Recruitment for clinical research in the neonatal intensive care unit (NICU) is difficult, which may lead to low enrollment rates, systematically skewed samples, and nongeneralizable results. Research without prior consent (RWPC), defined as obtaining consent only after infants have been randomized to a treatment arm, may improve enrollment but raises ethical challenges. There is a need to better understand how parents with lived experience of having an infant in the NICU consider RWPC’s impact on critical ethical values related to informed consent, including decision-making, respect, and trust. This mixed-methods study aimed to describe parental perceptions of the acceptability and ethical implications of RWPC for neonatal clinical research. Interviews were conducted with parents of infants recently admitted to the NICU across 6 US locations. Parents were asked a series of Likert-scale questions followed by open-ended questions with interactive probes about the acceptability of hypothetical study vignettes using either prospective informed consent or RWPC. Likert-scale responses were analyzed using mixed-effects linear regression models. Open-ended responses were inductively coded and thematically analyzed through a constructivist lens. Parents (n = 38) scored the acceptability of RWPC vignettes lower than prospective informed consent vignettes on mean adjusted total score and items about perceived control, values-aligned decision-making, and respect for babies and families. Four themes were identified as impacting parents’ views on acceptability of RWPC: (1) equipoise as the foundation for acceptability of consent approaches, (2) informational preferences for consent approaches, (3) complex interplay between consent approaches and research relationships, and (4) consent approaches as shaping perceived control. Parents’ perspectives illustrate key considerations for the potential use of RWPC as well as broader reflections on engagement about clinical research in the NICU setting. Situational factors in the NICU raise barriers to consent, and RWPC may be differentially acceptable depending on study specifics. Thoughtful communication about equipoise and attention to trust are essential when considering alternative methods of consent. Future research should further examine ethical trade-offs involved in RWPC and varied perceptions across study features.

Illness perception (IP) is how individuals interpret a medical condition through their values, beliefs and experiences. In paediatric and neonatal intensive care settings, IP has been associated with parental stress, decision making and engagement with care. Differences in IP between clinicians and parents are common and can contribute to delays in decision making, moral distress and fractured communication. One difficulty with IP is that it can be misidentified as a substitute for understanding. Clinicians may worry that misaligned IP therefore means families do not understand the medical facts. If families are not emotionally responding to the medical information as clinicians expect or framing goals accordingly, clinicians may suspect they have not understood. But this incorrectly conflates IP with being informed about the medical circumstances. IP is, instead, how that information is interpreted, mediated by subjective experience and values and contributes differently to decision making than the facts alone. We propose an approach to decision making that incorporates IP as a distinct feature to explore. By engaging these differences directly, we posit that clinicians can more effectively support families, foster value-concordant decisions and navigate ethically complex medical decisions.

IMPORTANCE:Neonatal clinical trials frequently encounter low enrolment rates, challenges obtaining consent and biased research populations. Alternative approaches to consent have been proposed to address these concerns but introduce complex ethical trade-offs. OBJECTIVE:Using a modified Delphi approach with diverse stakeholders, we aimed to create recommendations for the use of alternative methods of consent in neonatal clinical trials. FINDINGS:Our process resulted in 21 recommendations within three categories. In 'deciding whether to use alternative methods of consent', we present five statements to guide whether alternative methods are appropriate. For example, heightened justification may be required for early phase research or allocation arms that are highly preference-sensitive for families. In 'preallocation information and ability to opt-out', we present 11 statements related to information sharing with families of potential participants. These include guidance on researcher communication and guidance for passive information sharing such as via flyers. In 'postallocation information and decision to continue participation', we present five statements to guide later information sharing. These focus on best practices for researcher communication postallocation. For two items, our Working Group could not reach consensus. These items were not included in our recommendations. CONCLUSIONS AND RELEVANCE:Our recommendations may guide researchers, clinicians, regulators and funders in the consideration and conduct of alternative methods of consent for neonatal clinical trials. Future work must evaluate these recommendations within neonatal clinical trials and the areas of lack of consensus among our Working Group.

