One size does not fit all: the personal nature of completed embryo donation.

PURPOSE: To assess factors associated with embryo donation among individuals interested in donation in the United States. METHODS: An invitation to complete the 123-item survey was emailed from June to September 2022 to patients at a private practice fertility clinic with interest in donation at the time of IVF. Survey questions included disposition decision, attitudes about embryo status and genetic relatedness, donation disclosure, ideal donation arrangement, and decision satisfaction. RESULTS: Three hundred thirty-seven completed the survey. Two hundred thirty donated to another person(s), 75 discarded embryos, 25 remained undecided, and disposition was unknown for 7 respondents. There were no demographic differences between groups based on final disposition or use of donor gametes. Few gamete recipients were interested in donation due to biological attachment to embryos. Final embryo disposition was associated with religious factors, not wanting to waste embryos, and storage fee concerns. Final disposition was also significantly associated with concern about donor-conceived children's (DCP) welfare, being denied the ability to complete donation, personal IVF outcomes, financial or legal issues, future contact with DCP, cognitive appraisal of disposition, beliefs about embryos, someone else raising their genetic child, anonymity, and beliefs about DCP not knowing genetic relationships (p < .001). Donation to others was associated with less regret and greater satisfaction with the emotional/medical aspects of donation and counseling compared to those who discarded embryos (p < .001). CONCLUSION: The decision to donate embryos to another person(s) is complex. Counseling that considers individual circumstances, values, and evolving dynamics may facilitate informed decision-making for those navigating infertility treatment, family building, and embryo disposition.

Preimplantation genetic testing for sickle cell disease: a cost-effectiveness analysis.

Objective: To evaluate the cost-effectiveness of in vitro fertilization with preimplantation genetic testing for monogenic disease (IVF + PGT-M) in the conception of a nonsickle cell disease (non-SCD) individual compared with standard of care treatment for a naturally conceived, sickle cell disease (SCD)-affected individual. Design: A Markov simulation model was constructed to evaluate a one-time IVF + PGT-M treatment compared with the lifetime standard of care costs of treatment for an individual potentially born with SCD. Using an annual discount rate of 3% for cost and outcome measures, quality-adjusted life years were constructed from utility weights and life expectancy values and then used as the effectiveness measurement. An incremental cost-effectiveness ratio was calculated for both treatment arms, and a willingness-to-pay threshold of $50,000 per quality-adjusted life year was assumed. Setting: Tertiary care or university medical center. Patients: A hypothetical cohort of 10,000 patients was analzyed over a lifetime horizon using yearly cycles. Interventions: In vitro fertilization with preimplantation genetic testing for monogenic disease use in conception of a non-SCD individual. Main Outcome Measures: The primary outcomes of interest were the incremental cost and effectiveness of an IVF+PGT-M conception compared with the SOC treatment of an SCD-affected individual. Results: In vitro fertilization with preimplantation genetic testing for monogenic disease was the optimal strategy in 93.17% of the iterations. An incremental savings of $137,594 was demonstrated with a gain of 1.96 QALYs and 3.69 life years over a lifetime. Sensitivity analysis demonstrated that SOC treatment never met equivalent cost-effectiveness. Conclusions: Our model demonstrates that IVF + PGT-M for selection against SCD, compared with lifetime SOC treatment for those affected, is the most cost-effective strategy within the United States healthcare sector.

Investigation of interest in and timing preference for cancer predisposition testing and expanded carrier screening among women of reproductive age.

Objective: To examine cognitive, relational, and social predictors of interest in and timing preference for cancer predisposition testing (CPT) and expanded carrier screening (ECS) offered in routine gynecologic care for women of reproductive age. Methods: Women between 20 and 35 years old who were currently pregnant or had a prior pregnancy (N = 351) completed an online survey. Bivariate and multivariable analyses were used to identify significant predictors of women's interest in and timing preference for CPT and ECS. Results: Most respondents reported high interest in CPT and ECS and preferred to have them when planning for a pregnancy. Perceived importance of genetic information and negative attitude towards uncertainty predicted interest in CPT and ECS in multivariable models. Genetic knowledge predicted preference for CPT or ECS when planning for a pregnancy. Conclusion: Educational and decision support tools should be developed to enhance women's knowledge and awareness of CPT and ECS and to provide them with strategies to manage uncertainty. Innovation: We examined women's timing preference for CPT and ECS and the impact of partner support and trust with gynecologist. A context-specific attitudes toward uncertainty scale was used to investigate women's particular perceptions of uncertainty in genetic testing.

