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.

Health needs assessment for medical genetic services for congenital disorders in middle- and low-income nations.

Medical genetic services for the care and prevention of congenital disorders have received little attention in most middle- and low-income countries to date. In 2010, the World Health Organisation prioritized services for the care and prevention of birth defects in these nations, emphasising their importance in assisting such countries to reach their Millennium Development Goals. Health Needs Assessment is an inclusive, rational, epidemiological-assisted approach for providing information to plan, introduce and beneficially change health care services to improve the health of populations.

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.

Issues concerning the evaluation and regulation of predictive genetic testing.

This paper is a précis of my keynote address at the Symposium on Predictive Genetic Testing organised by the Robert Koch Institute in Berlin. The talk is based on reflections which I have had over a number of years on genetic testing and its evaluation and regulation. It presents a thesis, which I hope will generate discussion and comment.

The impact of genomics on public health practice: the case for change.

Public health practice will not be able in the 21st century to ignore the impact of genomics, cell and molecular biology. It will need to take into consideration issues that include, among others: the complementary nature of social and biological models of disease, genetic exceptionalism, the readiness of public and patient to respond to genomic information, the relationship between individuals and populations, and concepts of population stratification. Health systems will need to adapt their practice and organisation to include new sequencing technologies, bioinformatic expertise and proper evaluation of genetic and molecular tests.

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.

Extending the reach of public health genomics: what should be the agenda for public health in an era of genome-based and “personalized” medicine?

The decade following the completion of the Human Genome Project has been marked by divergent claims about the utility of genomics for improving population health. On the one hand, genomics is viewed as the harbinger of a brave new world in which novel treatments rectify known causes of disease. On the other hand, genomics may have little practical relevance to the principal causes or remedies of diseases which are predominantly social or environmental in origin, particularly in low- and middle-income countries.

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.

Testing challenges: evaluation of novel diagnostics and molecular biomarkers.

Through the lens of public health genomics, this article probes certain issues that concern the evaluation of diagnostic tests and molecular biomarkers, and the accompanying policy and regulatory implications. It begins with some conceptual remarks followed by a discussion of evaluation, translation, and regulation, and their importance for public health.

Predicting the likelihood of carrying a BRCA1 or BRCA2 mutation: validation of BOADICEA, BRCAPRO, IBIS, Myriad and the Manchester scoring system using data from UK genetics clinics.

Objectives: Genetic testing for the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 has important implications for the clinical management of people found to carry a mutation. However, genetic testing is expensive and may be associated with adverse psychosocial effects. To provide a cost-efficient and clinically appropriate genetic counselling service, genetic testing should be targeted at those individuals most likely to carry pathogenic mutations.

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.