Informed nondissent is a form of shared decision-making in which clinicians provide a medically appropriate recommendation while observing for explicit objection, rather than requiring affirmative agreement. This approach emphasizes transparency, clinician responsibility, and the opportunity for dissent. Clinicians and parents in the neonatal intensive care unit (NICU) are frequently tasked with values-based, emotionally charged goals-of-care decisions for critically ill newborns with poor prognoses. When NICU parents indirectly express readiness to change goals of care without explicitly verbalizing it, prudent use of informed nondissent can improve alignment between parental values and goals and clinical care, prevent decisional conflict, and decrease moral distress. In this paper, we critically examine the benefits of informed nondissent and offer practical guidance for its effective application within NICU shared decision-making. We address its potential pitfalls, emphasizing that informed nondissent must be applied carefully to preserve parental authority and maintain parental ability to participate in decision-making.

Objective:Interactions with families are essential to successful recruitment conversations that promote informed decision-making about clinical research enrollment. However, there is little evidence about how to implement communication-oriented recruitment training among pediatric clinical research teams. Our objective was to evaluate the feasibility and acceptability of Better Research Interactions for Every Family (BRIEF), a multipart educational intervention to improve relationship-based conversations about clinical trial enrollment with families in the neonatal setting. Study Design:We piloted BRIEF in partnership with a neonatal clinical research team. Research team members completed surveys following the BRIEF intervention's online module and the BRIEF group training session. They completed self-assessments after consent discussions before and after the BRIEF intervention, in which they rated their achievement of recruitment skills taught in BRIEF. Research team members also completed a final study interview to provide feedback on the intervention components, training content, and use of skills in practice. Results:All nine research team members completed all components of BRIEF. Survey responses showed moderate to low satisfaction with previous recruitment training before BRIEF and high satisfaction with the BRIEF training. Self-assessments showed significant increases in reported partnership with bedside nursing (p = 0.02) and confirmation of family names (p = 0.05) after BRIEF training. Interviews provided further evidence of overall satisfaction with the BRIEF training, its content, and the skills learned, as well as opportunities for improvement, particularly in supporting challenging conversations. Conclusion:This pilot study demonstrated the feasibility and acceptability of the BRIEF intervention, as well as opportunities for improvement in future training. Key Points:· It was feasible to implement the BRIEF researcher training in a single-site NICU trial.. · BRIEF training was acceptable to research team members.. · BRIEF training shows potential to improve relationship-based research communication..

Artificial intelligence (AI) adoption in health care is rapidly accelerating, with pediatrics positioned to benefit from improvements in quality, efficiency, and access to care. Recent frameworks have articulated ethical commitments for trustworthy AI in pediatrics, but less attention has been paid to the foundational infrastructure required to achieve them. In this article, we examine the challenges that emerge at the intersection of AI and pediatrics: unique challenges that AI poses for pediatric care, including nonintuitive errors, impacts on clinician cognition, and new infrastructure requirements; and unique challenges that pediatrics poses for AI, including adequate training data, accommodation of developmental heterogeneity, and navigation of evolving patient autonomy. We then outline the data systems, governance structures, validation frameworks, and public trust infrastructure that must be established before the field can meet these challenges. We conclude with concrete recommendations for clinicians, caregivers, health care systems, government, technologists, and academic institutions seeking to lay the foundation for trustworthy and beneficial AI in pediatrics.

OBJECTIVE:Recruiting for neonatal clinical trials is difficult for families and participation rates are low. We partnered with the DIVI (Darbepoetin plus slow-release IntraVenous Iron) trial for pilot feasibility evaluation of the BRIEF (Better Research Interactions for Every Family) intervention. STUDY DESIGN:Pre/post design to compare infant data and parent surveys and interviews before and after the BRIEF intervention as well as comparing DIVI enrolled and DIVI not enrolled. RESULTS:Enrollment rates and parental experiences were similar in pre- and post-BRIEF eras. Most respondents reported positive interactions with researchers. Parents who declined DIVI reported somewhat  worse experiences compared to those who enrolled. Interview respondents reported widely variable experiences. The narrow enrollment window emerged as particularly important to parents' recruitment experience. CONCLUSIONS:The BRIEF intervention was well received and is ready for larger scale testing to assess its impact on parental experience and enrollment rates. Future work should address short enrollment windows common in neonatal clinical trials.

