European Legislative Proposals Presage New Rules for Clinical Trials

The European Union's rules on clinical trials and studies are not the principal object of the mass of proposals for the update of the bloc's pharmaceutical legislation that dates back more than 20 years. But at a conservative estimate, some 20,000 of the hundreds of thousands of words in the draft released in late April will have consequences for the current framework that the clinical trials community has to work with every day.

The proposal¹, developed over the last three years by the European Commission range widely—from marketing authorization requirements, incentives for drug developers, and pediatric and orphan products to issues such as shortages and product labeling. And more specifically, they cover matters as crucial as access to individual patient data from clinical studies in structured format, intellectual property protection, or updating product information (to "include both positive and negative results of clinical trials or other studies in all therapeutic indications and populations, whether or not included in the marketing authorization, as well as data on the use of the medicinal product where such use is outside the terms of the marketing authorization.")

The current rules will be tweaked to streamline the regulatory framework and to take account of the fact that the pharmaceutical sector and the development of medicinal products are global, and "research and clinical trials conducted on one continent will support development and authorization in other continents. In order to meet unmet medical needs of patients, "it may be necessary to grant marketing authorization on the basis of less complete data than is normally the case." Cost reductions for business and administrations "are expected to come from adaptations to accommodate new concepts such as adaptive clinical trials, a medicinal product’s mechanism of action, use of real-world evidence, and new uses of health data within the regulatory framework," the draft predicts. It entertains the prospect of secondary use of health data and regulatory sandboxes – for situations where "scientific or regulatory challenges arising from characteristics or methods related to the product" make development impossible in compliance with the current requirements.

Authorization timelines are to be speeded up, and approvals granted for an unlimited time, with renewals required only in exceptional cases. The European Medicines Agency (EMA) "may take advantage of all the potential of supercomputing, artificial intelligence, and big data science to fulfil its mandate, without compromising privacy rights."

The proposal seeks to "allow for more informative advice on clinical trial applications and, therefore, a more integrated development advice in view of future data requirements for marketing authorization applications," and provides for EMA to consult "with representatives from member states with clinical trial expertise" as well as "other bodies" in developing scientific guidelines on unmet medical needs and the design of clinical trials. But decisions on clinical trial applications "should remain within the competence of the member states."

But the changes envisioned are not always to the benefit of drug developers. The standard period of regulatory data protection for orphan drugs will be reduced from eight years to six years, although marketing authorization holders can win some of this back in return for quality of innovation or ease of access, obtaining, for instance, a further six months if they conduct comparative clinical trials. The explicit intention is to incentivize the generation of evidence that can support subsequent health technology assessments and national decisions on pricing and reimbursement. But the criteria are still to be agreed, with EMA delegated to set the scientific guidelines on criteria for proposing a comparator.

A tighter policy focus on protecting patients spells out that clinical trials, and "in particular those conducted outside the EU," must adequately demonstrate they fully met the principles of good clinical practice. The protection of clinical trial data will be weakened to allow generic companies to prepare launch of copy products on patent expiry. The pediatric waiver would be limited, with the obligation maintained for new products to prepare a pediatric investigation plan if the product, "due to its molecular mechanism of action," is expected to be effective against a different disease in children. And EMA "may process personal health data from sources other than clinical trials for the purpose of improving the robustness of its scientific assessment or verifying claims of the applicant." In addition, to avoid unnecessary animal testing, marketing authorization applicants "should make all efforts to reuse animal study results."

There is much more in this package of legislative proposals, which are now entering the long phase of review by the EU's formal legislative bodies, the European Parliament and the Council. This will involve detailed—and often heated—discussion of each of the contentious elements, and this column will doubtless be returning to many of these proposals over the coming months and (yes!) years to reflect on the implications for clinical trials as the debates evolve.

Reference

1. https://health.ec.europa.eu/medicinal-products/pharmaceutical-strategy-europe/reform-eu-pharmaceutical-legislation_en