Will the EU Medical Device Regulation help to improve the safety and performance of medical AI devices?

Concerns have been raised over the quality of evidence on the performance of medical artificial intelligence devices, including devices that are already on the market in the USA and Europe. Recently, the Medical Device Regulation, which aims to set high standards of safety and quality, has become applicable in the European Union. The aim of this article is to discuss whether, and how, the Medical Device Regulation will help improve the safety and performance of medical artificial intelligence devices entering the market. The Medical Device Regulation introduces new rules for risk classification of the devices, which will result in more devices subjected to a higher degree of scrutiny before entering the market; more stringent requirements on clinical evaluation, including the requirement for appraisal of clinical data; new requirements for post-market surveillance, which may help spot early on any new, unexpected side effects and risks of the devices; and requirements for notified bodies, including for expertise of the personnel and consideration of relevant best practice documents. The guidance of the Medical Device Coordination Group on clinical evaluation of medical device software and the MEDDEV2.7 guideline on clinical evaluation also attend to some of the problems identified in studies on medical artificial intelligence devices. The Medical Device Regulation will likely help improve the safety and performance of the medical artificial intelligence devices on the European market. The impact of the Regulation, however, is also dependent on its adequate enforcement by the European Union member states

Ethical, legal and social issues related to the offer of whole exome and whole genome sequencing

Whole genome and exome sequencing (WGS and WES) raise numerous ethical, legal and social issues (ELSI), such as related to informed consent and usage of sequencing data in research. These concerns may be amplified when genomic sequencing is offered direct-to-consumer (DTC) bypassing the traditional heathcare system. This thesis discusses ELSI related to WES/WGS and DTC genetic testing, provides an overview of current DTC genetic testing market, and analyses the impact of the recently adopted Regulation of the European Parliament and of the Council on in vitro diagnostic medical devices on DTC genetic testing. To provide insights into how ethical issues are addressed in DTC offer of WES/WGS, content analysis of websites of relevant DTC companies was conducted; the results were compared to relevant recommendations of expert groups. The analysis revealed the following concerns: lack of pre-test counselling, inadequate informed consent documents for genetic testing and/or for research activities on consumers’ samples and data, lack of relevant information and/or presence of potentially misleading descriptions in some of the companies studied. Consequently, consumers might not be aware of all the implications of undergoing WGS/WES, and their informed consent may be compromised. Another study presented in this thesis evaluated readability of informed consent forms for clinical WGS and WES using the SMOG and the Flesch-Kincaid formulas. All 36 forms studied failed to meet the average recommended reading grade level for informed consent forms, indicating that the content of the forms may not be comprehensible to many patients. In order to respect patients/consumers, the compliance with ethical standards when offering genetic testing should be strived for, also in the commercial DTC offer of WES and WGS. The findings presented herein indicate specific areas in which practices should be improved and provide reference and guidance for well-informed and potentially policy-relevant discussions between various stakeholders

Readability of informed consent forms for whole-exome and whole-genome sequencing

Whole-exome and whole-genome sequencing (WES, WGS) can generate an unprecedented amount of complex information, making the informed consent (IC) process challenging. The aim of our study was to assess the readability of English IC forms for clinical whole-exome and whole-genome sequencing using the SMOG and Flesch-Kincaid formulas. We analysed 36 forms, most of which were from US providers. The median readability grade levels were 14.75 (the SMOG formula) and 12.2 (the Flesch-Kincaid formula); these values indicate the years of education after which a person would be able to understand a text studied. All forms studied seem to fail to meet the average recommended readability grade level of 8 (e.g. by Institutional Review Boards of US medical schools) for IC forms, indicating that the content of the forms may not be comprehensible to many patients. The sections aimed at health care professionals (HCPs) in the forms indicate that HCPs should be responsible for explaining IC information to the patients. However, WES and WGS may be increasingly offered by primary care professionals who may not (yet) have sufficient training to be able to communicate effectively with patients about genomics. Therefore, to secure an adequate, truly informed consent process, the task of developing good, legible examples of IC forms along with educating HCPs in genomics should be taken seriously, and adequate resources should be allocated to enable these tasks

Willingness to donate genomic and other medical data: results from Germany.

This paper reports findings from Germany-based participants in the "Your DNA, Your Say" study, a collaborative effort among researchers in more than 20 countries across the world to explore public attitudes, values and opinions towards willingness to donate genomic and other personal data for use by others. Based on a representative sample of German residents (n = 1506) who completed the German-language version of the survey, we found that views of genetic exceptionalism were less prevalent in the German-language arm of the study than in the English-language arm (43% versus 52%). Also, people's willingness to make their data available for research was lower in the German than in the English-language samples of the study (56% versus 67%). In the German sample, those who were more familiar with genetics, and those holding views of genetic exceptionalism were more likely to be willing to donate data than others. We explain these findings with reference to the important role that the "right of informational self-determination" plays in German public discourse. Rather than being a particularly strict interpretation of privacy in the sense of a right to be left alone, the German understanding of informational self-determination bestows on each citizen the responsibility to carefully consider how their personal data should be used to protect important rights and to serve the public good

Willingness to donate genomic and other medical data: results from Germany.

