Towards a Responsible Transition to Learning Healthcare Systems in Precision Medicine: Ethical Points to Consider

Abstract

Learning healthcare systems have recently emerged as a strategy to continuously use experiences and outcomes of clinical care for research purposes in precision medicine. Although it is known that learning healthcare transitions in general raise important ethical challenges, the ethical ramifications of such transitions in the specific context of precision medicine have not extensively been discussed. Here, we describe three levers that institutions can pull to advance learning healthcare systems in precision medicine: (1) changing testing of individual variability (such as genes); (2) changing prescription of treatments on the basis of (genomic) test results; and/or (3) changing the handling of data that link variability and treatment to clinical outcomes. Subsequently, we evaluate how patients can be affected if one of these levers are pulled: (1) patients are tested for different or more factors than before the transformation, (2) patients receive different treatments than before the transformation and/or (3) patients’ data obtained through clinical care are used, or used more extensively, for research purposes. Based on an analysis of the aforementioned mechanisms and how these potentially affect patients, we analyze why learning healthcare systems in precision medicine need a different ethical approach and discuss crucial points to consider regarding this approach.

Building a Sustainable Learning Health Care System for Pregnant and Lactating People: Interview Study Among Data Access Providers

“…The topic list was based on the topic list used for another qualitative interview study, in which we asked women during preconception, pregnancy, and nursing what they thought about an LHS for pregnant and lactating women [20]. The topic list was also based on an analysis of the challenges of public-private partnerships, LHSs, and responsible data sharing [1,10,21], as well as discussions among the research team. To mitigate the potential for socially desirable responses from our respondents, it was determined that the topic of moral responsibility regarding the use of data and the dissemination of research findings would not be included in the general topic list.…”

“…In many areas of health care, learning health care systems (LHSs) are seen as a promising method for learning from real-world experiences [1,2]. In an LHS, health care and research are aligned to accelerate research and outcomes for patients and have the potential to develop scientific knowledge based on health information and research data by directly implementing new insights from analyses to the clinical practice [3].…”

The Role of Genome Sequencing in Neonatal Intensive Care Units

“…Genetic heterogeneity of fetal and neonatal phenotypes, overrepresentation of novel and rare genomic variants in the NICU population, the high fraction of affected infants in NICUs with undiagnosed congenital anomalies or metabolic disorders, the significant contribution of genetic disorders to morbidity and mortality among infants, and the proven record of rWES and rWGS to change clinical management and identify individualized therapeutic strategies make the integration of rWGS into NICU clinical care a high priority (102,103). As illustrated by the framework developed by Rady Children's Institute for Genomic Medicine described above (45), acceleration of this integration will require an intentional commitment to implementation of a sustainable genomic learning healthcare system through implementation science that uses knowledge and experience derived from NICU and prenatal clinical care for cycles of continuous improvement and research to improve patient outcomes through enhanced diagnostic success, clinical efficiency, and discovery of genotype-guided therapeutics (36,60,61,102,103,109). Multiple stakeholders-including parents, payers, bioinformaticians, geneticists, genetic counselors, neonatologists, obstetricians, pediatric subspecialists, developmental biologists, model organism investigators, experts in strategies to rescue variant-encoded disruption (e.g., with gene therapy, antisense oligonucleotides, small molecules, genome editing, or repurposed FDA-approved drugs), clinical investigators, genomicists, and institutional leaders-will need to participate in the development of a genomic learning healthcare system for NICUs.…”

“…Multiple stakeholders-including parents, payers, bioinformaticians, geneticists, genetic counselors, neonatologists, obstetricians, pediatric subspecialists, developmental biologists, model organism investigators, experts in strategies to rescue variant-encoded disruption (e.g., with gene therapy, antisense oligonucleotides, small molecules, genome editing, or repurposed FDA-approved drugs), clinical investigators, genomicists, and institutional leaders-will need to participate in the development of a genomic learning healthcare system for NICUs. The challenges in implementing this system include facilitating a cultural shift among providers from phenotype-first to genotype-first diagnosis, creating governance structures that can adapt to new ethical and operational questions, standardizing genomic and phenotypic information in EHRs, enabling more reliable computational and functional evaluation of novel and rare VUSs that are clinically actionable, and developing consent strategies that permit the inclusion of an individual's clinical and genomic data while protecting patient confidentiality (61,101,109). However, NICUs have a long record of commitment to quality improvement through implementation science and, more recently, of supporting valuebased quality initiatives (32).…”

Evolving assessment pathways for precision oncology medicines to improve patient access: a tumor-agnostic lens

“… 4 Sharing and using these data could create a “learning health care system” that uses real-world evidence (RWE) to target treatment and learn about treatment outcomes, with spillover effects beyond oncology. 5 …”