Clinical trials are the studies performed in humans to evaluate new medicines or potentially new uses of previously authorised medicinal products. Clinical trial objectives include the assessment of safety, tolerability, and/or efficacy, among others and there are several phases.
Early phase I trials usually recruit a smaller number of participants, often, but not always, healthy volunteers, meaning individuals who do not present health conditions that might interfere with the proposed study. The objective of phase I is to assess the safe dose range and to look for any side effects of the studied medicine. This is called pharmacokinetics.
Phase II studies recruit a larger group of participants with the health conditions relevant to the study and are designed to find out whether the medicine is safe and show preliminary efficacy for these specific conditions. Phase III or pivotal trials study recruit an even larger number of participants to further assess the efficacy and safety of the medicine.
How is the data obtained in the vaccine clinical trials managed? Once finished, the data obtained through clinical studies is presented to the relevant regulatory authorities, such as the European Medicines Agency (EMA), in a marketing authorisation application (MAA). After MAA approval, Phase IV or post authorisation studies may also be performed or required to complement efficacy data and gather long-term data about how well the medicine works when used in a wider population. Trials may also be international and all types of products require clinical trials, including biological products and vaccines such as BIMERVAX and studies in paediatric participants. In the EU/European Economic Area (EEA), around 4,000 clinical trials are authorised each year. Thus, clinical trials represent a major part of the MAA and are an important area of pharmaceutical regulation.
Given the relevance of clinical trials in the marketing authorisation, their regulation is crucial and consists of several regulatory aspects that may vary in different regions. The most important regulatory aspects for clinical trials include: (i) clinical trial applications (CTAs); (ii) good clinical practice (GCP) and ethics requirements; (iii) pharmacovigilance and reporting requirements including transparency.
In the European Union (EU), clinical trials, including vaccine clinical trials such as the ones performed in the RBDCOV project, follow the Clinical Trials Regulation (CTR) 536/2014/EU, which entered in force in 2014 and is applied since 31st of January 2022.
The Clinical Trials Regulation requires that for a clinical trial to be conducted, a Clinical Trial Application (CTA) is prepared and submitted. CTA evaluation and authorisation takes place at a national level, depends on the National Competent Authorities (NCAs) of each member state where the trial will take place and not on the European Medicines Agency (EMA). However, the EMA may evaluate the final marketing authorisation application (MAA) for certain types of products, including most vaccines. The NCAs may also evaluate certain types of MAAs.
Starting from 31st January 2023, all new clinical trials require the use of a new EU CTA submission portal and database, called the Clinical Trials Information System (CTIS). The CTIS was also designed to facilitate public access to information around the clinical trials that are performed in the EU, such as their data and documentation.
Another important aspect of the Clinical Trials Regulation is the protection of participants, which includes new requirements for informed consent and transparency. These aspects are also contemplated under the Good Clinical Practice (GCP). Additionally, there are also specific good manufacturing practice (GMP) requirements for medicinal products used in clinical trials to assure that products that are used meet the appropriate manufacturing standards.
This specialized article has been created by the research team of Christopher Mann from ASPHALION, who is responsible for providing leading services in the field of Regulatory, Scientific & Safety Consulting in Life Sciences for the vaccine clinical trial of RBDCOV.