The EFGCP Report on The Procedure for the Ethical Review of Protocols for Clinical Research Projects in Europe (Update: April 2011) Estonia

Transcription

1 The Procedure for the Ethical Review of Protocols for Clinical Research Projects in Europe (Update: April 2011) Estonia Question 1: What laws or regulations apply to an application for conducting a clinical trial in Estonia? National law and regulation: The Medicinal Products Act 2005 (upgraded 2009), with details provided by regulations issued by the Minister of Social Affairs. This Act covers the regulation of clinical research and implements the Directive 2001/20/EC. Decree No 77 (2001) refers to the establishment of research ethics committees. Special law for regulation the activity (data collection, research projects and data release) of the Estonian Genome Center University of Tartu Human Genes Research Act ( Inimgeeniuuringute seadus ), valid from and upgraded in The Personal Data Protection Act International laws: The European Council s Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine, Additional Protocol to the Convention Concerning Biomedical Research. The Declaration of Helsinki of the World Medical Association Good practice of conducting clinical trials. Good epidemiological practice. Estonia - 1

2 Question 2: Which government, legal or authoritative body or bodies is or are responsible for the establishment and/or accreditation of (research) ethics committees for IMPs, and for their supervision and quality? Are there different (research) ethics committees reviewing other projects? There are two independent research ethics committees that consider medical research and clinical trials in Estonia one in Tartu and another in Tallinn. The ethics committees of hospitals are not responsible for clinical trials and medical research. The Research Ethics Committee of the University of Tartu operates also as ethics Committee of the Estonian Genome Center University of Tartu. The Estonian Council of Bioethics, established by the Ministry of Social Affairs, is the national co-ordinating centre. Question 3: What is the process for achieving clinical trial authorisation from the competent authority in Estonia? Notification of the clinical trial needs to be submitted to the State Agency using the EudraCT format 60 days before the planned commencement of the trial at latest. A formal letter of no objection is given, often earlier than the legally stipulated 60 days. The time taken by the Agency depends directly on the quality and completeness of the documentation submitted. Together with the notification, a signed declaration by the head of the health-care institution study centre) has to be submitted. Where applicable, after that the import certificate for the study medications can be applied for. The EudraCT application form is available at The website for the State Agency of Medicines is at Question 4: What is the process for obtaining ethical review of a clinical trial protocol by a competent (research) ethics committee in Estonia? The application for a clinical trial must be submitted to the secretary of the (research) ethics committee (EC) at least 10 days before the EC meeting, held in every month. The relevant parts of the application are sent to all EC committee members and the research project will be discussed at the next meeting of EC. If there are questions or problems they will be presented to the principal investigator (study coordinator), the answers will be revised and if there are relevant changes they will be discussed on the next meeting. The committee has to give a decision within 60 days after the submission of all documents. Upon application for the clinical trial of a medicinal product, gene therapy, cell therapy or an immunological medicinal product as well as using a genetically modified organism, the Committee shall make a resolution within 90 days Estonia - 2

3 Question 5: Is there a single organisation to which to apply for ethical review of a clinical trial for an investigational medicinal product, regardless of whether this is for a single site or multiple sites? Yes, application is to either of the two Ethics Committees (see 9. below). Question 6: What is the website for the organisation that issues guidelines on the ethical review of a clinical trial for an investigational medicinal product? The website of the State Agency of Medicines, which is the official body responsible for issuing guidelines on all aspects of clinical research involving investigational medicinal products is at Question 7: Is there a procedural interaction between the national or local competent authority and the (research) ethics committee during the approval process? It depends, usually not, but if the problems are complicated, consultation takes place. Question 8: Does the application to the REC and to the competent authority have to be submitted in parallel, or, if not, in which order? In parallel, but the competent authority does not give its authorisation before the approval of the (research) ethics committee. Question 9: How many (research) ethics committees are there in Estonia? There are two Ethics Committees on Human Research that have equal rights to review all kinds of human studies and medical research: 1. Research Ethics Committee of the University of Tartu. 2. Tallinn Medical Research Ethics Committee (attached to the National Health Development Institute). Question 10: How are RECs funded in Estonia? Do they charge fees? If yes, what is their scale of fees? Ethics committees are not funded by the state. The fee charged for assessing the protocol for a clinical trial is 383 euros. For protocol variations there is no fee. Estonia - 3

4 Question 11: Who is responsible for submitting the request for ethical review to the competent (research) ethics committee for single-site and for multi-site clinical trials? The sponsor or the investigator may submit the request. Question 12: How is a single opinion achieved for multi-site studies? In accordance with the Medicinal Products Act the single opinion is mandatory. There is no experience of a situation when applications were submitted to both ECs. Question 13: How many members serve on a REC? 13. Question 14: How many members constitute a quorum? A majority of appointed members (i.e. 50% + 1). Question 15: How are REC members appointed? By the authorities of the two medical and research institutions that have them, based on the principle of securing great variety in professions and competences. Question 16: How is the independence of members ensured? Any EC member who could be interested in the results of an EC decision cannot participate in the vote. Question 17: How are conflicts of interest of REC members avoided? Committee members sign a conflict of interest declaration. Question 18: What backgrounds and/or qualifications of members are actively sought? They are from different fields third part from committee contains medical doctors and other members are philosopher, lawyer, priest, psychologists, pharmacologist, sociologists, representatives of sports sciences and geneticists. Question 19: How do RECs obtain specialist expertise? When there are contradictions or more competence is needed, the EC will decide to seek expertise from appropriate field specialists. Estonia - 4

