National Organization for Medicines (EOF), the Greek Regulatory Authority, was established in 1983 with Law 1316 announced in Government’s Bulletin in 1983.

National Ethics Committee establishment (within EOF facilities) took place in 2003 with Ministerial Decision ΔΥΓ3/89292/30.12.2003 with start of operations May 2004.

Greece joined European Union in 1981, adopted the Clinical Trials Directive, changed and improved the Regulatory Framework and complied with high Ethical Standards following the GCP requirements.

Despite the short journey of Clinical Trials in Greece, we should not ignore the origin of any current and future Ethical Code for the conduct of Clinical Practice and Clinical Research: Hippocratis Oath.

Hippocratis Oath has contributed to the adoption of the Concept of Medical Ethics and Humanitarian Morals, the Declaration of Geneva (Physician’s Oath) and the overall principals for the protection of the clinical trial participants’ safety and well-being.

Statistics (of the recent years)

We have a steadily increasing growth of Clinical Trials within the last years in Greece. According to EOF official data, 153 Clinical Trials have been conducted in Greece in 2015. The relevant number of the year 2014 has been 127 Clinical Trials and 123 Clinical Trials in 2013.

Regulatory Procedures

The Submission process in Greece is sequential and involves Local and Central (National) Ethics Committee (i.e. LEC and NEC) and Competent Authority (EOF).

In each Hospital, there is a dedicated Scientific Council that acts as a Local Ethics Committee (LEC). Scientific Councils are not always constituted according to the GCP_ICH requirements in terms of their Memberships (i.e. most of the members are medical doctors).

Submission takes place to LECs and sequentially to NEC. EOF submission though can take place in parallel (or even prior) to LEC submission.

Prerequisites for a Clinical Trials conduct, is the LEC approval or tacit approval, NEC’s positive opinion, EOF’s notification of acceptance or tacit acceptance and a fully executed Investigator Agreement.

LEC has a 30 days’ timeline to raise comments/ objections to the submission file and all related documentation. If the 30 days’ timeline passes, then we consider that tacit (silent) approval is available.

In parallel (or even prior) to LEC submission, the applicant moves on with EOF submission. In terms of Investigational site documentation, only the Protocol signature page is required, signed by both Sponsor and PI.

EOF has a 60 days’ timeline to approve the study including a 10 days’ validation period following a valid submission.

Sequentially to the Submission to LEC and upon receipt of PIs’ submission letter to the LEC, the applicant moves on with the NEC submission.

NEC has a 60 days’ timeline (as EOF mentioned above) to approve the study including a 10 days’ validation period following a valid submission.

The execution of Investigator Agreements is running in parallel to the Submission process.  The Investigator Agreement signature is allowed prior to the availability of NEC/ EOF authorizations but the signatures are deemed as valid only upon these approvals’ availability.

By Greek Law, there is a quadripartite Agreement template applicable to all interventional studies running in Greek hospitals/Institutions, (signatory parties: investigator, sponsor/CRO, Institution, Regional Health Authority/ELKE).

Greece: an attractive place to conduct clinical trials in EU

Currently, there is common feeling in the pharma world/ CROs and any involved party in the Clinical Trials’ conduct that we are reaching a new era in Greece.

Greek authorities and especially the Greek competent authority (EOF) is currently highly motivated and Greek Regulators are now more prepared, qualified, adequately trained and competent enough to undertake and manage demanding undertakings. EOF is more open to communications and encourages interactions with stakeholders (pharma companies/ CROs).

EOF works with all required efforts towards the smooth implementation of the EU Regulation on Clinical Trials (536/2014).

To this end, they (EOF) are participating in the user Testing phases of the EU portal and database as these are mandatory pre-requisites for the launch of the new regulatory environment. During the period of 2012-2014, they have actively participated in the conversations and formulation of the context of the new EU Regulation. It is worth mentioning that they have also participated in VHP process -precursor of the EU Regulation.

