Closure of population biobanks and direct-to-consumer genetic testing companies.

Genetic research gained new momentum with the completion of the Human Genome Project in 2003. Formerly centered on the investigation of single-gene disorders, genetic research is increasingly targeting common complex diseases and in doing so is studying the whole genome, the environment and its impact on genomic variation. Consequently, biobanking initiatives have emerged around the world as a tool to sustain such progress. Whether they are small scale or longitudinal, public or private, commercial or non-commercial, biobanks should consider the possibility of closure. Interestingly, while raising important ethical issues, this topic has hardly been explored in the literature. Indeed, ethical issues associated with sale, insolvency, end of funding, or transfer of materials to other entities (which are all issues either related to or possible consequences of closure) are seldom the subject of discussion. In an attempt to fill this gap, this paper will discuss-using population and direct-to-consumer (DTC) genetic testing companies' biobanks as case studies-(1) international and national normative documents addressing the issue of closure and (2) the internal policies of population biobanks and DTC genetic testing companies. The analysis will inform the debate on biobank closure and elucidate the underlying ethical issues, which include, but are not limited to informed consent, storage and privacy.

Implications of a first trimester Down syndrome screening program on timing of malformation detection.

OBJECTIVE: To determine the impact which introduction of the 11-14 week scan has had on the gestational age at which fetal malformations are detected by ultrasound in an unselected population of pregnant women. DESIGN: Retrospective study. SETTING: University hospital, Copenhagen, Denmark, covering the period 1 January 2003 to 30 June 2007. POPULATION: All pregnant women who chose a nuchal translucency scan at 11-14 weeks for Down syndrome risk estimate, and a scan at 18-20 weeks to screen for fetal malformations. METHODS: Review of cases detected ante- and postnatally. MAIN OUTCOME MEASURES: Detection rates at 11-14 weeks relative to all malformations in the population. RESULTS: A total of 216 anomalies were detected in 200 fetuses among the 9 324 fetuses included, while 70 anomalies were diagnosed in 59 infants postnatally. The prevalence of fetuses with anomalies was 2.8% (259 of 9 324). After excluding cases of pyelectasis (127), which may be considered physiological and transitory changes, the prevalence of malformed fetuses was 1.4% (132 of 9 324). Of the malformations detected antenatally, 25.8% were detected before week 15 and 59.6% in weeks 16-22. The remaining 14.6% of malformations were discovered after week 22. Among the lethal malformations, 50% were diagnosed before week 15. CONCLUSIONS: Although the purpose of the first trimester scan is to screen for Down syndrome and not for malformations, the introduction of the 11-14 week scan has resulted in the detection of approximately 26% of fetal malformations.

Newborn hearing concurrent gene screening can improve care for hearing loss: a study on 14,913 Chinese newborns.

OBJECTIVE: Newborn hearing screening has been widely adopted and made an achievement to some degree. Current screening protocols rely solely on detecting existing auditory disorders at the time of screening and are unable to identify individuals susceptible to auditory disorders in later life. Even if the hearing loss newborn is referred, most cases could not be diagnosed until 6-12 months old with no etiology being elucidated. This study reports the first effort to combine traditional hearing screening with genetic screening to improve the efficacy of newborn hearing screening. METHODS: This study was undertaken in 12 regional hospitals located in 11 provinces of China. 14,913 newborn babies received hearing concurrent genetic screening. The hearing screening was performed with OAE or AABR. Blood sample was collected with a universal newborn genetic screening card. And three common gene, mtDNA 12S rRNA, GJB2 and SLC26A4 were screened with standard protocol. RESULTS: Among all the 14,913 newborns, 86.1% (12,837/14,913) individuals passed the first-step hearing screening, 7.8% (1168/14,913) babies passed only one side, and the other 6.1% (908/14,913) were bilaterally referred. Gene screening found 306 individuals had one or two mutant alleles, the carrier rate is 2.05% (306/14,913) among the entire newborn population. The risk for hearing loss was 100% (7/7) for those newborns carrying causative GJB2 or SLC26A4 mutations (homozygotes or compound heterozygotes), 14.4% (23/160) for GJB2 heterozygote carriers, 12.3% (15/122) for SLC26A2 heterozygous carriers, and the total prevalence of referral hearing screening was approximately 14.7% (45/306). However, 85.3% (261/306) newborns passed hearing screening among these carriers including 18 newborns with 12S rRNA mt.1555A>G pathogenic mutation, who would suffer from sudden hearing loss once applying aminoglycoside drugs. CONCLUSION: The cohort studies provided the essential population parameters for developing effective programs for hearing care of newborns in China. Hearing concurrent gene screening in newborns may confirm the abnormal results from hearing screening tests, help to find the etiologic of the hearing loss, and better recognize infants at risk for late-onset hearing loss occurring prior to speech and language development. In conclusion, a survey on 14,913 Chinese newborns proved that concurrent genetic screening could improve newborn hearing screening for hearing defects.

