A qualitative study looking at informed choice in the context of non-invasive prenatal testing for aneuploidy

OBJECTIVE: To explore women's attitudes towards non-invasive prenatal testing (NIPT) and determine factors influencing their decisions around uptake of NIPT. METHOD: We conducted qualitative interviews to assess knowledge, attitude and deliberation amongst women offered NIPT in a public health service. In total, 45 women took part in telephone interviews (79% participation rate). RESULTS: Most women could recount the key aspects of NIPT discussed during pre-test counselling but had variable knowledge about Down syndrome. Analysis of women's attitudes towards undergoing NIPT revealed three dominant factors they considered when reflecting on the test: (1) how NIPT compared with alternative testing options, (2) reflections on coping and (3) moral or religious values. Exploring the deliberative process revealed the different paths women take when making decisions. For some, it was an extension of the decision to have Down syndrome screening; some considered it early on following the booking-in appointment; others made step-wise decisions about NIPT when it became relevant to them. CONCLUSION: Our findings support the importance of personalised counselling, whereby women and their partners have the opportunity to reflect on the implications of the test results in the context of their own lives and values. Our data highlight the influence of personal circumstances on decision-making

The 100 000 Genomes Project: What it means for paediatrics

The 100 000 Genomes Project is a unique, national programme combining research and transformation of clinical care, by undertaking whole genome sequencing (WGS) in patients with rare diseases and cancer. Made possible by technological advances in next-generation sequencing1 and falling costs, this project aims to find the genes which cause a patient's rare disease and identify genetic changes which occur in the tumour of a child or adult with cancer, to understand the mechanism of disease and develop therapies to personalise treatment. Patients are recruited through the National Health Service (NHS) and their medical course is tracked for life through their NHS number with results fed back through routine NHS services. It will also lay the foundations for a new ‘genomic medicine’ service for the NHS.2 The project is coordinated by Genomics England, with participants enrolled through one of 13 NHS Genomic Medicine Centres (figure 1), covering all of England. Unlike genome projects in other countries3 that have yielded information on variants associated with common diseases and ancestry, the scale of the 100 000 Genomes Project is much greater. The ability to track long-term outcomes through the patients' NHS number provides a unique opportunity to link genomic and phenotypic data to hospital admissions (via hospital episode statistics) as well as lifelong response to interventions and treatments

Stakeholder attitudes and needs regarding cell-free fetal DNA testing

PURPOSE OF REVIEW: To explore stakeholder views on cell-free DNA testing and highlight findings important for successful implementation and the provision of best practice in counseling. RECENT FINDINGS: Noninvasive tests based on the analysis of cell-free fetal DNA are now widely available in clinical practice and applications are expanding rapidly. It is essential that stakeholder views are considered in order to identify and address any ethical and social issues. We provide an overview of stakeholder viewpoints and then focus on the key issues of informed decision making, test uptake, service delivery and information sources. SUMMARY: Stakeholders are positive about the introduction of cell-free fetal DNA testing into clinical practice. They describe both practical and psychological benefits arising from tests that are safe and can potentially be performed earlier in pregnancy. Key concerns, which include the potential for these tests to have a negative impact on informed decision making and increased societal pressure to have testing, can be addressed through careful parent-directed counseling. As applications for these tests expand it is increasingly important to develop innovative approaches to facilitate good understanding for parents who are offered noninvasive prenatal testing

Development and validation of a measure of informed choice for women undergoing non-invasive prenatal testing for aneuploidy.

Non-invasive prenatal testing (NIPT) using cell-free DNA for aneuploidy is a highly accurate screening test; however, concerns exist around the potential for routinisation of testing. The multidimensional measure of informed choice (MMIC) is a quantitative instrument developed to assess informed choice for Down syndrome screening (DSS). We have validated a modified MMIC for NIPT and measured informed choice among women offered NIPT in a public health service. The measure was distributed to women recruited across eight maternity units in the United Kingdom who had accepted DSS. Construct validity was assessed by simultaneously conducting qualitative interviews. Five hundred and eighty-five questionnaires were completed and 45 interviews conducted after blood-draw (or equivalent for those that declined NIPT). The measure demonstrated good internal consistency and internal validity. Results indicate the vast majority of women (89%) made an informed choice; 95% were judged to have good knowledge, 88% had a positive attitude and 92% had deliberated. Of the 11% judged to have made an uninformed choice, 55% had not deliberated, 41% had insufficient knowledge, and 19% had a negative attitude. Ethnicity (OR=2.78, P=0.003) and accepting NIPT (OR=16.05, P=0.021) were found to be significant predictors of informed choice. The high rate of informed choice is likely to reflect the importance placed on the provision of pre-test counselling in this study. It will be vital to ensure that this is maintained once NIPT is offered in routine clinical practice

Time and travel costs incurred by women attending antenatal tests: A costing study

