Health Data Linkage for Public Interest Research in the UK: Key Obstacles and Solutions

Introduction: Analysis of linked health data can generate important, even life-saving, insights into population health. Yet obstacles both legal and organisational in nature can impede this work. Approach: We focus on three UK infrastructures set up to link and share data for research: the Administrative Data Research Network, NHS Digital, and the Secure Anonymised Information Linkage Databank. Bringing an interdisciplinary perspective, we identify key issues underpinning their challenges and successes in linking health data for research. Results: We identify examples of uncertainty surrounding legal powers to share and link data, and around data protection obligations, as well as systemic delays and historic public backlash. These issues require updated official guidance on the relevant law, approaches to linkage which are planned for impact and ongoing utility, greater transparency between data providers and researchers, and engagement with the patient population which is both high-profile and carefully considered. Conclusions: Health data linkage for research presents varied challenges, to which there can be no single solution. Our recommendations would require action from a number of data providers and regulators to be meaningfully advanced. This illustrates the scale and complexity of the challenge of health data linkage, in the UK and beyond: a challenge which our case studies suggest no single organisation can combat alone. Planned programmes of linkage are critical because they allow time for organisations to address these challenges without adversely affecting the feasibility of individual research projects.</p

Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.

The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities. [Abstract copyright: © 2023. The Author(s).

Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue

Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue

Author Correction:Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models

In the version of this article initially published, Cristina Leal Rodríguez (Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark) was omitted from the author list. The error has been corrected in the HTML and PDF versions of the article</p

Anonymity in EU health law: Not an alternative to information governance

Data sharing has long been a cornerstone of healthcare and research and is only due to become more important with the rise of Big Data analytics and advanced therapies. Cell therapies, for example, rely not only on donated cells but also essentially on donated information to make them traceable. Despite the associated importance of concepts such as ‘donor anonymity’, the concept of anonymisation remains contentious. The Article 29 Working Party’s 2014 guidance on ‘Anonymisation Techniques’ has perhaps helped encourage a perception that anonymity is the result of data modification ‘techniques’, rather than a broader process involving management of information and context. In light of this enduring ambiguity, this article advocates a ‘relative’ understanding of anonymity and supports this interpretation with reference not only to the General Data Protection Regulation but also to European Union health-related legislation, which also alludes to the concept. Anonymity, I suggest, should be understood not as a ‘technique’ which removes the need for information governance but rather as a legal standard of reasonable risk-management, which can only be satisfied by effective data protection. As such, anonymity can be not so much an alternative to data protection as its mirror, requiring similar safeguards to maintain privacy and confidentiality

Gene therapy regulation: Could in-body editing fall through the net?

Somatic gene therapies may be authorised for marketing in the EU under the advanced therapy medicinal product regulation. These therapeutic compounds are sufficiently novel and complex in their potential effects to require specialist evaluation. However, the current definition of gene therapy medicinal products (‘GTMP’) risks excluding molecules which are not manufactured through techniques involving recombination. We consider the way, in which the ‘recombinant nucleic acid’ aspect of the GTMP definition is challenged by developments in gene-editing technology, and why a broader scope of GTMP regulation may be desirable

The Data Protection Bill – virtues out of necessity?

A number of claims have been made for the Data Protection Bill, as it serves a number of purposes—modernisation, ensuring data flows post-Brexit, and exercising derogations under the GDPR to create a more ‘nationalised’ law

The Data Protection Bill – virtues out of necessity?

A number of claims have been made for the Data Protection Bill, as it serves a number of purposes—modernisation, ensuring data flows post-Brexit, and exercising derogations under the GDPR to create a more ‘nationalised’ law