The Future of Ethics: A European Perspective

April 1, 2005
Applied Clinical Trials

A recent conference featured debate on the role of research ethics committees.

A recent conference featured debate on the role of research ethics committees.


Last month this column briefly remarked on the conference in Brussels on "Research Ethics Committees in Europe: Facing the Future Together." It was a significant first gathering of hundreds of representatives of local and regional ethics committees (ECs) from all across Europe. In view of its importance, it is appropriate to offer a snapshot of how far the meeting went in raising understanding between researchers, regulators, and ethicists about the challenges that ECs face.

The challenge is apparently huge. Even after research ethics committees (RECs) have been reviewing clinical trials for 20 years, fundamental questions about their role, scope, and structure remain a matter of debate, not consensus.

Organization of RECs
A workshop on the organization, infrastructure, and role of RECs at the country level revealed differences on everything from assuring independence to expertise of members, and from mechanisms of funding to levels of transparency.

If RECs are to play their role as guardians of the dignity of research subjects, insisted Dr. Jiri Simek of the Institute of Medical Ethics at Charles University in Prague, they must keep their independence from sponsors, researchers, institutes, regulatory authorities, and even from central ECs. Methods of nomination, qualifications for membership, and training are crucial influences on independence, he argued.

There were strong defenders of the voluntary approach to REC membership as a guarantee of independence. With ethics review seen as a matter of adventure rather than bureaucracy, it was recognized that some controls were required. Some saw the evolution towards greater professionalism as a guarantee of independence. Others viewed it as a threat to independent thinking.

Differing views were expressed on how to cope with the risk that independence might be compromised by close relationships between local committees and local investigators and sponsors, or by payment of REC members. Institutional RECs were depicted as being closer to--and more confident in--investigators, entailing the need for independence to be guaranteed by supervision. By contrast, regional committees may enjoy a greater detachment from investigators, but may be subject to influence from their appointing authority.

Caroline Trouet, of the Belgian pharmaceutical industry association pharma.be, noted the increasing complexity of the tasks facing RECs, their gradual assumption of legal status, and their subjection to national and EU legal controls and even legal liability. But she also highlighted the diversity of responses countries had adopted to meet these new circumstances, and the consequent challenges posed by any attempt at harmonization or standardization.

Overall, although some participants considered the composition of RECs to be insufficiently precisely laid down in the EU clinical trials directive, some consensus emerged. The merits of wide membership of RECs were both to boost independence and also to provide the widest possible range of expertise to cope with ever more sophisticated demands.

Easier communication between RECs was described as part of a move away from a system of secrecy and lack of mutual confidence to a sort of "peer review" system in which RECs routinely justify their opinions. A general raising of standards was also desirable to prevent REC-shopping by sponsors looking for a lax assessment.

Cristina Avendao-Sol offered an overview of the development of the Spanish RECs system in the wake of the EU clinical trials directive. It has brought a new level of coherence and transparency to the review process by establishing a "lead" REC to give an opinion on a multicenter trial. There is obligatory consultation among all other RECs involved, and an online register of multicenter trials.

Sigrid Skavlid of the central secretariat for RECs in Norway also provoked widespread interest. She told of the new electronically based application system in operation there since the start of 2005, aimed at bringing greater transparency into clinical trials review procedures.

Funding of RECs
Much of the discussion focused on how to fund RECs adequately--and from what sources. Workshop examples suggested RECs' fees ranged up to E2500 per assessment, with many concessions made to academic research. Many participants saw a risk to impartiality if there are direct payments from clients to RECs for services provided. "You don't pay the judge to get justice," observed Bert Vanderhaegen of the Ghent University Hospital EC.

But payment from the state was merited, it was argued, since the state was demanding the service. The clinical trials directive has not only required a central opinion on a multicenter trial, but has required a fast turnaround time which is often difficult to meet. RECs need administrative support to be able to meet their new obligations.

And even where new systems have been set up by the state, there are often serious resource problems in making the system function. In Spain, the authority that inspects and demands performance from RECs is not the one that provides the resources. There is a resource gap because of an institutional gap.

