Crunch-Time for Europe's Clinical Trials Rules

What might be the determining phase of discussions on new clinical trials rules for Europe is starting this autumn.

Talks are scheduled to begin November between the three European Union institutions that must reach a final view on the proposed new rules. This is the stage of EU legislation when members of the European Parliament slug it out with the Council of Ministers­—which consists of national governments—under the watchful gaze of the European Commission, which drafted the initial proposal.

Compromise is supposed to be the name of the game—and there are plenty of areas where compromise is going to be needed. Divergences of view exist on everything from data transparency to the role of ethics committees, from time-frames for decisions to the requirements for informed consent, and from sponsors' responsibilities to insurance and indemnification.

But on some of the issues—and notably on data transparency—the positions are so far apart that compromise seems difficult, if not downright unlikely. Add to that the urgency forced onto the talks by a tight legislative calendar, and you have all the ingredients for an explosive rather than an emollient negotiation.

The urgency springs from the parliament's own timetable. There are now barely six months left in the current EU legislature. The current European Parliament dissolves in April 2014, in time for the May election of a new batch of 751 MEPs for the next five years. Any unfinished legislation may simply lapse. If the talks go well, there is the prospect of a deal without the need for a second reading by the parliament. That could allow the legislation to be signed off—in the EU's elephantine procedures—by everyone by March, just in time to squeeze through before the limbo imposed by elections. But there is little slack in the timetable to accommodate any delay, and without a strong spirit of compromise a second reading could be demanded by the parliament, almost certainly condemning the proposal to death.

Data transparency

One of the potentially explosive issues is data transparency, and on the eve of the talks, the battle-lines were clearly drawn. On one side was the parliament, whose health committee has unanimously agreed that "in general the data included in clinical-trial study reports should not be considered commercially confidential once a marketing authorization has been granted or the decision-making process on an application for marketing authorization has been completed."

The amendments sought by the committee go much further than the commission's initial proposal, and it remains to be seen how willing the commission will be to accept any of the changes sought.

Within the council too, although no public position has been taken yet, there are many national voices reluctant to go as far as the parliament wishes on access to clinical trials data.

The confrontation is being stoked by advocates from both sides. The European consumers association, BEUC, has urged member states to "stand for transparency and further improve the requirements for the publication of clinical trials results," and the European Patients Forum says it "strongly supports more effective data sharing from clinical trials to enable researchers to revisit and reanalyze clinical trials data."

But the research-based industry is ferociously opposed to the enthusiasms of the transparency zealots. The European Federation of Pharmaceutical Industries and Associations has attacked "the unbalanced approach adopted by the committee on the issue of confidentiality of clinical data." It has warned that if the committee's view prevails, it "will jeopardize patient privacy, the integrity of regulatory systems, and incentives for investment in biomedical research in Europe."

National hesitations

The parliament's position is clear, because it results from open public debate. The position of the council is, as ever, much more opaque. National officials have held some 20 meetings so far to examine the proposal—but their meetings take place behind closed doors, and diplomatic reticence and discretion about the proceedings is the rule.

However, among the hints that have emerged, Poland believes the proposal already goes too far in arrogating what should be done at European level, at the cost of national sovereignty—even before the parliament's more buccaneering approach is taken into account.

The time limits envisaged for authorization and validation of clinical trials are still too short, say many national governments, who fear they will not be able to cope. There are particular concerns at the provision that trials should receive tacit approval if time limits are not complied with.

Some national governments are still holding out for an explicit reference in the proposal to the role of ethics committees in the ethical evaluation of clinical trials. And where the proposal deals with the protection of subjects and informed consent, some countries want an explicit reference to national laws on the protection of volunteers. There are also rival schools of thought among member states about the correct approach to the conduct of clinical trials in emergency situations.

Plans to oblige member states to set up a national indemnification scheme for damage compensation in clinical trials have also come under attack in some countries. The whole question of damage compensation, insurance, and indemnification has raised further concerns in some countries about how these rules should apply to damage that might be suffered by subjects in low-intervention trials.

Even the concept of a centralized EU portal through which clinical trial applications will be made—widely welcomed by national governments—has prompted questions about how fast this portal will function and how much it will cost, as well as who will pay for it. There is some resentment among member states at the suggestion the commission makes that its own inspections and controls should be conducted on national systems to audit their efficiency.

UK support

One member state which has been less bashful about its position is the United Kingdom. Although it still maintains a "scrutiny reserve" on the proposal (which in effect means that it considers nothing agreed until everything is agreed), it has indicated strong support for the overall concept of the proposed new rules.

This frank admission emerges from an unlikely source—the recently-published "review of the balance of competences" documents from the British government. This bizarrely-titled exercise is part of the wider UK discussion of whether to stay in the European Union or not. The foreign affairs ministry commissioned an extensive public consultation into what the European Union should be responsible for, and what should be decided at the national level.

One of the chapters explored health, and the clinical trials rules featured prominently in this. The government's conclusions about EU intervention are not universally favorable, but on this particular issue, the European Union's bid to bring in new rules is hailed as very welcome.

The 2001 directive that the European Union is aiming to replace is the object of repeated criticism in the UK government paper: "Certain directives have had adverse consequences for the United Kingdom, such as the clinical trials directive," it says. The directive "was having a negative impact on the attractiveness of the European Union as a place to conduct clinical trials." It increased bureaucracy and suffered from inconsistent implementation across member states, with some countries imposing additional requirements due to different national approaches or the lack of detailed guidance. This "made it difficult to conduct cross-border trials and expensive to get approval for a clinical trial in the European Union." As a result, "many researchers have started conducting research outside of the European Union," according to the government's analysis of the current problems.

Now, the United Kingdom gratefully says, "We recognize the positive steps that have been taken to resolve this particular issue." Following feedback from the UK government, "the recent proposal for a clinical trials regulation to replace the current directive is an excellent example." It could harmonize the currently divergent requirements across the European Union, and ensure consistent implementation across member states. This is because it is couched as a regulation rather than just a directive: a regulation applies directly in national law, removing the scope for member states to transpose the rules into national legislation, and removing the risk of differing interpretations.

"It is the government's view that it is important that steps are taken across the whole of Europe to harmonize the research environment, remove barriers to transnational research, and ensure quality of conduct and protection of participants in clinical trials and studies," it says. "The new regulation will decrease the burden on researchers whilst patients are protected appropriately. As a result, it will become less burdensome and easier to conduct multi-state trials across the European Union."

This, it says, "is an example of the fact that mistakes can be corrected effectively at the European level." And, with a small self-congratulatory pat on the back, it adds that "many of the proposed improvements in the commission proposal reflect UK practice."

So it can be safely assumed that at least one member state is going to be rooting for an effective compromise as the talks get underway. Whether the views of that particular—and frequently troublesome—member state will help ensure a successful crunch will emerge only later in the autumn.

Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.