Forward to 2004 or Back to 1984?

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Applied Clinical Trials

Applied Clinical Trials, Applied Clinical Trials-03-01-2002,

Facing an immediate future of rapid growth, the EU is looking to clarify its clinical trials policies, but it?s having some problems.

Fin de sicle is finished in Brussels, and the turn of the century is forgotten. No one is looking backward anymore in millennial mood. Its all eyes ahead for the new challengesand in the field of developing new European medicines, there is everything to play for.

In 2004, the 15-member European Union is likely to become the 25-member European Union, as eight of the former communist states of central Europe join, along with Cyprus and Malta. And by then the aim is to have clearer policies in place for medicines development and regulation. It is not just the clinical trials directive that will beor should befinally in force by then. A wide range of other changes are under way that will also have their effect on the development of new medicines. At stake is partly the efficiency of the mechanisms of the future EU, because it will be much larger, and much more diverse. But equally critical is the extent to which the new regulatory framework will helpor hinderthe European drug industrys ability to stay up with the leaders in international competition.

So right now Brussels is trying to bring several major exercises in the pharmaceutical sphere to a satisfactory conclusion. One is the updating of the EUs authorization systemthe so-called Review 2001 process. Another is a broad-ranging review of how to increase the effectiveness of the European biotechnology industryone of the major themes of the EUs bid to boost growth and employment generally. The third main strand in EU planning is the work of the so-called G10 groupthe 10 top politicians, officials, and drug company executives who have been looking since last year at how to improve European drug industry competitiveness and innovative capacity without crippling European health care agencies with exorbitant drug bills.

As Thomas Lnngren, the executive director of the European Medicines Agency, says in his 2002 workplan,

The European system for the authorization and supervision of medicines, and the EMEA as part of that system, enters 2002 with a number of challenges ahead of it . . . The establishment of effective pharmacovigilance mechanisms for the supervision of medicines. . . the proposals to reform EU pharmaceutical legislation [the Review 2001 exercise] and indeed the role of the EMEA itself. These reforms can be expected to come into force at the same time as the European Union welcomes new member states. This is a unique opportunity to integrate the planning and preparation processes for these two events . . . Our focus will also be on preparation for a number of other initiatives, including our future responsibility for the developments and operation of the EU pharmaceutical regulatory IT strategy from 2003 onwards, the implementation of the directive on clinical trials by 2004 at the latest . . . measures to further improve transparency of the regulatory system . . . and the need to improve scientific advice to the European research-based pharmaceutical industry, [and to] develop our activities in relation to orphan medicinal products.

For biotechnology, the European Commission adopted at the end of January what it termed a major policy initiative for the development of life sciences and biotechnology in Europe. This strategy paper includes an action plan with recommendations for member states, local authorities, industry, and other stakeholders. Its stated aim is to help Europe master the frontier technologies that could make a major contribution to the goal, set at the March 2000 Lisbon European Council, of becoming the worlds most competitive, knowledge-based and sustainable economy within a decade.

Commission President Romano Prodi said,

It is of key importance for Europe to master the new frontier technologies, which will be at the core of a knowledge-based economy. Life sciences and biotechnology are developing rapidly and globally and have given rise to intense public debate. Europe needs to address the challenges of biotech by developing responsible policies to exploit these new opportunities in a manner that is consistent with European values and standards. Commitment to fundamental ethical values will be crucial to build confidence and foster public acceptance of new biotechnology. With this initiative, the Commission sends a strong signal to the public and private actors who must work together for Europe to be successful.

According to the Commission, Europe is faced with a major policy choice. Either we accept a passive role, and bear the implications of the development of these technologies elsewhere, or we develop pro-active policies to exploit them in a responsible manner. Life sciences and biotechnology are widely recognized to be, after information technology, the next wave of technological revolution in the knowledge-based economy, creating new opportunities for our societies and economies.

Echoes of 1984
With all this focus on forward progress, and on developing an efficient and effective enterprise culture, why is it then that there is a curious redolence of the past in some of the emerging thinking? Most notably, the latest draft of the G10 proposalswhich are due to be finalized and published in Aprilcontains some eerie echoes of 1984the book by George Orwell.

It urges, for instance, The creation of the European virtual institutes of health, connecting all existing competence centers on fundamental and clinical research into a European network of excellence. It is not just the evocation of Orwells Ministry of Truth that disturbs. There is a curiously corporatist, almost totalitarian, tone to the explanation of the concept.

On the face of it, the logic of the basic proposition that European research is very fragmented is hard to fault. An effective dynamic science base in Europe is fundamental to ensuring the continuing development of innovation and research in the pharmaceutical industry in the EU, the group argues, adding, However, the effective exploitation of the science base in the EU is hampered by relatively weak links between research centers in different member states. The science base is often further fragmented between member states due to poor collaboration between public and privately funded research.

