Experiences and preferences for learning about neonatal research: insights from parent interviews

Abstract

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.

INTRODUCTION

Neonatal trial recruitment is especially difficult because sick infants must often be enrolled quickly and at times of high stress for family members [1–3]. Within multi-centered neonatal randomized controlled trials (RCTs), enrollment rates can vary widely by site, the causes of which are yet to be well elucidated [4, 5].

Within adult clinical research, marginalized populations are well documented as having even greater enrollment difficulties [6]. For children, the data are more limited, and while not universal [7, 8], most studies have showed that minoritized and low-socioeconomic status (SES) populations are under-represented within pediatric research [9–11]. In prior work, parents from minoritized racial or ethnicities or reporting lower income or educational attainment were less likely to participate in neonatal research [12, 13]. Under-representation threatens to exacerbate existing health disparities within neonatology because infants from marginalized populations have worse outcomes for many common neonatal problems, including extreme prematurity [14, 15], with associated morbidity, mortality, cost, and disability [16, 17].

Processes for the conduct of neonatal research are based on what regulators, funders, and researchers think parents need as they are approached for NICU research. Concerns that parents may be misled into thinking their infant will benefit from research participation lead to an emphasis on direct risks to infants during consent conversations. Other items, such as potential benefits to the infant or burdens to the family, are deemphasized. Minimal information exists about how parents themselves want to learn about NICU research, especially those from marginalized populations and those who declined research participation [12, 18–23].

In this study, we utilized qualitative interviews with a diverse set of parents across the US approached for a variety of neonatal research studies, including both those who declined and participated, in order to inform approaches for neonatal research recruitment and to guide the development of novel interventions. We aimed to describe parents’ experiences and preferences related to learning about neonatal research opportunities for their infant.

METHODS

Overview

We conducted semi-structured interviews with parents of children currently or recently in the NICU who were asked to participate in neonatal clinical research to allow for in-depth discussion of their experiences and perspectives [24].

Terminology

In this manuscript, we use the term “minoritized” because it reflect that social (e.g., racial) groups are treated unequally due to systematic oppression [25]. This is different from “minority” which simply reflects the numbers of particular demographic groups [26]. Similarly, we use “marginalized” to indicate a group treated as lesser, insignificant, or peripheral compared to others in society [27]. Although there is no current consensus, these terms are increasingly being used in the medical literature including within pediatrics [28–31].

Recruitment

Parents proficient in spoken English who had been recently approached for participation in neonatal research were referred to our research team. We prioritized those who had been invited to join a neonatal clinical trial (based on the NIH definition) [32]. Parents were asked by their local research team whether they wanted to learn about our interview study. If they agreed, a member of our research team contacted them to obtain consent and perform the interview. To include a range of experiences, each neonatal research study was capped at eight completed interviews. Purposive sampling was utilized to prioritize including parents who had declined research participation. Referring sites were selected to include representation across parent race/ethnicity, SES status, and US region. Parents who consented to neonatal research but whose infant was not eligible (e.g., due to no longer meeting inclusion criteria at time of birth) were also invited to participate. Participants were offered compensation and the study was approved by the Institutional Review Board at Seattle Children’s Research Institute.

Interviews

We developed a semi-structured interview guide based on insights from our prior work in the area [12, 18, 33], a review of the literature, and input from experts in neonatal research and a NICU parent advisory panel. We aimed to refine our understanding of which potentially modifiable factors are most important to parents, particularly those from under-represented populations, as they decide whether to enroll in neonatal clinical trials. The guide included questions about parental experience and preferences related to recruitment. We conducted three pilot interviews and revised the guide for length, clarity, and content.

One member of the team (AM) conducted all interviews via secure video conferencing or telephone between [May 24, 2021] and [April 25, 2022]. Interviews lasted up to 60 min. Audio recordings were professionally transcribed, de-identified, verified for accuracy, and transcripts were uploaded to Dedoose [34] to facilitate analysis. We evaluated transcripts in batches as they were completed so that we could evaluated for thematic saturation, the point at which further transcripts no longer add additional themes. We ended recruitment when no new themes emerged.

