Applied Clinical Trials
Peter O’Donnell explores potential parallels of the U.S. “right-to-try” debate in Europe.
Renewed attempts in the U.S. to win legislative approval for the right-to-try concept have again focused attention on that inevitably grey area between hoping a new medicine is going to be effective and demonstrating that it can be. As the debate highlights so sharply, patients in desperate straits are likely to be more inclined toward hope than insistent on demonstration. Regulators find themselves constantly challenged to defend their own red lines in what is a constantly shifting context, where technology and scientific innovation demand perpetual reassessment of the decision-making rationale.
Europe is not so far down the track as some US legislators and pressure groups. Access to unlicensed medicines is provided for, of course, via compassionate use and on a named-patient basis, but divergent national reticences persist. A young British epileptic patient responsive to cannabis oil prescribed in the Netherlands is currently fighting the UK authorities for access to what Her Majesty’s Government deems a prescribed drug.
An additional light has been shone on the debate by a strongly-worded statement from Belgium’s feisty health minister, Maggie De Block. Now the Belgian authorities find themselves swept up in the controversy, after reports that De Block had suggested to the girl’s mother that she should move abroad to obtain the treatment.
De Block flatly denies having advised the mother to take the child to a different country in pursuit of cannabis oil. But more interestingly for the wider world, the minister goes on to make a strong defense of the concept of government action to protect the public against unlicensed treatments.
While cannabis oil may help some children, she conceded, “it is very harmful, and even deadly, for others.” She expanded on that specific point to draw a broader generalization: “That’s why we need irrefutable evidence that cannabis oil is safe for health and its effects are beneficial for everyone.”
De Block was careful to take account in her argument of some of the tensions underlying the provision of novel treatments. She noted that cannabis can be marketed as a licensed drug for the treatment of some specified conditions, such as to treat spasms and pain in multiple sclerosis.
But, she added, the unfortunate reality is that unmet need continues to exist. Effective pain relief is not available for all cases and conditions, and “international drug research is not always progressing as quickly as we would like. It often takes a very long time to reach a scientific breakthrough.” Her conclusion is crystal clear-and will offer some comfort to drug developers facing dirigiste pressures from regulators or governments keen to dictate research agendas.
Little movement on MAPPs
The European discussions about earlier access are taking place in the somewhat tamer framework of adaptive pathways, or MAPPs-as this blogger noted in February (“Removing the risks from adaptive pathways: planning for the possible?”). The EU’s ADAPTSMART project, which has been exploring the feasibility of MAPPs for the last three years, reached its climax in late March at a closing conference in Budapest, where the benefits and the challenges were given a gratifyingly candid airing.
Everyone there agreed on the merits of access to beneficial treatments for specific, well-defined, patient groups with a high unmet medical need at the earliest appropriate time in the product life-span in a sustainable and affordable fashion. More realistically, Hans-Georg Eichler, senior medical officer of the European Medicines Agency (EMA), and one of the key figures in European MAPPs, claimed some progress in promoting an evolution of mindset so that the approval of needed medicines is no longer seen in a standard linear approach, but at the same time acknowledged that “this opinion is not unanimous.”
According to Wim Goettsch, the special health technology assessment (HTA) advisor for the Zorginstituut Nederland, and an early advocate of MAPPs, “the acceptance of MAPPs amongst many HTA bodies is low”-so much so that he posed the question “Is MAPPs deceased?” And Francesca Cerreta, scientific administrator of the EMA, said: “We have some remaining uncertainties.”
In addition to widespread hesitancy over the concept of MAPPs, there is a formidable list of evident and immediate concrete challenges, including the lack of an agreed definition for high unmet medical need, insufficient systemization of real-world evidence, gaping infrastructure deficiencies, and establishing a coherent link between the regulatory issues of authorization and the economic issues of payment.
Valentina Strammiello of the European Patients’ Forum pointed to gaps in national capacities for collecting real-world data, and Jacoline Bouvy of NICE commented that “the responsibility of collecting the data will fall to healthcare professionals, and they are already saying they are over committed for time and resources.” Just as crucially, while some HTA bodies are willing to use real-world evidence to make assessments, others are not. According to Goettsch: “We’ve had many experiences where we’ve asked companies for real-world evidence and the data we get is not what we wanted. For MAPPs to work, the data needs to be addressing the endpoints where we expect evidence.”
Industry concerns as well were recorded about the need to commit both to a smaller first population at the start of the 10-year exclusivity period, with potential limits to revenues over time, and to a requirement to generate evidence over the long-term. Solange Corriol-Rohou of AstraZeneca, a key figure in ADAPTSMART, admitted that MAPPs “still is a highly sensitive and controversial concept,” and could offer the meeting the reassurance only that “We try to have broader collaboration with payers and healthcare providers.” But the President of the Dutch Medicine Evaluation Committee, Ad Schuurman, expressed disappointment that “so far, none of the companies seem willing to come forward and try to do MAPPs for real.”
The conference did agree on a series of action points, covering some of the unresolved issues-from evidence collection to payment methodologies, and from involving payers more actively in discussions to setting up MAPPs pilots. The European debate, currently, is more about the right to try MAPPs than the right to try unlicensed medicines.
Peter O'Donnell is a freelance journalist who specializes in European health affairs and is based in Brussels, Belgium