Our objective was to conduct a scoping review of the literature to inform a modified taxonomy of uncertainty in the NICU, for the purpose of better identifying and defining different experiences of uncertainty for parents and medical teams. We conducted a systematic literature search for studies examining an element of uncertainty in the NICU. Data extraction was guided by Han’s taxonomy of uncertainty and a thematic analysis informed the modified taxonomy. We included 55 articles, leading to three major alterations of Han’s taxonomy. We believe this modified taxonomy of uncertainty in the NICU provides a more nuanced understanding of the specific uncertainties faced in this context, leading to a better understanding of the different needs of families and medical teams. It also highlights the need for targeted strategies to further explore and manage these uncertainties.

Climate change has severe consequences for neonatal health. Neonates are uniquely vulnerable to the impacts of climate change due to their developing bodies and immature immune and thermoregulatory systems. Climate change increases the risk of severe weather events, including extreme heat and natural disasters, as well as pollution and chemical exposures. The physiologic fragility of neonates and dependence on a stable environment require healthcare systems and policymakers to ensure protections are in place to mitigate health risks and potential impacts that will have long-lasting effects on individual development and well-being. The current article details the impacts of climate change on neonatal health across the lifecycle as well as the disproportionate consequences for communities most vulnerable to climate change. We provide evidence as to why this is a bioethical issue and offer recommendations for policies to protect neonatal health and promote environmental and climate justice.

Objective Whether to participate in clinical research is a special type of decision for parents with infants in the neonatal intensive care unit (NICU). Parents often report negative experiences being approached for NICU research and researchers struggle to enroll a representative sample. We consider how enrollment decision-making might be better supported by integrating learnings from clinical decision-making. Finding Approaches to supporting decision-making about clinical research, though distinct from those for clinical decision-making, share many similarities. We consider ways researchers may incorporate advances in knowledge about clinical decision-making to: (a) improve documents used for regulatory purposes (e.g., consent forms), and (b) better support relationship building between researchers and parents considering research enrollment. Conclusion Researchers may benefit from considering approaches to enrollment decision-making that draw on clinical decision-making methods. Future work should assess the impact of such approaches on parental experiences of recruitment; enrollment and retention rates; and representative inclusion of NICU populations.

Artificial intelligence (AI) offers tremendous potential to transform neonatology through improved diagnostics, personalized treatments, and earlier prevention of complications. However, there are many challenges to address before AI is ready for clinical practice. This review defines key AI concepts and discusses ethical considerations and implicit biases associated with AI. Next we will review literature examples of AI already being explored in neonatology research and we will suggest future potentials for AI work. Examples discussed in this article include predicting outcomes such as sepsis, optimizing oxygen therapy, and image analysis to detect brain injury and retinopathy of prematurity. Realizing AI’s potential necessitates collaboration between diverse stakeholders across the entire process of incorporating AI tools in the NICU to address testability, usability, bias, and transparency. With multi-center and multi-disciplinary collaboration, AI holds tremendous potential to transform the future of neonatology.

ImportanceResults of clinical trials can only represent included participants, and many neonatal trials fail due to insufficient participation. Infants not included in research may differ from those included in meaningful ways, biasing the sample and limiting the generalizability of findings.ObjectiveTo describe the proportion of eligible infants included in neonatal clinical trials and the reasons for noninclusion.Evidence ReviewA systematic search of Cochrane CENTRAL was performed by retrieving articles meeting the following inclusion criteria: full-length, peer-reviewed articles describing clinical trial results in at least 20 human infants from US neonatal intensive care units, published in English, and added to Cochrane CENTRAL between 2017 and 2022. Retrieved articles were screened for inclusion by 2 independent researchers.FindingsIn total 120 articles met inclusion criteria and 91 of these (75.8%) reported the number of infants eligible for participation, which totaled 26 854 in aggregate. Drawing from these, an aggregate of 11 924 eligible infants (44.4%) were included in reported results. Among all eligible infants, most reasons for noninclusion in results were classified as modifiable or potentially modifiable by the research team. Parents declining to participate (8004 infants [29.8%]) or never being approached (2507 infants [9.3%]) were the 2 predominant reasons for noninclusion. Other modifiable reasons included factors related to study logistics, such as failure to appropriately collect data on enrolled infants (859 of 26 854 infants [3.2%]) and other reasons (1907 of 26 854 infants [7.1%]), such as loss to follow-up or eligible participants that were unaccounted for. Nonmodifiable reasons, including clinical change or death, accounted for a small proportion of eligible infants who were not included (858 of 26 854 infants [3.2%]).Conclusions and RelevanceThis systematic review of reporting on eligible infants included and not included in neonatal clinical trials highlights the need for improved documentation on the flow of eligible infants through neonatal clinical trials and may also inform recruitment expectations for trialists designing future protocols. Improved adherence to standardized reporting may clarify which potential participants are being missed, improving understanding of the generalizability of research findings. Furthermore, these findings suggest that future work to understand why parents decline to participate in neonatal research trials and why some are never approached about research may help increase overall participation.