5 Question 20: What are the training requirements for members of RECs? 2 training seminars are held annually. Attendance at international meetings is encouraged, but opportunities are rare. Question 21: What training programmes are available for REC members in Estonia? Relatively few: there is a two-day seminar each year with both medical research EC members and some rare possibilities to attend international conferences. Question 22: What are the timelines for the assessment of single- and multi-site studies? As a rule assessment will be completed within 60 days for biomedical research and 90 days for genetic research as the legislation requires, but when additional documents are needed or problems arise then correspondence with the applicant may last much longer. Question 23: How are substantial amendments submitted during the review process dealt with? They are submitted with a summary of the amendment and are discussed at the next regular EC meeting. Question 24: How does a REC assess the suitability of investigators and of sites? The sites must have the correct conditions for trials to take place and the investigators must have required skills and experiences. A CV is requested from every investigator planned in a project. Question 25: How are the requirements for (research) ethics committees to review the contractual or financial arrangements in clinical trials for both investigators and hospitals handled? The contractual/financial arrangements in clinical trials are reviewed by the EC. Question 26: How are the requirements for (research) ethics committees to review the compensation arrangements for study subjects handled? The compensation of study subjects is always observed it cannot be too high nor too low. Estonia - 5

6 Question 27: Is there an ongoing quality assurance process (e.g. audits, inspections, internal SOP) for (research) ethics committees in Estonia? As either of the two ECs belong to an institution (in Tartu to the University, in Tallinn to National Health Development Institute) they are monitored by these institutions and their audits, inspections etc. Within the Estonian Ministry of Social Affairs is the Council of Bioethics (see 2.above), which, whilst not performing expertise, provides a co-ordinating role and also audits some of the work of ECs. Additionally, the Agency has the right to inspect all aspects of a clinical trial as well as the performance of the Ethics Committees. Updated information about the requirements and contact addresses is available on the website of State Agency of Medicines at Question 28: Is there an appeal mechanism? The decision of an EC can be taken to Court. Question 29: How do RECs deal with SUSAR reports and Annual Safety Reports? All SUSARs are reported at least quarterly, as a line listing accompanied by a brief report by the sponsor. The SUSARs and Annual Reports are submitted for analysis to some of EC members and they are discussed at the EC meetings. Question 30: How are substantial amendments defined? Substantial amendments may affect the safety of the trial subjects, or may alter the assessment of the scientific documents supporting the trial, or be required when previous trial results make the amendment of the written patient information necessary. Question 31: What are the indemnity insurance requirements for research projects? Indemnity insurance must be in place to cover any health injury in connection with the trial. Question 32: What are the indemnity insurance requirements for (research) ethics committee members themselves? There is a discussion of insurance requirements of members as part of the meeting but there are any insurance requirements for ethics committee members themselves. Estonia - 6

7 Question 33: How is informed consent obtained from vulnerable subjects who are potentially to be involved in a clinical trial? They can be involved when there is a direct benefit for them or if there is a consent of a legal representative (e.g. for children). Question 34: How do RECs assess the progress and outcome of research projects that they have approved? The final report of the study after its termination is demanded, and it will be given to EC members and in most complicated cases it will be discussed in EC meetings. Progress may also be assessed through the evaluation of serious adverse reactions. Question 35: How does the REC ensure reception of the Annual Safety Report and the Summary of the Final Report of a research project that it has approved? It is required by law and demanded if it is not submitted. Question 36: Do national regulations in Estonia allow research on healthy volunteer children (subjects under 16)? No volunteer studies (Phase I) are permitted on children under the age of 18. Further Information: In general terms, approval by one of the two Independent Ethics Committees and informed consent by the study subject, according to the international codes and Declaration of Helsinki, is mandatory. Clinical trial medication should be manufactured according to the principles of Good Manufacturing Practice (GMP) and the trials should be performed and the data generated in compliance with the principles of Good Clinical Practice (GCP) to ensure the ethical and scientific integrity of the trial (GCP code close to the Nordic document by the NLN was mandatory since 1991, later the ICH GCP was adopted and is currently directly referred to by the legislation). Details of the Research Ethics Committee University of Tartu is available on the following website: Details concerning the Estonian Council of Bioethics can be found on the website of Tartu University at Question 37: Do national regulations in Estonia allow payment, (other than expenses), to children taking part in research? No. Estonia - 7

8 Question 38: Do RECs invite or allow a) applicants or b) observers to attend committee meetings? Applicants may be permitted to present their cases and expert advisers may be invited to attend but to take no part in the decision-making process for a case. Question 39: Are the minutes of (research) ethics committee meetings made public? No. Question 40: Is there any scope for Chairman s actions in between meetings? The task of the chair of the Committee is to organize the work of the Committee, to call the meetings and to act as a representative of the Committee. Question 41: Do (research) ethics committees ever appoint subcommittees for any specific purpose? They do not appoint subcommittees. Question 42: Is there a national policy on the registration of clinical trials before they start? No. Question 43: If the answer to Question 42 is yes, do (research) ethics committees have any role to play in reviewing such registration? N/A Question 44: If the answer to Question 42 is yes, is this register of clinical trials made available to the public? N/A EFGCP May 2011 Estonia - 8