Applied Clinical Trials
It isn't all that long ago that everyone at the cutting edge of drug development was talking excitedly about the merits of adaptive licensing as the key to unlocking new benefits to patients and to innovators in medicines. Breaking down the rigidity of authorization procedures and opening up new flexibilities in clinical trials could, it was argued, transform the prospects for better use of medicines in healthcare.
The idea remains as valid as ever - but in Europe it is increasingly seen these days as being a vital part, but only a part, of the changes that need to be made to ensure momentum in new drug development. The harsh reality - as perceived, certainly, from the point of view of the pharmaceutical industry, but even to a growing extent by patient groups and healthcare analysts - is that no matter how fast the authorization process operates, the merits of innovation will not be felt until they reach patients. And the barrier between authorization and patient access remains, in most of Europe, the issue of reimbursement.
Consequently, the mantra is moving on beyond adaptive licensing, to what a leading figure in the European pharmaceutical industry described to this columnist last week as "progressive patient access." Some of the reasoning for the shift has been set out by a group of industry experts in another journal (1) this month. The authors, all linked to the European Federation of Pharmaceutical Industries and Associations, advance the now-familiar arguments about the need for new research and development models, and appropriate regulatory pathways. But they place greater emphasis on completing a virtuous circle of innovation, authorisation and reward.
Their tour d'horizon naturally takes in adaptive approaches to trial design, which can more fully harness knowledge from outside the trial and allow ongoing trials to be modified in response to information they elicit while maintaining statistical rigour. It notes the proposals circulating in Europe and the United States for monitoring and revising the benefit–risk profile during the entire life cycle of a drug, along with the idea of using evidence from trials to allow access to a new drug in specific non-trial settings, and laments that at present "there is no agreement among stakeholders regarding benefit–risk methodologies, conclusions and outputs." And it acknowledges the EMA's suggested investigation of a “staggered” approval approach to assessing the benefit–risk profile for a broader population, for which earlier access may be granted to a “better-defined or more restricted population of good responders” before full market authorization.
The authors are in favour of going further than anything envisaged under the current EU conditional marketing authorization, towards "progressive early access through a progressive marketing authorization model" for unmet need. Crucially, however, they add that any such move "would fail if reimbursement systems do not reflect the need for targeted patient access and repeatedly adjust their policies based on new knowledge".
This is the key to the virtuous circle approach they recommend, where proposals are harmonized as a comprehensive package through extensive collaboration among the European Commission, the European Medicines Agency and reimbursement bodies. That, as my industry informant insisted last week, is what is needed for progressive patient access.
(1) NATURE REVIEWS | DRUG DISCOVERY VOLUME 12 | APRIL 2013 | 247, Priorities for improving drug research, development and regulation, Susan R. Forda, Richard Bergström, Magda Chlebus, Richard Barker and Peter Høngaard Andersen