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Will the clinical trials community assemble their arguments, and will they do it in time?
Autumn is the time for reflection in Europe. The heady days of summer are over, and the resumption of political and business activity provokes re-evaluations of achievements to date, and of what might be the way ahead.
For health policy in Europe, this autumn is particularly pregnant with assessments and plans—and the nature of the discussions underway prompts the question as to just how much Europe cares about clinical trials in a changing world. The narrative behind European health policy is undergoing a profound change—and the result doesn't seem to leave a lot of room for clinical trials.
Take the discourse of Zsuzsanna Jakab, WHO Regional Director for Europe, and a key influence on the way European governments perceive the healthcare challenge. During September she delivered a lengthy update of WHO thinking about Europe, based largely on a strategy adopted last year, known as Health 2020. This envisages governments linking policies, investments, and services in health policy—and focusing on reducing inequalities. "Political commitment to this process is essential," she said, insisting on the need for "common purpose and broad collaborative effort by people and organizations across society in every country: governments, nongovernmental organizations, civil society, the private sector, science and academia, and health professionals."
For Jakab, Europe is on the brink of a "brave new world," in which good health is recognized as essential for economic and social development, and now features prominently on the political and social agenda. But it is hard to see just where health professionals in the clinical trials community could fit into the picture she paints. Jakab, like a growing number of politicians and senior officials in Europe, is acutely conscious of the challenges in healthcare, and her recommendations do not put much emphasis on Europe medicating its way out of trouble. "Governments may feel daunted by growing health expenditure. The development and introduction of expensive medical technologies and treatments drive up the cost of managing chronic diseases and multiple morbidities," she remarks.
Her conclusion is that these cost pressures "provide a strong economic case for moving upstream to promote health and prevent disease". Action promoting health and well-being, along with effective preventive measures within and beyond the healthcare sector, "could prevent a tangible share of the burden of disease and of the economic costs associated with it," she emphasizes. In the longer term, non-communicable diseases can be tackled cost-effectively through changed behavior and lifestyle. Depression, for instance, can be prevented by "early action in childhood to strengthen social and emotional learning, coping skills, and improved bonds between parents and children"—but not a word about psychotropics. Her emphasis in health policy is on nutrition, on prevention of motoring accidents, and of tackling environmental chemical hazards.
But many countries are not reacting fast enough to these possibilities, says Jakab. Budgets and policies lack either a health or equity focus, she laments, and only 3% of health expenditure is committed to these upstream programs. "In this brave new world, all this simply has to change," she declares.
Jakab is not alone in her view. The current president of the European Union's health council performed variations on the same theme in September too. Vytenis Povilas Andriukaitis, Lithuania's Minister of Health, made clear the main priority of his country's turn in the EU chair—which lasts until the end of this year—is "modern, accessible, and sustainable health systems." Elaborating on just what that means, he spoke at length about "measuring and monitoring the effectiveness of investments in health." This is not good news for healthcare industries that depend on the successful development and launch of products designed for treatment. As prevention and lifestyle adaptation become increasingly important for policymakers, the merits of intensive (and expensive) work on bringing new medicines from concept to clinic inevitably pale by comparison—and the risk grows that the money and support will follow the political bandwagon.
The economic crisis is one of the factors behind the closer attention to efficiency of health spending, and is seen by many EU officials and politicians as an opportunity for deep change in restructuring healthcare services. A major EU-wide review this year of economic growth prospects recommended reforming health systems to ensure their cost-effectiveness and sustainability, and a re-assessment of how efficiently they perform in using of public resources. The guidance came from the European Union's economic and financial affairs council. It was the culmination of a six-month exercise in checking national spending plans to make sure that they meet the objectives of European economic recovery.
The so-called "guidance" included tough instructions to European countries to get a grip on health spending—with specific criticisms levelled at the way some of them are managing pharmaceutical spending. The nature of the guidance—backed by EU leaders at their June summit, and which is, in effect, binding—marks a new phase in the European Union's gradual assertion of powers over national health spending. France was told that medium and long-term public health expenditure was set to increase, requiring "greater scrutiny and efficiency, in particular in pharmaceutical spending." Germany "has made only limited efforts to improve the efficiency of public spending on healthcare," and "past reform efforts in the health sector as well as this year's reform of long-term care appear insufficient to contain expected future cost increases." The recommendations for Germany in 2013-2014 include "a stronger focus on prevention." Belgium was also told to explore "improved cost-efficiency of public spending on long-term care services and cost-saving measures of health prevention." And on-going reform of health services in Finland must be geared to "deliver productivity gains and cost savings" in the provision of services.
Against this somber background of cost containment and an incipient shift from treatment to prevention, what factors still militate in support of clinical trials? Center-stage, of course, is the current discussion of an update of the European Union's rules on clinical trials—but this is still stuck in discussions among EU governments, many of which are resistant to what they see as infringement of their own autonomy in a bid to streamline trial authorization. The vigor of the clinical trials industry in Europe has won recognition from many EU officials and politicians—particularly attractive at a time when Europe is desperate to find ways of asserting and retaining its superiority in high-tech sectors as its overall competitiveness comes under increasing threat in a globalized economy. But no revision of the EU rules—and still less the revision currently under discussion—is of itself going to be enough to guarantee continued success.
Other pressures also offer some succor to the beleaguered sector. The growing push from academics, physicians, and industry for recognition of the special case of personalized medicine inevitably puts clinical trials—albeit modified forms of clinical trials—in the spotlight. At the senior EU level there is also lip-service paid to the prospects that personalized medicine can offer, both for healthcare and as a potential contributor to Europe's global competitiveness. But so far the thinking about what could be achieved in this complex field remains inchoate—and the ideas about how clinical trials should be promoted remain confused.
For years the EU has been straining to deliver a strategy paper on how 'omics could contribute to personalized medicine—and how trials could be adapted. But it has still not completed its reflections—and all the latest draft is able to offer on clinical trials are vague ideas like the following: "A range of new more flexible alternative designs, statistical methods, and analysis tools need to be considered, (e.g., adaptive trial designs, computationally, and logistically complex), and which need intensive modelling and simulation, enrichment designs when sound biomarkers can accelerate the clinical development of 'personalized' medicines meant to address unmet needs."
Meanwhile, a broadly-based European alliance to promote personalized medicines has released its own view of the way ahead—which notes that "the classical approach to clinical trials cannot capture the necessary data adequately." Now that subgroups of patients can be identified within a broad disease category via prognostic or predictive biomarkers, "these scientific advances in diagnostic refinement and stratification have to be incorporated into the format of clinical trials"—which means that the legal framework in Europe needs adapting, not only to permit easier access to smaller groups of subjects, but also to recognize the validity of results from trials much smaller than the classic randomized approach.
At the European Medicines Agency too, support is growing for adaptive licensing methods that will be based on a new paradigm for clinical trials. In the European Parliament in late September, Francesco Pignati of the European Medicines Agency highlighted the gap often observed between efficacy as demonstrated by clinical trials, and effectiveness when a medicine is used in clinical practice. Acknowledging the work of EMA colleague Hans-Georg Eichler, who has been one of the leading exponents of modifying drug registration rules to reflect more accurately the state of knowledge of a medicine at any given time, Pignati said flexibility was urgently needed to overcome the knowledge gaps.
But so far, it must be said, the arguments for greater attention to clinical trials are less developed, and less trenchant, than the calls from the big battalions of economic affairs ministers and health campaigners for a step away from medicines development and several steps toward preventive medicine. Will the clinical trials community muster their arguments more strongly? And will they do it in time?
Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.