Is it worth conducting clinical trials of modern drugs and devices in the European Union? Is the EU attractive for investment compared to other parts of the world?
Publication date: April 03, 2024
The sale of a new drug or medical device and clinical trials is a process between two opposing interest groups. On the one hand, it is about patient protection and the safety of the pharmaceutical market. On the other hand, it is about creating a legal environment that will accelerate the creation of new drugs.
Both goals are important. It is important to create the right legal balance. The balance between patient protection and facilitation of modern medicines and medical devices makes Europe attractive for locating new innovations in technology and creating new medicines and medical devices.
Placing legal priorities in creating law is a political compromise between the speed of producing a new drug and blocking innovation justified by patient safety.
The attractiveness of Europe for the pharmaceutical business compared to other global markets depends on the proper placement of priorities.
The attractiveness of Europe for the pharmaceutical industry is demonstrated by a comprehensive analysis of the recitals of REGULATION (EU) No. 536/2014 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 April 2014 on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC.
The table below groups all the pros and cons of locating new drugs and medical devices in Europe. The table analyses all 85 extensive recitals in the preamble to a key piece of legislation in the European Union. The recitals contain tips, guidelines, and often examples of the correct application of the provisions of the clinical trials. That is why it is so important to interpret the principles of clinical trials in the light of these recitals.
CLINICAL TRIALS IN EUROPEAN ENVIRONMENT
| ARGUMENTS IN FAVOUR | ARGUMENTS AGAINST |
|---|---|
/OPPORTUNITIES/ | /OBSTACLES/ |
| ARGUMENTS IN FAVOUR |
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/OPPORTUNITIES/ |
1. Access to CTIS (Clinical Trials Information System).
It aims to increase the transparency of information about clinical trials, facilitate access to these trials and increase patient safety.
It will ensure harmonization and simplification of the electronic application procedure throughout the duration of clinical trials in the EU or EEA.
The exchange of information between sponsors and member states is completely electronic, which allows for the improvement of the entire communication chain.
CTIS allows to search and export structured clinical trial data, allowing researchers to efficiently report. The conduct of a clinical trial may be extended to more Member States, e.g. to improve recruitment.
Possibility to conduct research across the EU at once.
Two safe work areas have been identified in the CITS area:
CTIS for sponsors covers access to the system for persons such as:
- Clinical trial sponsors
- Applicants and holders of authorizations to place medicines on the market
- Other organizations involved in conducting clinical trials.
The system enables the above-mentioned persons:
- Manage registered users and user roles,
- Create clinical trial applications for new, updated or ongoing trials,
- Cross-referencing product documents in other clinical trials,
- Submission of clinical trial applications and updates for evaluation by Member States,
- Receive alerts and notifications regarding ongoing research,
- Respond to requests for information and review appointments,
- Search and access clinical trials,
- Issue notifications regarding key stages of the study life cycle (e.g. start of recruitment, end of recruitment),
- Registration of clinical trial results.
CTIS for authorities covers access to the system of such entities as:
- National competent authorities of EU Member States and EEA countries,
- Ethics committees of EU Member States and EEA countries (national procedures for access to CTIS for ethics committees may vary),
- European Commission.
The system enables the above-mentioned:
- Manage registered users and user roles,
- Review dossiers (files relating to certain matters or people) of applications for clinical trials,
- Manage tasks related to the evaluation of clinical trials,
- Cooperation within and between Member States,
- Receive alerts and notifications regarding ongoing research,
- Download documents submitted by clinical trial sponsors,
- Recording of site inspections and clinical examinations,
- Carrying out EU controls.
Currently:
From January 31, 2023, all permit applications for clinical trials in the EU and EEA must be submitted via CITS in accordance with the Clinical Trials Regulation. (3-year transition period).
From 31 January 2025 all ongoing studies must be transferred and registered in the CTIS system. (3-year transition period).
EU regulations resulting from Regulation 536/2014 will make it easier for investors to research new therapies.
According to the new rules, the research sponsor, often a pharmaceutical company, will already submit an application for registration on the EU portal, as a result of which all countries in which the sponsor is interested will be able to learn about the research. These countries will have the opportunity to express their consent to conduct research within their territory on the same portal. This means significant simplification of the legislation.
2. High standard regarding the regulation of clinical trials, their quality and safety regulated by EU regulations supervised by the European Medicines Agency and the national authorities of the countries in whose territory the trial takes place.
Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC (OJ EU L. of 2014, No. 158, page 1, as amended). It regulates in detail, among other things, the protection of research participants (Chapter V), which may contribute to increasing the number of people willing to participate in clinical trials and also ensures transparency and clarity of the conditions for conducting a clinical trial for both parties. It is worth noting that the regulations protecting the entity also constitute a safety buffer for the entity conducting the research against the possibility of possible lawsuits from the entity.
