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Dismay over the level of anti-pharma feeling in the EU is not just "crying wolf."
Dismay over the level of anti-pharma feeling in the EU is not just "crying wolf."
"You have to be kidding!" Hearing that is a familiar experience for many European clinical trials professionals when they spell out some of the operating conditions for clinical trials in Europe to world colleagues. It is often hard for those not working in Europe to grasp quite how many barriers to innovation and creativity there are in Europe's regulatory and political climate.
The alternative frustration that Europeans suffer when recounting abroad their difficulties at home is: "Ahhh, you're always saying that!" Like the shepherd boy who lost all credibility by crying wolf too often, Europeans are frequently met by weary dismissiveness when they list the obstacles that hamper their efforts to bring new medicines to patients. "Europeans are always moaning," runs the oft-heard refrain.But the reality is that things in Europe are not good-and they are not getting better. Neither the clinical trials community, nor the pharmaceutical and medical sectors it serves, can be confident of the future. The virtues they have all been built upon, of energy, enterprise and excellence, may not continue to be prized.
As the most superficial example, just take the triumphalist tone of the Medicines in Europe Forum this month, in its guarded welcome for the new EU rules on medicines. This organization is run by well-meaning people proclaiming the supremacy of the patient and the citizen. But it is polarizing the debate about medicines in Europe in a way that does not better the climate for improved provision of medicines.
"For more than two years the pharmaceutical majors and their lobbyists took it for granted that they could obtain made-to-measure legislation supporting their own narrow financial interests, with scant regard for public health or for the economic survival of national health care systems," says the Forum in the July-August issue of the French magazine Prescrire, looking back on the lengthy debate.
"What we achieved," continues the Forum, "was a major change of perspective: in the end, European legislators endorsed the view that medicines are not just another consumer good." It goes on to list what it sees as improvements that it won in the EU approach to regulating new medicines-and makes clear its view that Europe is changing to accept the Forum's point of view: "In future, 'Europe' will be increasingly synonymous with welfare and public services, chief among which is health care," it predicts, content to consign to the past a Europe geared to developing trade and the promotion of wealth creation. And, it warns, "many battles remain, given the inevitable clashes between major financial interests and basic human health needs." It concludes ominously with a promise that "We stand shoulder to shoulder with all those defending accessible, high-quality health care."
What is disturbing is the unquestioned assumption that the interests of citizens and patients are diametrically opposed to the interests of the industrial sector that provides medicines for patients (to say nothing of jobs for citizens). Legitimate debate starts to lose all sense when "accessible, high-quality health care" is perceived as something utterly distinct from-even mutually exclusive with-the well-being of the pharmaceutical sector.
The "successes" claimed by the Forum in modifications won in the new EU drug rules reinforce this artificial distinction.
Greater public access to product documentation and publication of penalties for companies that don't comply with the rules are just two of the minor amendments the Forum hails. More serious is the rationale for these changes: "If citizens remain vigilant to ensure that these measures are fully and durably implemented, medicines agencies' notorious secrecy will be a thing of the past," it remarks with open hostility.
Conflict of interest rules
Similarly, the Forum greets with glee new conflict of interest provisions for regulators. "Currently, medicines agencies' main sources of funding are the fees paid directly to them by pharmaceutical firms, notably for evaluating marketing applications. As the experts who work for these agencies are also often involved in assessing drugs on companies' behalf, drug companies wield considerable influence over medicines agencies' decisions," it says, rejoicing over the additional measures on public declaration of financial interests by the staff who grant marketing authorizations.
Industry suspicion is also the reason for the Forum's welcome of more independence in pharmacovigilance supervising and the publicly accessible European medicines database. "These obligations may appear to represent the strict minimum. But at a time when drug companies are funding more and more public-sector activities, these obligations are a major victory for those seeking to ensure that medicines agencies are and remain independent," it claims.
And the retention of long timelines for drug assessment procedures is perceived as "another victory for EU citizens," just because companies-and the European Commission-"were seeking a shorter period." So "(d)espite drug companies' lobbying to have their products authorised more rapidly, only the time allowed for certain administrative tasks has been shortened. In principle, the scientific assessment should not be botched because of unreasonably tight deadlines," says the Forum.
The Forum even presents one of the few direct references to clinical trials in the new rules as a victory for citizens and a blow against the pharmaceutical industry. "An important document has now been added to the list that applicants must provide (for both national procedures and the European centralised procedure)" it states regarding the rule that clinical trials carried out outside the European Union meet the ethical requirements of the EU's new clinical trials rules (Directive 2001/20/EC). "Thus, the principles of [the Directive] must be followed, with respect to the protection of participants, ethics committee and adverse event reports, even when a drug intended for the European market is tested outside the EU," crows the Forum.
