Search

With the introduction of Next Generation Sequencing (NGS) techniques increasing numbers of disease-associated variants are being identified. This ongoing progress might lead to diagnoses in formerly undiagnosed patients and novel insights in already solved cases. Therefore, many studies suggest introducing systematic reanalysis of NGS data in routine diagnostics. Introduction will, however, also have ethical, economic, legal and (psycho)social (ELSI) implications that Genetic Health Professionals (GHPs) from laboratories should consider before possible implementation of systematic reanalysis. To get a first impression we performed a scoping literature review. Our findings show that for the vast majority of included articles ELSI aspects were not mentioned as such. However, often these issues were raised implicitly. In total, we identified nine ELSI aspects, such as (perceived) professional responsibilities, implications for consent and cost-effectiveness. The identified ELSI aspects brought forward necessary trade-offs for GHPs to consciously take into account when considering responsible implementation of systematic reanalysis of NGS data in routine diagnostics, balancing the various strains on their laboratories and personnel while creating optimal results for new and former patients. Some important aspects are not well explored yet. For example, our study shows GHPs see the values of systematic reanalysis but also experience barriers, often mentioned as being practical or financial only, but in fact also being ethical or psychosocial. Engagement of these GHPs in further research on ELSI aspects is important for sustainable implementation., (© 2024. The Author(s).)

There has been considerable recent progress in the implementation of public health genomics policy throughout the developed world. However, in the developing world, genetic services still remain limited, or unavailable to most. Here, we discuss challenges and opportunities related to the implementation of public health genomics in developing countries. We focus on Pakistan, a country with one of the world's highest rates of inter-family marriages and prevalence of inherited genetic conditions. Pakistan still lacks a national newborn screening programme, clinical genetic testing services, or public health genomics framework. The medical infrastructure in Pakistan, characterized by limited publicly-funded health services and a significant burden of infectious disease, may contribute to de-prioritization of genetic health services. In addition, there are a number of societal, cultural and religious factors to consider. Recently a number of large research studies have been conducted in populations of Pakistani descent, mostly in collaboration with major US, UK and European institutions. Some of these have yielded high-impact scientific findings, but have yet to translate into public health outcomes in Pakistan. Before the benefits of genomics can be realized in developing countries, the first initial steps towards strategic prioritization, resourcing, and long-term goal setting are required. We propose some practical recommendations and possible first steps forward.

Efforts are underway to harmonise the return of individual results and incidental findings from whole genome sequencing (WGS) across research contexts and countries. We reviewed international, regional and national laws and policies applying to return across 20 countries to identify areas of convergence and divergence. Discrepancies between laws and policies are most problematic where they cannot be reconciled through harmonisation of project-level governance. Rules for the return of results apply at different levels in different jurisdictions (e.g., human subjects research, biobanks, clinical trials, genomic sequencing, and genetic/personal data), complicating comparison. A particular concern for harmonisation are the (often contradictory) rules about when results must, should, may, or must not be returned. Adding confusion are different thresholds for utility (medical, familial, reproductive, and/or personal). The importance of respecting individual choices to know or not know is widely recognised, though some norms emphasise respect for personal preferences. Another troubling observation is that requirements for data quality, variant assessment, and the effective communication of results are evolving in uneven ways. There is a growing gap between researchers with the expertise, infrastructure, and resources to meet these requirements and those without, threatening international collaboration. Best practices for the return of individual genomic results are sorely needed to inform not only the ethical return of results, but also future legislative and policy efforts.

The Global Alliance for Genomics and Health (GA4GH) proposes a data access policy model-"registered access"-to increase and improve access to data requiring an agreement to basic terms and conditions, such as the use of DNA sequence and health data in research. A registered access policy would enable a range of categories of users to gain access, starting with researchers and clinical care professionals. It would also facilitate general use and reuse of data but within the bounds of consent restrictions and other ethical obligations. In piloting registered access with the Scientific Demonstration data sharing projects of GA4GH, we provide additional ethics, policy and technical guidance to facilitate the implementation of this access model in an international setting.