Analysis

We developed a codebook using both inductive and deductive techniques based in thematic and content analytic methods [35]. This was followed by an iterative open coding and coding revision process in which three team members independently coded transcripts and then met to reach consensus. This process was repeated for three transcripts, findings reviewed with the full study team, and the codebook was revised as needed. Two trained coders independently coded the remaining transcripts. Discrepancies were resolved by discussion between two coders with remaining discrepancies resolved through consensus. Excerpts were grouped by code and each code was summarized to identify and refine themes.

RESULTS

Respondent characteristics and overview

We completed 44 interviews out of 93 parents referred to our team whom we attempted to contact prior to reaching thematic saturation. Reasons for non-inclusion were: did not meet inclusion criteria (3); no response to initial contact (18); no response to follow-up contact (19); and declined (9). Table 1 shows parent self-reported demographics. Fifteen studies across 9 US sites referred parents (Table 2).

Table 1.

Interview participant characteristics.

	Enrolled in target study (N = 22)	Declined target study (N = 22)
Race
Asian	1	4
Black	5	8
Native American	0	1
Unknown	1	0
White	16	11
Ethnicity
Hispanic or Latino	3	1
Not Hispanic or Latino	19	21
Gender
Female	21	19
Male	1	3
Education
High school or less	3	7
Some college	8	3
Bachelor’s degree	7	6
Graduate school	4	6
Medicaid
Yes	9	11
No	13	11
Median age years (range)	29 (20–40)	31 (21–39)
Region
Midwest	11	9
Northeast	5	4
South	4	7
West	2	2

Race: equals >100% because respondents could select more than one race. One respondent not answering race question is indicated as “unknown.”

Table 2.

Studies referring parents for interviews.

