Optimising Exome Prenatal Sequencing Services (EXPRESS): a study protocol to evaluate rapid prenatal exome sequencing in the NHS Genomic Medicine Service.

Background: Prenatal exome sequencing (ES) for the diagnosis of fetal anomalies was implemented nationally in England in October 2020 by the NHS Genomic Medicine Service (GMS). is the GMS is based around seven regional Genomic Laboratory Hubs (GLHs). Prenatal ES has the potential to significantly improve NHS prenatal diagnostic services by increasing genetic diagnoses and informing prenatal decision-making.

Towards implementation of comprehensive breast cancer risk prediction tools in health care for personalised prevention.

Advances in knowledge about breast cancer risk factors have led to the development of more comprehensive risk models. These integrate information on a variety of risk factors such as lifestyle, genetics, family history, and breast density. These risk models have the potential to deliver more personalised breast cancer prevention.

How can we address the uncertainties regarding the potential clinical utility of polygenic score-based tests?

As common low penetrance variants associated with diseases are uncovered, attempts continue to be made to harness this knowledge for improving healthcare. Polygenic scores have been developed as the mechanism by which knowledge of common variants can be used to investigate genetic contributions to disease risk. They serve as a biomarker to provide an estimate of the genetic liability for a particular disease.

Understanding polygenic models, their development and the potential application of polygenic scores in healthcare.

The use of genomic information to better understand and prevent common complex diseases has been an ongoing goal of genetic research. Over the past few years, research in this area has proliferated with several proposed methods of generating polygenic scores. This has been driven by the availability of larger data sets, primarily from genome-wide association studies and concomitant developments in statistical methodologies.

Risk stratification, genomic data and the law.

Risk prediction models have a key role in stratified disease prevention, and the incorporation of genomic data into these models promises more effective personalisation. Although the clinical utility of incorporating genomic data into risk prediction tools is increasingly compelling, at least for some applications and disease types, the legal and regulatory implications have not been examined and have been overshadowed by discussions about clinical and scientific utility and feasibility. We held a workshop to explore relevant legal and regulatory perspectives from four EU Member States: France, Germany, the Netherlands and the UK.

Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down's syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units.

Objective:  To investigate the benefits and costs of implementing non-invasive prenatal testing (NIPT) for Down's syndrome into the NHS maternity care pathway.

Design:  Prospective cohort study.

Setting:  Eight maternity units across the United Kingdom between 1 November 2013 and 28 February 2015.

Implications of using whole genome sequencing to test unselected populations for high risk breast cancer genes: a modelling study.

Background: The decision to test for high risk breast cancer gene mutations is traditionally based on risk scores derived from age, family and personal cancer history. Next generation sequencing technologies such as whole genome sequencing (WGS) make wider population testing more feasible. In the UK's 100,000 Genomes Project, mutations in 16 genes including BRCA1 and BRCA2 are to be actively sought regardless of clinical presentation.

Points to consider for prioritizing clinical genetic testing services: a European consensus process oriented at accountability for reasonableness.

Given the cost constraints of the European health-care systems, criteria are needed to decide which genetic services to fund from the public budgets, if not all can be covered. To ensure that high-priority services are available equitably within and across the European countries, a shared set of prioritization criteria would be desirable. A decision process following the accountability for reasonableness framework was undertaken, including a multidisciplinary EuroGentest/PPPC-ESHG workshop to develop shared prioritization criteria.

Evaluation of non-invasive prenatal testing (NIPT) for aneuploidy in an NHS setting: a reliable accurate prenatal non-invasive diagnosis (RAPID) protocol.

Background: Non-invasive prenatal testing (NIPT) for aneuploidies is now available through commercial companies in many countries, including through private practice in the United Kingdom (UK). Thorough evaluation of service delivery requirements are needed to facilitate NIPT being offered more widely within state funded healthcare systems such as the UK's National Health Service (NHS). Successful implementation will require the development of laboratory standards, consideration of stakeholder views, an analysis of costs and development of patient and health professional educational materials.

'Personalized medicine': what's in a name?

Over the last decade genomics and other molecular biosciences have enabled new capabilities that, according to many, have the potential to revolutionize medicine and healthcare. These developments have been associated with a range of terminologies, including 'precision', 'personalized', 'individualized' and 'stratified' medicine. In this article, based on a literature review, we examine how the terms have arisen and their various meanings and definitions.

