Keeping a Cool Head Amidst Turmoil

April 1, 2012

Applied Clinical Trials

Applied Clinical Trials, Applied Clinical Trials-04-01-2012, Volume 21, Issue 4

The new Executive Director of the EMA has managed to stay calm under financial and political pressure.

Europe is still in turmoil economically and politically, even after the brief moment of relief when dressings were skillfully applied to staunch the hemorrhage in Greece's finances after the summit of EU leaders in early March. That is no more than a temporary solution, and the public debts carried by many of the European Union's member states leave them still in a critical moment. Longer-term therapy remains necessary before stability is restored. And for healthcare, there are countless repercussions of the crisis. The pharmaceutical market has shrunk by 30% in Greece, according to the European Federation of Pharmaceutical Industries and Associations, and the emergency treatment for Greece's debt has left many pharmaceutical companies facing a write-down of as much as 50% of the money they were owed for medicines supplied. Similar problems are bubbling away in Portugal, Spain, and Italy. And right across Europe, healthcare systems in general are subject to immediate cost constraints and imminent radical reforms.

Peter O’Donnell

It needs a cool head to stay serene and make good judgment calls in such a hot-house environment. Not much of that was in evidence at a public meeting in Brussels in mid-March on healthcare and the economic crisis, provocatively entitled "Time for New Thinking." While advocates of pharmaceutical research pleaded the case for investment in smarter treatment, senior figures from the world of public health argued that the emphasis on medicines was disproportionately large in discussions of health, and urged a dramatic shift towards prevention.

Josep Figueras, MD, PhD, Director of WHO's European Observatory on Health Systems and Policies, spoke of "real problems over the sustainability of healthcare services," which, he said, demanded a change in paradigm, with closer attention to combating health inequalities.

The social aspects of public health were also at the center of the preoccupations of Professor Mark McCarthy, Emeritus Professor of Public Health at University College London. He expressed dismay at the high level of EU spending on biomedical research—90% of its health research budget, he claimed—and the low priority given to prevention.

He was dismissive too of the merits of personalized medicine, revealing a profound resistance to any personalization of his own genetic profile by companies that then—he claimed—"will want to sell me products they say I will need."

Michel Goldman, the academic who now runs the Innovative Medicines Initiative, valiantly put the case for the sort of advanced research that this public-private partnership works towards. Rejecting the "either-or" view in which prevention and treatment as mutually exclusive, he claimed there is a continuum across the two approaches, and that personalized medicine has its analogy in prevention too. Research can play a major role in identifying major risk factors and targeting preventive measures, he contended.

And rejecting a view of consumers and patients as nothing other than passive victims of a care system driven principally by profit and technology, Goldman also saw a greater role for patients, enabled by technology, to be increasingly involved in the conduct of clinical trials, with self-reporting via smartphones or other devices.

Cool at the helm

Someone displaying a commendable sense of cool at present is the new Executive Director of the European Medicines Agency, Guido Rasi. He has stepped onto the bridge of this heavily laden vessel as it traverses the most turbulent waters it has encountered since it was launched in 1995.

Only weeks ago, the European Parliament was discussing whether or not to sign off on the agency's $200 million annual accounts, because of doubts about its performance and even its probity. The EU's own auditors qualified their 2009 opinion on the legality and regularity of its transactions, the Parliament last year postponed approval of the way the agency's budget had been implemented, because of "serious weaknesses disclosed" in its conduct, and eventually imposed conditions on the endorsement it finally granted. These included full information on better management of conflicts of interest, and more precise remuneration of national authorities, "based on real costs," for services provided. Parliament also demanded to be told of the remedies adopted to "shortcomings in procurement procedures" and "weaknesses in the validating of creditor claims" from IT contractors.

These squalls come in addition to questions raised repeatedly over the course of 2011 about the agency's assiduity in pursuing adverse reaction reports of the French anti-diabetic drug Mediator, and about the propriety of the abrupt switch that the previous executive director made to work in pharmaceutical industry consultancy.

So Rasi, a keen amateur sailor in his private life, has taken on a formidable challenge. On top of restoring the reputation of the agency, he has also to navigate through some of the most pressing tasks the agency has faced in more than a decade—not least the administration of the EU's new pharmacovigilance rules, which require the processing of millions of pieces of data on all products on the EU market before July this year.

As if that were not enough, Rasi has plenty of other plans too—including in the area of clinical trials. In a bid to provide maximum transparency about what the agency is doing and how it makes its decisions, he is aiming to release for publication all the clinical data that contributed to each of the agency's recommendations on marketing authorization applications.

To cope with the obvious challenges of respect for privacy and personal data protection, and for commercial confidentiality, he is working on a standardized approach to clinical trial documentation. By imposing a modular method of data submission, he is requiring companies to separate out in advance the personal or commercial material, presenting the data only in certain sections of the application. In this way, the modules that contain no personal or commercial data can be made accessible without the need for the (highly labor intensive) redaction to remove these elements prior to publication.

He is determined to go further, too. He is in the process of persuading national agencies to adopt a common approach on handling requests from the public for access to clinical trials data. His strong line is that the data is not, prima facie, confidential. His belief is that by showing leadership in this, the agency can make it easier for national agencies to follow. And already he has declared the ambition to move next year towards the agency taking on the task of re-analyzing the raw clinical trials data submitted to it.

Cooling the brain

At risk of perpetrating a pun of questionable taste, another form of cooling came to wider attention in March. A new stroke treatment has been backed by EU research funding to start a Phase III clinical trial, with 60 participating universities and hospitals in 25 different countries.

The idea is that cooling the brain within six hours of a stroke can save patients and reduce brain damage—and pilot studies have offered some promising evidence. So the EU has provided more than $13 million to treat 1,500 volunteer stroke victims with mild hypothermia. If the expected benefits are confirmed, the procedure can be rolled out across Europe, with—the project claims—the potential of benefiting hundreds of thousands of patients each year.

The launch of EUROHYP-1, as it is known, aims to tackle the largest killer in Europe (after ischemic heart disease), for which, as yet, there are only limited treatments available. "A project of this scale would not be possible without a pan-European approach—no one country or smaller group of member states has yet managed to organize a clinical trial of therapeutic cooling for stroke," said Malcolm Macleod, PhD, of the Center for Clinical Brain Sciences at the University of Edinburgh.

"The challenge now is to recruit in a fairly short time 1,500 patients with acute ischemic stroke, with particular focus on those who currently do not have access to a truly effective treatment or who exhibit limited response to the existing, standard interventions," according to Professor Stefan Schwab of the Friedrich-Alexander-University in Erlangen-Nürnberg.

EUROHYP-1 will exploit the cooling experience acquired from ongoing Phase II studies by some of its members, and will share this experience with other centers new to this technique, using pioneering telemedicine techniques.

There are 1.8 million hospital discharges for stroke each year, and incidence of first-in-a-lifetime stroke is estimated to reach 1.4 million by 2016. If therapeutic cooling achieves widespread adoption throughout Europe, around 350,000 patients per year might be treated, resulting in 14,700 fewer deaths and in 25,000 more patients per year with disability-free survival, the project leaders predict. And, with due seriousness, none of the project leaders fell prey during their launch press conference to the temptation that plagued this columnist, of remarking admiringly: "That's cool, dude!"

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

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