Preclinical and Clinical Trial Requirements
The key requirements for conducting pre-clinical and clinical trials in Greece. Prepared in association with Calavros Law Firm, a leading global law firm, this is an extract from The Pharma Legal Handbook: Greece, available to purchase here for USD 99.
1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?
No. Article 9 par. 3 of Ministerial Decision Δ.ΥΓ3α/Γ.Π. 32221/Government Gazette B 1049/2013, issued in application of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use, providing for the essential content of any application in view of marketing approval before the National Medicines Organization (E.O.F.), sets no such requirement as to the clinical trials related to the use of the medicinal product under approval.
2. How are clinical trials funded?
Clinical trials may either be funded by a private entity, including a pharmaceutical company, or by any entity not acting, directly or indirectly, on behalf of any entity belonging in the pharmaceutical industry. In the latter case, the clinical trial is defined as non – commercial and may be sponsored by either a university, public hospital, public scientific entity, non-profit organization, patients’ organization or independent researcher, in accordance with the provisions of Ministerial Decision G5(a)/59676 Government Gazette B 4131 2016 on clinical trials conducted on humans.
3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?
Clinical trials to be conducted in Greece are subject to scientific approval by the National Medicines Organization (E.O.F.) according to the procedure described in article 5 of Regulation EU 536/2014 on Clinical Trials, as well as ethical approval by the National Ethics Committee, as provided in Ministerial Decision G5(a) Government Gazette 4131 2016 on clinical trials conducted on humans. Key requirements specific to Greece include the obligation to file the application, the trial protocol, the information material destined to patients, the informed consent document, the labeling of the medicines to be administered, the patients’ cards, as well as the insurance contract required in the Greek language. The remaining elements of the file may be submitted in English, subject to any request by E.O.F. for those to be filed in official translation in Greek at any given time. As far as suitability of the persons conducting the trial are concerned, the main researcher of any trial conducted in Greece must be a clinical physician holding a permit to exercise the medical profession in Greece, never having been suspended, removed or revoked in the past. The same requirement must be met by all participating researchers.
While the examination of an application by E.O.F. focuses on the scientific aspects as listed in article 6 of Regulation EU 536/2014, the examination by the National Ethics Committee focuses on the aspects listed in article 7 Regulation EU 536/2014, namely the suggested procedure relevant to obtaining the participating patients’ informed consent, the participants’ compensation terms, the suggested recruitment procedure, as well as the respect of any rules applicable to the collection and storage for future use of the participants’ biological samples.
4. What are the requirements for consent by participants in clinical trials?
According to article 9 of Ministerial Decision G5(a)/59676 Government Gazette B 4131 2016 on clinical trials conducted on humans, participants’ informed consent must be supplied prior to their engagement in the trial in writing; it must be dated and signed by the main researcher or any member of the research time specifically authorized by the latter. Prior to giving the required consent, the candidate must have been informed by means of an interview, equally dated and signed by an authorized research member, in a language easily understandable by the candidate, who must also have been allowed the opportunity to ask any questions, as well as sufficient time to consider his/her decision. Deaf candidates must be informed in writing and offered the opportunity to raise any questions, which must also be answered in writing, before giving consent. The same opportunities must be allowed to dumb candidates, in addition to the opportunity to ask questions in writing. In the latter two cases, a witness capable of legal action and not associated with the clinical trial in any way must be present and sign all relevant documentation. In case the candidate may neither read nor write, both the information and the consent documents may be signed by the authorized research member and two witnesses capable of legal action and not associated with the clinical trial in any way.
Alternatively, consent may be recorded on suitable audiovisual media in the presence of one witness capable of legal action and not associated with the clinical trial in any way. The information provided to the candidates must be concise and easily accessible by non-experts, as well as sufficient as regards i) the nature, purposes, potential benefits, consequences, dangers and unpleasant effects of the clinical trial, ii) the participant’s rights and the warranties in view of their protection, iii) the procedure of the clinical trial, including the expected duration of participation in the latter, iv) alternative treatments, including monitoring measures, should participation in the clinical trial be terminated. Information relevant to the insurance policy of the sponsor covering any liability associated with the clinical trial must also be included in the information provided to the candidate in view of obtaining informed consent. Article 10 of Ministerial Decision G5(a)/59676/2016 provides for minor candidates, as well as candidates incapable of legal action, whose informed consent must always be sought to the extent that they are able to realize the implications of their participation in the trial. Specifically, consent must be obtained in the cases of both minor candidates of a minimum 10 years of age and candidates incapable of legal action in a position to understand the potential benefits and dangers associated to the trial; in both cases the consent of the parents or any legal representative of the concerned candidates must also be obtained. In both cases, the express desire of the candidate not to participate in or withdraw from the clinical trial is binding.
5. May participants in clinical trials be compensated?
Compensation of the participants in a clinical trial is not excluded by law. However, the amount of compensation is included among the items of the application in view of approval of the trial and as such examined by the National Ethics Committee, as provided in article 20 of Ministerial Decision G5(a)/59676/2016. The latter must establish prior to approval of any compensation of the participants that no unfair influence, among others of an economic nature, has been exercised on the participants in order to participate in the clinical trial, as provided in article 28 of Regulation EU 536/2014.
6. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?
By virtue of article 15 of Ministerial Decision G5(a)/59676/2016, the sponsor of any clinical trial must enter into an insurance contract with a trustworthy insurance company seated in an EU member state, covering any liability which might arise in the persons of the sponsor, the main researcher, as well as of the members of the research team. As far as clinical trials conducted in research centers situated in Greece are concerned, the insurance must cover any potential damages due to injuries or disabilities which may be incurred as a result of the participation therein, and shall amount to a minimum of 300,000.00 € per participant in the event of death or permanent incapacity to work.
All medicines administered, medical devices used and procedures followed throughout the clinical trial, including the diagnosis and treatment of any adverse reactions, are provided by the sponsor at no cost of the research centre, the participant or the public insurance fund of the latter. The above costs entirely undertaken by the sponsor include the cost of exceptional travel expenses incurred by participants to and from the research centre for safety reasons, travel expenses to and from specialized diagnostic centres in view of specialized diagnostic examinations either according to the trial protocol or in the event of any adverse reaction in the context of the trial. Any clause of the consent document contrary to the above is considered to be null and void regardless of any decision or note to this effect made by either E.O.F. or the National Ethics Committee in the context of examination of the approval application as to the present requirement.