Study	Population	Intervention	Primary outcome	Enrollment (actual or target)	Sites total	Sites referring for interviews	Parents interviewed (E, D, C)a
A Dose-Ranging Study to Determine the Efficacy, Safety and Tolerability of AeroFact	Premature infants between 26.0–31.6 EGA and under 2000 g BW with a respiratory severity score of 1.4–2.0	AeroFact-low dose SF-RI 1 vs. AeroFact-high-dose SF-RI 1	(1) Incidence of intubation/ cannulation and instilled surfactant within 7 days. (2) Percent of patients with respiratory symptoms requiring intervention across groups over 12 months. (3) Percent of patients requiring supplemental oxygen and visits for medical care over a 12- month period	261 (target)	39	1	2 (0,1,1)
Pediatric Study to Evaluate Risk of Developing Essential Fatty Acid Deficiency When Receiving Clinolipid or Standard-of-Care Lipid Emulsion	Premature infants and full- term infants/children who were expected to require PN for at least 7 days	Clinolipid (Lipid Injectable Emulsion, USP) 20% or Standard-of-Care Soybean Oil-Based Lipid Emulsion	Number of participants to develop Essential Fatty Acid Deficiency (EFAD) up to 90 days with intravenous administration	100 (actual)	9	1	1 (0,1,0)
Biorepository study	Premature babies <34 weeks, or term with FI IE, birth defects	None	Survival to discharge and common neonatal morbidities	430 ongoing (no goal)	1	1	4 (0,4,0)
Apnea in Flospitalized Preterm Infants Following the Administration of Routine Childhood Vaccines	Preterm infants deemed eligible to receive 2-month vaccines by a clinician with an EGA of < or equal to 32 weeks who are 6 weeks postnatal age or greater at randomization who have never been discharged home and won’t be for at least 60 h upon study entry	Randomized to receive either 2-month US licensed childhood vaccines (PCV13, DTaP, HBV, IPV an Hib) or no vaccines	Occurrence of Apnea within 60 h of randomization	224 (actual)	4	1	5 (3,2,0)
Cycled Phototherapy: A Safer Effective Method to Control the Serum Bilirubin Of Extremely Premature Infants?	Inborn Preterm infants <27 EGA and < or equal to 750 g at birth who were 12–36 h old at time of enrollment	Randomized to either cycled PT (>15 min/h to 30 min/h or 60 min/h) or continuous PT	Participant survival to discharge (up to 120 days of life)	1700 (target)	16	2	7 (4,3,0)
Finances for new parents	Infants ≥14 days old currently in the NICU or infants <1 year old seen in the NICU follow-up clinic with evolving medical complexityb	None	Primary outcome: Did finances impact family decision-making in the NICU?	27 (actual)	1	1	2 (0,2,0)
Fligh-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL)	Full-term infants with hypoxic-ischemic encephalopathy (HIE)	Erythropoietin 1000U/kg IV x 5 doses vs. placebo	Death or neurodevelopmental impairment at 22–26 months	501 (actual)	23	5	8 (4,4,0)
Home Values and Experiences Navigation Track (HomeVENT)	Parents and clinicians facing a decision about tracheostomy and home ventilation for NICU and PICU children	HomeVENT web-based decision aid for families and clinicians vs. standard of care	Pilot study of feasibility and acceptability	30 parents, 35 clinicians (actual)	1	1	2 (2,0,0)
IBP-9414 for the Prevention of Necrotizing Enterocolitis— The Connection Study	Preterm infants between 23–32 weeks EGA and a BW of 500–1500 g who were enrolled within 48 h after birth	Administration of IBP -9414 vs. Placebo	Confirmed necrotizing enterocolitis from first dose to weeks post-menstrual age. Time to sustained feeding tolerance from first dose to weeks post-menstrual age	2158 (target)	91	1	1 (0,0,0)
Intermittent Hypoxia and Caffeine in Infants Born Preterm (ICAF)	Preterm infants born at ≤30.6 days gestation. Infants who are currently being treated with routine caffeine, and who meet eligibility criteria, will be enrolled between 32 weeks and 36.6 weeks days PMA	On the day of randomization, but no later than the third day following last dose of routine caffeine, patients will be randomized to receive 5 mg/kg/of caffeine base, or equal volume of placebo	(1) Compare the extent of IH exposure, from randomization through 42 weeks + 6 days PMA (within each gestational week and overall), in infants randomized to extended caffeine treatment to infants assigned to receive placebo. (2) Compare changes in a panel of inflammation-related cytokines and chemokines, from enrollment to the target age of 38 weeks + 0 days PMA, in infants randomized to extended caffeine treatment to infants assigned to receive placebo. (3) Compare changes in quantitative MRI structural, microstructural from enrollment to 43–46 weeks PMA, in infants randomized to extended caffeine treatment to infants assigned to receive placebo	220 (target)	12	1	2 (1,0,1)
MRI Brain	Infants 35–45 weeks gestational age from 2 groups: healthy infants and those with HIE	None	Development of MRI techniques for CMR02 measurements (non-invasive measurements) that are ready for immediate applications in brain development and neonatal brain disorders	100 (target)	1	1	1 (0,1,0)
Milrinone in Congenital Diaphragmatic Hernia	Infants with PMA of 36 weeks or greater and weighed 2000 g or more with congenital diaphragmatic hernia (CDH) who were enrolled within 7 days after birth	The study intervention is an intravenous infusion of milrinone or placebo (5% Dextrose)	Oxygenation response 24 h after initiation of study drug	66 (target)	16	1	1 (0,1,0)
Randomized Controlled Trial of Home Therapy With Caffeine Citrate in Moderately Preterm Infants With Apnea of Prematurity	Inborn and outborn infants between 29–33.6 weeks EGA who were 35.6 PMA or younger at time of randomization and are receiving caffeine with plan to discontinue or just discontinued	Caffeine citrate given once daily at 10 mg/kg/ day vs. placebo given once daily before hospital discharge then 28 days after	The number of days of hospitalization from randomization to discharge up to 48 weeks postmenstrual age (PMA)	800 (target)	16	2	3 (0,3,0)
Use of NIRS to Detect Acute Kidney Injury in Preterm Infants	Preterm infants <32 weeks old who had an application of Near- infrared spectroscopy by 48 h of age	Application of regional NIRS sensors to brain and kidney sites in the first 48 h after birth to monitor regional tissue oxygenation for the first 7 days of age	Comparison of Renal saturation (Rsat) in neonates with AKI to those without AKI. RS02 will be recorded until 7 days of age. Median RS02 for 1 week and median for individual days 2–7 will be calculated	35 (actual)	1	1	4 (4,0,0)
Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia	Preterm infants with EGA of <29 weeks that are receiving positive airway pressure or mechanical ventilation and who were randomized between 7–29 days PMA	Cohort 1 sildenafil dose will be 0.125 mg/kg q 8 h IV or 0.25 mg/kg q 8 h enteral. Cohort 2 sildenafil dose will be 0.5 mg/kg q 8 h IV or 1.0 mg/kg q 8 h enteral. Cohort 3 sildenafil dose will be 1 mg/kg q 8 h IV or 2 mg/kg q 8 h enteral	Safety as determined by adverse event experienced by participants within 42 days following initial study-specific procedure	120 (target)	17	1	1 (1,0,0)

