Chaos, vulnerability and control: parental beliefs about neonatal clinical trials

Abstract

Objective

This study examined parental beliefs about participating in clinical trials involving greater than minimal risk to their neonate, and explored their views of their experiences.

Study Design

In this qualitative descriptive study, parents in the neonatal intensive care unit (NICU) who had been approached for permission for their neonates to be enrolled in research were asked to describe their decisions about their consent for or disagreement to their neonate’s research participation. A total of 27 parents from three different hospital NICUs in the Mid-Atlantic region of the United States participated. Transcribed interviews were analyzed using qualitative content analysis.

Results

Participant decisions developed through a dynamic process of meaning-making based on their beliefs about themselves and their neonates. The processes involved making sense of the chaos that they perceived in the environment and their own vulnerability, through taking control of their situation.

Introduction

Treatment in the neonatal intensive care unit (NICU) is increasingly driven by research protocols, yet despite growing consideration of the viewpoints of families involved in neonatal research, few investigations have looked at family experiences. Further, most studies of parents’ perceptions of neonatal research have been conducted in countries other than the United States. In Canadian studies of parents’ consent for their neonate’s research enrollment, sociodemographic attributes, attitudes toward research, perceived illness severity, perceptions of risks and benefits of research and trust in the physician were found to be significant predictors of consent.^1–3 European researchers have investigated parents’ understanding of clinical trial randomization procedures and informed consent.^4–6 Results of these studies revealed substantial numbers of parents who had difficulties with the informed consent process (competence, understanding and voluntariness) and a poor understanding of randomization procedures.

The traditional way for understanding choice about research enrollment, with its moral thrust on informed consent and autonomous decision-making, needs further development. Parents of critically ill neonates participating in research attempt to understand their child’s research protocols along with their infant’s illness, and to make sense of their experiences through their interactions with other family members and health-care providers.

A relatively small number of studies have examined parental beliefs about neonatal research. Researchers disagree about the factors that influence parents’ decisions to enroll their neonates in clinical trials. While sociodemographic attributes, including ethnicity, education and income, are believed to correlate with decision-making regarding research participation, studies to date have drawn dissimilar conclusions.^2,3 Nevertheless, the examinations of parents’ perceptions of neonatal research present an incomplete account because that research has been carried out primarily in countries with health systems and histories unlike those in the United States, and has been carried out using classic decision models for conceptual understandings.

Methods

One purpose of this study was to obtain parental reflections about research decisions made for their neonates. Consistent with this purpose, a qualitative descriptive design was used to answer the study questions. Qualitative description is a form of naturalistic inquiry that relies on straight description to stay close to the data, and allows presentation of the information in accessible language.⁷

For this qualitative descriptive study, parents in the NICU who had been approached for permission to enroll their neonates in research were asked to describe their decisions about their consent for or disagreement to their neonate’s research participation. Those parents who had enrolled their child in a research study with greater than minimal risk with prospect of direct benefit to the neonate were asked to recount their beliefs about and experiences with their neonate’s research participation. Neonatal research involving greater than minimal risk evokes additional issues (for example, increased risk for harm) for parents making decisions about their sick newborns when compared with decisions made about minimal risk research. In addition, by examining the entire process of their neonate’s research participation rather than focusing on a specific component (for example, validity of parental permission or understanding of randomization), a more nuanced and comprehensive view of parental perception was obtained.

Settings

Three hospitals in the Mid-Atlantic region of the United States were used as sites for the investigation. These NICUs had from 40 to 75 beds, and all had researchers active in clinical trials investigating various therapeutic options. After gaining IRB approval, parents were recruited through mass mailings to families of all discharged NICU neonates (unknown response rate), targeted mailings to parents asked to participate in neonatal research (21% response rate) and General Clinical Research Center (GCRC) nurse facilitation. Face-to-face recruitment by GCRC nurses yielded a 100% response rate. A few of the families approached by the GCRC nurses had refused or withdrawn from neonatal research, so tendency to participate in research did not appear to be a significant factor in consenting to this study.

Participants

Purposeful sampling based on diverse demographics and potential research protocols for children was used to interview a total of 27 parents. Participants who were custodial mothers or fathers who had been asked to enroll, within the previous 6 months, their infant in a clinical trial involving more than minimal risk to the neonate were invited to participate. The infant had to have been discharged to the parent’s care. Families who were unable to speak or understand English, and families whose neonate had died or had not been discharged home were excluded.

While the majority interviewed was parents of prematurely born children, participants also included five parents of children diagnosed prenatally with birth defects and one parent of a child experiencing distress in the neonatal period necessitating admission to the NICU. Neonatal studies included fetal interventions for relief of specific birth defects and research with various respiratory treatment modalities. These participants were well educated, with 9 having completed high school, 7 having completed a college education and 11 having completed graduate school. Interviews were with 20 females—13 White, 6 Black and 1 of more than 1 race, all Non-Hispanic—and with 7 men—6 White, non-Hispanic, and 1 White, Hispanic.

