SLOVAK REPUBLIC

Research Ethics Committees

I. Introduction and Historical Overview

The ethical review of biomedical research, including the clinical trials (CTs) of medicinal drugs, performed by ethics committees (ECs) has more than 17 years' tradition in the Slovak Republic (SR). ECs started to be established in a 'voluntary' manner since 1990, after the victory of the so-called "Velvet Revolution" in the former 'socialist' Czech-Slovakia. Even before that, biomedical research projects conducted under the 5-year 'socialist' state research plans were to be submitted to a rigorous scientific review. That review included also some appraisal of the ethical aspects of research with regard to mostly Hippocratic tradition of medical/health care ethics.

Since the first national "Guidelines on the establishment and work of ethics committees in health care and health research facilities" had been issued in June 1992 by the Ministry of Health of the SR, a lot was done in the SR to develop institutional and professional pre-requisites for a good quality, competent ethics review (and monitoring) of biomedical research projects and CTs' protocols. The SR has been taking great care to fully apply to its national legislation all the requirements of the European Union's legislation on medicinal drugs, CTs and Good Clinical Practice (GCP). In parallel, numerous institutional and non-institutional education and training activities are taking place, to ensure capacities and competence building among ECs members and users. Several international meetings and postgraduate courses devoted to these issues took place in SR during the previous period. Some of them were co-sponsored by international programs or projects of the Council of Europe (e.g. DEBRA Program) or of the European Commission.

Nowadays a high level of awareness and professionalism with regard to the ethics review of biomedical research, and in particular to the review of CTs, is present at the competent state authority (National Institute for Drug Control) and ECs in the SR. The same is true concerning the situation among researchers, health professionals, and health/research facilities' administrators. Clearly established legislative and institutional backing of the ECs system in the SR provides for a transparent, effective and fair ethics review process. Some practical deficiencies still present are dealt with on a systemic basis, so further improvements with regard to the ECs system's quality and performance are continuously introduced.

II. System of Local Research Ethics Committees; Institutional Affiliation

The following types of ethics committees are established in the Slovak Republic:

1. Ethics Committee of the Ministry of Health ('National' EC, formerly 'Central EC')

The Ethics Committee of the Ministry of Health is appointed by the minister of health according to the provisions of the Law No. 576/2004 Coll. on health care as an advisory body on questions of bioethics, including those connected with ethics of biomedical research and clinical trials.
It is to serve to the needs of the ministry of health in the first place, but it could also be approached for an opinion/advice/information on bioethical issues by other state institutions (other ministries, the parliament). It is also serves as a consulting body for the 'local' and 'regional' ECs in the SR. The committee represents the SR at the relevant international fora.
The committee only exceptionally performs the ethics review of projects or protocols for a specific research project (when for example, there is no other relevant or responsible ethics committee for the specific project).
The establishment and activities of the committee are governed by its Statutes and Working Procedures issued by the minister of health.

2. (Local) Ethics Committees

(Local) Ethics Committees are established by directors of health care facilities or biomedical research institutions. They are to review protocols of CTs or biomedical research projects planned to be performed in that facility/institution, and to provide a follow up of the research approved.
These ECs may also be required to advice the director of the facility/institution on ethical issues arising from the health care provision by the facility/institution, so to function also as the so-called "clinical ethics committees". Health care institutions, however, can establish different ethics committees to deal with 'research' or with 'clinical' ethics.

3. (Regional) Ethics Committees

Regional Ethics Committees are appointed by the regional state authority. Their task is to review and monitor the conduct of multicentre CTs and multicentre biomedical research projects (with an exception of the review of 'local aspects' of CTs/research projects), as well as of CTs/research projects performed on the outpatient basis (via doctors'/specialists' offices).
They also may be required to advice the regional state authority (e. g. the regional state physician) on ethical issues arising from the health care provision in the region.

Submitting the Request for Ethics Review

An opinion of the ethics committee (EC) should be sought for any CT or biomedical research project to be conducted in SR. The necessary authorization from the competent state authorities (see below) is granted only after the positive opinion from the EC has been obtained.

Medicinal Drug Clinical Trials (CTs)

For applications for drug clinical trials authorizations to the State Institute for Drug Control (SIDC) for phase I – III drug CTs, and for notifications of CTs for phase IV drug CTs, the Note for Guidance No. 7/2006 of SIDC for applicants for the authorization of drug clinical trials is relevant. The website of SIDC is at www.sukl.sk.

The provisions of the law No. 140/1998 and of the ministerial regulation No. 239/2004 are the most important for CTs review and authorization procedures, as well as for their conduct, monitoring, and reporting.

For single-site CTs of Phases I to III, an authorization from the State Institute for Drug Control (SIDC) is necessary, and for Phase IV studies notification to SIDC is required. Additionally, for all single-site clinical trials, an authorization should be sought at the "local level": if a CT is to be conducted in an inpatient health care facility or research institution, the authorization is given by the director of that facility/institution. The authorization is granted only when the opinion of the "local" EC (i.e. the EC based at that facility/institution) is positive.