^aFor each study we present the total N parents interviewed and in parenthesis the number each who (1) enrolled in target study; (2) declined target study; or (3) consented to participate in target study but did not join because infant was no longer eligible at birth.

^b“Evolving medical complexity” was defined as having any of the following: gestational age <26 weeks; serious anomaly (e.g., brain malformation, diaphragmatic hernia, spina bifida); symptomatic genetic condition; neonatal encephalopathy with expected impairment; chronic medical technology (e.g., gastrostomy tube, ventriculoperitoneal shunt, tracheostomy).

Parental views on the clinical team’s role in recruitment for neonatal research are reported first, followed by parents’ reflections on interactions with the research team. Parental experiences and preferences were inexorably bound to their own and their infant’s conditions at the time of recruitment. Therefore, we end by sharing parents’ reflections on how this context during recruitment influenced their experience and preferences. Although we share differences in themes by enrollment status (NICU study enrollees vs. decliners) and demographics (race, Ethnicity, and SES), this qualitative study was not designed to identify between-group differences: we report them as potential areas for future investigation.

Clinical team’s role in research recruitment

Many parents shared preferences regarding who should inform them about their infant’s eligibility for research (Table 3). Most indicated they would like to initially hear about eligibility from the clinical team but wanted to hear the details of participation from the research team. This view was universal among those who declined the target study and the majority of those who enrolled. This preference was not their experience as most learned about eligibility from the research team.

Table 3.

Clinical team’s role in recruitment for research.

Factor	Exemplar quotes and parent enrollment status and race/Ethnicity
Eligibility
Preference to hear from clinical team	I think it’s great that the first [information about research] comes from the person who’s taking care of the baby, someone that the parents already know, like for example a nurse or a doctor.
Would have been more receptive if heard from clinical team	I know I would’ve responded 100 times better and been way more open if [information about research] had [come from] one of the nurses that was taking care of the girls.
Research details
Clinical team input as having weight	I would say the doctor, the Neonatologist. Obviously, they’re not going to recommend a study, if it’s not appropriate. A doctor probably could tell me what his other patients did during the study, or say [the child] is appropriate for a study; I figured he is, but probably just more reassurance, ‘It’s not going to do any harm to him.’
Clinical team as less knowledgeable	If the Research Team for [the study] would’ve approached me instead of the nurse, it would have been totally better, they could’ve explained it a lot more.
Clinical team might feel coercive	Having <Child’s> doctor talk to me, that seems more coercive. It just feels like they [researcher and clinician] are all on one team together and I’m by myself. They all want me to do a study that will benefit the institution versus me, I’m a patient all by myself.
Guidance on participation
Encouragement	I remember <Doctor> being by the bedside and notifying all the physicians, ‘Guys, it’s a big study. I think it would be good.’ So, a little bit of her knowledge, leaning on <Doctor>, was a great influence.
Recommendation against participation	I asked the doctor a couple of questions and they were like ‘Well given what he’s going through right now, we might not want to do that at this time.’
Wish they would have gotten more input from medical team	Maybe a doctor’s input on it as well might’ve helped just a little bit. Hearing it from a doctor’s mouth and then having the NICU doctor also affirm, ‘This is really a great opportunity,’ might’ve impacted how we went.
Wanting better integration between research and clinical teams	I guess I would really like it to be more hand-in-hand with the experience at the hospital. So just have [research] be part of what we go through... that way it’s not two separate things, ‘cause we pay less attention to stuff that’s not related to our medical treatment... I guess it would help me really understand the importance of it, if it went hand-in-hand with what the doctors were doing."

