Public Preferences for Digital Health Data Sharing: Discrete Choice Experiment Study in 12 European Countries.

BACKGROUND: With new technologies, health data can be collected in a variety of different clinical, research, and public health contexts, and then can be used for a range of new purposes. Establishing the public's views about digital health data sharing is essential for policy makers to develop effective harmonization initiatives for digital health data governance at the European level. OBJECTIVE: This study investigated public preferences for digital health data sharing. METHODS: A discrete choice experiment survey was administered to a sample of European residents in 12 European countries (Austria, Denmark, France, Germany, Iceland, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom) from August 2020 to August 2021. Respondents answered whether hypothetical situations of data sharing were acceptable for them. Each hypothetical scenario was defined by 5 attributes ("data collector," "data user," "reason for data use," "information on data sharing and consent," and "availability of review process"), which had 3 to 4 attribute levels each. A latent class model was run across the whole data set and separately for different European regions (Northern, Central, and Southern Europe). Attribute relative importance was calculated for each latent class's pooled and regional data sets. RESULTS: A total of 5015 completed surveys were analyzed. In general, the most important attribute for respondents was the availability of information and consent during health data sharing. In the latent class model, 4 classes of preference patterns were identified. While respondents in 2 classes strongly expressed their preferences for data sharing with opposing positions, respondents in the other 2 classes preferred not to share their data, but attribute levels of the situation could have had an impact on their preferences. Respondents generally found the following to be the most acceptable: a national authority or academic research project as the data user; being informed and asked to consent; and a review process for data transfer and use, or transfer only. On the other hand, collection of their data by a technological company and data use for commercial communication were the least acceptable. There was preference heterogeneity across Europe and within European regions. CONCLUSIONS: This study showed the importance of transparency in data use and oversight of health-related data sharing for European respondents. Regional and intraregional preference heterogeneity for "data collector," "data user," "reason," "type of consent," and "review" calls for governance solutions that would grant data subjects the ability to control their digital health data being shared within different contexts. These results suggest that the use of data without consent will demand weighty and exceptional reasons. An interactive and dynamic informed consent model combined with oversight mechanisms may be a solution for policy initiatives aiming to harmonize health data use across Europe.

Participant perspective on the recall-by-genotype research approach: a mixed-method embedded study with participants of the CHRIS study.

Recall-by-genotype (RbG) research recruits participants previously involved in genetic research based on their genotype. RbG enables the further study of a particular variant of interest, but in recalling participants, it risks disclosing potentially unwanted or distressing genetic information. Any RbG strategy must therefore be done in a manner that addresses the potential ethical and social issues. As part of an RbG pilot on the penetrance of Parkinson's disease variants, we conducted an empirical mixed-method study with 51 participants of the Cooperative Health Research in South Tyrol (CHRIS) study to understand participant views on RbG research approach. Participants were disclosed the disease under investigation but not the individual variant carrier status. Results showed that participants filtered the information received through personal experience and enacted mechanisms to address the concerns raised by invitation by resorting to personal resources and the support provided by experts. While the non-disclosure of the Parkin variant carrier status was deemed acceptable, disclosing the disease under study was important for participants. Participant preferences for disclosure of the disease under investigation and the carrier status varied according to how the knowledge of individual carrier status was perceived to impact the participant's life. This study provided insights into participant response to the RbG research approach, which are relevant for RbG policy development. A suitable communication strategy and granular options addressing preferences for invitation in the original informed consent are critical for an ethically informed RbG policy.

Ethical, legal and social/societal implications (ELSI) of recall-by-genotype (RbG) and genotype-driven-research (GDR) approaches: a scoping review.

