range of patient circumstances that exist among much larger and more diverse patient populations encountered after launch. Rare side effects can often be identified only after a medicine has been launched and used in far greater numbers of patients and over longer periods of time.
We have comprehensive and rigorous pharmacovigilance systems in place for detecting and rapidly evaluating such effects, including mechanisms for highlighting those that require immediate attention.
We also work to identify whether particular types of patients may be more susceptible to the risks associated with a particular treatment, and what the early indicators of this might be, so that side effects can be avoided or minimised in these groups. Increasing our focus on personalising medicines will help to make sure that our products are used in the most optimal way.
How do you collect and evaluate safety data?
Safety information about our marketed medicines is gathered from a wide range of sources and recorded on our global patient safety database – the central source of information for those responsible for patient safety across our organisation, and for reporting to regulatory authorities. Our monitoring systems include mechanisms for highlighting adverse events (potential safety issues) that require immediate attention.
Like other pharmaceutical companies, we receive tens of thousands of adverse event reports every year. An adverse event can arise from a number of causes and we work with doctors and others to understand the event and whether it relates to one of our medicines. We use patient risk management plans to help us prioritise and focus our efforts, and you can read more about these below.
How are potential safety issues identified?
Information on possible side effects comes into AstraZeneca from many different sources, including doctors, pharmacists, regulatory authorities and patients. We also identify potential safety issues through our ongoing clinical trials; by reviewing reports in medical journals and scientific literature, and by monitoring healthcare databases maintained by doctors, health insurance companies and regulators.
Our sales representatives are trained to ask about adverse events when visiting doctors and our Code of Conduct requires all of our staff to report any that they become aware of.
We work to identify safety signals (data which suggests an adverse event may be associated with the use of one of our medicines) and respond appropriately - in most cases before we are asked to do so by the regulator. We aim to make sure that the majority of signals that necessitate updating of the core prescribing information come from our own surveillance processes, rather than from regulatory authorities.
What is a patient risk management plan?
We develop patient risk management plans for our medicines to help us identify and reduce risks to patients and, where appropriate, we provide these to the regulatory authorities as part of our submission for approval to market a new medicine.
Each plan has three parts:
- Safety specification – information on all known risks and side effects associated with the medicine. This includes potential side effects where more research is needed to establish or refute a link to the product. We also highlight missing information. For example, the medicine may not have been studied in certain patient groups such as children or women of child-bearing age.
- Pharmacovigilance plan – the activities we are going to undertake to confirm or refute potential risks or to fill in missing information. For example, plans to carry out further research studies.
- Risk minimisation activities – all plans include routine risk management activities such as product labelling and safety monitoring. For some medicines with potentially more serious side effects we may need to take further steps. For example, we may run an awareness campaign to educate doctors or restrict which groups of patients may receive the medicine.
Plans are reviewed regularly and updated with new safety information as our knowledge of the medicine’s safety profile evolves.
In the European Union, we are required to have patient risk management plans in place when new medicines are submitted for regulatory approval. We go beyond this requirement because we have found that risk management plans are beneficial to us during the research process. We therefore aim to establish a risk management plan for each product from the time it first goes into testing in humans (Phase 1 clinical trials).
The risk management plans are then adapted for the needs of different countries. Risk minimisation activities may need to be tailored to meet local variations in healthcare practice or local regulatory requirements. In the US, the risk minimisation activities may be recorded in a Risk Evaluation and Mitigation Strategy (REMS), if required by the FDA.
How do you know if an adverse event is caused by one of your medicines?
This is challenging because adverse events can be due to many different factors. So our evaluation may vary according to the seriousness of the issue, as determined by the impact on the individual patient or on public health. There is a universally accepted definition for evaluating the seriousness of an individual case report with ‘death’ and ‘life-threatening’ at the top of a scale that goes via ‘permanent disability’ to ‘medically important’ events. A particular focus for our pharmacovigilance and that of regulators is on ‘new and important’ safety information - normally interpreted as issues that have the potential to change the benefit/risk profile (adversely) of a medicine.
For example, when cases are reported by individual doctors, we work with the doctor to understand the possible causes and whether these are associated with our medicine. We look at factors such as:
- The health of the patient before they started taking our medicine.
- Whether the adverse event could be caused or influenced by disease and lifestyle factors, for example alcohol consumption or use of recreational drugs.
- Whether the symptoms resolve if a patient stops using our treatment and return if they start using it again.
We analyse reports in aggregate to identify similarities or differences between cases that may help to confirm or refute a link to our medicine. We may also re-examine our existing research data for the medicine or initiate new targeted clinical trials or observational studies to help us understand the effect and what we can do to mitigate it. Observational studies are similar to clinical trials, and are used to study potential side effects once a drug is on the market. We conduct observational studies for most newly approved medicines.
Alongside other pharmaceutical companies, we are investing in new techniques that will help improve patient safety and detection of side effects at an early stage. For example, we are developing technologies like safety biomarkers, imaging techniques, computer modelling and simulation and linking large sets of preclinical and clinical data. Much of this work is carried out through partnerships like the European Union’s Innovative Medicines Initiative and the US Food & Drug Administration’s Critical Path Initiative.
What's next in this section
Responding to new information
If we identify a new side effect we take action that may include carrying out further clinical trials or modifying the prescribing information.Read more
Clear and open communication
We work to make sure that accurate and up-to-date information is provided to support effective use of our medicines.Read more