Lygature

The European Commission (EC) has proposed redefining ‘unmet medical need’ to steer pharmaceutical innovation and link it to incentives and regulatory tools and procedures. A multistakeholder meeting of the Regulatory Science Network Netherlands (RSNN) discussed the impact of this proposal. Four principles were highlighted (flexibility, feasibility, fairness, and sensitivity to risk) that were not considered sufficiently addressed. Concerns were raised about whether innovation would be incentivised, given the diverse and complex reasons why areas of unmet medical need may remain unaddressed. A more high-level definition of unmet medical need that gives guidance but allows for specification for specific uses throughout the medicine lifecycle was generally preferred. As the legislative process unfolds, stakeholder engagement will be essential to refine the definition to achieve the intended policy goals.

The European Lead Factory (ELF) is a consortium of universities and small and medium-sized enterprises (SMEs) dedicated to drug discovery, and the pharmaceutical industry. This unprecedented consortium provides high-throughput screening, triage, and hit validation, including to non-consortium members. The ELF library was created through a novel compound-sharing model between nine pharmaceutical companies and expanded through library synthesis by chemistry-specialized SMEs. The library has been screened against ∼270 different targets and 15 phenotypic assays, and hits have been developed to form the basis of patents and spin-off companies. Here, we review the outcome of screening campaigns of the ELF, including the performance and physicochemical properties of the library, identification of possible frequent hitter compounds, and the effectiveness of the compound-sharing model.

The European Lead Factory (ELF) is a pan-European public-private partnership established in 2013 and funded by the Innovative Medicines Initiative (IMI). It developed infrastructure and expertise for research teams to perform high-throughput screens to investigate which chemical compounds work best on specified drug targets. A chemical library, built within the IMI-funded ELF project, was designed to be easily shared between the ELF partners, selected academics and small and medium-sized biotech companies throughout Europe. The library consists of over 535,000 compounds that can serve as starting points for the development of new small molecule therapeutics. A FAIRplus squad team, consisting of members of both the ELF and FAIRplus projects, was tasked with investigating what would be necessary to make this unique ELF resource more FAIR, thus making it more valuable for others if and when the compound library is made available to the wider scientific community.

The 1+MG HEOR working group reviewed EU initiatives related to the implementation of whole genome sequencing into clinical practice. The findings were published in a summary paper. As a next step the group formulated recommendations towards the EC and member states. This work is part of B1MG WP5 Personalised Medicine and impact.

High-field magnetic resonance-linear accelerators (MR-Linacs), linear accelerators combined with a diagnostic magnetic resonance imaging (MRI) scanner and online adaptive workflow, potentially give rise to novel online anatomic and response adaptive radiation therapy paradigms. The first high-field (1.5T) MR-Linac received regulatory approval in late 2018, and little is known about clinical use, patient tolerability of daily high-field MRI, and toxicity of treatments. Herein we report the initial experience within the MOMENTUM Study (NCT04075305), a prospective international registry of the MR-Linac Consortium. Patients were included between February 2019 and October 2020 at 7 institutions in 4 countries. We used descriptive statistics to describe the patterns of care, tolerability (the percentage of patients discontinuing their course early), and safety (grade 3-5 Common Terminology Criteria for Adverse Events v.5 acute toxicity within 3 months after the end of treatment). A total 943 patients participated in the MOMENTUM Study, 702 of whom had complete baseline data at the time of this analysis. Patients were primarily male (79%) with a median age of 68 years (range, 22-93) and were treated for 39 different indications. The most frequent indications were prostate (40%), oligometastatic lymph node (17%), brain (12%), and rectal (10%) cancers. The median number of fractions was 5 (range, 1-35). Six patients discontinued MR-Linac treatments, but none due to an inability to tolerate repeated high-field MRI. Of the 415 patients with complete data on acute toxicity at 3-month follow-up, 18 (4%) patients experienced grade 3 acute toxicity related to radiation. No grade 4 or 5 acute toxicity related to radiation was observed. In the first 21 months of our study, patterns of care were diverse with respect to clinical utilization, body sites, and radiation prescriptions. No patient discontinued treatment due to inability to tolerate daily high-field MRI scans, and the acute radiation toxicity experience was encouraging.

Aims: Recently, the use of novel remote monitoring technologies (RMTs) in trials has gained much interest. To facilitate regulatory learning, we evaluated qualification opinions (QOs) and advices (QAs) and scientific advices (SAs) of the Committee for Medicinal Products for Human Use (CHMP) to gain insight in the types of devices that are intended to be used in clinical trials for supporting/submitting application for obtaining marketing authorization (registration trials) and the main recommendations of the CHMP.Methods: QOs, QAs, and SAs of the CHMP that assessed RMTs between 2013 and 2019 were eligible for our study. The following information was extracted from the documents: year of advice/opinion, device and endpoints used, type of endpoint (primary, secondary, exploratory, or safety), and main recommendations of the CHMP.Results: In total two QOs, four QAs, and 59 SAs were included in our study (total of SAs between 2013 and 2019 = 4,054). In the SAs, accelerometers to measure activity and/or sleep parameters (n = 31) were the most frequently used devices, followed by mobile applications (n = 6) and glucose monitoring devices (n = 6). Usually, these measures were proposed as secondary or exploratory endpoints (n = 32). The main recommendations of the CHMP were related to relevance of the (novel) outcome measure; validation; precision, accuracy, sensitivity, and specificity; compliance; sampling interval; and data handling and privacy.Conclusions: Although there was a trend toward an increased use over time, the use of RMTs in registration trials is still relatively rare. In the absence of formal European regulatory guidance on mHealth technologies, insight in the main recommendations of the CHMP may stimulate the use of novel RMTs in a regulatory context.