Open Data in the Era of the GDPR: Lessons from the Human Cell Atlas.

The Human Cell Atlas (HCA) is striving to build an open community that is inclusive of all researchers adhering to its principles and as open as possible with respect to data access and use. However, open data sharing can pose certain challenges. For instance, being a global initiative, the HCA must contend with a patchwork of local and regional privacy rules. A notable example is the implementation of the European Union General Data Protection Regulation (GDPR), which caused some concern in the biomedical and genomic data-sharing community. We examine how the HCA's large, international group of researchers is investing tremendous efforts into ensuring appropriate sharing of data. We describe the HCA's objectives and governance, how it defines open data sharing, and ethico-legal challenges encountered early in its development; in particular, we describe the challenges prompted by the GDPR. Finally, we broaden the discussion to address tools and strategies that can be used to address ethical data governance.

Avoiding Liability and Other Legal Land Mines in the Evolving Genomics Landscape.

This article reviews evolving legal implications for clinicians and researchers as genomics is used more widely in both the clinic and in translational research, reflecting rapid changes in scientific knowledge as well as the surrounding cultural and political environment. Professionals will face new and changing duties to make or act upon a genetic diagnosis, address direct-to-consumer genetic testing in patient care, consider the health implications of results for patients' family members, and recontact patients when test results change over time. Professional duties in reproductive genetic testing will need to be recalibrated in response to disruptive changes to reproductive rights in the United States. We also review the debate over who controls the flow of genetic information and who is responsible for its protection, considering the globally influential European Union General Data Protection Regulation and the rapidly evolving data privacy law landscape of the United States.

Abrupt increase in harvested forest area over Europe after 2015.

Forests provide a series of ecosystem services that are crucial to our society. In the European Union (EU), forests account for approximately 38% of the total land surface1. These forests are important carbon sinks, and their conservation efforts are vital for the EU's vision of achieving climate neutrality by 20502. However, the increasing demand for forest services and products, driven by the bioeconomy, poses challenges for sustainable forest management. Here we use fine-scale satellite data to observe an increase in the harvested forest area (49 per cent) and an increase in biomass loss (69 per cent) over Europe for the period of 2016-2018 relative to 2011-2015, with large losses occurring on the Iberian Peninsula and in the Nordic and Baltic countries. Satellite imagery further reveals that the average patch size of harvested area increased by 34 per cent across Europe, with potential effects on biodiversity, soil erosion and water regulation. The increase in the rate of forest harvest is the result of the recent expansion of wood markets, as suggested by econometric indicators on forestry, wood-based bioenergy and international trade. If such a high rate of forest harvest continues, the post-2020 EU vision of forest-based climate mitigation may be hampered, and the additional carbon losses from forests would require extra emission reductions in other sectors in order to reach climate neutrality by 20503.

The effectiveness of moderating harmful online content.

In 2022, the European Union introduced the Digital Services Act (DSA), a new legislation to report and moderate harmful content from online social networks. Trusted flaggers are mandated to identify harmful content, which platforms must remove within a set delay (currently 24 h). Here, we analyze the likely effectiveness of EU-mandated mechanisms for regulating highly viral online content with short half-lives. We deploy self-exciting point processes to determine the relationship between the regulated moderation delay and the likely harm reduction achieved. We find that harm reduction is achievable for the most harmful content, even for fast-paced platforms such as Twitter. Our method estimates moderation effectiveness for a given platform and provides a rule of thumb for selecting content for investigation and flagging, managing flaggers' workload.

Regulation of Molecular Diagnostics.

Molecular diagnostic tests enable rapid analysis of genomic and proteomic markers. These tests are subject to diverging premarket access and postmarket surveillance requirements and mechanisms in the United States and the European Union. Each of these jurisdictions has its own challenges in keeping the regulations up to date with technological developments. A specific area of attention is that of laboratory-developed tests in the United States and health institution in-house-produced tests in the European Union, for which the United States and the European Union have markedly different regulatory approaches. Both jurisdictions have specific but differing requirements for the use of test samples and test-related data under their rules regarding the protection of (personal) health data, which can cause complexity when moving samples or sample-related data from one jurisdiction to the other.

Making the best of research investment in pathogens control through biocontrol. How is research correlated with agricultural microbial biological control product availability?

While using microbial biological control products (MBCPs) to limit pathogens is one of the alternatives to the ecologically unsustainable use of synthetic pesticides that received attention, the last 2 decades have not brought the foreseen leap in developing systematic alternatives based on low-risk plant protection products (PPPs) across the globe. To explain this limited progress, we map the evolution of research on the most successful microbial biological control agents (MBCAs) worldwide. We also map the financing structure in the top funding countries and the European Union (EU) to discern the relevant trends. Available data for the European Union Member States allowed us to discover a country-level and EU-level correlation between strain-level research and biocontrol products' approval based on those strains.

Science after Brexit: bright spots on the Horizon?

Is scientific partnership between the UK and EU on the Horizon?

Mind the (CRISPR) gaps: The European Commission's proposal for the use of NGTs in the EU.

The proposal by the European Commission to regulate New Genome Technique (NGT) plants is a leap forward, but it does not revise the current legislation on GMOs and includes many inconsistencies that may hinder the adoption of specific NGTs.

Quality and transparency of evidence for implantable cardiovascular medical devices assessed by the CORE-MD consortium.

BACKGROUND AND AIMS: The European Union Medical Device Regulation 2017/745 challenges key stakeholders to follow transparent and rigorous approaches to the clinical evaluation of medical devices. The purpose of this study is a systematic evaluation of published clinical evidence underlying selected high-risk cardiovascular medical devices before and after market access in the European Union (CE-marking) between 2000 and 2021. METHODS: Pre-specified strategies were applied to identify published studies of prospective design evaluating 71 high-risk cardiovascular devices in seven different classes (bioresorbable coronary scaffolds, left atrial appendage occlusion devices, transcatheter aortic valve implantation systems, transcatheter mitral valve repair/replacement systems, surgical aortic and mitral heart valves, leadless pacemakers, subcutaneous implantable cardioverter-defibrillator). The search time span covered 20 years (2000-21). Details of study design, patient population, intervention(s), and primary outcome(s) were summarized and assessed with respect to timing of the corresponding CE-mark approval. RESULTS: At least one prospective clinical trial was identified for 70% (50/71) of the pre-specified devices. Overall, 473 reports of 308 prospectively designed studies (enrolling 97 886 individuals) were deemed eligible, including 81% (251/308) prospective non-randomized clinical trials (66 186 individuals) and 19% (57/308) randomized clinical trials (31 700 individuals). Pre-registration of the study protocol was available in 49% (150/308) studies, and 16% (48/308) had a peer-reviewed publicly available protocol. Device-related adverse events were evaluated in 82% (253/308) of studies. An outcome adjudication process was reported in 39% (120/308) of the studies. Sample size was larger for randomized in comparison to non-randomized trials (median of 304 vs. 100 individuals, P < .001). No randomized clinical trial published before CE-mark approval for any of the devices was identified. Non-randomized clinical trials were predominantly published after the corresponding CE-mark approval of the device under evaluation (89%, 224/251). Sample sizes were smaller for studies published before (median of 31 individuals) than after (median of 135 individuals) CE-mark approval (P < .001). Clinical trials with larger sample sizes (>50 individuals) and those with longer recruitment periods were more likely to be published after CE-mark approval, and were more frequent during the period 2016-21. CONCLUSIONS: The quantity and quality of publicly available data from prospective clinical investigations across selected categories of cardiovascular devices, before and after CE approval during the period 2000-21, were deemed insufficient. The majority of studies was non-randomized, with increased risk of bias, and performed in small populations without provision of power calculations, and none of the reviewed devices had randomized trial results published prior to CE-mark certification.

Analysis and comparative evaluation of expedited programs for gene therapy products: insights from the United States, the European Union, Japan, and South Korea.

Gene therapy products (GTPs) used for incurable diseases can be expedited for early commercialization to fulfill unmet needs. This study analyzed the expedited programs available for GTPs in the US, EU, Japan, and South Korea using their regulatory authorities' websites, related regulations, and documents. In total, there were five expedited programs available for GTPs in the US, four in the EU, and three in both Japan and South Korea, of which four are tailored for GTPs. These programs, sharing similar objectives, can be categorized as those expediting drug development, review, and approval. However, variations are observed in eligibility criteria, specific benefits, and post-marketing study conditions across regulatory authorities. Additionally, the criteria for orphan drug designation for a rare disease differs in prevalence thresholds, incentive offered, and marketing exclusivity period. Overall, 19 GTPs were approved-13 in the US, 14 in the EU, eight in Japan, and three in South Korea-with majority obtaining regulatory approval through at least one expedited program. Therefore, future studies can analyze whether acquiring multiple expedited programs accelerates the drug development and commercialization of GTPs compared with when only one expedited program is processed. Additionally, inter-authority scientific discussion is encouraged for harmonization of expedited program requirements.

