Table 3 Main processes described in the articles.

Balasopoulou (2017)

Presents findings on the landscape of genomic testing and genetic counselling services in Malaysia.

Public and private genetic testing laboratories

This study identifies genomic laboratories providing genetic services in Malaysia where there is a high prevalence of genetic disorders such as hemoglobinopathies and metabolic disorders.

• Need to establish databases that allow the storage and management of genetic and clinical data

• Conferences to raise awareness

• Genome-wide association studies

• The University of Malaya is engaged in collaborative work with the Golden Helix Foundation to establish public health policies in the areas of pharmacogenomics and precision medicine.

Gaff (2017)

Implementation of a genomic programme across multiple autonomous institutions.

Collaborative, holistic approach for a phased implementation.

• Development of a proof-of-concept model including governance, policies, procedures, infrastructure, and software applications.

• Development of pathway for patient testing.

• Evaluation following hybrid effectiveness and implementation design.

Sperber (2017)

Challenges to genomic programme implementation in clinical settings, and strategies to overcome them.

The IGNITE (Implementing GeNomics In pracTicE) six projects vary in scope and design.

• Exploration of the use of genetic markers for disease risk prediction and prevention, development of tools for using family history data, incorporating pharmacogenomic data into clinical care, refining disease diagnosis using sequence-based mutation discovery, and creating novel educational approaches.

Spackman (2017)

Quantifying the value of genomic tests using Cost-Effectiveness Analysis (CEA).

Iterative approaches.

• The goal of the genomic test must be explicit.

• Consider potential additional findings/multiple disorders.

Bertier (2018)

Usage, limitations and benefits of the clinical use of Next Generation Sequencing (NGS) for paediatric patients.

Focus on four teams, two in France and two in Quebec. Two teams used whole exome sequencing (WES) to improve the diagnosis and treatment of paediatric patients and families affected by rare diseases. The two other teams used it to help paediatric patients understand their absence of response to standard treatments and find more effective alternative treatments.

• Public institutions in both countries have invested significant funding in NGS following a political push for personalised medicine.

• NGS is usually not considered to be routine care.

Laviolle (2018)

Recommendations to associate genomics with modern medicine based on reflections of scientific applications and operational and societal challenges.

Based on the “France genomics 2025” programme, which aims to integrate genomic tests into clinical practice for validated indications and develop a national genomics network including industrial partnerships.

• 4 pilot projects were set up in a diversity of contexts.

• 13 working groups in charge of driving coordination, pilot projects, industrial participation management, ethical, regulatory, or medico-economic aspects, training, and communication.

• 1 centre to define, validate, and implement the operational standards on sequencing platforms and data analysis and ensure the technological and computer research and developments required to deploy genomics.

Nadauld (2018)

Demonstrate the approaches and challenges associated with clinical implementation efforts designed to advance this treatment paradigm.

Precision oncology medicine programs are implemented by an integrated delivery system, a community care centre, and an academic medical centre.

• Pilot programme within a three-hospital region in the delivery network.

• The program was subsequently expanded across all twenty-two hospitals and associated clinics.

• The precision medicine workflow in oncology consists of three key features: an in-depth genomic analysis of the patient’s tumour, interpretation of genomic test results by a molecular tumour board (MTB), and drug procurement services.

Zebrowski (2019)

Implementation of genomic medicine in clinical settings (as opposed to individual level)

Based on IGNITE programme

• Apply the Consolidated Framework for Implementation Research (CFIR) to identify system-level factors that played a role in the implementation of genomic medicine within Implementing GeNomics in PracTicE (IGNITE) Network projects.

Abimiku (2019)

Build an internationally recognised biorepository for the receipt, processing, storage, and distribution of biospecimens for biomedical research.

With a focus on the Institute of Human Virology Nigeria (IHVN) H3Africa Biorepository (I-HAB) in Abuja, Nigeria

Quality management system (QMS)

• Despite infrastructural challenges and limited resources, it is possible to establish a biorepository in a resource-limited setting that operates at an international level, if resources are leveraged to support the methodical implementation of a strategy for improvement that is grounded in established best practices and continuous monitoring and adjustment to local challenges.

Delatycki (2019)

To identify different approaches to reproductive carrier screening across a variety of different countries.

Different programs target distinct groups (high school, premarital, couples before conception, couples attending fertility clinics, and pregnant women) as does the governance structure (public health initiative and user pays). Ancestry‐based offers of screening are being replaced by expanded carrier screening panels with multiple genes that are independent of ancestry.

• Illustrates how the variability in how RCS is offered across the globe. This relates to geographical variation in carrier frequencies of genetic conditions and local health care, financial, cultural, and religious factors.

Burns (2019)

Examine critical considerations in successfully integrating genomic technologies into healthcare systems from a government perspective.

The priority areas for successful implementation are genomic services, data, workforce, finances, and person-centred care.

