Abstract

INTRODUCTION

In the Baltic States of Estonia, Latvia and Lithuania, as in most countries of Central and Eastern Europe, systematic ethical review of biomedical research started in the late 1980s. Two decades have passed, but information on the day-to-day functioning of Research Ethics Committees (RECs) is still rather scarce and sporadic.¹ In this paper we attempt to close this information gap.

Our goal is twofold: (1) to present a general overview of ethical review of human research in the Baltic States and (2) to identify some of the problems related to the role of ethical review in establishing a high quality research environment. We believe that this overview may provide some important insights into the processes of ethical review and the protection of research participants not only in the Baltic States but also in other transition societies.

HISTORICAL AND STRUCTURAL OVERVIEW

The emergence of ethical review of human research in the Baltics, which began in late 1980s, can be traced back to certain individuals who were knowledgeable about the workings of ethical review in the West and who were eagerly anticipating the first chance to join international research.² However, even though the Baltic States share many socio-economic characteristics, all three have developed rather different institutional models of ethical review, despite their common motivation to facilitate local researcher involvement in international research.

In Estonia, ad hoc committees for clinical trials were created as early as 1989.³ The first permanent RECs were established in 1990 by the University of Tartu and in 1992 by the Institute of Experimental and Clinical Medicine (now National Institute for Health Development) in Tallinn. These two RECs, affiliated with and dependent upon mother institutions, also perform functions of regional RECs since they also review research proposals from outside their own institutions. A national bioethics board, the Estonian Council on Bioethics, was established in 1998. One of its tasks is to coordinate activities of regional RECs. A special REC to review research conducted within the Estonian Genome Project was established in 2001, but its functions were later passed to the Ethics Review Committee on Human Research of the University of Tartu. In 2008, a special kind of REC, reviewing only matters related to research with medical data from Estonian e-health databases, was established. It is called the Ethics Committee of the Health Information System.

The emergence of the Lithuanian ethical review system was similar to that of Estonia. Two RECs were created in the late 1980s as a consequence of local research institution initiative, and not as a realization of some national policy. In 1994, the Law on the Health System⁴ was adopted, thus setting the conditions for the official establishment of the national REC, the Lithuanian Medical Ethics Committee (now Lithuanian Bioethics Committee) a year later. The Committee functions as a national bioethics council and also has a subcommittee for ethical review of biomedical research. In 2001, the Law on Ethics of Biomedical Research⁵ introduced a two-tier system with regional RECs. The Kaunas Regional Biomedical Research Ethics Committee was thus established at Kaunas University of Medicine in 2001. The second regional REC was established at Vilnius University in 2008.

Latvia was the last of the Baltic States to start this process. The first committee was founded at the Latvian Institute of Cardiology in 1992 and was then called the Ethics Committee of Clinical and Experimental Research. The second REC was created by Riga Stradins University in 1996, prior to any legal provisions being enacted. In 1997, the Parliament adopted the Medical Treatment Law⁶ creating a legal platform for establishing medical ethics committees. In 1998, the Statutes of Central Medical Ethics Committee⁷ were approved.

The situation in Latvia is more complex than in the other two countries. There are several kinds of RECs with different jurisdictions and scopes of operation. There is a national body, the Central Medical Ethics Committee, and there are other RECs of two kinds: institutional ones and those which are sometimes referred to as ‘regional’.⁸ However, these so-called ‘regional’ committees are not assigned to any particular region, all are located in Riga, Latvia’s capital, and the law does not require that applications for ethical review be submitted according to region of origin. It would be more appropriate, therefore, to distinguish between RECs with a narrow scope of review and RECs with a wide scope of review. Three committees review only clinical drug trials, one reviews drug trials and other types of human biomedical research, while four review all types of biomedical research, except clinical drug trials.

In all three Baltic States, ethical review of human research developed in bottom-up fashion. Initially RECs were established in particular university hospitals or medical faculties and only then were legal regulations put in place. Consequently the institutional structure of ethical review was reshaped by legal developments.

Currently all three systems of ethical review can be seen as structures that include a national body and local or regional committees established at various institutions that engage in biomedical research. It is only in Lithuania and Estonia where such local or regional committees are assigned geographically defined jurisdictions although some Latvian committees could be regarded as ‘regional committees’ in that they review research proposals from outside their founding institution even though there is no defined geographic region.

The relationship between national and local or regional RECs differs a lot across the Baltic States. For example, Estonian RECs simply provide to the national body annual reports about main facts and trends of their operation. The RECs themselves have taken the initiative. While in Lithuania, the division of responsibilities and accountability between national and local bodies is clearly defined in different normative documents.

