Clinical Trials Funding on the Horizon

Clinical trials stand to benefit from major new funding that is under discussion this autumn in the European Union. Over the next few years, the European Union is planning to put some $100 billion behind a new European research program—and health is one of the priority areas identified, with a very specific provision for clinical trials. Right up front, the plan states that "drug and vaccine development processes are becoming more expensive and less effective."

Peter O'Donnell

Support for clinical trials will be provided, the plan promises unambiguously. There will also be funding for "the improvement of their practice," such as through "the development of better methodologies to allow trials to focus on relevant population groups, including those suffering from other concomitant diseases and/or already undergoing treatment." Other improvements envisaged include "the determination of comparative effectiveness of interventions and solutions," and "enhancing the use of databases and electronic health records as data sources for trials and knowledge transfer."

Horizon 2020

The research program—entitled Horizon 2020—is still a proposal from the European Commission, and it is now being examined by the European Parliament and by ministers from the European Union's 27 member states. It is scheduled to come into effect at the end of next year, when the current program (known as FP7) expires, and to run for the following seven years. An entire section of the proposed program is devoted to "health, demographic change, and well-being," with an indicative budget of more than $10 billion allocated.

The focus on health is partly driven by the rising costs of care and the impending challenges of an aging society—with an emphasis on chronic conditions. The commission points out in its proposal that the two million annual deaths in the European Union from cardiovascular disease cost the economy more than $200 billion, and the total cost of brain disorders is put at around $1 trillion. Meanwhile, "emerging epidemics and the threat of increasing anti-microbial resistance must also be prepared for," and the needs of developing countries should not be overlooked, it says. Support is planned for "the full spectrum of research and innovation activities, from basic research through translation of knowledge to large trials and demonstration actions." But "effective sharing of data and the linkage of these data with real-world, large scale cohort studies is also essential, as is the translation of research findings into the clinic, in particular through the conduct of clinical trials."

So the plan acknowledges the "need to support the improvement of cross-cutting support technologies for drugs, vaccines, and other therapeutic approaches, including transplantation, gene, and cell therapy." It aims to "increase success in the drug and vaccine development process (including alternative methods to replace classical safety and effectiveness testing)." In particular, it pinpoints the "need for more effective preventive vaccines (or alternative preventive interventions) and evidence-based vaccination schemes for an expanded range of diseases." It is committed to backing "regenerative medicine approaches, including approaches based on stem cells." It endorses the need for wider exploitation of computer simulation using patient specific data, or physiological modelling. And the use of "-omics," high throughput, and systems medicine approaches "will demand close linkage between fundamental and clinical research and with long term cohort studies," and with research and medical infrastructures such as databases and bio-banks.

The proposal highlights the merits of pooling of efforts and resources. "Many approaches, tools, and technologies have applicability across many of the research and innovation areas of this challenge and are best supported at Union level," it says. It also notes that "the requirements of specific populations are also best addressed in an integrated manner," instancing "the development of stratified and/or personalized medicine" and "the treatment of rare diseases." It urges interdisciplinary translational research on the patho-physiology of disease "to improve the understanding of all aspects of disease processes, including a re-classification of normal variation and disease based on molecular data, and to validate and use research results in clinical applications."

Not just altruism

The EU engagement is not solely altruistic. Better drug development process will be good for industry, as well as easing human suffering, it acknowledges. Part of the avowed aim is "strengthening the competitiveness of the European-based industries and development of new market opportunities." The basic premise of Horizon 2020 is that Europe's fragile economy can be resuscitated by taking advantage of the continent's research strengths.

The commission proposal notes some of the positive outcomes of earlier EU support to research. It cites a $2 million grant in 2006 to BioInvent and Thrombogenics (two small research-based companies from Sweden and Belgium) which allowed them to develop an innovative treatment for cancer that won a $60 million investment from Roche in 2009, and the possibility for increasing this investment 10-fold. The commission says that a 1% increase in public basic pharmaceutical research leads to a 1.7% increase in industry R&D after eight years, and a 1% increase in public clinical research leads to a 0.4% increase in industry R&D after three years.

Over the coming weeks and months, the likely final shape of the proposal will become clearer. Within the European Parliament, the research committee has already begun to examine the texts, and draft reports have been prepared by MEPs designated to lead the discussions. These reflect a broad welcome for the proposal—although with a number of requests for greater attention to diseases related to poverty, rare diseases, and diseases that particularly afflict developing countries. The committee will debate these draft reports this month, with the aim of reaching an agreed position by late October. That will then be passed to the Parliament as a whole for a formal view on the proposal, probably early in 2013. Meanwhile, ministers and officials from the member states are working steadily through the proposal within the EU Council. A favorable joint position from the council and the Parliament will be required next year for the proposal to come into effect.

Boosting clinical trials in Africa

Adoption of Horizon 2020 could give a boost to clinical trials in Africa. The commission's proposal notes that infectious diseases—notably HIV/AIDS, tuberculosis, and malaria—"are a global concern, accounting for 41% of the 1.5 billion disability adjusted life years worldwide, with 8% of these in Europe."

Partly in response, the plan makes provision for "strategic international cooperation," in particular with "the continuation of the European and Developing Countries Clinical Trials Partnership" (EDCTP). This partnership was established to accelerate the development of new or improved drugs, vaccines, microbiocides, and diagnostics against HIV/AIDS, tuberculosis, and malaria, with a focus on Phase II and III clinical trials in sub-Saharan Africa. Since it started operations in 2003, the EDCTP has handed out grants worth 356 million euros for 196 projects in Africa, ranging from large-scale clinical trials to funding fellowships. More than half of this money came from the European Union. But its funding runs out in just over a year.

The partnership has supported multicenter projects that combine clinical trials with networking, so that capacity is used to the fullest in conducting clinical trials in a sustainable manner. Recently completed studies include a comparison of the safety and efficacy of four artemisinin-based combination therapies in the treatment of uncomplicated malaria, a Phase III pivotal clinical trial of moxafloxacin for the treatment of tuberculosis, and a trial showing that the shorter treatment course of three doses of intravenous artesunate over two days was as effective as that of five doses spread over three days in treating severe malaria in children.

EDCTP Executive Director Charles Mgone is optimistic that the partnership will be not only be renewed but expanded. He says that the European Union and African countries in the partnership agree that a follow-up EDCTP should be "bigger, more ambitious, and covering a period of up to 12 years." A strategic business plan agreed early in the summer envisages an expansion to involve all clinical trial phases (I-IV), as well as research into health service optimization, other neglected infectious diseases, and cooperation with other developing countries beyond sub-Saharan Africa. A draft European Parliament report has already taken on board the EDCTP agenda, arguing for an expansion of the European Union's ambitions for the partnership to match its business plan.

One aspect where EDCTP has been particularly active in recent months is in building closer links with the pharmaceutical industry. Following up on a series of one-on-one meetings with companies, it held a workshop in late June with experts from Bayer, Boehringer-Ingelheim, GlaxoSmithKline, Johnson & Johnson, Merck-Serono, and Sanofi, among others—the first time that it had managed to bring big firms together. This made some progress, says Mgone, in defining a framework for collaboration in EDCTP-II, including discussion of an industry fellowship, pooling information from clinical trials, and possible post-authorization studies.

But for EDCTP and for every other interest group, company, or research institution in the clinical trials community, nothing can be taken for granted at this stage. Anyone who wants to ensure that they get a look-in on the benefits of Horizon 2020 had better book some time over the coming months to argue their case—against a lot of competition.

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