• Services: evaluation, ongoing advice, policy statements and national guidelines.

• Data: Sufficient data-storage capacity, data sharing technology, governance around genomic data.

• Workforce: Genomic education, interdisciplinary clinics, counselling and consent.

• Finances: government investment in basic infrastructure and workforce and development of expertise.

• Person-centred care: Culturally appropriate public health education and promotion programs.

Levy (2019)

To describe findings from the National Human Genome Research Institute’s (NHGRI) IGNITE Network in identifying key constructs, opportunities, and challenges associated with driving sustainability of genomic medicine in clinical practice.

The primary driver–stakeholder dyads were:

• Genomic training for providers, genomic clinical decision support (CDS) tools embedded in the electronic health record (EHR) third-party reimbursement for genomic testing.

• Six research institutions and 14 community partners funded to demonstrate the feasibility of genomic medicine in diverse settings. A further 16 affiliate institutions voluntarily collaborate with IGNITE to learn genomic medicine implementation techniques, share their experiences, and participate in network activities

Long (2019)

This study aimed to map and analyse interconnections between the members-a key feature of complexity-to capture the collaborations among the genomic community, document learning, assess Australian Genomics’ influence and identify key players.

A collaborative approach to implementation based on ‘hands-on learning’ and ‘making group decisions’

• Successful implementation of genomics requires the engagement of multidisciplinary teams across a range of conditions - Australian Genomics is facilitating this collaborative process by strategically building a genomic learning community

Pearce (2019)

Assess the readiness of the United Kingdom (UK) National Health Service to implement a Genomic Medicine Service

Mainstreaming

• The organisational, social, and cultural implications of reforming practice, highlight that demonstration of clinical utility and cost-effectiveness, attending to the compatibility of genomic medicine with clinical principles, and involving and engaging patients are key to successful implementation.

Riaz (2019)

Focus on Pakistan and the challenges to implementing genomics in the national healthcare system

-Preconception carrier screening or pre-natal

-Screening for chromosomal abnormalities

screening programme

- the Congenital Hypothyroidism Screening Programme

Propose an achievable, staged approach for the implementation of PHG, which includes setting short-term (3–5 year) goals, followed by longer-term (10–15 year) goals.

• Pakistan still lacks a national newborn screening programme, clinical genetic testing services, or public health genomics framework, despite having the world’s highest rates of inter-family marriages and prevalence of inherited genetic conditions

○ Initial steps towards strategic prioritisation, resourcing, and long-term goal setting are required.

Rowe (2019)

Evaluate the Expanded Universal Carrier Screening (EUCS) programmes.

There are considerable differences in panel composition between laboratories.

• The primary objective of a programme should be increased reproductive autonomy.

• Efficacy should be assessed by how the programme optimises informed choice.

• When and where EUCS could occur needs careful consideration, as it will influence cost, uptake, and the reproductive options available to couples.

Stark (2019)

To review the diverse approaches and current progress made by national genomic-medicine initiatives

in the UK, France, Australia, and the US and provide a roadmap for sharing strategies, standards, and data internationally to accelerate

implementation.

Evidence-based implementation through collaboration and data sharing

• These national genomic-medicine initiatives are driving transformative change under real-life conditions while simultaneously addressing barriers to implementation and gathering evidence for wider adoption.

Gaille (2020)

Presents a joint position of the UK-France Genomics and Ethics Network (UK-FR GENE), which has been established to reflect on ethical and social issues arising from the integration of genomics into routine clinical care in the UK and France.

National programmes funded by the state

• Despite each country’s strategy being at a different stage of implementation, the two countries face similar ethical issues

• each country tries to solve these issues by (re-)defining individual rights and collective duties in its way

• the social contract presents a useful tool to analyse the ways the UK and France address the ethical challenges raised by genomics.

Snir (2020)

Implementation challenges in the scaling of clinical genomic services.

Integration of software to support specialists such as genetic counsellors and medical geneticists in integrating genetics into primary care.

• Development of software to assist in electronic health record integration, the education of patients and providers, tools to stay abreast of guidelines, and simplification of the test ordering process.

• Proposes online educational videos, telehealth services, software to facilitate family history record taking, chatbots to answer frequent questions and conduct preliminary triage.

Tonkin (2020)

Guiding nurse leadership in the integration of genomic programmes in their services.

Proposes a maturity matrix to support the implementation of genomic programmes by nurses.

• Exploring and scoping factors of potential influence for change.

• Readiness planning (baseline/needs analysis, funding, governance).

• Raising awareness with stakeholders; building capacity and capability; mobilising resources.

• Active commitment to engage with and implement change.

• Culture of ongoing improvement in genomics is embedded, valued and sustainable.