Recall by Genotype (RbG), Genotype-driven-recall (GDR), and Genotype-based-recall (GBR) strategies are increasingly used to conduct genomic or biobanking sub-studies that single out participants as eligible because of their specific individual genotypic information. However, existing regulatory and governance frameworks do not apply to all aspects of genotype-driven research approaches. The recall strategies disclose or withhold personal genotypic information with uncertain clinical utility. Accordingly, this scoping review aims to identify peculiar, explicit and implicit ethical, legal, and societal/social implications (ELSI) of RbG study designs. We conducted a systematic literature search of three electronic databases from November 2020 to February 2021. We investigated qualitative and quantitative research methods used to report ELSI aspects in RbG research. Congruent with other research findings, we identified a lack of qualitative research investigating the particular ELSI challenges with RbG. We included and analysed the content of twenty-five publications. We found a consensus on RbG posing significant ethical issues, dilemmas, barriers, concerns and societal challenges. However, we found that the approaches to disclosure and study-specific recall and communication strategies employed consent models and Return of Research Results (RoRR) policies varied considerably. Furthermore, we identified a high heterogeneity in perspectives of participants and experts about ELSI of study-specific RbG policies. Therefore, further fine-mapping through qualitative and empirical research is needed to draw conclusions and re-fine ELSI frameworks.

Early Life Glucocorticoid Exposure Modulates Immune Function in Zebrafish (Danio rerio) Larvae.

In this study we have assessed the effects of increased cortisol levels during early embryonic development on immune function in zebrafish (Danio rerio) larvae. Fertilized eggs were exposed to either a cortisol-containing, a dexamethasone-containing (to stimulate the glucocorticoid receptor selectively) or a control medium for 6 h post-fertilization (0-6 hpf). First, we measured baseline expression of a number of immune-related genes (socs3a, mpeg1.1, mpeg1.2, and irg1l) 5 days post-fertilization (dpf) in larvae of the AB and TL strain to assess the effectiveness of our exposure procedure and potential strain differences. Cortisol and dexamethasone strongly up-regulated baseline expression of these genes independent of strain. The next series of experiments were therefore carried out in larvae of the AB strain only. We measured neutrophil/macrophage recruitment following tail fin amputation (performed at 3 dpf) and phenotypical changes as well as survival following LPS-induced sepsis (150 µg/ml; 4-5 dpf). Dexamethasone, but not cortisol, exposure at 0-6 hpf enhanced neutrophil recruitment 4 h post tail fin amputation. Cortisol and dexamethasone exposure at 0-6 hpf led to a milder phenotype (e.g., less tail fin damage) and enhanced survival following LPS challenge compared to control exposure. Gene-expression analysis showed accompanying differences in transcript abundance of tlr4bb, cxcr4a, myd88, il1ß, and il10. These data show that early-life exposure to cortisol, which may be considered to be a model or proxy of maternal stress, induces an adaptive response to immune challenges, which seems mediated via the glucocorticoid receptor.

Early life exposure to cortisol in zebrafish (Danio rerio): similarities and differences in behaviour and physiology between larvae of the AB and TL strains.

Maternal stress and early life stress affect development. Zebrafish (Danio rerio) are ideally suited to study this, as embryos develop externally into free-feeding larvae. The objective of this study was therefore to assess the effects of increased levels of cortisol, mimicking thereby maternal stress, on larval physiology and behaviour. We studied the effects in two common zebrafish strains, that is, AB and Tupfel long-fin (TL), to assess strain dependency of effects. Fertilized eggs were exposed to a cortisol-containing medium (1.1 µmol/l) or control medium from 0 to 6 h following fertilization, after which at 5-day following fertilization, larval behaviour and baseline hypothalamus-pituitary-interrenal cells axis functioning were measured. The data confirmed earlier observed differences between AB larvae and TL larvae: a lower hypothalamus-pituitary-interrenal axis activity in TL larvae than AB larvae, and slower habituation to repeated acoustic/vibrational stimuli in TL larvae than AB larvae. Following cortisol treatment, increased baseline levels of cortisol were found in AB larvae but not TL larvae. At the behavioural level, increased thigmotaxis or 'wall hugging' was found in AB larvae, but decreased thigmotaxis in TL larvae; however, both AB larvae and TL larvae showed decreased habituation to repeated acoustic/vibrational stimuli. The data emphasize that strain is a critical factor in zebrafish research. The habituation data suggest a robust effect of cortisol exposure, which is likely an adaptive response to increase the likelihood of detecting or responding to potentially threatening stimuli. This may enhance early life survival. Along with other studies, our study underlines the notion that zebrafish may be a powerful model animal to study the effects of maternal and early life stress on life history.