Clinical Trials

In addition to meeting European Union requirements, specific national requirements must be fulfilled throughout the different stages of a product’s lifecycle. It is crucial to work in a coordinated way with all European Union countries to effectively facilitate these national obligations for medicinal products.

The Implementation of the EU Clinical Trials Regulation (CTR)

The legal basis for clinical research with medicinal products in the European Union (EU) is the Clinical Trials Regulation (CTR), Regulation (EU) No 536/2014. This Regulation applied from the 31 January 2022 and repealed the previous legislation on clinical trials, the Clinical Trials Directive (CTD), Directive 2001/20/EC.
Trials continue to be governed (including amendments) by the previous Clinical Trials Directive (CTD) for a period of three years from the date of application of the Clinical Trials Regulation (CTR) with respect to:

• applications submitted before the date of application of the CTR
• applications submitted within one year after the date of application of the CTR (if the sponsor decides to still perform the clinical trial under the regime of the CTD.

The primary aim of the new regulation is to streamline the Clinical Trial Application (CTA) process and harmonise the assessment of interventional clinical trials (phases I to IV) among the EU Member States.
The European Medicines Agency (EMA) has introduced the Clinical Trials Information System (CTIS) – a platform used by sponsors/Contract Research Organisations (CROs) and Member States. This portal enables sponsors to submit a single clinical trial application to the intended EU Member States and receive a consolidated decision covering the relevant national competent authorities and Ethics Committees.

• Until 31 January 2023, sponsors could decide whether to submit a new clinical trial application under the CTD (Directive 2001/20/EC) or CTR (Regulation (EU) No 536/2014).
• From 31 January 2023, all new clinical trial applications must be submitted through CTIS under the CTR.
• From 31 January 2025, only the CTR will apply, and all clinical trials will be required to transition to the new system under CTR.

Various types of studies: observational studies versus clinical trials

In order to decide whether a planned study falls under the CTR or not, it is important to consider the differentiation between observational studies and clinical trials.
Observational (non-interventional) studies monitor patients under the conditions of current medical practice and do not assign a patient to a particular therapeutic strategy in advance according to a study protocol. Researchers gather information from these patients under the conditions of normal medical practice and compare changes over time with prescribed medicinal products and treatments. Non-interventional observational studies are excluded from the scope of the EU clinical trials legislation.
Clinical trials are research studies that test a medical, surgical, or behavioral intervention in people. These trials are the primary method by which researchers determine the safety and effectiveness of new treatments or prevention methods, such as new medicinal products according to a clinical trial protocol.

A clinical trial is designed to learn for example if a new treatment is more effective or has fewer side effects than existing treatments. Clinical trials can also have other objectives such as: assessing improvements in the quality of life for patients living with a life-threatening disease or chronic health conditions.
There are commonly three main phases of clinical research before a marketing authorisation application:

• Phase I clinical trials are conducted to determine the safety of a new medicinal product, treatment, or treatment combination. Subjects can be healthy or have the disease or condition being studied.
• Phase II clinical trials gather more information about the safety of the medicinal product or therapy in a larger group of subjects who have the disease or condition being studied.
• Phase III clinical trials test a treatment that showed promising results in a phase II clinical trial. Phase III are commonly confirmatory trials in patients comparing a new treatment with the standard treatment to determine if it is more effective, has fewer side effects, or both. Patients are usually assigned to different treatment groups.