51
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Assessing women’s preferences towards tests that may reveal uncertain results from prenatal genomic testing: Development of attributes for a discrete choice experiment, using a mixed-methods design

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Prenatal DNA tests, such as chromosomal microarray analysis or exome sequencing, increase the likelihood of receiving a diagnosis when fetal structural anomalies are identified. However, some parents will receive uncertain results such as variants of uncertain significance and secondary findings. We aimed to develop a set of attributes and associated levels for a discrete-choice experiment (DCE) that will examine parents’ preferences for tests that may reveal uncertain test results. A two phase mixed-methods approach was used to develop attributes for the DCE. In Phase 1, a “long list” of candidate attributes were identified via two approaches: 1) a systematic review of the literature around parental experiences of uncertainty following prenatal testing; 2) 16 semi-structured interviews with parents who had experienced uncertainty during pregnancy and 25 health professionals who return uncertain prenatal results. In Phase 2, a quantitative scoring exercise with parents prioritised the candidate attributes. Clinically appropriate levels for each attribute were then developed. A final set of five attributes and levels were identified: likelihood of getting a result, reporting of variants of uncertain significance, reporting of secondary findings, time taken to receive results, and who tells you about your result. These attributes will be used in an international DCE study to investigate preferences and differences across countries. This research will inform best practice for professionals supporting parents to manage uncertainty in the prenatal setting.

          Related collections

          Most cited references47

          • Record: found
          • Abstract: found
          • Article: not found

          Chromosomal microarray versus karyotyping for prenatal diagnosis.

          Chromosomal microarray analysis has emerged as a primary diagnostic tool for the evaluation of developmental delay and structural malformations in children. We aimed to evaluate the accuracy, efficacy, and incremental yield of chromosomal microarray analysis as compared with karyotyping for routine prenatal diagnosis. Samples from women undergoing prenatal diagnosis at 29 centers were sent to a central karyotyping laboratory. Each sample was split in two; standard karyotyping was performed on one portion and the other was sent to one of four laboratories for chromosomal microarray. We enrolled a total of 4406 women. Indications for prenatal diagnosis were advanced maternal age (46.6%), abnormal result on Down's syndrome screening (18.8%), structural anomalies on ultrasonography (25.2%), and other indications (9.4%). In 4340 (98.8%) of the fetal samples, microarray analysis was successful; 87.9% of samples could be used without tissue culture. Microarray analysis of the 4282 nonmosaic samples identified all the aneuploidies and unbalanced rearrangements identified on karyotyping but did not identify balanced translocations and fetal triploidy. In samples with a normal karyotype, microarray analysis revealed clinically relevant deletions or duplications in 6.0% with a structural anomaly and in 1.7% of those whose indications were advanced maternal age or positive screening results. In the context of prenatal diagnostic testing, chromosomal microarray analysis identified additional, clinically significant cytogenetic information as compared with karyotyping and was equally efficacious in identifying aneuploidies and unbalanced rearrangements but did not identify balanced translocations and triploidies. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT01279733.).
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Conducting discrete choice experiments to inform healthcare decision making: a user's guide.

            Discrete choice experiments (DCEs) are regularly used in health economics to elicit preferences for healthcare products and programmes. There is growing recognition that DCEs can provide more than information on preferences and, in particular, they have the potential to contribute more directly to outcome measurement for use in economic evaluation. Almost uniquely, DCEs could potentially contribute to outcome measurement for use in both cost-benefit and cost-utility analysis. Within this expanding remit, our intention is to provide a resource for current practitioners as well as those considering undertaking a DCE, using DCE results in a policy/commercial context, or reviewing a DCE. We present the fundamental principles and theory underlying DCEs. To aid in undertaking and assessing the quality of DCEs, we discuss the process of carrying out a choice study and have developed a checklist covering conceptualizing the choice process, selecting attributes and levels, experimental design, questionnaire design, pilot testing, sampling and sample size, data collection, coding of data, econometric analysis, validity, interpretation and welfare and policy analysis. In this fast-moving area, a number of issues remain on the research frontier. We therefore outline potentially fruitful areas for future research associated both with DCEs in general, and with health applications specifically, paying attention to how the results of DCEs can be used in economic evaluation. We also discuss emerging research trends. We conclude that if appropriately designed, implemented, analysed and interpreted, DCEs offer several advantages in the health sector, the most important of which is that they provide rich data sources for economic evaluation and decision making, allowing investigation of many types of questions, some of which otherwise would be intractable analytically. Thus, they offer viable alternatives and complements to existing methods of valuation and preference elicitation.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study