For CTs to be conducted in outpatient physicians' offices, an authorization from the "state physician" of the regional state authority should be sought. A positive opinion of a "regional" EC (i.e. EC established at that regional state authority) is required.

For multi-site clinical trials the authorization/notification process is similar to the one described above. If a CT is conducted in outpatient physicians' offices located at the territory of different regional authorities, the authorization should be sought from all "state physicians" of the authorities concerned. (The territory of Slovakia is divided into 8 such regions.)

The sponsor submits the request to both SIDC (for the authorization or notification, as appropriate) and to EC (for ethics review). Both submissions could be done in parallel to save time.

The single opinion for multicentric CTs (as required by Dir. 2001/20/EC) is given by one ethics committee, which is to be chosen by the sponsor. This is usually the ethics committee of the institution where the co-ordinating investigator is located. This ethics committee, however, is required by law, before giving its opinion, to consult ECs of all centres involved in the clinical trial.

In practice, to save time, it is recommended that the sponsor should submit the protocol and related materials to all the (research) ethics committees concerned. Local ECs should focus on solely local aspects of the clinical trial; however, they may make comments or suggestions concerning any scientific or ethical aspect of a CT protocol. A negative opinion from a local EC means that the clinical trial cannot be conducted at that facility/institution. Whenever a single opinion is positive, the clinical trial may be conducted in any centres whose local ECs have also given a positive opinion. There is no appeal mechanism against a negative opinion of an EC. An EC is required by law, however, to give clear justification for such an opinion. This justification is to make an integral part of the negative opinion.

The timelines for the assessment of single- and multi-site studies are provided for by law – 60 days, in accordance with the legislation. Substantial amendments to already approved CTs protocols have to be reviewed by EC within 35 days.

Biomedical Research Projects

Applications for the ethics review of biomedical research projects to ECs (and for authorization to either the director of the health care facility/biomedical research institution and/or to the state physician at the regional state health authority, as required by the law No. 576/2004) are to be submitted by the principle investigator/leading researcher. The requirements and procedures for single inpatient (institutional), or multicentre/outpatient research projects' review and authorization are closely similar (as appropriate) to those described above for CTs.

III. Legal Situation / Implementation of the DIRECTIVE 2001/20/EC

The first document devoted to ethics committees was published by the Ministry of Health of the SR (MH SR) in June 1992, entitled "Guidelines for the establishment and work of ethics committees in health care facilities and research institutions".

The term "ethics committee" (EC) is defined in general terms (for any biomedical research) in the Law No. 576/2004 Coll. on health care (as later amended). Some additional specifications for drug CTs – according to the principles and requirements of Good Clinical Practice – are provided for in the relevant paragraphs of the Law No. 140/1998 Coll. on drugs and medical devices (as later amended) and the Ministry's of Health Regulation No. 239/2004 Coll. on clinical investigations and good clinical practice.

Thus at present, from the legal point of view, ethics committees in the Slovak Republic are established and function according to the requirements of either:

• Law No. 576/2004 Coll. on health care (as later amended) covers biomedical research in general, including genetic research.
• Law No. 140/1998 Coll. on drugs and medical devices (as later amended) and the Ministry's of Health Regulation No. 239/2004 Coll. on clinical investigations and good clinical practice (issued under the Law No. 140/1998) specifically cover clinical trials of medicinal drugs, and of medical devices.

Directives 2001/20/EC as well as 2005/28/EC are fully implemented within this national legislation.

Both laws and the ministerial regulation are downloadable from the official web page of the Collection of Laws of the Slovak Republic (www.zbierka.sk) (Slovak versions only, English translation of chosen excerpts from the Law. No. 140/1998 Coll. could be found at the web page of SIDC – see below).

The State Institute for Drug Control (SIDC) (in Slovak: Štátny ústav pre kontrolu liečiv – ŠÚKL) – the state medicinal drugs regulation authority in SR, issues notes for guidance on applications for authorization of CTs of medicinal drugs and medical devices in SR: Note No. 7/2006 (the latest version), and on reporting of adverse events or adverse rections during CTs' conduct: Note No. 5/2005 (the latest version) – both downloadable from SIDC's web page: www.sukl.sk) (in Slovak, a brief synopsis in English is available).

• IV. Number and Composition of the Committees, Associations
• Number of ECs in the SR

According to the law (576/2004), each inpatient health care facility in Slovakia should have a (research) ethics committee, which is expected to assess applications for the ethics review of the clinical trial protocols and other biomedical research projects to be conducted at that facility. If chosen by the sponsor, that committee may give "the single opinion" for a multi-site clinical trial (as required by the Dir. 2001/20/EC.).

Also, according to the law, each regional state authority should have an EC established. There are 8 regional (research) ethics committees, and about 40-50 "local" (research) ethics committees.

ECs membership, interdisciplinary composition

ECs usually have between 5 and 9 members. The quorum is constituted by two-thirds of the appointed members. Their composition should be multidisciplinary.

