The issues concerned with legal aspects of trials in general – including non-interventional studies in the Czech Republic and Slovakia – are closely linked to the European legislation.
Act No. 378/2007 Coll., on Pharmaceuticals and on Amendments to Some Related Acts (Act on Pharmaceuticals) is the main legal act for clinical trials on pharmaceuticals in the Czech Republic. This Act was amended by Act No. 70/2013 Coll. Furthermore, Decree No. 228/2008 Coll. of MZ CR (Ministry of Health of the Czech Republic) on Marketing Authorisation of Medicinal Products, as subsequently amended, is also part of the legal framework.
Act No. 268/2014 Coll., on Medical Devices and on Amendments to Act No. 634/2004 Coll., on Administrative Fees, as Subsequently Amended, is the main legal act for clinical trials on medical devices in the Czech Republic.
According to the Czech legislation, a non-interventional post-authorisation study is defined as follows:
“Non-interventional post-authorisation study of a medicinal product for human use shall mean any study in which an authorised medicinal product for human use is prescribed in the usual manner in accordance with the terms of the marketing authorisation and in which the assignment of the patient to a particular therapeutic strategy is not decided in advance by a study protocol but falls within current practice and the prescription of the medicine by the attending physician is clearly separated from the decision to include the patient in the study, while no additional diagnostic or monitoring procedures are applied to the patients and epidemiological methods are used for the analysis of collected data; non-interventional post-authorisation studies include epidemiological, pharmacoeconomic and research studies.” (§ 3a par. 2)
The same legal norm also defines who is the investigator of a non-interventional clinical trial, and what are his/her obligations:
Section 59a of the Act on Pharmaceuticals stipulates that the investigator of a non-interventional post-authorisation study may be the marketing authorisation holder, contracted research organisation, medical doctor, healthcare service provider, expert medical society, medical faculty or pharmaceutical faculty. The investigator shall be obliged to notify the State Institute for Drug Control (SUKL) of the commencement and termination of the non-interventional post-authorisation study and, within 180 days of termination of that study, submit a final report to SUKL.
The above-mentioned paragraph does not apply to non-interventional post-authorisation safety studies, which might be carried out by the marketing authorisation holder. Non-interventional post-authorisation safety studies must comply to rules stipulated by the Section 93j of Act No. 70/2013 Coll. The PHV-3 guideline issued by SUKL provides a detailed description of terms, governs the conditions for performing the non-interventional post-authorisation safety studies. The PHV-3 guideline is available on the SUKL website.
Post-authorisation safety study of a medicinal product for human use shall mean any study relating to an authorised medicinal product for human use conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures.
Non-interventional post-authorisation safety study of a medicinal product for human use shall mean any study in which an authorised medicinal product for human use is prescribed in the usual manner in accordance with the terms of the marketing authorisation and in which the assignment of the patient to a particular therapeutic strategy is not decided in advance by a study protocol but falls within current practice and the prescription of the medicine by the attending physician is clearly separated from the decision to include the patient in the study, while no additional diagnostic or monitoring procedures are applied to the patients and epidemiological methods are used for the analysis of collected data; non-interventional post-authorisation studies include epidemiological, pharmaco-economic and research studies.
It is a subset of post-authorisation safety studies covered by this guideline. The term "non-interventional post-authorisation safety study" is reserved only for a study that meets all the following conditions:
Studies that do not meet all 10 conditions may not be described as "non-interventional post-authorisation safety studies".
All types of studies are carried out in compliance with Czech and European legislation in force. Act No. 101/2000 Coll., on the Protection of Personal Data and on Amendment to Some Acts, is the main legal act for the protection of personal data in the Czech Republic. Requirements and rules for personal data processing are based on EU requirements; therefore, personal data are processed in compliance with Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation), which came into force on 25 May 2018.
The company Institute of Biostatistics and Analyses Ltd runs a large number of registries, which have been designed and maintained in very different ways. In some cases, collected data are anonymised, whereas in other cases, pseudonymised data are collected; in exceptional cases, registries might also contain personal data.
Act No. 362/2011 Coll., on Medicinal Products and Medical Devices, as Amended, is the main legal act in Slovakia. This Act relates non-interventional clinical trials with various obligations. However, it is necessary to classify each study correctly, which defines whether the above-mentioned Act applies to that study or not.
The Act defines a non-interventional clinical trial in § 45 par. 1 in a way similar to the Czech legislation; in addition, however, it determines a person charged to carry out the non-interventional clinical trial, who is responsible for its expert processing (the so-called expert guarantor). Furthermore, the Act stipulates conditions to be met by the expert guarantor (§ 29 par. 11).
The Act also implies that if the project falls within the category of a non-interventional clinical trial, the trial can only be carried out after a written approval is issued by the health insurance company at which the respective trial participant is insured, and this approval is issued after the examination of protocol of the respective non-interventional clinical trial. However, the health insurance company stipulates conditions when approval will not be issued; one of the conditions for approval states that “...more than two years must have elapsed since the first marketing authorisation of that medicinal product for human use in Slovakia or since the approval in Slovakia of a new therapeutic indication of a medicinal product containing the same drug or having the same qualitative and quantitative characteristics of medicinal products for human use with the same dosage form.”
The protocol of each non-interventional clinical trial must contain precisely defined information and must be sent to the National Health Information Centre of the Slovak Republic, which will subsequently publish the protocol on their website.
Act No. 18/2018 Coll., on Personal Data Protection and on Changing and Amending of other Acts, deals with the issue of personal data protection in Slovakia.
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 is the main EU legislation dealing with the issue of clinical trials. This regulation does not apply to non-interventional trials. Among others, the above-mentioned regulation deals with:
Commission Directive 2005/28/EC (32005L0028) of 8 April 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products (also referred to as the “Good Clinical Practice Directive”) involves the following chapters:
The European Medicines Agency (EMA) is a European Union agency for the evaluation of medicinal products. Based in London, the EMA was born after more than seven years of negotiations among EU governments and replaced the Committee for Proprietary Medicinal Products and the Committee for Veterinary Medicinal Products. The Board includes one representative of each Member State, two representatives of the European Commission, two representatives of the European Parliament, two representatives of patients’ organisations, one representative of doctors’ organisations and one representative of veterinarians’ organisations.
Other EU legal acts dealing with the issue of clinical trials involve: