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Published in Frontiers in Medicine: the COVID-19 pandemic hampered the sharing of information with and securing of consent from clinical study participants, but did not impact GDPR compliance

CARE partner KU Leuven (KUL, Belgium) conducted an online survey followed by semistructured interviews to gain insights into compliance with the General Data Protection Regulation (GDPR) for clinical studies and general aspects related to obtaining electronic Informed Consent (eIC) in Europe and the UK, before and during the pandemic. The survey targeted data protection officers or legal experts working in the pharmaceutical industry, academia, and academic biobanks involved in clinical research, investigators (physicians), and members of ethics committees.

The first part of the study empirically elucidated numerous key legal and ethical issues related to GDPR compliance in the context of (cross-border) clinical research (Lalova-Spinks et al.). First, the lack of legal harmonization remains the biggest challenge in the field, and that it is present not only at the level of the interplay of key EU legislative acts and national implementation of the GDPR, but also when it comes to interpretation at local, regional and institutional levels. Secondly, although the majority of respondents were opposed to Ethics Committee having a role in the determination of core choices that are under the responsibility of the controller, experts seemed to agree that it would be useful to clarify their role in data protection in an official manner. Finally, the pandemic did not bring additional legal challenges. Indeed, although practical challenges were high due to the globally enacted crisis measures, the key problematic issues on (cross-border) health research, interpretations of the legal texts and compliance strategies remained largely the same.

The second part of the study aimed to investigate stakeholders’ experiences with alternative consenting methods as well as their views on any regulatory or legal guidelines for eIC implementation in clinical research (De Sutter et al., 2022). The COVID-19 pandemic has impacted the clinical research activity in many countries, posing multiple challenges to ensure study continuation while minimizing the risk of infection for the participants as well as the research team. One of them was informing research participants about study-related information and obtaining their Informed Consent. The survey indicates that all stakeholder groups support the use of eIC during the COVID-19 pandemic and beyond. eIC indeed offers the opportunity to convey information interactively, by making use of multimedia or by offering information in a layered approach. Nevertheless, stakeholders had little practical experience with eIC and reported some challenges that hinder its deployement.
In addition, there is a varying understanding of the term “eIC” as well as limited European or country-specific support, from a regulatory and legal point of view, to facilitate implementation. Finally, the survey results showed that the COVID-19 pandemic resulted in some additional challenges to convey study-related information to participants and to obtain their consent.

These exploratory studies provide a snapshot into the real-life practices and beliefs in relation to the application of GDPR in clinical research as well as eIC. They underline a need for legal harmonization and a common multinational database that would support a GDPR and data protection compliant effort into global research. In addition, as alternative Informed Consent practices may be incorporated into common clinical practices, in the future a multi-stakeholder, multi-national guidance could contribute to a more harmonized eIC approach in clinical research.

To learn more, click here:
Challenges related to data protection in clinical research before and during the COVID-19 pandemic: an exploratory study.

Rethinking informed consent in the time of COVID-19: an exploratory survey.

Published in Structure: An insight into nsp10-mediated modulation of nsp14 exonuclease activity

The CARE partners Jagiellonian University (JU, Poland) and the Universty of Dundee (UnivDun, UK) discovered a key component of the regulation of nsp14 exonuclease activity by nsp10 using X-ray crystallography.

During RNA replication, coronaviruses require proofreading to maintain the integrity of their large genomes. This is a role of the SARS-CoV-2 nonstructural protein nsp14, which associates with viral polymerase complex to excise the mismatched nucleotides. The nsp14 exonuclease activity is modulated by a protein co-factor nsp10, which binds to nsp14.

Although the nsp10/nsp14 complex structure was already available, the mechanistic basis for nsp10-mediated modulation remains unclear. This is now solved thank to Czarna et al who provide the crystal structure of nsp14 in an apo-form, i.e., the structure of nsp14 alone.

The comparison of the nsp14/nsp10 structure with the nsp14 structure led to the discovery that the N-terminal region of nsp14 acts as a lid, covering the nsp10 binding site in the absence of the protein co-factor. The lid rearranges its structure in the presence of nsp10 to create a significant interaction surface with nsp10.

Nsp14 being a valid target in SARS-CoV-2 fight, by revealing the allosteric nsp14 control mechanism and offering crystallization conditions suitable for soaking of small molecules, this study provides essential information that will facilitate the effort in the development of an anti-coronaviral drug.

To learn more, click here: Refolding of lid subdomain of SARS-CoV-2 nsp14 upon nsp10 interaction releases exonuclease activity.

Published in Nature Micobiology: a new monoclonal antibody neutralizing SARS-CoV-2 Omicron variants 

The CARE partner Centre Hospitalier Universitaire Vaudois (CHUV) isolated a monoclonal antibody (mAb) named P2G3 that does not lose activity towards Omicron BA.1 and BA.2 compared to other variants of concern (VOC) (Wild Type, Alpha, Beta and Delta) and is more potent than other current clinically authorized and/or clinically advanced mAbs in vitro.

The collaboration within CARE with the Vaccine Research Institute (Inserm-VRI, France), the French Alternative Energies and Atomic Energy Commission (CEA) and KU Leuven (KUL, Belgium) led to an extended characterisation of P2G3 in vitro and in vivo and gave some insight on why this mAb is a promising anti-Omicron drug. Indeed, P2G3 alone, or in combination with P5C3 (a broadly active Class 1 mAb previously identified; Fenwick et al, 2021), confers complete prophylactic or therapeutic protection in vivo.

P2G3 is a Class 3 mAb that recognizes an epitope on the receptor binding domain (RBD) different from those bound by all other therapeutic mAbs authorized or at an advanced stage of development. The binding epitope is largely non-overlapping with residues mutated in Omicron, a unique feature. Furthermore, the emerging Omicron BA.4 and BA.5 variants with RBD mutations L452R and F486V are distant from the P2G3 binding epitope and unlikely to impact neutralizing activity.

In a context where the emergence of the the Delta and Omicron variants reduced the efficacy of vaccines and potent neutralizing mAbs, leaving vulnerable populations such as immunocompromised individuals without protection, the broadly active combination of P2G3 and P5C3 has the potential to be a superior anti-SARS-CoV-2 mAb cocktail for prophylactic and therapeutic interventions against all current VOCs, and its breadth of activity suggests that it might be capable of neutralizing many future SARS-CoV-2 VOCs.

To learn more, click here: Patient-derived monoclonal antibody neutralizes SARS-CoV-2 omicron variants and confers full protection in monkeys.

CARE External Newsletter – December

We are proud to announce the publication of CARE 1st External Newsletter. In this edition, you can learn about the CARE project, its collaborative culture and ways you may be able to contribute.

Download the call for collaboration here: CARE External Newsletter – Dec 2022