Equally eloquent testimony comes from the Forum's "failures." "Pharmaceutical majors, with support from the European Commission's Enterprise Directorate General, succeeded in ensuring that the notion of 'added therapeutic value' will not be taken into account when considering whether or not to authorise new drugs, and that the 'clinical protection period' will be even longer than before," it says. And it issues another dire warning couched in quasimilitary terms: "EU citizens must remain mobilised to ensure that the texts are effectively enacted in national legislation and are strictly applied in patients' best interests. We must also be on the lookout for the tricks that the drug companies will inevitably employ to preserve their financial interests."
It regrets that there was nothing more than "lip-service to the notion of 'added therapeutic value.'" No comparative clinical evaluation is required to determine whether a new drug offers a real therapeutic advance relative to reference drug or nondrug treatments, it laments. But there are sufficient allusions to that concept in the new rules for the Forum to conclude: "The comparison of new drugs with available reference treatments, long demanded by patient groups and health care professionals, but rejected by pharmaceutical firms, finally appears in the European regulation on medicinal products. This comparison is not obligatory prior to marketing application, but at least a small step has been made in the right direction."
The Forum's most virulent criticism is reserved for what it depicts as "Industrial protectionism: a victory for drug companies." Certainly the question of for how long clinical trial data should be protected was one of the most contentious issues in the EU debate on these new rules. The Forum is not only disappointed at the outcome, but outraged at what it sees as the consequences for health care supply.
"Drug companies employed all the means at their disposal to prolong the period during which their drugs are protected from generics," it says. "After two years of intense debate and infighting between the powerful pharmaceutical majors and the less powerful generics manufacturers, clinical trial data protection in Europe was harmonised towards a longer period."
And protectionism has been aggravated, it charges, by "the invention of 'biogenerics.'" The definitions of generics and biogenerics "have been rendered sufficiently vague and complex to make it more difficult for generics manufacturers to obtain marketing authorization. In particular, it will be more difficult to avoid conducting new preclinical and clinical trials when the manufacturing process (especially when based on biotechnology) is only slightly different from that used for the originator product."
The views of the Forum-which is often aligned with the generic pharmaceutical industry-border on the actionable. "The money spent by pharmaceutical majors to influence deputies and ministers, and to spread malicious rumours on the potential risks of generic drugs, was well invested. Welfare organisations and mutual health insurers will soon feel the economic pinch," it warns. "The pharmaceutical companies have won a major victory for protectionism," it concludes.
The Medicines in Europe Forum is no isolated extremist group on the fringe of politics. It is a coalition of patients, consumers, health professionals, and health insurance organizations with a growing influence on the real world of European politics.
Of course, the Forum is not the only force in European affairs. Nor is it the principal force. But it is remarkably representative of the forces that increasingly shape Europe's destiny. It is characterized by hostility to the profit motive, suspicion that big business is in an unholy alliance with the authorities, skepticism about the merits of science and technology, and an assumption that it is more noble to focus on equitable distribution of assets rather than on the creation of wealth-an attitude frequently struck in conjunction with high moral claims to defend the interests of citizens, consumers, or society as a whole.
At the level of the pharmaceutical industry, the alarm is being raised again. The new annual report of the European Federation of Pharmaceutical Industries and Associations gives further evidence: "since the early 1990s, the research-based pharmaceutical industry in Europe has been losing competitiveness with respect to the U.S. Data for 2002 and preliminary figures for 2003 confirm the vulnerability of Europe's research-based pharmaceutical industry. Benchmarking and performance indicators show that the U.S. has continued to increase its relative position as a locus of innovation." Market evolution has "particularly benefited U.S.-based companies which have significantly increased their share in sales of new medicines and development of new molecules."
In conclusion, "As a whole, Europe remains less attractive for R&D investments than the U.S. The economic and regulatory framework, the science base, the investment conditions, and societal attitudes towards new technologies all contribute."
A key priority for EFPIA is to promote and develop Europe's pharmaceutical science base. It has set up a new group of research directors to help plan how to fight the current brain-drain by attracting and retaining the best scientists in Europe. "We must secure a vibrant and innovative science-based industry in Europe that delivers breakthrough treatments which European patients rightly deserve," according to Jonathan Knowles, the new group's director. And a key element in improving the competitiveness of the research-based pharmaceutical industry in Europe is in creating a regulatory and political environment which stimulates R&D in Europe and rewards innovation.
The challenge facing the clinical trials and pharmaceutical sector is widely reproduced across Europe. The long-term EU plan of creating a competitive economy by 2010 is-by common consent-running into the sand even before the midpoint review due next year. Meanwhile, report after report demonstrates the failure of key EU economies (notably Germany and France) to carry out the structural reforms necessary to boost growth and stimulate competitiveness.
For those whose intuitive response is "You have to be kidding!" or "Ahhh, you're always saying that," remember the end of the shepherd boy fable. When the wolf finally appeared, the boy's cries for help went unheeded, and he and his flock fell prey to the marauders from the outside world.