              Summary Background Fetal structural anomalies, which are detected by ultrasonography, have a range of genetic causes, including chromosomal aneuploidy, copy number variations (CNVs; which are detectable by chromosomal microarrays), and pathogenic sequence variants in developmental genes. Testing for aneuploidy and CNVs is routine during the investigation of fetal structural anomalies, but there is little information on the clinical usefulness of genome-wide next-generation sequencing in the prenatal setting. We therefore aimed to evaluate the proportion of fetuses with structural abnormalities that had identifiable variants in genes associated with developmental disorders when assessed with whole-exome sequencing (WES). Methods In this prospective cohort study, two groups in Birmingham and London recruited patients from 34 fetal medicine units in England and Scotland. We used whole-exome sequencing (WES) to evaluate the presence of genetic variants in developmental disorder genes (diagnostic genetic variants) in a cohort of fetuses with structural anomalies and samples from their parents, after exclusion of aneuploidy and large CNVs. Women were eligible for inclusion if they were undergoing invasive testing for identified nuchal translucency or structural anomalies in their fetus, as detected by ultrasound after 11 weeks of gestation. The partners of these women also had to consent to participate. Sequencing results were interpreted with a targeted virtual gene panel for developmental disorders that comprised 1628 genes. Genetic results related to fetal structural anomaly phenotypes were then validated and reported postnatally. The primary endpoint, which was assessed in all fetuses, was the detection of diagnostic genetic variants considered to have caused the fetal developmental anomaly. Findings The cohort was recruited between Oct 22, 2014, and June 29, 2017, and clinical data were collected until March 31, 2018. After exclusion of fetuses with aneuploidy and CNVs, 610 fetuses with structural anomalies and 1202 matched parental samples (analysed as 596 fetus-parental trios, including two sets of twins, and 14 fetus-parent dyads) were analysed by WES. After bioinformatic filtering and prioritisation according to allele frequency and effect on protein and inheritance pattern, 321 genetic variants (representing 255 potential diagnoses) were selected as potentially pathogenic genetic variants (diagnostic genetic variants), and these variants were reviewed by a multidisciplinary clinical review panel. A diagnostic genetic variant was identified in 52 (8·5%; 95% CI 6·4–11·0) of 610 fetuses assessed and an additional 24 (3·9%) fetuses had a variant of uncertain significance that had potential clinical usefulness. Detection of diagnostic genetic variants enabled us to distinguish between syndromic and non-syndromic fetal anomalies (eg, congenital heart disease only vs a syndrome with congenital heart disease and learning disability). Diagnostic genetic variants were present in 22 (15·4%) of 143 fetuses with multisystem anomalies (ie, more than one fetal structural anomaly), nine (11·1%) of 81 fetuses with cardiac anomalies, and ten (15·4%) of 65 fetuses with skeletal anomalies; these phenotypes were most commonly associated with diagnostic variants. However, diagnostic genetic variants were least common in fetuses with isolated increased nuchal translucency (≥4·0 mm) in the first trimester (in three [3·2%] of 93 fetuses). Interpretation WES facilitates genetic diagnosis of fetal structural anomalies, which enables more accurate predictions of fetal prognosis and risk of recurrence in future pregnancies. However, the overall detection of diagnostic genetic variants in a prospectively ascertained cohort with a broad range of fetal structural anomalies is lower than that suggested by previous smaller-scale studies of fewer phenotypes. WES improved the identification of genetic disorders in fetuses with structural abnormalities; however, before clinical implementation, careful consideration should be given to case selection to maximise clinical usefulness. Funding UK Department of Health and Social Care and The Wellcome Trust.
                Bookmark