Creating a postmortem examination decision aid: Suggestions from bereaved parents of a stillborn.

OBJECTIVES: To understand the postmortem decision-making needs and preferences of parents of a stillborn. METHODS: A qualitative content analysis was conducted. Patients who received stillbirth care at the University of Utah in the last 5 years, were 18 years of age or older, and English speakers, were invited to participate via an email and follow-up phone call. Participants were interviewed about their experiences, values, beliefs, decision-making experience regarding the postmortem examinations of their stillborn, and suggestions for how to assist their decision-making needs. RESULTS: Nineteen participants who consented to one or more postmortem examination of their stillborn were interviewed. They expressed needing information, altruism, and/or a belief in science as reasons for consenting. The most common reason for declining was already knowing the stillbirth cause. Recommendations for a decision aid included a description of all stillbirth evaluation options, risks and benefits, and a timeline. CONCLUSION: Participants had a variety of reasons for consenting to or declining postmortem examinations of their stillborn. Recommendations for a decision aid include a full description of each examination, the risks and benefits, and a timeline. PRACTICAL IMPLICATIONS: An example decision aid was created from recommendations, which presents balanced information to help support couple's decision-making.

The economic burden associated with stillbirth: A systematic review.

BACKGROUND: Evidence on the economic burden of stillbirth is limited. In this systematic review, we aimed to identify studies focusing on the economic burden of stillbirth, describe the methods used, and summarize the findings. METHOD: We performed a systematic search in Medline, EMBASE, Cochrane library, and EconLit from inception to July 2021. Original studies reporting the cost of illness, economic burden, or health care expenditures related to stillbirth were included. Two reviewers independently extracted data and evaluated study quality using the Larg and Moss checklist. A narrative synthesis was performed. Costs were presented in US dollars (US$) in 2020. RESULTS: From the 602 records identified, a total of four studies were included. Eligible studies were from high-income countries. Only one study estimated both direct and indirect costs. Among three cost-of-illness studies, two studies undertook a prevalence-based approach. The quality of these studies varied and was substantially under-reported. Four studies describing direct costs ranged from $6934 to $9220 per stillbirth. Indirect costs account for around 97% of overall costs. No studies have incorporated intangible cost components. CONCLUSIONS: The economic burden of stillbirth has been underestimated and not extensively studied. There are no data on the cost of stillbirth from countries that bear a higher burden of stillbirth. Extensive variation in methodologies and cost components was observed in the studies reviewed. Future research should incorporate all costs, including intangible costs, to provide a comprehensive picture of the true economic impact of stillbirth on society.

Understanding the experiences and perspectives of prenatal screening among a diverse cohort.

INTRODUCTION: Rapid advances in prenatal genetic screening technology make it difficult for providers to deliver adequate prenatal counseling. The aim of this study was to understand how prenatal screening educational approaches can meet the needs of patients. METHODS: Qualitative content analysis was conducted on a diverse population who were interviewed to explore their perceived experiences and preferences for prenatal screening educational delivery. RESULTS: Twenty-two women from three US sites were interviewed. Participants were racially/ethnically diverse with 22.7% identifying as Black or African American (n = 5), 40.9% as Hispanic (n = 9), and 4.5% as Pacific Islander (n = 1). Four themes were identified: prenatal screening education, prenatal screening decision-making, return of results, and suggestions for creating a decision aid. Most results were consistent with previous research not targeting a diverse population. DISCUSSION/CONCLUSION: Our results indicate that learning style preferences vary between patients and that current methods are not consistently satisfying patient's desire for understanding, particularly with 'high-risk' results, suggesting that a standardized tool could improve knowledge and decrease decisional conflict. This diverse cohort suggested a list and description of each of the testing options offered, information about each condition being screened for, a timeline for the testing and return of results, costs associated, and non-technical language.

Evaluating visual imagery for participant understanding of research concepts in genomics research.

Informed consent is crucial for participant understanding, engagement, and partnering for research. However, current written informed consents have significant limitations, particularly for complex topics such as genomics and biobanking. Our goal was to identify how participants visually conceptualize terminology used in genomics and biobanking research studies, which might provide a novel approach for informed consent. An online convenience sample was used from May to July 2020 to collect data. Participants were asked to draw 10 randomly chosen words out of 32 possible words commonly used in consent forms for genomics and biobanking research. An electronic application captured drawings that were downloaded into a qualitative software program for analysis. A total of 739 drawings by 269 participants were captured. Participants were mostly female (61.3%), eight different race/ethnicities were represented (15.6% Black, 13.8% Hispanic), and most had some college education (68.8%). Some words had consistent visual themes such as different types of risky activities for risk or consistent specific images such as a double helix for DNA. Several words were frequently misunderstood (e.g., ascend for assent), while others returned few submissions (e.g., phenotype or whole genome sequencing). We found that although some words used in genomics and biobanking research were visually conceptualized in a common fashion, but misunderstood or less well-known words had no, few, or mistaken drawings. Future research can explore the incorporation of visual images to improve participant comprehension during consent processes, and how to utilize visual imagery to address more challenging concepts.

