Thinking Ahead on Clinical Research

November 1, 2001

Applied Clinical Trials

Applied Clinical Trials, Applied Clinical Trials-11-01-2001, Volume 8, Issue 11

A high-level group explores ways to support EU pharmaceutical industry research without too much cost to the EU health agencies that pay for medicines.

A high-level group explores ways to support EU pharmaceutical industry research without too much cost to the EU health agencies that pay for medicines.

A top-level European think tank is urging an increase in national and European Union public research funds devoted to clinical research and development, and efforts to promote bilateral and multilateral research cooperation. It is also suggesting the development of a European clinical research agenda that would identify public health priorities for fundamental research on new medicinal therapies needed in both the industrialized and the developing world.

Think tanks are, of course, ten a penny, and their ideas do not necessarily translate into policy. But this think tank is different. It consists of 10 of the most influential politicians, officials, and pharmaceutical industry executives in Europe. And its initial thinking stands a better chance than most of becoming policy.

This is the group that has styled itself the G-10. A grandiose title. But its pretensions are in line with the grandiosity of its chosen title. Its fuller title is the high-level group on innovation and provision of medicines. It was set up by the European Commission early in 2001 to find new answers to perennial problems of European pharmaceutical industry competitiveness. It is due to present a report by April 2002 to European Commission President Romano Prodi with recommendations on how to support EU pharmaceutical industry research without too much cost to EU health agencies that pay for medicines.

It is co-chaired by two European Commissioners: Erkki Liikanen, who is responsible for industry affairs, and David Byrne, who is in charge of health and consumer protection. And its other members include health and industry ministers from the major EU member states, the CEO of Sanofi-Synthlabo, and the European president of GlaxoSmithKline.

Signals in the consultation paper
After some six months of preparatory work, the group has just produced a consultation document that outlines its thinking on how to deal with the challenges of supporting drug development without bankrupting the social security agencies that pay for most medicines in Europe. The documents scope ranges widelybut what it has to say about clinical research is particularly revealing of the groups agenda.

Examine for a moment the propositions that head up this article. An increase in national and European Union public research funds devoted to clinical research and development, for instance. A good thing, of course, to have more funds plowed into clinical research and developmentalthough it tends to fly in the face of the received wisdom that most clinical research and development for new medicines is conducted within the private sector.

Or look at the idea of efforts to promote bilateral and multilateral research cooperation. Cooperation is, naturally, a good thing in principle. But if it is successful, it will raise questions about which of the bilateral or multilateral partners will have the rights to exploit the results.

The real clues, however, lie in the passage that refers to the development of a European clinical research agenda, which would identify public health priorities for fundamental research on new medicinal therapies needed in the industrialized and in the developing world. Curiosity is immediately provoked about who would set this European clinical research agenda, about what the criteria would be to identify public health priorities for fundamental research, and about the source of the omniscience to decide in advance on which are the new medicinal therapies needed in the industrialized and in the developing world.

Everyone who has ever worked in clinical research will instantly recognize the tell-tale signs of latent dirigisme in this formulation. And everyone who has ever brushed against European politicsand particularly European Union politics with respect to medicineswill immediately perceive that a series of trade-offs are already in the making in the way the subject is being approached.

An agenda of compromise
The clues are, in fact, even more obvious than that. How can a think tank dealing with competitiveness be co-chaired in such a way that the man responsible for industrial affairs sits alongside the man responsible for public health and consumer affairs in Europe? In some respects their interests may overlapbut in others they are diametrically opposed. Developing new drugs costs money. The money comes from profits on drug salesand in simple terms, the more the profit, the more research can be done. That is the obvious way to promote industry competitiveness, and the innovation it depends on. But the interests of public health and consumer affairs, by contrast, are to have high-quality drugs available as widely and as cheaply as possible.

There are more clues. The membership of the G-10 also includes senior figures from the generic and nonprescription medicines industrieswhose interests hardly overlap with those of research-based companies. It also includes distinguished representatives of patients groups and social security agencieswho tend to argue for access to medicines at the lowest possible price.

The reality of the G-10 group is that it is already a compromise in its composition, and is almost certain to come up with a compromise in its recommendations. The compromise was forged far back in the history of the European Union. When the EU was set up, the member states decided what the EU would deal with, and what they would continue to deal with themselves. They agreed to pool responsibility for industrial policy, for instance, and they decided to remove all barriers to cross-border trade within the EU borders. But they decided to keep for themselves responsibility for some sensitive national matterssuch as taxation, and the way that medicines are paid for and reimbursed. More than forty years on, this remains the case. So while there may be pressure to boost the pharmaceutical industrys research potential as a matter of industrial policy, this always runs headlong into national pressures to keep down the price of drugs and control the amount that social security agencies have to pay out for them in reimbursement or copayment.