This paper reports findings from Germany-based participants in the "Your DNA, Your Say" study, a collaborative effort among researchers in more than 20 countries across the world to explore public attitudes, values and opinions towards willingness to donate genomic and other personal data for use by others. Based on a representative sample of German residents (n = 1506) who completed the German-language version of the survey, we found that views of genetic exceptionalism were less prevalent in the German-language arm of the study than in the English-language arm (43% versus 52%). Also, people's willingness to make their data available for research was lower in the German than in the English-language samples of the study (56% versus 67%). In the German sample, those who were more familiar with genetics, and those holding views of genetic exceptionalism were more likely to be willing to donate data than others. We explain these findings with reference to the important role that the "right of informational self-determination" plays in German public discourse. Rather than being a particularly strict interpretation of privacy in the sense of a right to be left alone, the German understanding of informational self-determination bestows on each citizen the responsibility to carefully consider how their personal data should be used to protect important rights and to serve the public good

Attitudes of publics who are unwilling to donate DNA data for research

With the use of genetic technology, researchers have the potential to inform medical diagnoses and treatment in actionable ways. Accurate variant interpretation is a necessary condition for the utility of genetic technology to unfold. This relies on the ability to access large genomic datasets so that comparisons can be made between variants of interest. This can only be successful if DNA and medical data are donated by large numbers of people to 'research', including clinical, non-profit and for-profit research initiatives, in order to be accessed by scientists and clinicians worldwide. The objective of the 'Your DNA, Your Say' global survey is to explore public attitudes, values and opinions towards willingness to donate and concerns regarding the donation of one's personal data for use by others. Using a representative sample of 8967 English-speaking publics from the UK, the USA, Canada and Australia, we explore the characteristics of people who are unwilling (n = 1426) to donate their DNA and medical information, together with an exploration of their reasons. Understanding this perspective is important for making sense of the interaction between science and society. It also helps to focus engagement initiatives on the issues of concern to some publics.This work was supported by Wellcome grant [206194] paid to AM, LF, KIM, RM via Wellcome Genome Campus Society and Ethics Research Group, Connecting Science. We would like to thank the following people from GA4GH for their encouragement and infrastructure support: Peter Goodhand, Julia Wilson, Bartha Knoppers. This work was also supported by Global Alliance for Genomics and Health, with their funding delivered via Wellcome (GA4GH grant, with thanks to Audrey Duncansen). DV acknowledges the infrastructure funding received from the Victorian State Government through the Operational Infrastructure Support (OIS) Program

Trust in genomic data sharing among members of the general public in the UK, USA, Canada and Australia

Abstract: Trust may be important in shaping public attitudes to genetics and intentions to participate in genomics research and big data initiatives. As such, we examined trust in data sharing among the general public. A cross-sectional online survey collected responses from representative publics in the USA, Canada, UK and Australia (n = 8967). Participants were most likely to trust their medical doctor and less likely to trust other entities named. Company researchers were least likely to be trusted. Low, Variable and High Trust classes were defined using latent class analysis. Members of the High Trust class were more likely to be under 50 years, male, with children, hold religious beliefs, have personal experience of genetics and be from the USA. They were most likely to be willing to donate their genomic and health data for clinical and research uses. The Low Trust class were less reassured than other respondents by laws preventing exploitation of donated information. Variation in trust, its relation to areas of concern about the use of genomic data and potential of legislation are considered. These findings have relevance for efforts to expand genomic medicine and data sharing beyond those with personal experience of genetics or research participants

Proteomic and transcriptomic experiments reveal an essential role of RNA degradosome complexes in shaping the transcriptome of Mycobacterium tuberculosis.

The phenotypic adjustments of Mycobacterium tuberculosis are commonly inferred from the analysis of transcript abundance. While mechanisms of transcriptional regulation have been extensively analysed in mycobacteria, little is known about mechanisms that shape the transcriptome by regulating RNA decay rates. The aim of the present study is to identify the core components of the RNA degradosome of M. tuberculosis and to analyse their function in RNA metabolism. Using an approach involving cross-linking to 4-thiouridine-labelled RNA, we mapped the mycobacterial RNA-bound proteome and identified degradosome-related enzymes polynucleotide phosphorylase (PNPase), ATP-dependent RNA helicase (RhlE), ribonuclease E (RNase E) and ribonuclease J (RNase J) as major components. We then carried out affinity purification of eGFP-tagged recombinant constructs to identify protein-protein interactions. This identified further interactions with cold-shock proteins and novel KH-domain proteins. Engineering and transcriptional profiling of strains with a reduced level of expression of core degradosome ribonucleases provided evidence of important pleiotropic roles of the enzymes in mycobacterial RNA metabolism highlighting their potential vulnerability as drug targets

Members of the public in the USA, UK, Canada and Australia expressing genetic exceptionalism say they are more willing to donate genomic data

Funder: State Government of Victoria (Victorian Government); doi: https://doi.org/10.13039/501100004752Funder: Victorian State GovernmentAbstract: Public acceptance is critical for sharing of genomic data at scale. This paper examines how acceptance of data sharing pertains to the perceived similarities and differences between DNA and other forms of personal data. It explores the perceptions of representative publics from the USA, Canada, the UK and Australia (n = 8967) towards the donation of DNA and health data. Fifty-two percent of this public held ‘exceptionalist’ views about genetics (i.e., believed DNA is different or ‘special’ compared to other types of medical information). This group was more likely to be familiar with or have had personal experience with genomics and to perceive DNA information as having personal as well as clinical and scientific value. Those with personal experience with genetics and genetic exceptionalist views were nearly six times more likely to be willing to donate their anonymous DNA and medical information for research than other respondents. Perceived harms from re-identification did not appear to dissuade publics from being willing to participate in research. The interplay between exceptionalist views about genetics and the personal, scientific and clinical value attributed to data would be a valuable focus for future research