Introduction Parents struggle with being asked to participate in neonatal research. Past work has largely failed to include views of minoritized parents, low-socioeconomic status parents, and those who declined research. We aimed to describe parents’ preferences related to learning about eligibility for neonatal research. Methods Qualitative interviews of parents who were asked to enroll their infant in neonatal research. Themes related to parental experiences and preferences for learning about neonatal research were identified using content analysis. Results Many parents desired greater involvement of their clinical team. Emotions at the time of recruitment were critically important to parents’ experience, where were deeply impacted by interpersonal relationships with research staff. Discussion Increased involvement of the clinical team and greater sensitivity to the stressors around parent and infant conditions at the time of recruitment for neonatal research should be considered by those attempting to improve recruitment for neonatal research.

Background:Researchers and research organizations acknowledge the importance of paying research participants but often overlook the process of providing participant payments as a locus for improving equity and inclusion in clinical research. In this conceptual paper, we argue that participants' lived experiences and social context should be recognized and respected when developing these processes. Methods:We consider how participant payment processes that require specific payment types, delay the timing of payment, or require sharing sensitive information may impose barriers to equitable research. Building on findings from empirical research of participants' perspectives on respect in research and a relational ethics framework of person-oriented research ethics, we explore how researchers and research organizations can better demonstrate respect through the research participation payment process. Results:We propose five considerations for demonstrating respect when providing payment: (1) practice cultural humility, (2) be mindful of socioeconomic factors, (3) be flexible, (4) be transparent, and (5) maintain open communication. These considerations are intended to address the lack of existing ethical guidance around the process for participant payments and promote more inclusive clinical research. We provide a set of sample questions for research teams to consider how they could modify their payment processes to better demonstrate respect. Conclusions:By better demonstrating respect for participants when providing payment, researchers can work toward ensuring that their research procedures are more inclusive, respond to the needs of diverse communities, and result in more equitable relationships with participants.

BACKGROUND:Recruitment for neonatal clinical trials can be particularly challenging. Low enrollment rates bias the research population and decrease generalizability of findings. We identified a critical need for an intervention to improve how researchers recruit for neonatal clinical trials. Working within the US neonatal research context, we developed the Better Research Interactions for Every Family (BRIEF) Intervention, which had two overarching goals: to improve the recruitment experience for all parents, focusing on minoritized populations, and to increase participation, focusing on decreasing disparities in research participation. METHODS:We used intervention mapping (IM) to guide all steps of intervention development. IM is a planning framework that provides a systematic process and detailed protocol for step-by-step decision-making for intervention development, implementation, and evaluation. RESULTS:We performed IM's six steps. In step 1, we convened two stakeholder groups, a parent panel and an expert panel, who provided guidance through development of all BRIEF components. Through a recent systematic review, empirical data collected by our team, and consultations with the panels, we identified key determinants (barriers and facilitators) of low enrollment rates and research team members as change agents. In step 2, we iteratively refined our list of key factors to include and linked determinants of behavior changes to these performance objectives. In step 3, we chose three theories (social cognitive theory, theory of information processing, and the trans-theoretical model), methods from identified practical applications suitable for the population (research team members) and the context (busy research NICU teams). In step 4, we developed and refined the intervention components, including self-guided pre-work and a single in-person session. In step 5, we identified the Darbepoetin plus slow-release intravenous iron trial as our partner study in which to pilot BRIEF. In step 6, we developed a multi-stage evaluation plan that included five distinct levels of outcomes. CONCLUSIONS:This manuscript shares our rationale and processes for the creation of a research team member-facing intervention aiming to improve recruitment processes for neonatal clinical trials. Our approach can inform those aiming to improve recruitment for neonatal clinical trials and those who may be considering use of IM within similar contexts.