OBJECTIVE: to estimate the costs to women, their friends and family for different antenatal tests in the Down's syndrome (DS) screening pathway. DESIGN: questionnaire-based costing study. SETTING: eight maternity clinics across the UK. PARTICIPANTS: pregnant women (n=574) attending an appointment for DS screening, NIPT or invasive testing between December 2013 and September 2014. MEASUREMENTS: using data collected from the questionnaires we calculated the total costs to women by multiplying the time spent at the hospital and travelling to and from it by the opportunity costs of the women and accompanying person and adding travel and childcare costs. Assumptions about the value of opportunity costs were tested in one-way sensitivity analyses. The main outcome measure was the mean cost to the women and friends/family for each test (DS screening, NIPT, and invasive testing). FINDINGS: mean costs to women and their family/friend were £33.96 per visit, of which £22.47 were time costs, £9.15 were travel costs and £2.34 were childcare costs. Costs were lowest for NIPT (£22), £32 for DS screening (£44 if combined with NIPT), and highest for invasive testing (£60). Sensitivity analysis revealed that variations around the value of leisure time opportunity costs had the largest influence on the results. KEY CONCLUSIONS: there are considerable costs to women, their friends and family when attending different tests in the DS screening pathway. IMPLICATIONS FOR PRACTICE: when assessing the cost-effectiveness of changes to this pathway, costs to women should be considered

Development and evaluation of training resources to prepare health professionals for counselling pregnant women about non-invasive prenatal testing for Down syndrome: a mixed methods study

BACKGROUND: The availability of non-invasive prenatal testing (NIPT) for aneuploidies is expanding rapidly throughout the world. Training health professionals to offer NIPT in a way that supports informed choice is essential for implementation. The aim of this study was to develop and evaluate a training package for health professionals to support the introduction of NIPT into clinical practice. METHODS: Training on NIPT was offered to health professionals, primarily midwives, involved in Down syndrome screening and testing in eight hospitals located in England and Scotland as part of a research study evaluating the implementation of NIPT in the UK National Health Service. Training was evaluated using a mixed methods approach that included quantitative questionnaires at three time points and post-training qualitative interviews. The questionnaires measured confidence, self-perceived knowledge and actual knowledge about NIPT for Down syndrome. Interviews explored opinions about the training and experiences of offering NIPT. RESULTS: The training provided to the health professionals was found to positively impact on their confidence in discussing NIPT with women in their clinic, and both their perceived and actual knowledge and understanding of NIPT was improved. Knowledge remained weak in four areas; cell-free fetal DNA levels increase with gestation; turnaround time for NIPT results; cell-free fetal DNA is placental in origin; and NIPT false positive rate. CONCLUSIONS: Training materials, including a lesson plan, PowerPoint presentation and written factsheet on NIPT, have been developed and evaluated for use in educating midwives and supporting the introduction of NIPT. Implementation of training should include a greater focus on the areas where knowledge remained low. Some groups of midwives will need additional training or support to optimise their confidence in discussing NIPT with women

Lung aeration on post-mortem magnetic resonance imaging is a useful marker of live birth versus stillbirth.

Aim of this study was to investigate whether lung assessment on post-mortem magnetic resonance imaging (PMMR) can reliably differentiate between live birth and stillbirth

Preferences for prenatal diagnosis of sickle-cell disorder: A discrete choice experiment comparing potential service users and health-care providers

BACKGROUND: Non-invasive prenatal diagnosis (NIPD) for sickle-cell disorder (SCD) is moving closer to implementation and studies considering stakeholder preferences are required to underpin strategies for offering NIPD in clinical practice. OBJECTIVE: Determine service user and provider preferences for key attributes of prenatal diagnostic tests for SCD and examine views on NIPD. METHOD: A questionnaire that includes a discrete choice experiment was used to determine the preferences of service users and providers for prenatal tests that varied across three attributes: accuracy, time of test and risk of miscarriage. RESULTS: Adults who were carriers of SCD or affected with the condition (N=67) were recruited from haemoglobinopathy clinics at two maternity units. Health professionals, predominately midwives, who offer antenatal care (N=62) were recruited from one maternity unit. No miscarriage risk was a key driver of decision making for both service users and providers. Service providers placed greater emphasis on accuracy than service users. Current uptake of invasive tests was 63%, whilst predicted uptake of NIPD was 93.8%. Many service users (55.4%) and providers (52.5%) think pressure to have prenatal testing will increase when NIPD for SCD becomes available. CONCLUSIONS: There are clear differences between service users and health professionals' preferences for prenatal tests for sickle-cell disorder. The safety of NIPD is welcomed by parents and uptake is likely to be high. To promote informed choice, pretest counselling should be balanced and not exclusively focused on test safety. Counselling strategies that are sensitive to feelings of pressure to test will be essential

Non-invasive prenatal diagnosis (NIPD) for single gene disorders: cost analysis of NIPD and invasive testing pathways

OBJECTIVE: Evaluate the costs of offering non-invasive prenatal diagnosis (NIPD) for single gene disorders compared to traditional invasive testing to inform NIPD implementation into clinical practice. METHOD: Total costs of diagnosis using NIPD or invasive testing pathways were compared for a representative set of single gene disorders. RESULTS: For autosomal dominant conditions, where NIPD molecular techniques are straightforward, NIPD cost £314 less than invasive testing. NIPD for autosomal recessive and X-linked conditions requires more complicated technical approaches and total costs were more than invasive testing, e.g. NIPD for spinal muscular atrophy was £1090 more than invasive testing. Impact of test uptake on costs was assessed using sickle cell disorder as an example. Anticipated high uptake of NIPD resulted in an incremental cost of NIPD over invasive testing of £48 635 per 100 pregnancies at risk of sickle cell disorder. CONCLUSIONS: Total costs of NIPD are dependent upon the complexity of the testing technique required. Anticipated increased demand for testing may have economic implications for prenatal diagnostic services. Ethical issues requiring further consideration are highlighted including directing resources to NIPD when used for information only and restricting access to safe tests if it is not cost-effective to develop NIPD for rare conditions