All three national bodies (the Estonian Council on Bioethics, the Latvian Central Medical Ethics Committee and the Lithuanian Bioethics Committee) are state institutions. For example, the Lithuanian Bioethics Committee is an institution subordinate to the Ministry of Health. However, national bodies differ in their functions. For example, it is only the Lithuanian committee that supervises the rest of the committees and reviews their decisions upon appeal. The Lithuanian and Latvian committees differ from their Estonian counterpart in that they review research protocols. Before the introduction of the two-tiered system, the Lithuanian committee was the sole reviewer in the country. It is still the only body that issues decisions on clinical drug trials and on biomedical research studies that take place in more than one region. The Latvian committee reviews: (a) research proposals that are related to the National Genome Project and (b) non-drug trials. The Estonian Council on Bioethics does not review research.

In all three countries approvals of clinical trials of medicinal products cannot be granted by RECs alone. Each country has a State Agency of Medicines (called State Medicines Control Agency in Lithuania) that also participates in approval process. REC approval is a necessary but not sufficient condition of issuing an approval for a trial of this type. This is a direct outcome of the adoption of the Directive 2001/20/EC.⁹

REC workload, summarized in Table 1, lists the number of approvals by country (the figures exclude student research).

Figures 1–3 depict the organizational structure of ethical review in the Baltic States. Solid lines show which institutions issue approvals (or recommendations to issue approvals) for particular types of research. Punctuated lines show accountability of institutions. Dashed lines (in Lithuanian figure only) show recommendations to other committee.

Open in a separate window

Figure 1

Ethical review system in Lithuania.

Open in a separate window

Figure 3

Ethical review system in Estonia.

ETHICAL REVIEW AND QUALITY RESEARCH ENVIRONMENT

As reflected in Figures 1–3, the Baltic States have developed the legal and institutional structure for the ethical review of human research. However, the fact that a basic legal and institutional structure exists, does not automatically guarantee high quality ethical review. Although there can be no guarantees, there could be more confidence in a review process that at a minimum required: transparency in reporting REC activities and findings; clear, precise and justifiable rules and principles governing committee processes; specification of the composition and required qualifications for committee members, requirements for reporting of research process and findings; reliable funding and facilities for the committee; and legal protection of intellectual property. In this section we will briefly address several problematic areas connected to the quality of ethical review. These include: (a) availability of information, (b) management of conflicts of interest, (c) committee composition and motivation of REC members, and (d) differing stringency of ethical review for different types of studies.

CONCLUDING REMARKS

The experience of the Baltic States, as transition societies, may well be relevant to other transition societies. Over the past two decades, the ethical review of human research in the Baltic States has undergone significant legal and institutional development, with each country evolving in a separate direction. In many ways, the resulting systems adhere to international standards. However, problems remain. For example, the limited transparency and procedural clarity of ethical review hinder the creation of a quality research environment. RECs should be encouraged to increase the availability of data on reviewed protocols on their websites. New methods to manage conflicts of interest need to be created taking into account the influence that the structure of RECs has on those conflicts. More effort should be made to establish the optimal REC model in terms of composition of committees and motivation of their members. The legal environment should also be improved. Networking among RECs could be a potent tool to encourage the above-mentioned processes.

Acknowledgments

Footnotes

References

1. One of the first descriptions of RECs in Baltic States can be found in Glasa J, editor. Ethics Committees in Central and Eastern Europe. Strasbourg: Council of Europe; 2000. [Google Scholar]However, recently there have been some Europe-wide initiatives to collect information on ethical review of human research that also covered the Baltic States. One important source is the PRIVIREAL project, started in 2002. However, the information provided by the project’s website ( Privireal. Research Ethics Committees – Countries. Sheffield, UK: Privireal; 2005. [Accessed 31 Mar 2010]. Available at: http://www.privireal.org/content/rec/countries.php. [Google Scholar].) is in some respects already outdated. Results were published as Beyleveld D, Townend D, Wright J, editors. Research Ethics Committees, Data Protection and Medical Research in European Countries. Hants: Ashgate; 2005. [Google Scholar]. Another initiative is the European Forum for Good Clinical Practice (EFGCP) ongoing survey of ethical review procedures and practices related to clinical drug trials. Even though information provided by this survey is very recent (report was published in 2007 ( EFGCP Ethics Working Party on the Structure and Function of Research Ethics Committees in the European Union. The Procedure for the Ethical Review of Protocols for Clinical Research Projects in the European Union. Int J Pharm Med. 2007;21:1–113. [Google Scholar].); updates on the website are correct as of 2009 ( EFGCP. Update of the Report, as of 2009. Brussels: EFGCP; 2009. [Accessed 31 Mar 2010]. Available at: http://www.efgcp.be/html.asp?what=efgcpreport.htm&L1=5&L2=1. [Google Scholar].)) and comprehensive, it covers only a limited area of human research because drug-unrelated clinical trials as well as other types of biomedical research are not covered by the EU Clinical Trials Directive ( European Commission. Directive 2001/20/EC of 4 April 2001, of the European Parliament and of the Council on the approximation of the laws, Regulations and administrative provisions of the Member States relating to implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. OJ L. 2001 Jan 05;121:34. [Abstract] [Google Scholar].) that the EFGCP activities are based on.