When asked about clinical team involvement in recruitment for research, parents’ responses varied from positive (e.g., positive experiences with clinical team, views clinical team involvement as positive, or prefers clinical team involvement), to neutral (e.g., clinical team wasn’t involved but family doesn’t care), to negative (e.g., clinical team involvement felt to be coercive).

Similarly, both positive and negative dimensions emerged related to the proper role of the clinical team in supporting a parent’s decision whether to participate in neonatal research. Many parents shared a desire for more clinical team participation, as clinicians best understand an infant’s medical condition. Parents shared that clinician involvement may serve to dispel concerns about the risks of research to their infant. These positive dimensions were mostly reported by parents who identified as non-Hispanic White and who enrolled in the target study. Others reported clinical team involvement as neutral or negative toward research participation. Some of these parents shared they wished they had received more input from their physician—a sentiment that was more common among parents who declined the target study. Finally, some parents discussed a desire for better integration between research and clinical teams.

Interactions with research team members

Three themes emerged related to interactions with the research team: (1) interpersonal relationship with research team members; (2) timing of learning about research details; and (3) information disclosed by the research team (Table 4).

Table 4.

Interactions with research team members.

Factor	Exemplar quotes and parent enrollment status and race/Ethnicity
Interpersonal
Research team as most informed	the Research Team... they knew the most about it,they’re the ones doing the study. I think they went about it in a very good way and a very professional way. [The researcher] was very educated [about the research] and it showed, and that makes people in our situation (parents) feel secure and feel good about the care that their child’s receiving.
Research team as friendly	They were very respectful. They approached us cautiously. They were not overbearing. They just kind of put that out there, and they were very friendly... I mean, overall, it was a good encounter.
Research team as not pushy	I feel like the NICU is such an emotional and draining place for a parent, if I had somebody who was pressuring me to do something, on top of what we were already going through, I think it would just be an immediate no from us.
Not kind	If they have a bad attitude at the time they’re trying to come [ask me to participate in research], that’s something that makes me iffy about medical researchers.
Pushy	I was in the shower. The [researcher] knock on the door of my bathroom, ‘we’re making sure you said no [to the study].’ So, my whole experience with them... they’re trying to throw this thing down my throat.
Uninformed about baby	Really just knowing her [the child’s] history is a big one to me. If they know her background it shows me that they took into consideration the whole picture of her health.
Timing of learning about research
Approached too soon	I know it needed to be within a certain amount of time, but just telling us the very first day he was born was kind of overwhelming. By the second day, it was okay, ready to talk about it.
Approached while busy with other tasks	It was over the phone... I was at the grocery store. I think studies are great and everything else, but it just wasn’t the right time.
Approached during bonding with child	So I think, looking back, something that would’ve helped is maybe if they had tried to approach me before I was in the middle of trying to see my [NICU twins] kids for the day and spend time with them... just not when I was with my girls. I didn’t want to be approached about something like that while I was with my kids.
Challenges of finding right time	It is a good time to approach as long as their child is actually at a calm period... not in the time that they’re doing surgery or in the middle of doing something drastic, or doing skin-to-skin, [or] breastfeeding... I guess you could say the non-intrusive times. So I don’t know if it’s a right time, or a wrong time. It can’t really be a right time or a wrong time to ask a NICU parent about something like that.

Parents shared thoughts about how the interpersonal relationship with research team member(s) impacted their experience learning about the research study, including both positive and negative experiences. Positive interpersonal perceptions included that research team member was well-informed and therefore best positioned to discuss research specifics, and research team member was described as friendly, kind, professional, accommodating, and not pushy. These themes did not differ by parental demographics. Enrollees in the target study more commonly shared that the research team member was friendly and kind. While less frequently discussed, negative interpersonal perceptions included: research team member was pushy or aggressive, lacked knowledge of infant’s clinical status, or was not thoughtful, kind, or respectful. These negative perceptions were more commonly shared by parents who declined the target study and those from minoritized groups.