Advancing rare disease treatment: EMA's decade-long insights into engineered adoptive cell therapy for rare cancers and orphan designation.

Adoptive cell therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has emerged as a promising approach for targeting and treating rare oncological conditions. The orphan medicinal product designation by the European Union (EU) plays a crucial role in promoting development of medicines for rare conditions according to the EU Orphan Regulation.This regulatory landscape analysis examines the evolution, regulatory challenges, and clinical outcomes of genetically engineered ACT, with a focus on CAR-T cell therapies, based on the European Medicines Agency's Committee for Orphan Medicinal Products review of applications evaluated for orphan designation and maintenance of the status over a 10-year period. In total, 30 of 36 applications were granted an orphan status, and 14 subsequently applied for maintenance of the status at time of marketing authorisation or extension of indication. Most of the products were autologous cell therapies using a lentiviral vector and were developed for the treatment of rare haematological B-cell malignancies. The findings revealed that 80% (29/36) of the submissions for orphan designation were supported by preliminary clinical data showing a potential efficacy of the candidate products and an added clinical benefit over currently authorised medicines for the proposed orphan condition. Notably, in 89% (32/36) of the cases significant benefit of the new products was accepted based on a clinically relevant advantage over existing therapies. Twelve of fourteen submissions reviewed for maintenance of the status at time of marketing authorisation or extension of indication demonstrated significant benefit of the products over existing satisfactory methods of treatment within the approved therapeutic indications, but one of the applications was withdrawn during the regulatory evaluation.This article summarises the key findings related to the use of engineered ACT, primarily CAR-T cell therapies, in targeting and treating rare cancers in the EU. It emphasises the importance of use of clinical data in supporting medical plausibility and significant benefit at the stage of orphan designation and highlights the high success rate for these products in obtaining initial orphan designations and subsequent maintaining the status at the time of marketing authorisation or extension of indication.

Exercise for the Prevention of Anthracycline-Induced Functional Disability and Cardiac Dysfunction: The BREXIT Study.

BACKGROUND: Breast cancer survivors treated with anthracycline-based chemotherapy (AC) have increased risk of functional limitation and cardiac dysfunction. We conducted a 12-month randomized controlled trial in 104 patients with early-stage breast cancer scheduled for AC to determine whether 12 months of exercise training (ExT) could attenuate functional disability (primary end point), improve cardiorespiratory fitness (VO2peak), and prevent cardiac dysfunction. METHODS: Women 40 to 75 years of age with stage I to III breast cancer scheduled for AC were randomized to 3 to 4 days per week aerobic and resistance ExT for 12 months (n=52) or usual care (UC; n=52). Functional measures were performed at baseline, at 4 weeks after AC (4 months), and at 12 months, comprising: (1) cardiopulmonary exercise testing to quantify VO2peak and functional disability (VO2peak ≤18.0 mL·kg-1·min-1); (2) cardiac reserve (response from rest to peak exercise), quantified with exercise cardiac magnetic resonance measures to determine changes in left and right ventricular ejection fraction, cardiac output, and stroke volume; (3) standard-of-care echocardiography-derived resting left ventricular ejection fraction and global longitudinal strain; and (4) biochemistry (troponin and BNP [B-type natriuretic peptide]). RESULTS: Among 104 participants randomized, greater study attrition was observed among UC participants (P=0.031), with 93 women assessed at 4 months (ExT, n=49; UC, n=44) and 87 women assessed at 12 months (ExT, n=49; UC, n=38). ExT attenuated functional disability at 4 months (odds ratio, 0.32 [95% CI, 0.11-0.94]; P=0.03) but not at 12 months (odds ratio, 0.27 [95% CI, 0.06-1.12]; P=0.07). In a per-protocol analysis, functional disability was prevented entirely at 12 months among participants adherent to ExT (ExT, 0% versus UC, 20%; P=0.005). Compared with UC at 12 months, ExT was associated with a net 3.5-mL·kg-1·min-1 improvement in VO2peak that coincided with greater cardiac output, stroke volume, and left and right ventricular ejection fraction reserve (P<0.001 for all). There was no effect of ExT on resting measures of left ventricular function. Postchemotherapy troponin increased less in ExT than in UC (8-fold versus 16-fold increase; P=0.002). There were no changes in BNP in either group. CONCLUSIONS: In women with early-stage breast cancer undergoing AC, 12 months of ExT did not attenuate functional disability, but provided large, clinically meaningful benefits on VO2peak and cardiac reserve. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12617001408370.