White (2020)

To identify the barriers and facilitators to integrating genetics and genomics into nurses’ and physicians’ usual practice

Mainstreaming

• Building the capacity of nurses and physicians to integrate genetics and genomics into routine clinical care is essential if opportunities afforded by precision medicine are to be fully realised.

Best (2021)

Focuses exclusively on healthcare practitioners’ perceptions of barriers and enablers of reproductive genetic carrier screenings (RGCS) - because literature tends to focus on the attitudes of patients and families of those affected by genetic conditions.

Identifying the determinants of implementation is an essential first step in designing implementation strategies to overcome barriers.

• The use and potential impact of RGCS, including factors influencing equity of service take up and focus on the client

• Practitioners’ beliefs and expectations about the process of delivering RGCS, including the ability to deliver RGCS, knowledge about and support for RGCS, opinions about RGCS, and external influences on practitioners

• Resources available for practitioners for RGCS, including counselling, models of care delivery and other nonclinical barriers to delivery of RGCS.

Denommé-Pichon (2021)

FASTGENOMICS is a French national, multicentre, prospective pilot study in new-borns and infants suspected of genetic disease and hospitalised in neonatal or paediatric ICUs.

The pilot is designed to evaluate the feasibility of implementing trio-GS to deliver a result in less than 45 days while minimising extra costs by adapting the organisation to integrate urgent requests as a priority into the usual, not urgent workflow to identify the technical or organisational obstacles encountered.

• Speeding up the time to diagnosis using GS.

• Includes patients from multiple hospitals but relies on only one laboratory and one sequencing platform.

• Limit additional costs.

Elsink (2021)

Inborn errors of immunity (IEI) are a heterogeneous group of disorders, affecting different components of the immune system. This makes the early application of next-generation sequencing (NGS) as a diagnostic method in the evaluation of IEI a promising development

Early application of an NGS-based IEI panel

• With the rapidly evolving field of IEI-related genes, assessing genetic defects within these patients should be an ongoing process; periodic reanalysis of the WES data is advisable

Long (2021)

To develop a rich picture of the entire national Australia genomic program and its link and relationships with the broader context and show key stakeholders, agencies and processes and their interdependencies. (Holistic study of the programme)

Six research institutions and 14 community partners funded to demonstrate the feasibility of genomic medicine in diverse settings. A further 16 affiliate institutions voluntarily collaborate with IGNITE to learn genomic medicine implementation techniques, share their experiences, and participate in network activities.

• Uncertainty: who owns the data? How will it be reused in the future? How to deal with unexpected findings? will everyone adapt and adopt genomics modern technologies? what is the demand for genome sequencing?

• Non-linear processes: i.e., patients worry about how genomic tests may affect their insurance

• Unintended consequences: time commitments and need for more funding

• Interdependencies: nature of the workforce is linked to funding, which is linked to capacity and experience.

Lynch (2021)

To explore parents’ experiences of rapid Genomic Sequencing (rGS) for their critically unwell infant or child

Feasibility programme

• Identifies tensions between the medical imperative of rGS and parents’ decision-making, which need to be addressed as rGS becomes routine clinical care.

Prins (2021)

The way advances in genomic research will transform the future of personalised prevention and medicine in Estonia.

Translational research

• Genetic discoveries are improving personalised prediction and advance functional insights into the link between genetics and disease

Traversi (2021)

Review the emerging field of public health genomics in Italy and its integration into sanitary regulations and governance instruments.

Since 2013, personalised health has been a pillar of the National Prevention Plan. Recent educational efforts geared towards professionals, citizens, and decision-makers complement it.

• Genomic predictive tests are used in public settings to investigate monogenetic disorders.

• Genetic screening for complex diseases has been applied to a few conditions.

• Since 2011, two practical distance training courses on genetics and genomics have been released for physicians.

• Other initiatives were directed at a larger audience of healthcare professionals.

Vidgen (2021)

Presenting the genomic program in Queensland and the model for its integration into the broader healthcare system.

The structure and management of the Queensland Genomics program are based on adaptive management philosophy.

• The adaptive management strategy establishes processes that feedback lessons learnt based on experiences of running the program and have mechanisms to enable change reflecting this learning.

• It is applied in complex adaptive systems, such as healthcare so that programs can operate in situations of uncertainty.

• This program model was selected as genomics is a discipline experiencing fast technological changes and an evolving knowledge base.

Vinkšel (2021)

Implementation of NGS in diagnosing rare diseases and present advantages and challenges of diagnostic approach, with a focus on Slovenia.

NGS testing is offered via a clinical genetic service.

• Ensures responsible and efficient use of the recent technology to achieve economic sustainability.

• Patients referred from various medical specialities are evaluated by a clinical geneticist who checks for appropriateness of the referral (diagnostic hypothesis, probability of genetic aetiology, clinical utility), performs phenotyping of the patient, communicates with the NGS diagnostic unit in terms of interpretation of the result and provides pre and post-test genetic counselling.