Many parents, mostly those who declined the target study, shared that the timing of being invited to participate in research heavily colored their experience and ultimate enrollment decision. Parents varied widely from being approached prenatally, soon after birth, within the infant’s first week of life, or at a more distant time during their NICU stay. Several shared that they were approached too soon for research. Others, mostly those from minoritized racial or ethnic groups, acknowledged that there may be no good time to approach parents. Several shared the importance of research staff finding a calm, non-intrusive time and reading the room after entering.

Several parents shared their experiences related to information disclosure from research team members. Most of them reported positive experiences related to research information, including comprehensiveness, answers to questions, and quality of written material. These positive responses were more commonly reported by those who enrolled in the target study and by those from minoritized racial or ethnic groups. Conversely, some parents reported negative experiences related to research information sharing, including suboptimal comprehension, lengthy written material, or researchers using jargon making the study difficult to understand. These negative responses did not vary by parent demographics but were more common among those who declined.

Parent condition at the time of recruitment

Parents shared that their own physical, mental, and emotional condition when approached for research deeply influenced their recruitment experience and enrollment decision (Table 5). Many brought up that they or their partner was recovering from childbirth or otherwise not in the best physical condition. Poor physical state was more frequently mentioned by those who declined. Others shared that their emotional state at the time of recruitment impacted their enrollment decision, describing feelings of being traumatized by the NICU stay, stress, anxiety, being overwhelmed, and a lack of ability to think clearly. Further, some parents, mostly those who declined, shared that learning about research itself triggered negative emotional responses such as anger, annoyance, frustration, and fear.

Table 5.

Parent and infant condition at the time of recruitment.

Factor	Exemplar quotes and parent enrollment status and race/Ethnicity
Parent physical state	I don’t think they could have done anything, it was just the circumstances... if my wife was better at that time, we would have made a different decision. I just remember being very tired and very overwhelmed. ...lots of people are coming by to check on you all the time and not letting you sleep.... things had already been kind of traumatic with having the urgent C-section and I was in a lot of pain.
Parent emotional state	I just had a baby, was hormonal, an emotional wreck, so I just wasn’t taking in things, unless it was going to make a difference one way or another.
Parent felt angry	I remember the first time we were approached for a study, I was like What is happening? Seriously, you’re going to ask me to do something?’ ‘This is the last thing I need to do right now.’
Parent felt scared	It scared me a little bit. ‘Do I really want to put my kid through this?’. all the side effects just scared me. I remember it could affect her a lot worse than the condition she was in before.
Parent felt good, special	It actually made me feel kind of special to know that I was asked to be part of a study. ‘Wow. They want me to help, be a part of something?’
Infant sick and parents not well informed by clinical team	I was like ‘Nah. I’m okay, because I don’t really know what’s going on with her.’ It was such an unknown at the time.... we didn’t know what her health was. We didn’t know if she was alive, basically... at the time we were asked, we didn’t know anything about her health status. It was just a whole spectrum of really not knowing anything that was going to happen with him or that kind of thing, how bad it was going to be. I thought something happened to him, or something was happening to him. I’m like ‘Why do these people want to do research? What research do they want to do? Do they want to experiment on my child? What is going on?’ So my mind was racing a lot.
Infant sick paired with hope for benefit from study participation	Well we were just of the mindset like that anything that could potentially help her, we were gonna do it. We were basically just you know throwing it all at the wall and seeing what stuck.
Infant improving, doing well, or stable	Obviously had he been really sick, I probably would not have had the energy or the time to think about any research... [but with] things being so good for him, it makes it easier for me to focus on other things as well. So her health was stable. Still getting respiratory support and nutrition support, but overall stable.... I think [this stability] probably persuaded me to join the study It depends on how the baby is doing. That’s what really guides you. If my baby’s having a horrible week, I’m not gonna be let him participate in research, ‘cause I’m worried about the baby.
Infant too tiny, too fragile	‘This girl is too small. She’s three days on. She’s in the NICU. I’m not trying to add anything else.’ I think that was the only worry, ‘cause you’re dealing with a newborn baby, a fragile, little creature. I just think my automatic, my brain just went and said ‘No. I don’t want to experiment with a life that’s already not. might not make it.’ I feel like it’s one thing to do research when you’re healthy, but (I don’t know) once you’re so fragile. She was 4 pounds. No.