Demonstration Project: Transitioning a Research Network to New Single IRB Platforms.

Since the 2016 National Institutes of Health (NIH) mandate to use a single IRB (sIRB) in multicenter research, institutions have struggled to operationalize the process. In this demonstration project, the University of Utah Trial Innovation Center assisted the Collaborative Pediatric Critical Care Research Network to transition from using individually negotiated reliance agreements and paper-based documentation to a new sIRB master agreement and an informatics platform to capture reliance documentation. Lessons learned that can guide other academic institutions and IRBs as they operationalize sIRBs included the need for sites to understand what type of engagement or reliance is required and their need to understand the difference between reliance and activation. Requirements around local review remain poorly understood. Further research is needed to determine approaches that can achieve the NIH vision of reviews becoming more efficient and improving study start-up times, relieving administrative burden while advancing human research protections.

Using single IRB consultations to meet the educational needs of investigative teams.

Single IRB (SIRB) consultation resources were established by the Utah Trial Innovation Center to assist and educate investigative teams prior to the submission of funding applications for multisite, cooperative research. Qualitative analysis of the written consultation materials and meeting minutes revealed the most common areas of education needed by investigative teams, including (a) the differences and relationships between the IRB and a Human Research Protection Program (HRPP); (b) the main phases of the SIRB process; and (c) the use of technology platforms for documentation of SIRB review processes. For investigative teams who are inexperienced with using a SIRB, such consultation in the pre-award period is likely to fill in knowledge gaps and improve the study start-up process.

Exploring the use of a Comic for Education about Expanded Carrier Screening among a Diverse Group of Mothers.

Purpose: Expanded carrier screening (ECS) during prenatal care is an important test for identifying prospective parents' risk of inherited genetic diseases. However, barriers remain for effectively educating patients about ECS. Graphic medicine (i.e. comics) has grown as a mechanism for patient education. The purpose of this study was to explore attitudes and opinions of a comic to educate about ECS during prental care. Methods: Focus groups were conducted with pregnant women or women who recently gave birth (6 groups, n=54). The participants were all female, 44.4% Latino/Hispanic, 16.7% Bi-Racial/Other, and 43.3% reporting some college education or high school degree. Results: Most participants reported high enjoyment with the comic due to their relatability to the characters, simplicity of the story, description of medical outcomes in everyday terms and the exploration of multiple outcomes possible with ECS. In addition, participants reported that during pregnancy their reading habits increase as well as emotional reactions to the content and some participants stated they avoided reading information that may cause stress or anxiety. Conclusion: More research is needed to assess what features of the comic promote understanding and how that influences decisions and pre-test patient education for ECS. The use of graphic narratives may enable individuals to better understand medical information in general.

An Approach to Reviewing Local Context for Exception from Informed Consent Trials Using a Single IRB.

In the context of emergency research, researchers can ask the institutional review board (IRB) to waive the regulatory requirement that individuals provide informed consent when enrolling in research studies. A requirement of the waiver of informed consent is that the reviewing IRB must review and approve a community consultation and public disclosure plan. It is critical that an IRB serving as the single IRB (sIRB) for multisite research be thoroughly versed in the local context concerns for each participating site to determine whether the site's community is being adequately consulted about the research in which individuals will be enrolled under an exception to the informed consent requirement. We designed an sIRB review model for evaluating site-specific community consultation plans that included a local evaluation and feedback step, and we piloted the model with a four-site, pediatric exception from informed consent (EFIC) clinical trial. We identified three key roles for the model: the sIRB, the investigators, and the representative of the institution's human research protection program (HRPP). We successfully collected the information and local input needed to evaluate each site's community consultation plan and applied the information to a thorough IRB review, despite the geographic distance between the study site and the sIRB.

Lived experiences of patients with placenta accreta spectrum in Utah: a qualitative study of semi-structured interviews.

