Prenatal Preparation: Actions and Results (PREPARE)
PI: Marsha Michie
Using Down syndrome as a case study, the objectives of this project are to identify and analyze the components of preparation following a prenatal genetic finding; to identify (in)congruities in the models of preparation used by different stakeholders; and to better understand how a prenatal genetic finding (including the ways it is delivered and supported) impacts identity, health-seeking, and social behaviors. This research will elucidate families’ expectations and needs regarding prenatal preparation after genetic testing, and how existing clinical and social supports meet or fail to meet them. We anticipate that this effort to define the term preparation, which has historically served to justify prenatal testing and screening for many conditions, will advance ongoing bioethical and clinical conversations about what, when, and how prenatal tests are considered imperative, important, reasonable, and/or necessary, and under what circumstances; and will inform guidelines for clinician counseling and parental decision-making about these tests.
Factors Influencing Access and Utilization of Genetic Prenatal Care Services Among Women from Underserved Populations
PI: Megan Allyse
Prenatal genetic services have expanded at an extraordinary pace over the past 4 years with the development of fetal genome sequencing using cell-free placental DNA in maternal serum. Some commentators predict that this new technology, which allows for noninvasive determination of an increasingly wide range of maternal-fetal health conditions, will improve prenatal care, especially in lower-resource areas. However, this assumption is challenged by research findings on the lower uptake of existing prenatal screening and diagnostic services among ethnic and racially diverse minorities, even when structural barriers to access are removed. These disparities have led to differential outcomes among some populations, including higher rates of live births affected by a genetic condition and higher maternal-infant morbidity and mortality. We will conduct community based participatory qualitative research with women of Black and Latina ethnicity to assess their understanding of and desire to accept prenatal genetic services. Through our community partners, we will feed the results of our research back into the communities in question in order to facilitate fruitful discussions and interpretation for future interventions to increase access in ethnic and racial minority populations.
Mapping an ELSI-Integrated Translational Pathway with Cell-Free Fetal DNA Testing
PI: Marsha Michie
The long-term goal of the research project is to map out an ELSI-integrated translational pathway for genetic innovations: building a model of crucial points for, and types of, ELSI guidance throughout these translational processes. The specific Aims of this project are: (1) To follow the unfolding translational pathway of cffDNA testing technology, as a case study in translation processes for genetic innovations; and (2) To map crucial points for ELSI guidance along the translational pathway of genetic innovations. Through individual interviews with stakeholders and observations of meetings and conferences of stakeholders, this mapping project will examine the case of cell-free fetal DNA (cffDNA) testing and the actors and networks that influence its development toward potential clinical applications. Comparing features of this process with those of other translations of genetic innovations, it will identify critical moments, turning points, and intersections at which important decisions shape the unfolding translational pathway. Finally, through collaboration with key stakeholders in cffDNA and non-invasive prenatal testing, a model will be developed that proposes types of ethical and social guidance for these crucial points that would likely be most beneficial.
Intellectual Property And Access To Noninvasive Prenatal Genetic Testing
PI: Subhashini Chandrasekharan
The purpose of this study is to provide empirical data on effects of intellectual property (IP) and commercialization on clinical translation of noninvasive prenatal genetic testing (NIPT) and identify potential barriers to clinical adoption and patient access. Advances in technologies for genetic analysis of cell-free fetal DNA could make NIPT routine. Early clinical trials indicate that sequencing-based NIPT tests for chromosomal aneuploidies are more accurate than currently used noninvasive screening tests. A commercial NIPT test for Down Syndrome recently became available and tests for common genetic conditions are in prospect. It is still too early to know the clinical utility and cost effectiveness of these tests. Nevertheless, NIPT could significantly change the paradigm of prenatal testing and screening and potentialy even lower costs. Intellectual property (IP) and commercialization promise to be important components in the emerging debate about when and how such technologies should enter clinical practice. IP could induce commercial investment in R&D, in regulatory approval, and in securing third-party payment. But exclusive IP rights could also hamper innovation, increase transaction costs for test developers and providers, and decrease patient access, especially if monopolies emerge. Indeed patents on foundational NIPT technologies have been exclusively licensed to companies, raising such concerns. The commercial landscape is quickly evolving and companies are already involved in patent litigation. The disposition of these patents could determine who can offer the tests and the business models that will prevail, which in turn can impact clinical adoption and patient access. The IP landscape for NIPT appears complex and is unclear. Few if any data are also available on stakeholders’ views about effects of IP vs non-IP factors on clinical adoption, and patient access to NIPT.. This study will address these gaps with the following specific aims: 1) map IP relevant to NIPT and assess potential IP effects on development of new NIPT genetic tests; 2) identify and rank IP versus non-IP barriers to clinical adoption and patient access based on stakeholders’ views; and 3) identify ethical and policy implications of potential barriers to patiet access. A multidisciplinary team of researchers with expertise in genetics, IP law, health policy, bioethics, health economics, maternal and fetal medicine and health law will use established qualitative research methods combined with legal, ethical, and policy analysis. One outcome of this study will be a careful empirical analysis of whether and how IP can affect patient access to NIPT genetic testing. This analysis will be enabled by a publicly available IP and commercialization landscape for NIPT technologies that we will create. Another expected outcome is a forecast of barriers to clinical adoption and patient access ranked by stakeholders. A workshop at the conclusion of the study will include stakeholder representatives groups and experts from relevant domains to identify approaches and policy priorities for reducing barriers to clinical translation and promoting patient access to NIPT.