Genetic cancer risk assessment.

OBJECTIVES: To describe critical elements of cancer risk assessment as identified through professional standards. DATA SOURCES: Professional guidelines, policy statements, and other published literature. CONCLUSION: The continually increasing integration of genetics/genomics into oncology care mandates that oncology nurses be familiar with the cancer risk assessment process, complexities, and implications for personalized risk reduction and early detection recommendations and for cancer treatment, including targeted therapies. IMPLICATIONS FOR NURSING PRACTICE: Informed nurses can identify genetic cancer risk factors, educate patients about cancer risk and risk management/treatment strategies, and refer appropriate patients to a cancer genetics nurse or other genetics professional for comprehensive risk assessment.

Guiding policy decisions for genetic screening: developing a systematic and transparent approach.

With the ever-widening gap between what is technologically possible and services available, jurisdictions around the world are faced with complex decisions regarding the introduction and expansion of genetic screening programs. A series of literature reviews and consultations with stakeholders and experts led to the development of a decision support guide for genetic screening policy-making. This involved establishing a preliminary list of core criteria synthesized from the growing literature on genetic screening, which was then transformed through a series of consultations into a more elaborate decision guide. Although certain perennial challenges in genetic screening policy-making remain, the decision support guide aims to promote a fair and evidence-informed process that makes explicit the ethical dilemmas often inherent to such policy decisions.

[Optimization of monogenic diabetes screening programme--initial report on recruitment efficacy of the TEAM project]. / Optymalizacja programu poszukiwania cukrzyc monogenowych - wstepne wyniki dzialan rekrutacyjnych projektu TEAM.

INTRODUCTION: Due to the lack of precise diagnostic criteria, current search strategy for monogenic diabetes is predominantly based on atypical clinical course of diabetes and intuition of the attending physician. Yet another issue is the common view that monogenic diabetes is rare. It discourages from performing deepened diagnostics and makes it difficult to gain experience necessary to select appropriate patients for genetic examination. AIM OF THE STUDY: Estimating the true incidence of patients with a high probability of monogenic background of the disease and compare their search strategies based on clinical practice or structured databases. MATERIAL AND METHODS: The authors compared the current strategy of selecting candidates for screening with a directed search strategy based on immunologic (lack of islet autoantibodies), functional (presence or complete lack of c-peptide at onset and follow-up) and familial (dominant pattern of inheritance) criteria. The number of patients selected for the screening was chosen as efficacy measure selected among 1281 diabetic patients diagnosed and treated between 1983-2009. RESULTS: Screening based on clinical assessment yielded 37 patients (2.9%) chosen for genetic screening. Criteria used by the physicians were based on up-to-date guidelines and unusual clinical course. Active search of the database according to predefined criteria resulted in selecting: 121 patients (9.4%) with likely monogenic background of diabetes (71 - lack of autoantibodies, 8 - normal C-peptide, 6 - lack of both c-peptide and autoantibodies, 36 - diabetes in at least one parent). The difference in screening efficacy was statistically significant (p <0.0001). CONCLUSIONS: Periodic reevaluation of patients' data allows a significant increase in the number of candidates subjected to genetic screening and potentially achieving beneficial therapeutic effects by means of pharmacogenetics.

Epidermolysis bullosa care in Israel.

The Israeli population is characterized by unique demographic features including high genetic homogeneity within many closed communities. As a consequence the molecular epidemiology of epidermolysis bullosa differs markedly in this country and surrounding areas from that reported in the Western world.

Antenatal screening for haemoglobinopathies in primary care: a cohort study and cluster randomised trial to inform a simulation model. The Screening for Haemoglobinopathies in First Trimester (SHIFT) trial.