The law (576/2004) requires that at least 50% of EC's members should be health professionals. It also requires the membership of a lay person, a lawyer, and members with qualifications deemed necessary for the EC's work. Usually, a theologian (priest, minister, rabbi) and a psychologist are sought. A clinical pharmacologist usually is the secretary or chair of the EC, if available. A nurse is also usually a member of the EC. An independent member (from outside of the health care/biomedical research facility/institution) is also usually appointed.

Besides relying on the expertise of their own members, ECs could also ask for opinions of external experts. This 'service' should be paid by the appointing authority.

Appointment of ECs' members

The director of the health care facility or biomedical research institution appoints members of the "local" ECs. The director may be advised on this by e.g. a scientific council of the institution, or by the EC itself, if it already exists (regarding the appointment of new members).

The president of the regional state authority appoints members of the "regional" ECs. Usual term of service of ECs' members is 4 years, may be renewed.

Independence, conflict of interest

The independence of members or ECs is not ensured by any specific provision of the law. It is usually stated, however, in the EC's statutes, while the appointing authority is asked to avoid any inappropriate external pressures being exerted on the members.

The law requires an EC member to disclose any conflict of interest with regard to a clinical trial being assessed by the committee. Such member must not take part in discussing/reviewing the CT, nor in the process of producing, or voting on, the EC's opinion concerning that CT.

Funding of ECs, fees

Ethics committees usually do not have their own budget. Health care facilities/research institutions/regional state authorities should provide necessary means for ECs' activities (office space, secretarial support, etc.). Usually, a tentative budget for the EC is set within the budget of the health care facility/research institution/regional state authority, but the EC usually has no direct control over this budget.

ECs do charge fees but these go to the budget of their appointing health care facility, research institution, or regional state authority.

ECs' Association

There is no ECs' association at the present in SR. The ('National') Ethics Committee at the Ministry of Health in collaboration with Institute of Medical Ethics and Bioethics n. f. in Bratislava are taking care at present for ECs' needs and development, also in relationships with relevant state authorities.

Registration of ECs is foreseen in Slovakia, which would allow for quality assurance of their establishment, composition and work. This is to be provided for by the ministerial regulation on ECs, which is pending. The office maintaining such register of EC (database) in SR will be established (probably at the Ministry of Health).

ECs education and training

So far no training requirements for members of ECs are officially laid down. However, earlier guidelines for ECs asked for regular continuous education and training of ECs members. This education and training was provided and co-ordinated by the Institute of Medical Ethics and Bioethics in Bratislava. The ministerial regulation/guidelines pending should provide backing for an introductory and continuous education of EC members. At present, a state-accredited study program in "clinical investigation and Good Clinical Practice" is hosted at the Institute of Pharmacology and Clinical Pharmacology of the Slovak Medical University SMU www.szu.sk/en in Bratislava. After passing the program, and subsequent state board exam, a state certificate is awarded. . There are also postgraduate courses in bioethics held at the Slovak Medical University in Bratislava, usually organized by the Institute of Medical Ethics and Bioethics IMEB www.bioethics.sk.

Quality assurance of ECs

No centralized authority currently supervises or audits ethics committees, or checks for their quality. SIDC, however, within its inspections, may raise such questions with the director of the health care facility or research institution inspected.

Indemnity insurance for ECs members

This is not yet covered at all. There are limited discussions on the issue so far. Probably, this will be covered explicitly in the future by the appointing authority. The cases of negligence may also be litigated. However, no such litigations have taken place in Slovakia so far.

V. Current Debate

Public debate on bioethics issues has not been developed very much so far in the SR. Occasionally, especially when ignited by media, or by an appealing case, the debate or polemic is launched. It is mostly seen and conducted as a "media issue", only seldom it is related more closely to a concrete legislation initiative debated at the same time at the Slovak parliament.

Local or regional ECs have not been involved in public debate so far. The ("National") Ethics Committee has been involved in the debates repeatedly, but not directly as such. Rather, either its opinions were referred to, or its members were consulted as single persons/experts by the media or various stakeholders taking part in the debate.

The topics of the debate so far included: abortion and abortion legislation, right to life, demography and population control, contraception, gay rights, stem cells, embryo research, health care system reform, euthanasia.

VI. Contact / Addresses

Ethics Committee at the Ministry of Health of the Slovak Republic
Standing Working Group on Ethics Committees
Chairperson: Assoc. Prof. Jozef Glasa, MD, PhD.
Limbová 2
83752 Bratislava, Slovak Republic
josef.glasa@szu.sk, glasa.imeb@szu.sk
tel.: 00421 2 59 36 94 72
fax: 00421 2 59 36 95 06
www.health.gov.sk/Titulka (go to "Etická komisia")

Ethics Committee at the Ministry of Health of the Slovak Republic
Chairperson: Dr. Peter Križan, MD, PhD.
Secretary: Mgr. Milan Valúch
Limbová 2
83752 Bratislava, Slovak Republic
URL www.health.gov.sk/Titulka (go to "Etická komisia")

State Institute for Drug Control
Štátny ústav pre kontrolu liečiv
Kvetná 11
825 08 Bratislava 26, Slovak Republic
URL www.sukl.sk