OBJECTIVE: To describe the lived experience of patients undergoing diagnosis and treatment of placenta accreta spectrum (PAS). DESIGN: Qualitative study of semi-structured interviews. A content analysis was used to analyse interview data using a consistent set of codes to designate data segments that contain similar material. Codes were analysed and grouped based on thematic similarities. Thematic results were systematically reviewed, verified and audited to address trustworthiness and rigour of the data and analysis. SETTING: A single PAS programme in Utah, USA, from 2017 to 2020. PARTICIPANTS: Patients with PAS during the study period were eligible. Those experiencing fetal demise or termination were excluded. Of 25 patients contacted at random, 17 agreed to participate in interviews. Those included were predominantly non-Hispanic white, highly parous, with average age of 34.7 years. RESULTS: The lived experiences of patients with PAS emerged across the time continuum from diagnosis, pregnancy, birth, to postpartum care and recovery. Themes common across the care continuum were: the emotional burden of diagnosis and management; fear and uncertainty related to health outcomes; and lack of autonomy and medical helplessness related to medical decision-making. Many patients experienced birth-related trauma, mourned the loss of future fertility and were dissatisfied with the lack of options for treatment for this serious pregnancy complication. CONCLUSIONS: Patients undergoing diagnosis and treatment for PAS often experienced care that conflicted with their goals for pregnancy and birth. Clinical care for PAS would benefit from interventions aiming to engage patients and providers in shared decision-making and systems designed to address the social, psychological and emotional needs of patients with PAS.

Informed consent: Old and new challenges in the context of the COVID-19 pandemic.

In this paper, we address how the COVID-19 pandemic has impacted informed consent for clinical research through examining experiences within Clinical and Translation Science Award (CTSA) institutions. We begin with a brief overview of informed consent and the challenges that existed prior to COVID-19. Then, we discuss how informed consent processes were modified or changed to address the pandemic, consider what lessons were learned, and present research and policy steps to prepare for future research and public health crises. The experiences and challenges for CTSA institutions offer an important perspective for examining what we have learned about informed consent and determining the next steps for improving the consent process.

Challenges and lessons learned for institutional review board procedures during the COVID-19 pandemic.

The COVID-19 pandemic changed the clinical research landscape in America. The most urgent challenge has been to rapidly review protocols submitted by investigators that were designed to learn more about or intervene in COVID-19. International Review Board (IRB) offices developed plans to rapidly review protocols related to the COVID-19 pandemic. An online survey was conducted with the IRB Directors at Clinical and Translational Science Awards (CTSA) institutions as well as two focus groups. Across the CTSA institutions, 66% reviewed COVID-19 protocols across all their IRB committees, 22% assigned protocols to just one committee, and 10% created a new committee for COVID-19 protocols. Fifty-two percent reported COVID-19 protocols were reviewed much faster, 41% somewhat faster, and 7% at the same speed as other protocols. Three percent reported that the COVID-19 protocols were reviewed with much better quality, 32% reported slightly better quality, and 65% reported the reviews were of the same quality as similar protocols before the COVID-19 pandemic. IRBs were able to respond to the emergent demand for reviewing COVID-19 protocols. Most of the increased review capacity was due to extra effort by IRB staff and members and not changes that will be easily implemented across all research going forward.

Women's Experiences With Palliative Care During Pregnancy.

OBJECTIVE: To explore the experiences of women who received life-limiting fetal diagnoses during pregnancy and support from a perinatal palliative care program. DESIGN: Descriptive qualitative. SETTING: The perinatal palliative care program is part of a not-for-profit system of 24 hospitals serving the U.S. Intermountain West region. PARTICIPANTS: A convenience sample of 12 women who experienced pregnancies with life-limiting fetal diagnoses and received care from a perinatal palliative care program. METHODS: Women chose to participate from mailed invitations or responded to a post on private social media and then completed semistructured interviews about their experiences surrounding the fetal diagnoses and support from a perinatal palliative care program. Interviews were approximately 40 minutes in length and were conducted over the phone, recorded, and then transcribed. We performed content analysis by coding, forming categories of similar coded data, and constructing themes by recontextualizing categories through iterative, team-based meetings. RESULTS: We identified four themes from the data: Importance of Memorabilia to Cope With the Death and Documentation of Pregnancy, Acceptance of Death as Part of the Pregnancy Experience, Continued Life Without a Child, and Importance of Empathy Throughout the Process. CONCLUSION: The themes support the existing research findings about the needs of pregnant women as they cope with difficult situations. Our findings show the necessity and importance of perinatal palliative care programs.

Electronic informed consent information for residual newborn specimen research: findings from focus groups with diverse populations.