OBJECTIVES: To assess the effectiveness, cost-effectiveness, acceptability and feasibility of offering universal antenatal sickle cell and thalassaemia (SCT) screening in primary care when pregnancy is first confirmed and to model the cost-effectiveness of early screening in primary care versus standard care. DESIGN: A population-based cohort study, cluster randomised trial and refinement of a published decision model. SETTING: Twenty-five general practices from two UK primary care trusts (PCTs) in two inner city boroughs with a high proportion of residents from minority ethnic groups. PARTICIPANTS: Practices were considered eligible if they agreed to be randomised and they were able to provide anonymous data on all eligible pregnant women. Participants were at least 18 years old and consented to take part in the evaluation. INTERVENTIONS: Practices were allocated to intervention, using minimisation and stratifying for PCT and number of partners at the practice, as follows: screening in primary care with parallel father testing (test offered to mother and father simultaneously; n = 8 clusters, 1010 participants); screening in primary care with sequential father testing (test offered to father only if mother identified as carrier; n = 9 clusters, 792 participants); and screening in secondary care with sequential father testing (standard care; n = 8 clusters, 619 participants). MAIN OUTCOME MEASURES: Data on gestational age at pregnancy confirmation and screening date were collected from trial practices for 6 months before randomisation in the cohort phase. The primary outcome measure was timing of SCT screening, measured as the proportion of women screened before 70 days' (10 weeks') gestation. Other outcomes included: offer of screening, rates of informed choice and proportion of women who knew the carrier status of their baby's father by 77 days (11 weeks). RESULTS: For 1441 eligible women in the cohort phase, the median [interquartile range (IQR)] gestational age at pregnancy confirmation was 7.6 weeks (6.0 to 10.7 weeks) and 74% presented in primary care before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR 12.6 to 18.0 weeks). Only 4.4% were screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7 to 9.3 weeks). In the intervention phase, 1708 pregnancies from 25 practices were assessed for the primary outcome measure. Completed questionnaires were obtained from 464 women who met eligibility criteria for the main analysis. The proportion of women screened by 10 weeks (70 days) was 9/441 (2%) in standard care, compared with 161/677 (24%) in primary care with parallel testing, and 167/590 (28%) in primary care with sequential testing. The proportion of women offered screening by 10 weeks (70 days) was 3/90 (3%) in standard care (note offer of test ascertained for questionnaire respondents only), compared with 321/677 (47%) in primary care with parallel testing, and 281/590 (48%) in primary care with sequential testing. The proportion of women screened by 26 weeks (182 days) was similar across the three groups: 324/441 (73%) in standard care, 571/677 (84%, 0.09) in primary care with parallel testing, and 481/590 (82%, 0.148) in primary care with sequential testing. The screening uptake of fathers was 51/677 (8%) in primary care with parallel testing, and 16/590 (3%) in primary care with sequential testing, and 13/441 (3%) in standard care. The predicted average total cost per pregnancy of offering antenatal SCT screening was estimated to be 13 pounds in standard care, 18.50 pounds in primary care with parallel testing, and 16.40 pounds in primary care with sequential testing. The incremental cost-effectiveness ratio (ICER) was 23 pounds in primary care with parallel testing and 12 pounds in primary care with sequential testing when compared with standard care. Women offered testing in primary care were as likely to make an informed choice as those offered screening by midwives later in pregnancy, but less than one-third of women overall made an informed choice about screening. CONCLUSIONS: Offering antenatal SCT screening as part of pregnancy-confirmation consultations significantly increased the proportion of women screened before 10 weeks (70 days), from 2% in standard care to between 16% and 27% in primary care, but additional resources may be required to implement this. There was no evidence to support offering fathers screening at the same time as women. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00677850.

Improvement in the care of multiple endocrine neoplasia type 1 through a regional multidisciplinary clinic.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is associated with significant morbidity and mortality. Timely detection of MEN1 kindred, together with treatment of associated tumours, results in an improved outcome. We describe how the development of a dedicated multidisciplinary MEN clinic has improved the diagnosis and treatment of MEN1-associated endocrinopathies. DESIGN AND PATIENTS: A dedicated MEN clinic was developed at Aintree University Hospital, Liverpool in 2002 for patients living in Merseyside, Cheshire and North Wales. The multidisciplinary approach adopted, aimed to improve communication and continuity of care. Patients see all clinicians involved in their care (Consultant Endocrinologist, Paediatrician, Clinical Geneticist and Endocrine Surgeon) simultaneously, allowing for a unified, clear approach and a reduction in unnecessary attendances. The clinicians adopt a proactive approach to tracing the relatives of patients, with the aim of identifying kindred with previously asymptomatic disease. RESULTS: In 2002, 16 patients from 5 families were diagnosed clinically with MEN1. Twenty MEN1-associated endocrinopathies had been diagnosed and 21 surgical procedures had been performed. By the end of 2008, 45 patients from 15 families had been identified, with 83 endocrinopathies diagnosed and 50 surgical procedures performed. Ninety-four known relatives are awaiting screening for MEN1. CONCLUSION: The successful identification of patients with MEN1 has resulted in an exponential increase in the number of patients attending the clinic. As relatives undergo screening, the diagnosis of MEN is likely to increase. The ever increasing numbers of patients requiring screening, surveillance and treatment has implications in the planning of future service provision.

