Pharmacovigilance in clinical trials

Clinical trials and the role of pharmacovigilance

Before a new drug can be authorised, its safety and efficacy must be tested in a clinical trial. Clinical trials are therefore an important part of medical research.
However, trials are also associated with risks. Pharmacovigilance therefore ensures that the safety of participants is guaranteed during clinical trials and that all safety-relevant information is recorded and reported at an early stage.

What are clinical trials?

To test the safety and efficacy of new drugs, vaccines, medical devices or treatments, systematic investigations are carried out on humans in clinical trials. These follow a study protocol that specifies how the study is to be conducted, which patients may participate and which results are to be measured.

Basically, there are two study types:

• Non-interventional studies: Observational studies without any targeted intervention.
• Interventional study: These studies are usually therapy studies in which a new treatment method is actively tested, for example the intake of a new drug. An intervention is a measure designed to prevent the onset or progression of a disease.

Phases of clinical trials

Interventional (drug) trials are divided into four phases.

However, before an active substance can be tested on humans, it undergoes a preclinical development programme in which the substance is tested for possible harmful effects. A substance may only be tested on humans if it has passed all the prescribed preclinical tests.

• Phase I trials focus on the safety and tolerability of a new drug. They are conducted on a small group of healthy volunteers.
• Phase II trials are somewhat larger and investigate the dosage, efficacy and possible side effects of the drug in patients suffering from the disease for which the drug is to be used.
• Phase III trials are usually comparative studies in which patients receiving the treatment under investigation are compared with a control group receiving a different treatment.
• Phase IV trials take place when the drug is already on the market. Drugs can thus be tested for long-term effects and rare side effects.

In each phase of these trials, it is crucial that any side effects that occur are closely monitored and documented to ensure the safety of participants and fulfil regulatory requirements.

Legal basis of clinical trials

To comply with ethical and regulatory standards and ensure the protection of trial participants, the legal basis of clinical trials is defined by a number of regulations and guidelines.
International guidelines such as the Declaration of Helsinki, GCP standards and specific legal regulations such as EU Regulation 536/2014 (Clinical Trial Regulation) ensure that clinical trials are conducted responsibly and transparently.

Tasks of pharmacovigilance in clinical trials

Pharmacovigilance plays a central role in monitoring safety during clinical trials. The central tasks include:

1. Recording and monitoring of adverse events:

All adverse events that occur during a clinical trial must be recorded and evaluated. These can range from mild reactions, such as nausea or headaches, to serious events, such as life-threatening conditions or deaths. The data is continuously monitored to identify patterns or unexpected clusters of adverse reactions.

2. Reporting of SUSARs (Suspected Unexpected Serious Adverse Reactions):

One of the most important tasks of pharmacovigilance in clinical trials is the reporting of suspected unexpected serious adverse drug reactions (SUSARs). The definition is based on the combination of the terms serious adverse reaction (adverse reaction that leads to death, is life-threatening, requires or prolongs hospitalisation, leads to permanent or severe disability or incapacity, or causes congenital anomalies or birth defects) and unexpected adverse reaction (adverse reaction that is not consistent in type or severity with the available information on the investigational medicinal product). For a serious unexpected adverse reaction to become a SUSAR, a causal relationship to the investigational product must also be established.

Since SUSARs are both unexpected and serious, they must be reported immediately to the competent authorities to enable rapid reactions, such as adaptation of the study protocol or, in extreme cases, discontinuation of the study. SUSARs are reported via EudraVigilance using the Clinical Trial Module.

3. Periodic reports and assessment of the benefit-risk profile:

Based on the data collected in the studies, pharmacovigilance continuously assesses the risk-benefit ratio of the medicinal product. By systematically recording and analysing safety data, potential risks can be identified at an early stage and appropriate measures can be taken.
Pharmacovigilance also contributes to the preparation of periodic reports (Development Safety Update Reports (DSURs). These must be submitted once a year or on request and provide an overview of the safety profile of the product and its development over the course of the study.

The importance of pharmacovigilance for the success of clinical trials

Pharmacovigilance plays a crucial role in clinical trials. It ensures that all safety-relevant data is correctly recorded and evaluated in order to correctly assess the risk of new drugs or new treatments. As knowledge of investigational medicinal products is initially limited, the continuous recording and evaluation of adverse events helps to optimise the risk-benefit assessment of a new drug. This ensures that new drugs are not only effective, but also safe.