But the G10 recommendations on how to deal with this fragmentation might almost have slipped from the pages of a Stalinist five-year plan. The group believes that to exploit effectively the high quality research that exists in Europe there has to be much greater integration of research across national borders within the EU. This should help foster a critical mass of research in particular areas and allow much greater commercial exploitation of research. One almost searches instinctively for a footnote giving figures on tractor production and wheat yields. Some entrepreneurial spirits in the European pharmaceutical industryeven within clinical development divisionsmay recoil from this all-join-hands-and-work-for-the-common-good approach. There are other ways of driving commercial success.


Similarly, there is slightly sinister tone to the passage on incentives for researchwhich adopts a particularly dirigisme approach to clinical trials. The greater integration of the European science base must be actively supported at EU and member state level. The coordination of clinical trials on a European scale would help to make existing clinical trials more effective and reduce the risk of duplication. Underpinning this with a database on clinical research results would provide an invaluable tool to researchers, both public and private, throughout Europe.

Of course many researchers and clinical trial staff in the private sector have frequently expressed interest in the possibility of greater access to some databut not usually with quite such enthusiasm for coordination from some higher authority, nor with quite so much scorn for theoften inevitablerisk of duplication. For this reason, there is a hint of a double-edged sword in the terse G10 recommendation at the end of this section of its draft conclusions: Commission and member states co-ordinate and support the conduct of clinical trials on a European scale, establish a database on clinical research results.

And again, in a prose-style drawn from Kafka, the shadow of Big Brother (the Orwellian despot) falls across a passage about the need for greater coordination of assessments of relative efficacy.

The existing EU regulatory structure governing the control of medicines is focused on ensuring that all medicines meet high standards of quality, safety and efficacy. Member states are increasingly supplementing this with national requirements concerning the relative clinical and cost-effectiveness of new medicines to ensure the efficient use of increasingly scarce resources. Although the assessment of relative effectiveness is a matter for national competence there could be value in facilitating the exchange of information on national practices between member states.

The G10 draft maintains, with all the clarity of a bureaucratic nightmare, This increased transparency should improve the quality, consistency, and speed of reimbursement and pricing decisions across the EU and provide industry with a clearer understanding of the criteria used and the reasons for their use.

This looks dangerously like Newspeakthe Orwellian language rendering acceptable the unacceptable. The drug industry is largely hostile to the idea of relative efficacy assessments anyway, and doesnt want it to spread from the countries that exercise it to the ones that dont. So there is probably no value in facilitating the exchange of information. Quite the reverse. In addition, why should anyone believe that this increased transparency will in any way speed reimbursement and pricing decisions? There is no reason whatever (or certainly no justification advanced) for the suggestion. And as for providing industry with a clearer understanding, this sounds like being given a detailed life-size photograph of the guillotine before having your head chopped off. It is an insult to suggest it could be any sort of benefit.

Nonetheless, the draft of the G10 group recommends that

The Commission should organize a European reflection to explore how member states can improve ways of sharing information and data requirements to achieve greater certainty and reliability for all stakeholders, even if the decisions they take may differ. The objective is to improve the value of health technology assessment, and to share national experiences and data while recognizing that relative evaluation should remain a responsibility of member states. Member states should be encouraged in developing systems to focus equally on assessments of clinical and cost-effectiveness.

Game, set, and match to the Thought Police.

Part of the menace of this document lies in the studious neutrality of the language employed. It has an utterly soulless quality, purring on evenly like a motor yacht across some of the most contentious issues in EU drug provision, without so much as an acknowledgement of the troubled waters it is navigating. It is of a piece with the rest of the document; and its recommendations are, in some areas, of a banality that almost defies beliefyet delivered with the same imperturbable sonority.

On pharmacovigilance, for instance, it says: Once medicines are authorized to be placed on the market, industry and national regulatory authorities undertake regular monitoring to ensure that they continue to meet the required standards of safety, quality, and efficacy. This is a vital role played by national regulatory authorities and critical to the continuing confidence EU citizens have in the medicines they are using. Incontrovertible, of course. But utterly self-evident. And the recommendation it makes is, accordingly, no more than the most obvious commonplace: That systems for postmarketing surveillance should be optimized to ensure that coordinated processes are in place to gather data on adverse events and patient safety.

The EU proposals on biotechnology are also dappled with tones of public as well as genetic manipulation. Boiled down to its simplest form, much of the Commission plan is to get public opinion on its side. If its strategy were really clear, it would probably say, We, the Commission, know that biotech is a good thing. Public opinion in Europe is causing some national governments to put brakes on its progress. Were going to change that. Were going to persuade everyone it is a good thing. But were not going to use crude propaganda. Were going to infiltrate public opinion through supposedly objective debatesjust as long as they lead to the conclusion we want. But what the Commission actually says is: The strategys cooperative and consistent approach to fostering sustainable development is designed to address the complex ethical and societal concerns and support the broad public debate. In line with the principles of governance, the initiative is based on a wide public consultation that included a conference with a broad range of stakeholders. Sound familiar?