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Several initiatives are focused on integrating biomarkers and personalized medicine techniques into studies.
What has been obvious to strategists-and to most readers of this publication-for a long time is now becoming evident to a wider population in Europe: the classic methods for evaluating new medicines are being overtaken by science. In other words, new thinking is needed on clinical trials.
So the autumn is seeing a wave of European initiatives to explore just how things ought to change.
In late September, the subject is high on the agenda of the European Society for Medical Oncology (ESMO)-European CanCer Organization (ECCO) Congress in Vienna, and one of the first into the fray is the European Alliance for Personalized Medicine (EAPM), one of the most vocal advocates of change. EAPM is holding an event under the banner of “modernizing clinical trials for the benefit of Europe’s patients,” with the aim of promoting consensus on the policy initiatives that the oncology community should focus on for the next two years.
Mark Lawler of Queen’s University Belfast and Anastassia Negrouk from the European Organization for Research and Treatment of Cancer (EORTC) will be among those calling for new thinking across the range of trials, biobanks, and data sharing. The group has already been energetic in promoting understanding among members of the European Parliament and other legislators of how one-time informed consent be handled to ensure that the patient understands the benefits and risks of conducting future research based on archived samples, or how access to clinical trials can be handled to prioritize the evaluation of technologies that have the highest potential for clinical utility and avoid exhausting valuable samples unnecessarily. It has also been working on exploring standards that could ensure multiple clinical trials addressing the same questions are comparable, both from a clinical and analytical perspective.
Among the suggestions the group is now canvassing are the idea of setting the efficacy bars much higher than at present at the start of trials, and the development of a well-defined biomarker strategy embedded in the clinical trial process, with regulatory review and implementation based on best international practices.
Then in early October, the annual gathering of Europe’s great and good at Gastein, a village in the Austrian mountains, will pick up the reflections, with a seminar on how patients will be impacted by adaptive pathways and breakthrough designations. “While the long-awaited promise of personalized medicine is finally arriving, the regulatory structures required for their evaluation and reimbursement are still based around the blockbuster models of the last century,” proclaims the blurb for the meeting. And senior figures including Carole Longson from the National Institute for Health and Care Excellence (NICE), Gordon McVie of the European Institute of Oncology, and Barbara Kerstiens of the European Commission’s public health research department will lead the discussion.
In late October, the next meeting of the European Commission’s expert group on safe and timely access to medicines for patients-another bizarrely concocted European Union (EU) name to permit the equally bizarre acronym of STAMP (safe and timely access to medicines for patients)-will resume its reflections on real-world data and registries, and pursue its exploration of national schemes for early links between marketing authorization applicants and authorities to reinforce dialogue and regulatory support for new medicines addressing major public health needs. It will also review possible modifications of conditional marketing authorization procedures in Europe that are now under consideration.
All the while, the European Medicines Agency’s (EMA) own pilot project on adaptive pathways is humming along quietly, sifting through the proposals submitted by drugmakers as possible test cases as the mechanisms are studied. So far, one of the lessons to emerge is that companies need to be better prepared to get involved with authorities, but just when the pilot phase will be completed and evaluated remains clouded in uncertainty.
Further toward the end of the year, the EU is expected to agree on broad principles on personalized medicine that will have significant implications for clinical trials. Luxembourg, the country currently holding the rotating presidency of the EU council of ministers, has been working with diplomats and officials over recent weeks to draft a plan, which it says will be “patient-centered” but will take account of the need for adaptations in evidence-gathering and evaluation.
Meanwhile, another informal EU group of individuals from national authorities, academia, and industry have circulated a paper of their own on personalized medicine, which gives a flavor of how the debate in Europe is proceeding. Entitled “Ten actions to stimulate patient access to personalized medicine in Europe,” this extends across the entire range of adaptations it says are needed in what it calls “a fast-moving field.” It says “this new approach to medicine will foster more collaborative and interdisciplinary working methods amongst health professionals, induce the use of big data, and imply a change for the regulatory framework,” and calls for “disruptive change to the traditional way of working and thinking.”
Not surprisingly, this study devotes much of its attention to trials. “A key challenge for companies investing in innovative personalized medicine is to develop compelling evidence about the added value of the personalized approach in a timely and efficient way. However, the current clinical development paradigm and the traditional rather rigid requirements for trial designs are not adapted to the specific development challenges,” it says. There will be “an increased need to endorse and accept flexible trial designs that are adapted to the type of the diagnostic-therapy relationship and allow the identification of optimal combinations,” it adds.
In addition, “the collection of a standardized baseline biomarker data and associated treatment, and treatment outcomes in large national or supranational databases will be essential to support the future development and clinical use of personalized medicine.” Databases of this sort “would help the real-life positioning of treatments providing outcomes in specific patient subgroups.” Adaptive pathways “need to become more established and formalized,” and “it should finally be acknowledged” that comprehensive evidence about benefit and risk “is only going to be clear once diagnostic tools and medicines are on the market, based on real-life data. Evidence generation is a continuum.” Inevitably, “the lack of solid and complete evidence at the time of market authorization will require agreement on the application of principles of risk management.”
To make all this possible, the study insists, the full introduction of electronic patient records containing all health-related data of European citizens is essential, not just for development of innovations but to observe and guide the appropriate use of innovative treatments. But it complains that current efforts to
establish registries are still insufficient, and “greater governance is needed to speed up this process towards full capacity health informatics systems.”
Then in December, the EMA and industry association Emerging Biopharmaceutical Entreprises is holding a conference on how to get emerging medicines from laboratory to patient, with a particular focus on how regulators should respond to the challenges posed by innovative medicines, and how regulators and developers can work together early in the development process.
Whether this process can move forward fast enough and with sufficient coherence to keep up with the pace of change in product development is another question. But at last, there is a sense that pioneers are no longer voices crying in the wilderness, but are shifting wider perceptions that their messages are now increasingly being integrated into mainstream thinking.
Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium.