Advancing Clinical Research in Europe
Bringing Medicines to Patients Faster

Sandra Blumenrath
DIA Science Writer

he roads are increasingly converging for clinical research and how it is regulated. The new EU Clinical Trial Regulation optimizes safety surveillance at the Member State (MS) level, but while progressive, its implementation also poses new challenges for both Member States and Sponsors to meet the expectation of regulators. Sessions in this topic area focused on the impact of the new regulation on clinical trial stakeholders and discussed other opportunities to further European clinical trials, including the use of patient registries, innovative clinical trial designs, and the incorporation of real world data (RWD).

Key Takeaways

• EU Member States are progressing well in preparing for the implementation of the EU Clinical Trial Regulation. Remaining challenges include aggressive review timelines, harmonization of application outcomes, fee structures defined by MS to predict needed resources, and safety work sharing.
• Some registry studies have led to successful regulatory decision-making and serve as a valuable learning experience for both the regulators as well as the respective sponsors. Early interactions between regulators and registry holders during the development process can ensure that the quantity and quality of the collected data is in line with regulatory requirements.
• Complex, innovative clinical trial designs, such as basket, umbrella, and platform trials, have entered clinical research, and an increasing number of clinical trials now follow adaptive designs.
• Real world data are now commonly integrated into clinical research to enrich clinical trials and ensure decision-making that is complementary to randomized controlled trials.

Why this is important: To advance healthcare product development, we need to increase the efficiency of clinical trial design, avoid delays and costs, and plan for different outcome scenarios in the trial design process. Changes in the regulatory landscape as well as the use of new research approaches and technologies have the potential to advance clinical trials in Europe and bring medicines to patients faster.

The New Clinical Trial Regulation

The way clinical trials are conducted in the EU will change significantly when the new Clinical Trial Regulation (EU No. 536/2014) takes effect in 2019. The goal is to harmonize the assessment and supervision processes for clinical trials, ensuring consistent rules for conducting clinical trials throughout the EU, increased trial transparency, and the highest safety standards for participants. Its key benefits, however, also pose certain challenges for MSs. While it improves collaboration, information sharing and decision-making among MSs in multinational clinical trials, collaborative review and approval timelines are short and require meticulous internal planning and coordination as well as quick feedback mechanisms. Thorough preparation will be key at every step of the regulatory process to achieve a successful outcome for applications submitted under the new Regulation.

Patient Registries

High-quality patient registries can make valuable contributions to public health by providing a source for evaluating and monitoring the safety of medicines. The objective of the European Medicines Agency Patient Registry Initiative is to facilitate discussions early on in the authorization procedure – both to increase the use of existing patient registries and to support the creation of new registries. Some of the challenges prior to the Initiative have been low patient accrual rates, concerns about data quality, and gaps between what is collected and what is requested by regulatory agencies. The EU regulatory network is developing tools that address these challenges while supporting the use of data from disease registries. Two case studies demonstrated that the use of consistent and reproducible registry data was integral to the successful approval of medicines.

Innovative and ‘Smart’ Clinical Trials

Increasingly complex medical conditions and small patient populations require different, and often more complex, trial design options to increase clinical trial efficiency while maintaining scientific accuracy and data quality. Basket trials, for example, are a cost-effective option, in which the effect of a therapy is tested on multiple diseases caused by the same mutation. Umbrella trials, on the other hand, have many different treatment arms in the same trial, with patients being assigned to one of the treatment arms. Similarly, with adaptive platform trials it is possible to simultaneously study multiple therapies for a given disease, evaluate and adapt treatment arms based on decision-algorithms, and efficiently arrive at the most promising therapy.

All of these designs are cost-effective, time-saving options compared to traditional, randomized controlled clinical trials (RCTs), allowing for quicker patient access to targeted therapies. However, Health Technology Assessment (HTA) bodies will have to be educated about complex trial design options, because their current expertise with these designs varies widely. Interactions with regulators, on the other hand, require sound planning and a detailed scientific rationale for master protocols. Regulators recommend seeking their scientific advice, especially for confirmatory trials.

The clinical realm is also embracing Big Data, and various enrichment strategies are suggested to make clinical trials ‘smarter.’ For example, real world data (RWD) and the real word evidence (RWE) derived from them can be leveraged to optimize clinical trial design by fine-tuning target populations, improving site selection and patient recruitment, and complementing evidence from traditional clinical trials – as long as best practices are applied and limitations are known. Here again, regulators strongly recommend extensive planning and seeking their scientific advice when designing RWD studies.

This article summarizes key takeaways from sessions in “Topic I: How Can We Enable Clinical Research in Europe Further?”