                Author and article information

                Contributors
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 January 2022
                2022
                : 17
                : 1
                : e0261898
                Affiliations
                [1 ] North Thames Genomic Laboratory Hub, Great Ormond Street Hospital, London, United Kingdom
                [2 ] Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
                [3 ] Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
                [4 ] Center for Fetal Diagnostics, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
                [5 ] Department of Genetics and Stanford Center for Biomedical Ethics, Stanford University School of Medicine, Stanford, CA, United States America
                [6 ] Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
                [7 ] Department of Perinatal Medicine, Mercy Hospital for Women, Heidelberg, Victoria, Australia
                [8 ] Department of Obstetrics and Gynaecology, Northern Health, Epping, VIC, Australia
                [9 ] Reproductive Epidemiology, Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia
                [10 ] Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
                [11 ] Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, England, United Kindom
                [12 ] National Institute for Health Research Oxford Biomedical Research Centre, Oxford, England, United Kindom
                [13 ] Department of Clinical Genetics, Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden
                [14 ] Center for Fetal Medicine, Karolinska University Hospital, Stockholm, Sweden
                [15 ] Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
                [16 ] BSc Paediatrics and Child Health, The UCL Great Ormond Street Institute of Child Health, London, United Kingdom
                Children’s Hospital of Los Angeles, UNITED STATES
                Author notes

                Competing Interests: The authors have read the journal’s policy and have the following competing interests: JB received travel support from Illumina to attend conferences. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                [¤a]

                Current address: Health Ethics and Policy Lab, Department of Health Science and Technology, ETH Zurich, Zurich, Switzerland

                [¤b]

                Current address: Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, London, United Kingdom

                ‡ JH and JEK share first authorship on this work. MH and CL are joint senior authors on this work.

                Author information
                https://orcid.org/0000-0002-6775-6561
                https://orcid.org/0000-0002-1033-0818
                https://orcid.org/0000-0001-7169-1521
                Article
                PONE-D-21-12941
                10.1371/journal.pone.0261898
                8797177
                35089945
                4cff967e-0999-4d0b-a0b7-bb6393d7228f
                © 2022 Hammond et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 April 2021
                : 14 December 2021
                Page count
                Figures: 1, Tables: 4, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100004440, Wellcome Trust;
                Award ID: 211288/Z/18/Z
                Award Recipient :
                CL received a Wellcome Trust Small Grant in Humanities and Social Science to conduct this work (grant number 211288/Z/18/Z). https://wellcome.org/grant-funding/schemes/small-grants-humanities-and-social-science JB received travel support from Illumina to attend conferences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Genetics
                Genomics
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Medicine and Health Sciences
                Diagnostic Medicine
                Prenatal Diagnosis
                People and places
                Geographical locations
                Europe
                European Union
                Netherlands
                Medicine and Health Sciences
                Clinical Genetics
                Genetic Counseling
                Biology and Life Sciences
                Genetics
                Genomics
                Genomic Medicine
                Genetic Counseling
                Biology and Life Sciences
                Genetics
                Human Genetics
                Genetic Counseling
                Medicine and Health Sciences
                Clinical Genetics
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Birth
                Labor and Delivery
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Birth
                Labor and Delivery
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article

                scite_
                0
                0
                0
                0
                Smart Citations
                0
                0
                0
                0
                Citing PublicationsSupportingMentioningContrasting
                View Citations

                See how this article has been cited at scite.ai

                scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

                Similar content110

                Cited by3

                Most referenced authors643