2. As is indicated by Lithuanian bioethicists, ‘[t]he process of development of ethical review in Lithuania (and probably many other Central and Eastern European countries) […] was strongly facilitated by foreign pharmaceutical companies.’ Cekanauskaite A, Gefenas E. Research Ethics Committees in Lithuania. In: Beyleveld, et al., editors. op cit. 2005. pp. 140–147.pp. 141 note 1. [Google Scholar]. Similar views were expressed by Estonian and Latvian experts as well. In the questionnaire received from one of the Estonian RECs, it was indicated that the motive for the establishment was to embrace ‘new possibilities to take part in international medical research. […] The international requirements demanded independent body for the overview of research projects.’ One of the Latvian RECs also reported that the main motive was ‘the necessity to review the research involving human participants, as well as rapid development of drugs clinical research’.

3. Veidebaum T. Research Ethics in Estonia. In: Beyleveld, et al., editors. op cit. 2005. pp. 41–43.pp. 41 note 1. [Google Scholar]

4. Seimas of the Republic of Lithuania. Republic of Lithuania Law on the Health System. [Accessed 31 Mar 2010];Parliamentary Record. 1995 Dec 01;:12. Available at: http://www3.lrs.lt/pls/inter3/dokpaieska.showdoc_e?p_id=23358.

5. Seimas of the Republic of Lithuania. [Accessed 31 Mar 2010];Republic of Lithuania Law on Ethics of Biomedical Research. 2000 Available at: http://www3.lrs.lt/pls/inter3/dokpaieska.showdoc_e?p_id=148740.

6. Latvijas Republikas Saeima (Saeima of the Republic of Latvia) Ārstniecbas likums (Medical Treatment Law) [Accessed 31 Mar 2010];Latvijas vēstnesis. 1998 Jan 07;(Nr. 167) Available at: http://www.likumi.lv/doc.php?id=44108.

7. Latvijas Republikas Ministru kabinets (Cabinet of Ministers of the Republic of Latvia) Centrālās medicnas ētikas komitejas nolikums (Statutes of Central Medical Ethics Committee) [Accessed 31 Mar 2010];Latvijas vēstnesis. 1998 15 01;(Nr. 10) Available at: http://www.likumi.lv/doc.php?id=46597.

8. Eg. Privireal. Latvia – RECs and Medical Research. Sheffield, UK: Privireal; 2005. [Accessed 31 Mar 2010]. Available at: http://www.privireal.org/content/rec/latvia.php. [Google Scholar]

9. European Commission. op cit. note 1. [Google Scholar]

10. An exception is the website of the Lithuanian Bioethics Committee ( [Accessed 31 Mar 2010]; Available at: http://bioetika.sam.lt.). This institution also has an official template for information requests and is obliged to answer inquiries. However, even here information sometimes is not regularly updated. For example, at the time of this research, statistics on the number of reviewed protocols had not been updated since mid-2005.

11. An example of one such database is ClinicalTrials.gov, a service of the US National Institutes of Health. [Accessed 31 Mar 2010]; Available at: http://clinicaltrials.gov.). Also, Article 19 of Helsinki Declaration ( World Medical Association. Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects. Helsinki: 1964. [Abstract] [Google Scholar]; amended Tokyo: 1975; Venice: 1983; Hong Kong: 1989; Republic of South Africa: 1996; Edinburgh: 2000; Washington: 2002; Tokyo 2004; Seoul 2008). [Accessed 31 Mar 2010]; Available at: http://www.wma.net/en/30publications/10policies/b3/index.html..) states that: ‘Every clinical trial must be registered in a publicly accessible database before recruitment of the first subject.’ This idea was also supported by the International Committee of Editors of Medical Journals which stipulates that member journals require authors to register their trials (including methodology) in a registry that is accessible to the public free of charge ( International Committee of Medical Journal Editors. [Accessed 31 Mar 2010];Obligation to Register Clinical Trials. 2009 Available at: http://www.icmje.org/publishing_10register.html..). The European Commission also issued guidelines on the list of fields contained in the EudraCT clinical trials database that should be made publicly available ( European Commission. List of fields contained in the ‘EudraCT’ clinical trials database to be made public, in accordance with Article 57(2) of Regulation (EC) No 726/2004 and its implementing guideline 2008/C168/02. [Accessed 31 Mar 2010];2009 Available at: http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-10/2009_02_04_guideline.pdf..).