Workgroups of Greek authorities, including both EOF and YPEs (Regional Health Authorities, responsible for the financial aspects of clinical trials in Greece) have agreed to perform regular meetings in order to achieve:

1. a) Smooth implementation of the new EU regulation taking into consideration the national aspects that will be required towards this goal. A great effort is being made to this end.
2. b) The development of a “National Clinical Trials Registry”.

Only a few months ago (i.e. May 2016), EOF taking the opportunity of the International Clinical Trials (Celebration) Day, organized a press conference with open invitation to all concerned parties. The data disclosed during the press conference were very optimistic as EOF was for the first time in the position to provide statistical evidence of the increased number (on a yearly increased rate) of clinical trials conducted in Greece. In addition, they (EOF) announced 2 significant innovation actions that are about to implement:

• The constitution of an ongoing educational process for medical doctors and clinical trial investigator in the Clinical Trial Procedures (i.e. Good Clinical Practices) within EOF (and other) facilities.
• The “inquiry” of the appropriated framework for the “awarding” and funding non-commercial clinical trials (or at least 3 non-commercial trials) on an annual basis.

In parallel, the secretariat of the Greek National Ethical Committee (NEC), is now enforced with additional personnel with significant scientific background.  NEC has started to conduct two assessment meeting on a monthly basis and to comply with defined approval timelines (both for initial and substantial amendments) according to the available legislation.

Events, workshops and ongoing education of clinical trial teams (clinical trial personnel is site and clinical trial personnel within companies) are now approached as in investment for Greek pharma, Local/Regional CROs and International ones, either conducting or monitoring Clinical Trials in Greek.

Greece should be considered as an attractive place for Clinical Research. Greek sites are in fairly good situation with an evident increasing sites’ readiness qualifying many of them as sites of excellence despite the economy crisis.  Joint Site Inspections by EOF, EMA and FDA do confirm the positive situation.

Apart from the above mentioned achievements, we have an increasing patients’ awareness, a decrease of fear to “experiment”, and the most welcome patients’ representatives’ participation into clinical trials workshops, seminars and events.

References

• The Greek law 1316/83 article 37 – 2γ.
• The Ministerial Decree ΔΥΓ3/89292/03 (31-12-2003) “Harmonization of the Hellenic Legislation to the respective Community legislation in compliance with Directive 2001/20/EC of April 2001”.
• The Ministerial Decree ΔΥΓ3(α)69150/04 (7-10-2004) “Establishment and operating procedures of the National Ethics Committee for Clinical Trials”.
• Circular of NEC no. 47398/1-8-2005: Procedure for approval of interventional clinical trials and circular clarification/amendment 47150/09.07.2007.
• The Ministerial Decree ΔΥΓ3α/79602/25-1-07 “Harmonization of Greek legislation to the respective Community legislation in compliance with Directive 2005/28/EC of April 8, 2005”
• “Circular of EOF no. 88148/23-12-2010 “Detailed Guidelines on the Granting of an Authorization for an Interventional Clinical Trial, on the Procedures for the Notification of Substantial Amendments and for the Declaration of the End of a Clinical Trial” (implementation of the 2010/C 82/01 guidance of the European Commission).
• EOF announcement/ Press Release with effective date 1.4.2013: Submission documentation in electronic form
• Circular Letter of EOF no. 64745/ 7.7.2014: Procedures regarding the management and reporting of Safety Issues in the context of the clinical trials conduct
• The Ministerial Decree ΔΥΓ 3(α)/οικ. 18910/ FEK 390/21-02-2013: Supplementation of the Joint Ministerial Decision No ΔΥΓ3α/89282/2003 (Gov. Gazette B’ 1973) “Approximation of the laws of the Hellenic Republic to the respective European” in accordance with the Directive 2001/20/EC on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use” as amended and today in force, for the purposes of approximating, simplifying and rationalizing the procedures for the conduct of Clinical Trials”.

 The NEXT CRO Team