Infant condition at the time of recruitment

We asked about how parental perception of their infant’s clinical status might have impacted their enrollment decision, from which several themes emerged (Table 5). First was the perception that their infant was very sick and they were not well informed by the clinical team about their infant’s condition. This was often accompanied by feelings of uncertainty about outcomes, including whether the child would survive. These types of responses were more common among parents from minoritized racial and ethnic groups and those who declined. Second, a few parents, most of whom enrolled in the target study, linked their infant’s high severity of illness to a hope for direct benefit from study participation. Third, many parents shared that an improving clinical status or their infant being stable made them more likely to participate. This was more common among White parents and those who enrolled in the target study. Fourth, some parents, mostly those who declined the target study, brought up issues around the fragility of their infant, including being too small, fragile, young, or otherwise not in the proper condition for research participation.

DISCUSSION

The results from our interviews lend insights into parents’ experiences and preferences for learning about neonatal research. The overarching themes identified are important because of the diversity of our participants across race/ethnicity and enrollment status.

Roles of research and clinical teams

Our findings suggest a nuanced desire for integration of research and clinical teams but with each of them playing different roles in the process. Generally, parents wanted to learn about research eligibility from their clinical team and learn the details of participation from the research team. The latter is standard practice: research teams are tasked to provide information about research participation. The former may be a key area for improvement as clinical teams frequently play no role at all. We found that parents wanted the clinical team to have some degree of baseline knowledge about the research proposed so they could help determine whether it was a good option for their child. This desire was more common among parents who declined—again stressing the importance of clinical team participation as a key item of interest for future study. These findings are consistent with a growing body of work suggesting that parents not only want increased clinical team involvement in recruitment [18], but may be more likely to enroll when this occurs [36]. Parents have reported their child’s pediatrician’s involvement in [37, 38] or support of [39] a study as a reason to participate.

Parents want to feel research and clinical teams are on the same page and in communication with one another. While regulators have traditionally wanted to keep research separate from clinical care as a way to avoid undue pressures to participate, there is a growing appreciation that voluntariness is a complex phenomenon interacting in nuanced ways with relationships between patients, surrogates, clinicians, and researchers [40]. The learning healthcare system model suggests full integration of clinical care, quality improvement, and research [41]. Future work must evaluate ways to bring clinicians, including physicians and other members of clinical teams, into the recruitment process in a way that is responsive to preferences of potential participants in pediatric research.

Key role of interpersonal relationships with research staff

The interpersonal relationship with research staff was a key contributor to the parental experience. This is consistent with recent interviews of research staff, who also highlighted the importance of relationship building, even for very brief relationships [33]. Parental reports of a positive relationship with the research team was associated with parents choosing to participate in studies within anesthesia and surgery [42], nephrology [43], neonatology [18], and for a vaccine study [44]. How the research team chooses to approach parents (e.g., finding the best time to bring up research, being able to read the room and come back later as needed) was a critical theme. In an interview study of parents approached for pediatric intensive care research, timing of approach by the research team emerged as a key factor influencing enrollment decision [45]. Such findings may emphasize the importance of training research staff to decide whether to enter the room, how to prepare, and use of a script. A fitting analogy may be with medical trainees related to bedside manner, non-verbal communication, and physically sitting down to discuss care.

Parent emotional state at time of recruitment

Heightened parental emotional and physical state at the time of recruitment heavily influenced parental experience of being asked to participate in neonatal research and impacted their ultimate enrollment decision. Negatively valanced emotions such as anger, fear, and stress were often present. These feelings may make reassuring families (e.g., by providing information about the intensive scientific review process, organizational oversight approval, and/or safety data) and adequately conveying the incremental risk of study participation more difficult [46].