Professor Dominique Sprumont of the Institut de Droit de la Sant of the Universit de Neuchtel emphasized the emergence of a formal legal view of the role of RECs. This was exemplified by a landmark Swiss court ruling that their function is not to help researchers seeking funding for research projects, but to carry out what is a state duty to review clinical trials in respect of the public interest.

There was vigorous debate over how the imposition of new responsibilities on RECs was also creating increased liability for them. It was suggested that the state--and even researchers themselves--might be delegating more responsibility than they should onto shoulders that were ill equipped to carry such a burden. And it was pointed out that risks of liability were a strong disincentive to potential recruits to RECs.

The questions extended to the scope of ethics review (and even the scope of the meeting itself)--should it cover only interventive trials with medicines, all trials with medicines, or even wider, and at what cost? It was pointed out that clinical trials with medicines no longer hold a monopoly on discussions of ethics--even engineers nowadays conduct high-quality ethics assessments of new projects. Rainer Gerold, director at the European Commission, noted the wider need for discussions beyond bioethics--in nonmedical primate research, in nanotechnology, and the full range of EU-funded research projects.SOPs for RECs

A workshop on standard operating procedures and quality assurance examined how far RECs already follow standardized procedures and how far regulatory authorities are involved. Spain, Italy, the Netherlands, and the United Kingdom already accredit or inspect RECs, and wide support was expressed in the workshop for the idea. But it was stressed that care is needed in the balance between national and local powers, and in making clear the role of RECs in relation to other authorities.

Unanswered questions ranged across who should carry out site-specific assessments not based on ethical issues, on how to fix the limits to REC requests for further information from applicants, on the status of international guidance documents in quality assurance, and whether one REC refusal invalidates all parts of a multinational trial.

Interaction
How RECs should and should not interact with other parties was the focus of another workshop. Involvement of external expertise is often necessary, but there are potential risks in relation to confidentiality and security of data. Divergences of view between the REC and the national authority could create confusion among researchers and sponsors, increasing the risk of lawsuits against the RECs or the national authorities. And with the pharmaceutical industry, better dialogue is needed--and caution, particularly in respect of gifts, grants or other funding from the industry. Since most trials are commercially sponsored, financial interest is often bound to influence the design and planning of clinical trials.

Interaction with researchers was also, it was suggested, inadequate, and could be usefully boosted by better communication, including through better harnessing the power of the Internet. And some argued that laypersons on RECs should be genuine representatives of the local community.

Training
Training and dissemination of good practices was examined in one of the workshops--and revealed agreement on the merit of training, but practical difficulties in organizing and funding it.

Accurate targeting of training was emphasized, since different kinds of training are needed to match the different needs of REC members and administrators, and their different levels of experience. And the danger of professionalization of committee members was repeatedly raised: it was recognized that it is no easy task to promote a culture of ethical thinking that also maintains a healthy diversity of informed opinion.

Those who wish to know more can download the presentations and conclusions in full, from http://www.europa.eu.int/comm/research/conferences/2005/recs/programmetable_en.htm. Should they wish, they can also watch videos of the presentations, including the workshop summaries by your columnist, who was a rapporteur at the meeting.

But, as this column also suggested last month, the key performance indicator of the success of this meeting is what will come out of it. How many answers are found to the many questions raised? And that is something that will emerge only over the coming months and even years.

Quotes from the Meeting"The diversity of methods to respond to new circumstances is a challenge to harmonisation."--Caroline Trouet, deputy director of Pharma.be (the Belgian pharmaceutical industry association)
"The function of RECs is not to help researchers seeking funding for research projects."--Dominique Sprumont, Institut de Droit de la Sant of the Universit de Neuchtel
"Ethics review should be a matter of adventure rather than of bureaucracy."--Jiri Simek, Institute of Medical Ethics, Charles University, Prague
"Moving from secrecy to a sort of 'peer review' system."--Cristina Avendao-Sol, Puerto de Hierro hospital, Madrid
"You don't pay the judge to get justice."--Bert Vanderhaegen, Ghent University Hospital