12. The Ethics Review Committee on Human Research of the University of Tartu has published an annual list of all approvals since 2008; see Tartu Ülikooli inimuuringute eetika komitee (Ethics Review Committee on Human Research of the University of Tartu). 2009. Tartu Ülikooli inimuuringute eetika komitee menetlus 2008 (Approvals given by the Ethics Review Committee on Human Research of the University of Tartu in 2008). [Accessed 31 Mar 2010]; Available at: http://www.ut.ee/orb.aw/class=file/action=preview/id=595718/Ec_2008_kokkuv6te.pdf.

13. For example, the Statutes of Tallinn MREC [provided by the REC] simply state that members who are not ‘independent from the performers of the research’ may not vote.

14. In Latvia, it is true only of those RECs that review clinical drug trials.

15. Lietuvos Respublikos Sveikatos apsaugos ministerija (Ministry of Health of the Republic of Lithuania). 2008. Lietuvos Respublikos sveikatos apsaugos ministro įsakymas dėl regioninių biomedicininių tyrimų etikos komitetų narių skyrimo tvarkos aprašo patvirtinimo (Decree of the Minister of Health of the Republic of Lithuania on the Procedure of Nomination of the Members of Regional Biomedical Research Ethics Committees). Valstybės žinios, 2008-06-17, Nr. 69-2635. [Accessed 31 Mar 2010]; Available at: http://www3.lrs.lt/pls/inter3/dokpaieska.showdoc_l?p_id=322379&p_query=&p_tr2=

16. Lietuvos bioetikos komitetas (Lithuanian Bioethics Committee). 2007. Lietuvos bioetikos komiteto pirmininko įsakymas V-8 Dėl Lietuvos bioetikos komiteto biomedicininių tyrimų ekspertų grupės darbo reglamento patvirtinimo (Decree of the Lithuanian Bioethics Committee no. V-8 on the Working Procedures of the Biomedical Research Experts’ Group). Valstybės žinios, 2008-02-28, Nr. 24-893. [Accessed 31 Mar 2010]; Available at: http://www3.lrs.lt/pls/inter3/dokpaieska.showdoc_l?p_id=315164&p_query=&p_tr2=

17. Latvijas Republikas Ministru kabinets (Cabinet of Ministers of the Republic of Latvia), op. cit. note 7. Art. 3.

18. University of Tartu. [Accessed 31 Mar 2010];Statute of the Ethics Review Committee on Human Research of the University of Tartu. 2007 Available at: http://www.ut.ee/orb.aw/class=file/action=preview/id=276573/TY+Inimuuringute_et-en_070828_9015_statuut_en_ok-ED.pdf.

19. For a general argument that REC members should be adequately remunerated, see Druml Ch, et al. Research Ethics Committees in Europe: Trials and Tribulations. Intensive Care Med. 2009;35:1636–1640. [Abstract] [Google Scholar]

20. This also leads to the issue of rotation of REC members. Lack of potential candidates may be dealt with by having no formal term limits for an REC member. For example, in Estonia, term limits were introduced only in 2007.

21. European Commission. op cit. note 1. [Google Scholar]

22. Seimas of the Republic of Lithuania. op cit. note 5, Art 2.1. [Google Scholar]

23. Ibid: Art 3.1.

24. For Estonia, some guidance can be found in the Oviedo Convention (Council of Europe. 1997. 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. [Accessed 31 Mar 2010]; Available at: http://conventions.coe.int/Treaty/en/Treaties/Html/164.htm..). This treaty has been ratified by Estonia and Lithuania but not Latvia. The Convention states that human scientific research in the field of biology and biomedicine cannot be conducted without ‘multidisciplinary review of its ethical acceptability’ (Art 16.3).

25. Human research conducted by students in educational setting may also involve significant risks to research subjects and therefore should receive ethical scrutiny. However, it may be impracticable to apply stringent procedures to student research. There is no definition of student research in Lithuanian, Latvian or Estonian legislation. Most medical schools in the Baltic States have internal regulations concerning the need for ethical review of student research. These internal regulations are based on local initiative not on overarching national policies.

26. Information on the Baltic research ethics network activities can be found on the website of Lithuanian Bioethics Committee. Available at: [Accessed 31 Mar 2010]; http://bioetika.sam.lt/index.php?-809972162.