Spain, France, Greece, and many others of the current 15 EU member states continue to impose tough price and reimbursement controls on medicines. And inevitably, therefore, the EU doctrine of free movement of goods across borders tends to drive a parallel market in medicines. Wholesalers go to the countries with the toughest price controls, buy up large quantities of internationally successful medicines there, then ship them to the countries with less stringent controls (such as Germany or the UK). They sell them to retailers there at less than the local pricebut high enough to be able to make a profit themselves and to allow local retailers a cut, too. The net result is a reduction in the revenues of the companies producing those successful medicinesand a reduction in the profits available for research.

Countries like Spain, France, and Greece have no problem with this arrangement. They still get their medicinesincluding the internationally successful onesat low prices. But, as the European research-based industry has long argued, this compromises the overall European revenues that provide for the development of internationally successful medicines, which are generally developed and produced by companies in the countries with higher prices.

Negative perceptions
Alongside this stream of European confusion runs another that is equally confused: private sector research is wasteful, inefficient, too costly, and unfocused. It is a view often championed by European consumer organizations, and frequently supported by social security agencies. It also often overlaps some of the strong negative prejudices in Europe about the pharmaceutical industry as a parasitemaking extravagant profits from the sick, ignoring the real interests of patients. More recently, and to a large extent because of drug industry mismanagement of its relations with developing countries, it has also been widely perceived as a callous exploiter of profitable markets that turns its back on product development for poorer markets where real needs remain unmet. How much more rational it would be, runs this argument, to eliminate the wasteful self-indulgence and duplication of some drug companies research programs, and direct those programs from some more altruistic notion of what is really necessary.

This is why the G-10 group has a very mixed membership. It is the latest in a long series of EU attempts to square a circle, to reconcile innovation with low costs. This is why it offers hope of backing for innovation with one hand, then takes it away with the other in the name of health-care economies.

More mixed motives
There are other examples of these mixed motives in other aspects of the G-10 consultation paper. Systems for postmarketing surveillance should be reviewed to ensure that coordinated processes are in place in each of the member states to gather data on adverse events and patient safety, it says. And it urges that the European Commission should provide core funding for European patient groups to enable them to participate independently in the debate and decision-making on health matters at a European level.

The paper also suggests that the EU should develop a coherent policy in the field of clinical research aimed at improving its qualitywith a clear presumption that at present there are some deficiencies in its quality. Specifically, it urges organizing larger and more targeted clinical trials on a European scale, focussing on innovativeness criteria and based on all relevant results (including negative). The industry may have been its own worst enemy in allowing a situation to emerge where it is presumed to be excluding negative data from trial results (as the recent furor over publication of results has demonstrated so compellingly). The consequences are now evident. Even in the eyes of such a distinguished high-level group, the starting point is that industry is not to be trusted.

It is no credit to the industry to see the G-10 group come up with a suggestion that the European Commission could take initiatives to coordinate and publish data on morbidity and mortality across the European Union in different disease areas, similar to the role of the Centers for Disease Control and Prevention (CDC) in the United States. A key aspect of the role of CDC is that it is independent of the purchaser and provider healthcare framework. It is thus trusted by both patients and industry to provide impartial and accurate clinical data free from financial consideration, the group says.

Not all bad news
Because the paperlike the G-10 itselfis a compromise, not everything in it is bad news for the industry as a whole or the clinical trials sector in particular. For instance, it suggests decreasing the bureaucratic burden imposed by the EUs new clinical trials directive, and avoiding undue delays in access to new therapies (in particular those resulting from biotechnology research) although without affecting the high standards for clinical trials, which are essential for the quality of research outcomes and market approval.

The G-10 group urges the EU to support the development and marketing of pediatric forms and uses of medicines by developing incentives and other measures for pediatric research on new and existing medicines. Few will argue with its ideas on direct incentives to research (such as tax credits for research or tax allowances for investment), or on boosting access to venture capital by attracting private funds for new technologies.

Most will welcome its explicit recognition that all new medicines introduced on the market are the result of lengthy, costly, and risky research and development conducted by the pharmaceutical industry. And its assertion that the financing of such R&D costs requires a sustained and substantial cash flow that the company is only able to generate if it launches new medicines on the various national markets as quickly as possible, at the best possible price. Everyone who has tried to launch a drug in Europe will be glad to see that the G-10 group admits that

considerable delays are currently experienced in access to new, effective medicines in member states. These delays range from those occurring during the regulatory process itself, the issuing of product licenses after marketing authorization, in price negotiations and in reimbursement systems. There can be as much as four years between the first patient in the first member state having access to an innovative medicine and the first patient in the last member state enjoying the same access.

The document is only a consultation paper at this stage. It will be modified before April 2002, and will only then be fed into the EU policy-making process. It needs modifyingif only to smooth out some of its uneven quality, which often amounts to contradiction rather than conciliation. But the pressures to modify it will come from all sides, including those interests that seek to subjugate the industry rather than liberate it. The clinical trials community may care to make sure it gets its own views across clearly lest they be ignored by default.

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