The importance of emotional status in enrollment decisions has been previously reported. In a series of survey studies of parents asked to enroll in clinical anesthesia or surgery research, those who declined participation reported feeling more anxious than those who enrolled [42, 47]. Most parents who declined participation in an observational PICU study reported stress as a contributor to their decision [48]. Increased parental anxiety, as assessed by the impression of the individual obtaining consent, was associated with a lower likelihood of participation in the same study [48]. Parents who declined an observational NICU study cited tiredness, sleep deprivation, and stress as reasons for not participating [49]. “Shock” was a reason for not participating among parents recruited for a large multi-national European neonatal RCT [50].

Concern around birth mother’s physical state and feelings of anger, annoyance, and frustration were more commonly reported by those who declined the target study. These are likely key considerations for future work aiming to improve the recruitment experience for families as well as optimizing enrollment rates. Deferring approach of families in the NICU is frequently not possible and therefore examining how to better partner with families actively experiencing anger, fear, sleeplessness, and stress is warranted. Dickert et al. proposed the creation of new models of consent processes that better meet patients’ and surrogates’ needs within trials for acute myocardial infarction and stroke [51]. Rather than try to avoid these states, future research must endeavor to better engage with parents in such circumstances [52].

Parent perception of infant’s condition

Parental perceptions that their infant was sick and the clinical team was not providing the necessary information were most common among families from minoritize racial and ethnic groups and those who declined the target study. This raises two distinct but interrelated issues. First, perception of illness impacts enrollment decision-making in complex ways. Some parents may be more willing to enroll in neonatal research if they believe their infant is gravely ill [53, 54]. For example, parents who enrolled their infant in an RCT for neonatal encephalopathy reported their infant’s medical condition as more serious than those who declined [12]. Conversely, others have found that some parents decline research because of a perception that their infant was too sick to be part of research [55, 56]. Second, relationships with the clinical team set the stage for the research recruitment encounter. French parents reported that a positive trusting relationship with their clinical team was a major reason to consent [22]. Australian parents cited trust in the hospital as a reason to participate [57]. Parents approached to enroll their child in a clinical oncology or HIV study reported that poor confidence in their physicians made the enrollment decision more difficult [58].

Our findings underscore the importance of potential participants feeling adequately supported by their clinical team, suggesting that potential interventions to improve parental experience of recruitment and optimize enrollment rates must start further upstream in the process. These issues should be major targets for future research to improve the experience for marginalized populations and decrease disparities in research participation.

Consideration of alternative methods of consent

Challenges created by these realities at the time of consent discussions for neonatal research may suggest that alternatives to standard processes should be considered. Thoughtful deliberation with community advisory boards may decrease the role for standard consent discussions [59], particular during high-stress times such as immediately after the birth of an ill neonate. There is no consensus regarding appropriate consent requirements or processes in settings that merge components of research and clinical care [60], such as with the learning healthcare system [61] and for comparative effectiveness and pragmatic clinical trials [46, 62, 63]. Future work must evaluate whether judicious use of alternative approaches to consent within neonatal clinical trials may improve the processes of informed consent while also supporting parents’ needs.

Limitations.

Although we succeeded in including both those who participated and those who declined neonatal research, our sample may be biased limiting generalizability in two ways. First, parents who agreed to be referred to our team may differ from those who chose not to be referred to our team. Second, among those referred, those whom we were able to contact and agreed to participate in interviews may differ from those who did not. Our interviews were only conducted in English; parents without spoken English proficiency may have views that we were unable to capture.

CONCLUSION

The preferred roles of clinical and research teams in the recruitment process and the importance of researchers appreciating the often-challenging parent and infant conditions at the time of recruitment are important considerations in developing approaches to improve the parental experience during research recruitment. These findings can help inform clinical trialists, regulators, and funders attempting to improve recruitment processes for neonatal clinical trials.

DATA AVAILABILITY

Data that support the findings of this study are available on request from the corresponding author (EMW). The data are not publicly available due to restrictions on information that could compromise the privacy of research participants. Depending on the nature of the request, approval from the Seattle Children’s Hospital IRB may be required.