Conceptual issues for screening in the genomic era - time for an update?

Background: Screening tests are ubiquitous in modern medicine; however a consensus view on the criteria that distinguish screening from clinical testing remains strangely elusive. although numerous definitions of screening have been suggested, there is considerable variation amongst them, leading to confusion and disagreement amongst clinicians and public health professionals alike. In light of developments in genomics, the question of what screening entails is becoming increasingly pressing.

Revealing the results of whole-genome sequencing and whole-exome sequencing in research and clinical investigations: some ethical issues.

The introduction of new sequencing technologies whole-genome sequencing (WGS) and whole-exome sequencing (WES) that are much less finely targeted than previous genetic tests has resulted in ethical debate about what should be done with clinically significant findings that may arise during the sequencing process. In this piece we argue that, in addition to whether the finding has been intentionally sought or arises incidentally, the ethical issues concerning what should be done with WES and WGS findings are also influenced by whether sequencing occurs in a clinical or research setting. We argue that decisions about the disclosure of WGS and WES findings generated in the clinical context are much less ethically contentious than decision making about the feedback of research results.

Recommendations for returning genomic incidental findings? We need to talk!

The American College of Medical Genetics and Genomics recently issued recommendations for reporting incidental findings from clinical whole-genome sequencing and whole-exome sequencing. The recommendations call for evaluating a specific set of genes as part of all whole-genome sequencing/whole-exome sequencing and reporting all pathogenic variants irrespective of patient age. The genes are associated with highly penetrant disorders for which treatment or prevention is available.

Next-generation sequencing in the clinic: are we ready?

We are entering an era in which the cost of clinical whole-genome and targeted sequencing tests is no longer prohibitive to their application. However, currently the infrastructure is not in place to support both the patient and the physicians that encounter the resultant data. Here, we ask five experts to give their opinions on whether clinical data should be treated differently from other medical data, given the potential use of these tests, and on the areas that must be developed to improve patient outcome.

A collaboratively-derived science-policy research agenda.

The need for policy makers to understand science and for scientists to understand policy processes is widely recognised. However, the science-policy relationship is sometimes difficult and occasionally dysfunctional; it is also increasingly visible, because it must deal with contentious issues, or itself becomes a matter of public controversy, or both. We suggest that identifying key unanswered questions on the relationship between science and policy will catalyse and focus research in this field.

Regulating direct-to-consumer genetic tests: what is all the fuss about?

The number of genetic tests available direct-to-consumer has burgeoned over the last few years, prompting numerous calls for tighter regulation of these services. However, there is a lack of consensus about the most appropriate and achievable level of regulation, particularly given the global nature of the market. By consideration of potential for direct and indirect harms caused by genetic susceptibility or genomic profiling tests, in this study we offer an overarching framework that we believe to be feasible for the regulation of direct-to-consumer genetic tests and likely to be relevant to other forms of predictive testing.

A new strategic phase for genomic medicine in UK health services.

In June 2009, the Science and Technology Committee of the UK House of Lords published a report on genomic medicine, based on expert evidence collected over an 18-month period. Crucially, the report signaled that the use of genomic medicine was at a crossroads, due to the rapid development of new technologies, and opened up opportunities across the whole of medicine and healthcare. This commentary responds to the report's call for a new health service strategy, including a new genetics White Paper from the Government, and suggests some of the important elements that need further consideration.

Genetic tests for common diseases: new insights, old concerns.

The clinical utility of newly identified genetic variants associated with common diseases needs evaluation

EuroGentest: DNA-based testing for heritable disorders in Europe.

Objectives: Regarding the recent attention to develop policies regarding the provision of clinical genetic testing services, access to, acceptance, utilisation and regulation of genetic services was investigated in selected European countries as well as one non-European country.

Methods: Data were collected on the basis of relevant international reports and sources accessible via the internet, from self- designed, internationally administered surveys and with the help of a panel of experts from European countries participating in several workshops as well as from National European Societies of Human Genetics.

Results: A selection of divergent health care systems was reviewed and compared (e.

Will genomics widen or help heal the schism between medicine and public health?

We discuss the "schism" between medicine and public health in light of advances in genomics and the expected evolution of health care toward personalized treatment and prevention. Undoubtedly, genomics could deepen the divide between the two worlds, but it also represents an important and perhaps unique opportunity for healing the schism, given the volume of new scientific discoveries and their potential applications in all areas of health and disease. We argue that the integration of genomics into health care and disease prevention requires a strong medicine-public health partnership in the context of a population approach to a translational research agenda that includes four overlapping areas: (1) a joint focus on prevention-a traditional public health concern but now a promise of genomics in the realm of individualized primary prevention and early detection, (2) a population perspective, which requires a large amount of population-level data to validate gene discoveries for clinical applications, (3) commitment to evidence-based knowledge integration with thousands of potential genomic applications in practice, and (4) emphasis on health services research to evaluate outcomes, costs, and benefits in the real world.

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.

Getting ready for the future: integration of genomics into public health research, policy and practice in Europe and globally.

The integration of genomics into public health research, policy and practice will be one of the most important future challenges that our health care systems will face. The next decade will provide a window of opportunity to establish infrastructures that will enable the scientific advances to be translated into evidence-based policies and interventions that improve population health. Approaches for national, European and international institutionalization of public health genomics are shown that aim to champion these challenges.