A(nother) New Start for Trial Regulations in Europe?

“The beginning of an exciting new phase for clinical research in Europe” is how the European pharmaceutical industry has greeted the latest initiative from the European Union to boost clinical trials. The cause of the excitement is the announcement early in the new year of “Accelerating Clinical Trials in the EU,” a bid by the key EU medicines authorities with the explicit aim “to transform how clinical trials are initiated, designed and run.”

The European Medicines Agency, the European Commission, and the Heads of Medicines Agencies have come together with a plan to develop the EU “as a focal point for clinical research” and to better integrate clinical research into the European health system. Priorities for the next two years are enabling innovative trial methods, and setting up a platform where all the many stakeholders–from patients and payers to regulators and academia–can come together to support this evolution, taking account of the demands both of innovation and of patient safety.

The initiative is a concrete response to the evident changes in which clinical trial designs are becoming more innovative, with new formats offering possible efficiencies and a more patient-centric approach. Attention has been rising in Europe to complex clinical trial designs, decentralized trials, artificial intelligence, and the use of machine learning, digitalization, and the links of growing importance with in vitro diagnostic devices, as well as to the potential of digitalization for patient monitoring and data generation. Until now, however, the disparate groups affected have been lacking the coordination and collaboration that is increasingly seen as necessary on all sides.

The plan is to strengthen leadership and coordination on clinical trial authorization and execution, and at the same time to optimize ethical oversight, integrating ethics committees more closely into clinical trials and the related regulatory activity. This, it is expected, will also support the conduct of large-scale multinational clinical trials with broader geographical scope, and reduce administrative burden while
increasing efficiency.

In a candid assessment of the need for change, the launch document for “ACT-EU”—as it is already coming to be known—admits that even after two decades of EU legislation aimed at improving the environment for clinical trials, “disharmony of regulatory requirements between member states complicate the submission of multi-state trial applications,” and “the resulting slower trial authorizations could negatively affect research responsiveness,” while “the expenses to conduct trials are high.”

Specific objectives range widely, and include protection of trial participants, ensuring data robustness and transparency, tackling unmet medical needs and rare diseases, and helping development of vaccines and therapeutics as insurance against public health crises and pandemics. Additional aid is foreseen for health technology assessment bodies as well as for academic and smaller-company sponsors of trials, and the plans extend to better-coordinated scientific advice and—at the most ambitious—to enhancing “capacity in all aspects of drug development and
regulatory science.”

The expectations are that the first two years of ACT-EU will be taken up with preparatory work, building on the implementation of the EU’s new clinical trials regulation and clinical trials information system, while engaging the full range of stakeholders and expert groups involved across the clinical trials community, modernizing good clinical practice (GCP) in line with the development of guidance at the International Conference on Harmonization, and developing a clinical trials training curriculum for wide use.

The January announcement of ACT-EU is often rebarbative, with its reliance on buzzwords–leveraging, matrix structures, mapping and dashboards—and with what looks like a parody of management consultancy-speak in its plan for “a framework of Do, Require, Influence, Support.” But the evidence is largely undisputed of the genuine need for some greater European coordination in improving the environment for clinical trials.

For the industry, the desire for change is widely documented. Eucope, the European body representing smaller research companies, has told the European Commission that for newer technologies such as the cell and gene therapies that concern many of its members, “it is essential to generate evidence through pathways other than the classic approach reliant on pre-authorization randomized clinical trials.” Many such technologies would benefit from post-licensing evidence generation through real-world evidence (RWE), it says—as well as from “an appropriate process for early and regular engagement with the EMA.”