Goals And Practices For Next Generation Prenatal Testing
PI: Josephine Johnston
Prenatal testing is evolving in two important ways: first, advances in genomic medicine mean that samples of fetal DNA obtained with invasive methods (such as amniocentesis) can be analyzed using microarray analysis or whole genome sequencing, revealing far more information about the fetus’s genetic make-up than was previously possible; and second, new, non-invasive prenatal tests have been introduced that isolate fragments of fetal DNA circulating in a pregnant woman’s blood, making possible safe, highly accurate genetic testing much earlier in pregnancy than was previously possible. Currently the range of genetic traits that can be picked up by the new non-invasive tests is small. But it is set to expand rapidly as the technology develops, and it may one day soon extend to whole genome analysis allowing detection of the full range of traits, including those associated with increases in risk for disease, adult-onset conditions, and non-disease traits. These two changes mark the beginning of the next-generation of prenatal testing, which has the potential to dramatically alter the experience and care of the 4 million women who give birth in the United States alone each year. Thereby, these remarkable technological developments raise pressing ethical, which this project will address. First, which traits should be tested for, nd how ought testing be conducted? Second, which policies should be altered to support the ethical use of next-generation prenatal tests, and in what ways should these policies be changed? And third, what future empirical research is needed to examine how the ethics recommendations made by this project play out in practice? To address these questions, The Hastings Center has recruited experts and representatives from a wide range of sectors critical to the wise and effective use of next- generation prenatal tests, but who have not yet been brought together. Importantly, leaders from the major relevant clinical societies have agreed to participate because they realize that this project’s ethical analysis and recommendations will usefully inform their organizations’ future clinical guidelines. The Work Group also includes members conducting empirical research on first and second-generation prenatal testing, and members representing patients. Together, with this Work Group, the Lead Investigators will produce analysis and recommendations for clinicians, researchers, policy makers, opinion leaders and the public. A draft of this analysis and recommendations will be presented to four focus groups of pregnant women and the partners of pregnant women for their feedback. The final analysis and recommendation will be disseminated to relevant stakeholders via scholarly publications, conference presentations, a public meeting, and a project website.
PErsonalized Genomics for prenatal Aneuploidy Screening USing maternal blood
PI: François Rousseau, PIRC CO-I: Vardit Ravitsky
This project proposes to carry out an independent study that will validate the performance and utility of these new genomic technologies for screening for major fetal chromosome imbalances in pregnant women using maternal blood. The team of researchers will recruit 5600 pregnant women across Canada and compare the results of these new prenatal screening methods with the current prenatal screening approaches. They will determine whether those new tests are cost-effective as well as the most cost-effective strategy to implement of this new technology in the Canadian health care system. They will develop decision-making tools that will assist couples in making informed decisions, as well as educational tools for health care professionals, all integral components of the implementation of a validated genomics-based non-invasive prenatal diagnosis. The deliverables of this project will enable decision makers, pregnant women and their partner to make informed choices pertaining to prenatal genetic screening and diagnosis, such as screening for Down syndrome, and reduce the risk to pregnancies associated with amniocentesis.