We developed a video and an app for obtaining consent about allowing newborn blood spots (NBS) to be used as biospecimen resources for biobanking. Newborn screening programs test for treatable diseases and leave residual biospecimens that can be used in future research activities. We conducted focus groups and interviews with three diverse communities to determine (a) how well the consent tools worked and (b) participant familiarity with NBS. Participants preferred the video and noted that they were unaware that NBS could be used for future research. Providing information about how biospecimens could be used was a key issue.

Assessing clinical education tools for expanded carrier screening.

Expanded carrier screening (ECS) is increasingly offered to a broader population and raises challenges of how to best educate and counsel the volume of screened individuals. For this study, we compared three educational tools (brochure, video and comic) about ECS on knowledge and decision making. A convenience online sample of 151 pregnant women was randomized to one of three groups (Video, n = 42; Comic n = 54; Brochure n = 55). Knowledge scores were significantly higher for the comic group compared to the video or the brochure groups (p < .001). No significant differences in preparation for decision making, decisional conflict, or perceptions of shared decision making were identified between the study groups. This study suggests that a comic about ECS may improve patient attention and retention of information. The use of graphic narratives may enable individuals to better understand medical information in general.

Newborn Screening Knowledge and Attitudes Among Midwives and Out-of-Hospital-Birth Parents.

Midwifery and nursing are collaborative partners in both education and practice. Understanding needs and barriers to clinical services such as newborn screening is essential. This study examined knowledge and attitudes of midwives and out-of-hospital-birth parents about newborn blood spot screening (NBS). Descriptive and cross-sectional surveys were distributed to midwives and out-of-hospital-birth parents from birth center registries and the Utah Health Department of Vital Records. Seventeen midwife surveys (response rate: 17%) and 113 parent surveys (response rate: 31%) were returned. Most midwives and out-of-hospital-birth parents reported satisfactory knowledge scores about NBS. Only 5% of parents (n = 6) did not participate in NBS. Most midwives reported that NBS is important and encouraged patients to consider undergoing NBS. Some concerns included the lack of education for both midwives and out-of-hospital patients and the trauma and accuracy of the heel prick soon after birth. Both midwives and out-of-hospital-birth parents expressed a need for improved NBS education. Additional studies are needed to ascertain whether this trend is seen with similar populations throughout the United States, to further elucidate the factors that drive NBS nonparticipation, and to develop educational resources for midwives and their patients.

Demonstrating 'respect for persons' in clinical research: findings from qualitative interviews with diverse genomics research participants.

The ethical principle of 'respect for persons' in clinical research has traditionally focused on protecting individuals' autonomy rights, but respect for participants also includes broader, although less well understood, ethical obligations to regard individuals' rights, needs, interests and feelings. However, there is little empirical evidence about how to effectively convey respect to potential and current participants. To fill this gap, we conducted exploratory, qualitative interviews with participants in a clinical genomics implementation study. We interviewed 40 participants in English (n=30) or Spanish (n=10) about their experiences with respect in the study and perceptions of how researchers in a hypothetical observational study could convey respect or a lack thereof. Most interviewees were female (93%), identified as Hispanic/Latino(a) (43%) or non-Hispanic white (38%), reported annual household income under US$60 000 (70%) and did not have a Bachelor's degree (65%); 30% had limited health literacy. We identified four key domains for demonstrating respect: (1) personal study team interactions, with an emphasis on empathy, appreciation and non-judgment; (2) study communication processes, including following up and sharing results with participants; (3) inclusion, particularly ensuring materials are understandable and procedures are accessible; and (4) consent and authorisation, including providing a neutral informed consent and keeping promises regarding privacy protections. While the experience of respect is inherently subjective, these findings highlight four key domains that may meaningfully demonstrate respect to potential and current research participants. Further empirical and normative work is needed to substantiate these domains and evaluate how best to incorporate them into the practice of research.

The ethics of sensor technology use in clinical research.

Sensor-based technologies are used today in clinical practice, research, and for monitoring people's health in homes across the United States. Although the increasing growth and complexity of such technologies promises both direct and indirect benefits, significant ethical concerns are raised. We discuss several of these concerns, particularly those that arise in clinical research and outline ethical considerations that pertain to the concept of informed consent, participants' understanding of risks and benefits and the need for tailored and accessible information that will enable participants to fully understand research implications. Balancing the benefits with the potential risks of advanced information technology will require ethically astute researchers who can address the challenges that might arise while advancing knowledge with innovation that can improve the lives of patients and families.