A framework for the prioritization of investment in the provision of genetic tests.

Background: The UK Genetic Testing Network (UKGTN) established a process for the evaluation of genetic tests for entry onto the National Health Service (NHS) Directory of Molecular Genetic Testing. The Network requested the development and piloting of a prioritization framework that could be used for the commissioning of genetic tests by the NHS.

Methods: A selected working group developed and piloted a multi-criteria prioritization process using 10 genetic tests evaluated by the UKGTN.

Evaluation of genetic tests for susceptibility to common complex diseases: why, when and how?

Recent research into the human genome has generated a wealth of scientific knowledge and increased both public and professional interest in the concept of personalised medicine. Somewhat unexpectedly, in addition to increasing our understanding about the genetic basis for numerous diseases, these new discoveries have also spawned a burgeoning new industry of 'consumer genetic testing'. In this paper, we present the principles learnt though the evaluation of tests for single gene disorders and suggest a comparable framework for the evaluation of genetic tests for susceptibility to common complex diseases.

HER2 status in breast cancer--an example of pharmacogenetic testing.

The development of new drugs and associated pharmacogenetic tests will provide an increasing number of challenges to health care systems. In particular, how to evaluate their benefits, prioritize for commissioning purposes and implement a service to provide them in a timely manner. This paper presents an overview of HER2 testing for trastuzumab (Herceptin) treatment in breast cancer cases.

How can genetic tests be evaluated for clinical use? Experience of the UK Genetic Testing Network.

The UK Department of Health supported the establishment of the UK Genetic Testing Network (UKGTN) in 2002. The UKGTN is a collaborative network of NHS molecular genetic laboratories that offer tests for human single gene germ-line disorders. Its objective is to provide high quality and equitable services for patients and their families who require genetic advice, diagnosis and management.

The evaluation of genetic tests.

Scientific advances in genetics and molecular biology have been very successful in advancing our knowledge of biological mechanisms in health and disease, and in catalysing a variety of technological innovations. The number of genetic tests available has consequently increased exponentially over the last few years. Their development has not been accompanied by processes and systems to evaluate these tests in a proper and formal manner to establish their clinical validity and utility.

Array-based comparative genomic hybridization for investigating chromosomal abnormalities in patients with learning disability: systematic review meta-analysis of diagnostic and false-positive yields.

Purpose: Array-based comparative genomic hybridization is increasingly being used in patients with learning disability, in addition to existing cytogenetic techniques. This paper reports the results of an evaluation of this emerging technology and discusses the challenges faced in conducting the evaluation.

Methods: Systematic review and meta-analysis of studies investigating patients with learning disability and dysmorphic features in whom conventional cytogenetic analysis has proven negative.

How can the evaluation of genetic tests be enhanced? Lessons learned from the ACCE framework and evaluating genetic tests in the United Kingdom.

Advances in genetic technology are increasing the availability of genetic tests, not only for rare single gene disorders, but also for common diseases such as breast and colo-rectal cancer. Before there can be widespread uptake of these tests, they must be evaluated to confirm the benefits of their use. But how should genetic tests be evaluated, given the speed at which new tests are emerging? One highly influential approach is the analytic validity, clinical validity, clinical utility and ethical, legal and social issues (ACCE) framework, which has provided a benchmark for the evaluation of genetic tests.

Genetic tests and their evaluation: can we answer the key questions?

The rapid pace of research in the field of genetics has already yielded many benefits. The development of new genetic tests is one such example. Before there can be widespread uptake of these tests they need to be evaluated to confirm the benefits of their use.

Prehospital thrombolysis--calculated health benefit for catchment population of one hospital.

The health benefit of thrombolysis in acute myocardial infarction is greatest when patients are treated soon after onset of symptoms. One approach to reducing treatment delay is to give thrombolysis before the patient reaches hospital. When an ambulance trust proposed a prehospital thrombolysis service, local commissioners requested an estimate of its possible health impact.

Genetics. Gene genies.

A new white paper on genetics shows how it is starting to affect mainstream services, at both acute and primary care trust level. It is vital that managers begin to consider service redesign now. Many managers lack knowledge and do not know where to gain it.