A medicine is considered to be safe if its expected benefits are greater than the potential risks of adverse reaction which is associated with its administration. All medicines can cause adverse reactions. However, it is important to note that the majority of patients take medicines without experiencing any serious adverse reactions.
Before a medicine is placed on the market (pre-marketing period), extensive research must be conducted, namely: pre-clinical trials in animals and clinical trials in humans. Clinical trial programs follow strict rules and are designed to demonstrate positive benefit-risk balance of a medicine used in treatment for a specified indication and patient population.
The medicine shall be granted marketing authorization if its quality, efficacy and safety are proven, which includes that the positive benefit-risk balance has been demonstrated at the time of authorization (demonstrated therapeutic efficacy and risks, in the form of adverse reactions, may be considered acceptable at the time).
Clinical trials are conducted under specific conditions:
- Subjects are homogeneously selected specifically for this study according to strict criteria (gender, age, ethnicity, smoking, generally do not have associated diseases and do not use other medicines concomitantly, etc.),
- Number of subjects and duration of the study are limited,
- Subjects are continuously monitored during the study.
Common adverse reactions are known at the end of the clinical trial. After obtaining marketing authorization, the medicine is placed on the market and starts being used in routine clinical practice on a large number of patients. Still, the overall safety profile of the medicine is not yet known, i.e. the information is incomplete or not available at all about the rare adverse reactions and reactions after long-term exposure, interactions, resistance, potential for medical errors, unauthorized use of the medicine, abuse and misuse, administration of the medicine in specific categories of patients (children, elderly, pregnant women, breastfeeding women, patients with associated diseases: liver, kidney or heart failure, etc).
For these reasons, knowledge about the safety profile of the medicine is limited and must be expanded. Therefore, it is vital to monitor the safety of all medicines from the moment they are placed on the market – this is known as pharmacovigilance.
Pharmacovigilance is the process of:
- Monitoring the use of a medicine in day-to-day practice to identify previously unrecognized, unexpected adverse reactions or changes in the patterns (nature, severity, frequency) of adverse reactions,
- Assessing the risks and benefits of medicines in order to determine what actions should be taken, if necessary, to improve safe administration of a medicine,
- Providing information to healthcare professionals and patients in order to achieve safe and effective use of medicines,
- Monitoring the impact and results of the actions taken.
Information sources used for pharmacovigilance:
- Spontaneous adverse drug reaction reporting by healthcare professionals and patients,
- Clinical and epidemiological studies,
- Medical literature,
- Information from the pharmaceutical industry,
- Information from other worldwide regulatory authorities,
- Databases (mortality, morbidity, pregnant women, etc.).
Information from these sources is thoroughly reviewed and analyzed and may identify a new adverse reaction, which had not been known for a particular medicine, indicate that certain adverse reactions occur more commonly than shown in the previously conducted trials, or that certain patient populations more commonly experience adverse reactions, then may detect interactions, possible medical errors, misuse, abuse etc.
Regulatory actions for safety reasons:
When necessary, after the evaluation of collected data and identification of new safety findings, ALIMS takes steps to ensure that the medicine is used in a manner which minimizes risks and maximises the benefits. These actions usually include changes to safety information in the Summary of Product Characteristics and Patient Information Leaflet, as primary documents on the medicine, namely:
- In terms of adding new important warnings and precautions, and adverse reactions,
- New contraindications (e.g. Do not give this medicine to pregnant women, children, or use in certain medical conditions, etc.),
- Reduction of the recommended dose,
- Limitations in the administration of a medicine (as second-choice therapy, exclusion of a certain disease or group of patients in which a medicine is administered, define a more restrictive regime for the issuance of medicine, e.g. from over-the-counter to prescription only, etc.).
Other regulatory actions are also taken for risk management purposes, particularly in terms of risk minimization, and in rare cases, the decision can be made on termination of a marketing authorization, or to temporarily revoke a marketing authorization for safety reasons and to withdraw a medicine from the market, when it is demonstrated that the potential risk is greater than the expected benefit in normal therapeutic administration of a medicine.