Legislation on medical research in different EU member states

The European Clinical Trials Directive had been adopted in most of the present member states by 2004. In various countries national legislation based on European Directives was enacted to regulate different areas of medical research. These laws varied across the EU: some countries had very detailed legislation, while others had only a few framework laws. Countries could be roughly divided into three categories according to how they regulated medical research: (1) those only regulating trials on medicinal products and medical devices; (2) those with legislation regulating trials on medical products and medical devices in addition to different legislation regulating other types of medical research; and (3) those where all medical research was handled in the same way (table 1).

In 2010, the Oviedo Convention regulating biomedical research had been ratified by 15 member states (Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, Greece, Hungary, Latvia, Lithuania, Portugal, Romania, Slovakia, Slovenia and Spain) and signed by six (France, Italy, Luxembourg, Netherlands, Poland and Sweden).

According to our findings, the majority of countries regulated medical research on the basis of the scope and content of the research. Clinical drug trials (or drug and device trials, subsequently called drug trials) were legally regulated in all EU countries, and most countries also regulated other types of research, but under different legislation, generally biomedical research and genetic studies. In many countries, there were no specific laws for trials using products other than drugs, genetic studies or registry-based studies. Only two countries (Denmark, Netherlands) regulated all medical research in the same way.

REC details

The number of RECs varied from one in Luxembourg and Romania to 215 in Belgium and 264 in Italy (table 2). In Cyprus, Denmark, Finland, France, Germany, Greece, Hungary, Latvia, Lithuania, Malta, Netherlands, Poland, Portugal, Slovakia, Slovenia and Sweden, there was one national ethics committee and several local or regional RECs. In most of these countries, the central ethics committee handled applications for clinical drug trials, while local RECs handled applications for other types of medical research. In some countries, the central committee also functioned as a coordinator for medical research and as an advisory institution for difficult cases.

In the countries with one central or national REC, its members were appointed by the ministry of health (or the health minister). The members of regional, local and institutional RECs were appointed by various bodies in different countries: research or healthcare institutions, universities, ministries of health, regional authorities or other appointing bodies.

Based on the mandate of RECs, countries can be divided as follows: (1) countries where RECs are responsible only for clinical drug trials; (2) countries where medical research has to be approved by RECs; and (3) countries where all research on human subjects is reviewed by RECs (table 1).

In the majority of countries, the mandates of RECs coincided with the areas covered by national legislation (table 1), although there were exceptions. In Belgium, Malta, Poland and Portugal, specific legislation existed only for clinical drug trials, whereas all medical research had to be approved by RECs (and in Poland, all research on human subjects). In Greece, Latvia, Lithuania and Luxembourg, legislation also covered other types of research except clinical drug trials, but only applications for clinical drug trials had to be submitted to RECs.

According to results from the PRIVIREAL study, RECs in most countries had approval power. However, RECs had advisory power in Austria, Finland, France and Slovakia, and in the Czech Republic, Latvia, Malta and Portugal the type of power they had was determined by the type of research.15 However, the difference between approval power (expressly giving permission to conduct the research) and advisory power (voicing no objection to the research) is largely academic as it is not possible to carry out research if an REC opposes it. Still, it is easier to appeal against a decision than against advice.

The length of time for obtaining research permission varied from 15 to 90 days. In some countries, the same rules were applied for all types of research (France, Greece, Malta, Poland, Slovakia, Slovenia, Swedenand UK). However, in others, the length of time also depended on the type of research (Austria, Belgium, Cyprus, Denmark, Estonia, Germany, Hungary, Italy, Netherlands and Spain), while in some countries, the length of time was specified only for drug trials but not for other types of research (Bulgaria, Czech Republic, Finland, Ireland, Latvia, Lithuania, Luxembourg, Portugal, Romania and Spain).

In most countries, there was no procedural interaction between the national competent authority (in most cases the national medicines agency) and the REC concerning the authorisation of a trial with a medicinal product: exceptions were Austria, Hungary, Lithuania and Netherlands. In some countries, despite the lack of legislated interaction, information was exchanged between the competent authority and RECs: Belgium, Denmark, Finland, France, Greece, Latvia, Luxembourg, Malta, Poland, Spain and UK.

Rules for obtaining informed consent from vulnerable persons in clinical drug trials differed depending on the country (table 3). The countries can be divided into four general categories: (1) those where more or less the same rules were applied to all vulnerable groups with no exceptions; (2) those where different rules were applied to different vulnerable groups, for example, minors, mentally ill patients, unconscious patients, etc, with no exemptions in specific cases; (3) those where informed consent was not required in certain specific cases (otherwise, either the same or different rules were applied to different vulnerable groups); and (4) direct involvement of the REC was needed for obtaining consent from vulnerable groups or for regulating the procedure.

After a negative decision from the REC, there was no appeal mechanism in 10 EU countries (Belgium, Czech Republic, Germany, Greece, Ireland, Italy, Malta, Romania, Slovakia and Spain), and the appeal mechanisms in the countries where it was available differed (table 4). In many countries, an appeal could be sent to the central ethics committee (Bulgaria, Cyprus, Denmark, Finland, Latvia, Lithuania, Netherlands and Sweden), in some it could be sent to another REC (France, Slovenia and UK) and in some countries, to the ministry of health (Luxembourg, Poland and Portugal). In Austria, the appeal had to be filed with the competent authority, in Estonia with the court, and in Hungary different rules were applied for different types of research. If the appeal body was the central ethics committee, the possibilities for appealing decisions varied. The nature of the appeal also varied; for example, in Finland, on request the central committee only issued opinions, not decisions, concerning rejected proposals or their handling.

The RECs were not accountable to any organisation in five countries (Czech Republic, Estonia, France, Spain and Sweden); in the rest, the body to whom they were accountable varied (table 2). In many countries, the central REC was accountable to the government or the ministry of health, and the local RECs to the central REC or to the institution that appointed its members. In Denmark, Latvia, Poland and Slovenia, the central REC was independent, and the local RECs were accountable to the central committee.