Genetic screening: a conceptual framework for programmes and policy-making.

OBJECTIVE: Policy-makers are faced with increasing pressures from a range of different stakeholders to introduce or expand genetic screening programmes. A shared understanding is therefore needed of the many factors influencing these complex policy decisions. Our aim was to develop a theoretical framework that highlights the multiple components and influences involved in genetic screening and the policy-making process. METHODS: As part of a larger research programme, existing policy frameworks relating to genetic screening were identified through a review of the literature. Major themes were identified and synthesized into an overarching framework, which was further refined through discussions with key informants. RESULTS: The framework consists of three parts. The first part conceptualizes genetic screening as an integrated public health programme. The second part describes the policy-making process at each stage in the life cycle of the programme. The third part depicts the broader context within which policy-making occurs. CONCLUSION: This framework can support policy-makers by fostering a common understanding and facilitating dialogue with stakeholders. The framework has also been used as the conceptual foundation for the development of a more elaborate decision-guide.

A nationwide genetic testing survey in Italy, year 2007.

OBJECTIVE: The aim of this study was to collect the practices of cytogenetic and molecular genetic testing and genetic counseling activities in Italy in the year 2007 and provide guidance to the national and regional health systems to improve the organization of genetic services. METHODS: A web-based survey was carried out to assess the total number and the type of analyses, the number and type of genetic counseling sessions, and the personnel attending these activities. The quality management system of the responding structures, in terms of certification and accreditation standards, was also investigated. The appropriateness of requests for genetic testing was evaluated for six disorders. RESULTS: Data were collected from 278 responding centers, half of which were located in the northern regions of the country. Twenty-eight percent of the total were certified according to quality standards. A total of 217 molecular genetic and 171 cytogenetic laboratories, and 102 clinical genetic services were surveyed. About 560,000 genetic tests, including 311,069 cytogenetic and 248,691 molecular genetic analyses of 556 genes, were recorded. The fetal karyotype was examined on either trophoblast or amniocytes in about one of every 4.4 pregnancies. Only 11.5% of cytogenetic analyses and 13.5% of molecular tests were accompanied by genetic counseling. Concerning the appropriateness of a request for genetic testing, a low congruity was found between the clinical diagnosis and the laboratory results. CONCLUSION: This study highlights the need for reorganizing the genetic structure network in Italy, which at present is oversized, improving the quality management systems, expanding the availability of testing for rare disease genes, and improving access to pretest and posttest genetic counseling.

Treatment-focused DNA testing for newly diagnosed breast cancer patients: some implications for clinical practice.

There is accumulating evidence that women with breast cancer due to a familial BRCA1 or BRCA2 mutation benefit from specific surgical and chemotherapeutic treatment strategies. However, the rapid identification of such patients during the acute phase of treatment raises a number of issues. This study investigated Australian opinion leaders' views on the issues arising from such 'treatment-focused' genetic testing. Semi-structured interviews with 34 opinion leaders working in cancer genetics were undertaken. Interviewees acknowledged the introduction of treatment-focused DNA testing has the potential to positively transform the management of breast cancer patients, but were concerned that certain ethical and logistical issues have yet to be addressed. These include decision-making and consent, the familial nature of genetic information, and the management of genetics services within familial cancer clinics in the public hospital system in Australia. Service providers will need to have policies and strategies for managing the increased demand. It will also be necessary to include genetic counseling services within familial cancer clinics in the care pathway for newly diagnosed patients prior to any DNA testing to determine adjuvant treatment; such services may be more cost-effective than expecting surgeons and medical oncologists to fulfill this role.

Nursing advocacy in a postgenomic age.

The Human Genome Project will change how health is defined and how disease is prevented, diagnosed, and treated. As the largest group of health care providers in contact with patients, nurses need to be competent in the science of genetics. Beyond this, nurses need to understand the complexities that arise in genomic health care. Ethical, legal, and social issues are integral to the delivery of genomic health care, and nurses must have an astute understanding of such complexities. What it means to know, to reason, and to act in this postgenomic age is explored.