3. Introduction of new forms of patient consent.
The introduction of new forms of patient consent by Regulation (EU) No. 536/2014 of the European Parliament and of the Council undoubtedly facilitates research teams, due to the possibility of expressing consent not only in writing but also in audio or visual form when the interested participant is unable to write (Article 29).
An important point is also the introduction of informed consent in emergency situations (Article 35), provided that this decision is taken at the time of the first intervention involving the participant, in accordance with the protocol of this clinical trial, and all the following conditions are met.
4. Establishing the possibility of co-sponsorship (Article 72 of Regulation (EU) No. 536/2014.
5. Changes in the conceptual scope.
Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC (OJ EU L. of 2014, No. 158, page 1, as amended) changed the definition of a clinical trial – a broader concept of biomedical research is in force, the category of which is a clinical trial.
The above-mentioned regulation also introduces the definition of low-intervention research, which will make it easier to conduct research (due to being subject to less restrictive regulations).
6. Introducing administrative simplifications in the requirements for clinical trials – this will make them more transparent (without reducing their quality), which will make it easier for pharmaceutical companies to conduct trials.
7. Recommendations for cooperation between countries – which may have a positive impact on the scale of research and its speed.
8. In justified cases, in the event of problems with the availability of auxiliary medicinal products authorized for marketing, it is possible to use products not authorized for marketing in a clinical trial – there is no paralysis in the performance of a clinical trial.
9. The possibility of existence in practice of loosely interconnected networks of researchers/research institutions that jointly conduct clinical trials (loose/informal connections allow to benefit from cooperation without having to devote time and resources to building a formal connection between researchers or research units).
| ARGUMENTS AGAINST |
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/OBSTACLES/ |
1. The first problem that may raise doubts as to the decision to conduct clinical trials in the European environment is the issue of terminology used in Regulation ( EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials of medicinal products for human use and repealing Directive 2001/20/EC (OJ EU. L. of 2014, No. 158, p. 1, as amended):
Pursuant to Art. 4 of the Regulation on Clinical Trials of Drugs No. 536/2014, “the clinical trial is subject to scientific and ethical evaluation” – the ethical evaluation is carried out by ethical committees in accordance with the law of the Member State concerned.
The meaning of the word “ethical”, as well as all the rules and norms of conduct at a given time and in a given environment, may cause interpretation difficulties for the ethics committee, which is each time obliged to evaluate a clinical trial, requiring a subjective assessment also based on objective premises regarding the facts. Conducting an ethical examination due to interpretation problems and the individualization of each examined case may lead to the extension of the entire procedure leading to the issuance of a permit and thus may expose the interested entity to incurring additional costs.
2. Scope of Member State supervision.
Pursuant to Art. 77 of the Regulation on Clinical Trials of Medicines No. 536/2014, if the Member State concerned has reasonable grounds to consider that the requirements set out in the above-mentioned Regulation are no longer met, it may take the following steps on its territory:
- Withdrawal of consent to clinical trials,
- Suspensions of clinical trials,
- A commitment by the sponsor to change any clinical aspect.
This regulation may have a negative impact on decisions to undertake clinical trials in the European environment due to the fact that the relatively broad possibilities of action of a Member State may result in the sponsor suffering damage disproportionate to the benefits received, may prolong the entire trial process and may force the sponsor to change aspects of the clinical trial, which is directly related to the need to incur costs related to the development of changes.
3. Incurring costs related to urgent security measures.
Pursuant to Art. 54 of the Regulation on Clinical Trials of Drugs No. 536/2014, in the event of an unexpected event that may have a serious impact on the benefit-risk ratio, the sponsor and the investigator shall take appropriate urgent safety measures to protect participants.
The above regulation may lead to sponsors and researchers fleeing to conduct research in an environment where the responsibility imposed on them is low; however, it should be noted that the above regulation may also have a positive impact on the access of sponsors and researchers to potential research participants, who, having legal security, will be more willing to take part in the entire process.
4. Not covered by the harmonization of criminal law under the TFEU (Article 83 (1) or (2) TFEU).
What is important is from the point of view of the importance of goods such as health and life involved in a clinical trial, as well as due to the legal status of Regulation (EU) No. 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials of medicinal products for human use and repealing Directive 2001/20/EC (OJ EU L. of 2014, No. 158, p. 1, as amended), which has direct binding force.
The introduction of greater requirements regarding reporting and data sharing may lead to the generation of additional costs and complicate management processes and lengthen the processes related to obtaining consent and conducting a clinical trial.
The regulation requires the publication of all clinical trial results, both positive and negative, in a publicly accessible register. In addition, entities conducting research are obliged to comply with guidelines on data sharing, which increases the transparency and availability of information about the research being conducted.