Data collection

The primary method of data collection was interviews with individual participants. The great majority of the interviews (82%) took place over the telephone, based on participant preference. With parents’ knowledge and consent, the interviews were audiotaped using a digital recorder. The author compared interviews done by telephone and those done in person and found no differences in the degree of response consideration and thoughtfulness. An interview guide was used to ensure that the same line of inquiry was assumed with each participant. The interview guide was constructed based on the literature and was augmented with questions about the context of parental decisions and experiences. The interview guide evolved on the basis of emerging data analyses. Data collection stopped when interviews yielded minimal new information to expand the findings.

Data analysis

All interviews were transcribed verbatim with paralinguistic communication included (for example, sighs, response latency, crying).⁸ Interview transcripts were reviewed with the tapes to ensure accuracy. During initial data analysis, codes obtained from the data were combined to form coding categories. These categories and subsequent themes were developed using content analysis, the recommended strategy used in qualitative descriptive analysis.⁷ Using qualitative content analysis and examining such things as repetitions, metaphors, and analogies, similarities and differences, themes were developed from the data in the texts.¹⁰ Examination of manifest data enabled discovery of latent data and later theme identification.⁹

Scientific adequacy

Scientific adequacy was addressed through efforts directed at establishing trustworthiness with data and analyses.¹¹ Credibility was increased through ‘peer debriefings’ with colleagues and through confirmation of initial perceptions from participants at the close of sessions. Transferability was enhanced through purposeful sampling with parents who had declined or consented to their neonate’s participation in clinical trials. Audit trails of documentation and reflexive journals were established to increase dependability and confirmability,¹² and these were facilitated by the use of Atlas/ti (Scientific Software Development).

Results

Data were gathered from 27 participants through in-depth, semistructured interviews. All participant names used here are pseudonyms. The themes that emerged from the analysis are organized in three broad categories (1) chaos, (2) vulnerability and (3) control.

Chaos

All of the participants spoke to their feelings of confusion, desperation and helplessness at the time of neonatal research decision. The chaos involved feelings of both fear and confusion. All parents expressed immediate concern for their child’s survival, coupled with doubt and disorientation, similar to findings of other research with parents of preterm newborns.^13–17 Their confusion was articulated by the parents or discerned through their misunderstandings about the research protocols in which they had been asked to enroll their children.

All the parents in this study who were asked to enroll their children in moderate-risk studies were asked about neonatal research enrollment when their child was still critically ill or soon after a prenatal diagnosis of great concern. For some parents, their child’s survival was by no means secure. One salient finding was that the parents of prematurely born children did not separate their experiences of research from their experiences of their child’s hospitalization. Steven, father of a prematurely born child, said, ‘How can you separate the medical experience from… the study… and that’s so important because it blurs together, it certainly blurs together.’

Codes and subcategories in the data yielded ‘concern for survival’ and ‘confusion’ within the chaos theme. The category, ‘concern for survival,’ reflects the parents’ overwhelming fear that their children would not live. Their constant dread, which was so pervasive in the beginning of the NICU stay, colored their perceptions of the decisions that had to be made for their children. Tina, the mother of a prematurely born child, explained the lack of boundaries between research and standard care in the NICU with stark imagery: ‘So like her whole birth and trying to survive was kind of like a study itself.’ When parents had not contemplated anything but a traditional birth, and then they were exposed to an environment so out of their ken, it is not surprising that a research proposal did not strike them as more unusual than what they were already experiencing. Tina elaborated further on her beliefs about the research protocol in which she had enrolled her daughter: ‘They didn’t know how much time she had to live so they tried to do everything as fast as they could… I was trying to do anything for her.’ Shannon, the mother of a prematurely born son concurred, ‘He was very, very sick, and I mean at the time, it (research decision) was like the least of my troubles. I was just like, whatever you want to do, fine.’ This fear of the child’s death, coupled with an atmosphere of uncertainty and time pressure engendered feelings of turmoil in nearly all of the parents.

Two mothers were surprised by their child’s initial survival. These mothers had been told to expect their child’s death before or soon after birth. Amy, the mother of growth-discordant twins was informed repeatedly during prenatal checkups to prepare for the fetal demise of the smaller twin. Lisa, who had previously suffered a late pregnancy loss and was now the mother of a prematurely born child, was told in the minutes before the delivery that her daughter had a ‘fifty-fifty shot of getting out of the delivery room.’ Both of these mothers refused moderate-risk studies with their children. Amy thought her daughter had already ‘gone through way too much as it was,’ and Lisa was ‘just happy (her daughter) was alive… and wasn’t tempting fate.’ While concern for children’s survival may impact parents’ choices about research enrollment, fear does not necessarily lead to affirmative enrollment, as these mothers demonstrate.

Confusion was another component of chaos. Parents often articulated bewilderment about the research protocols in which they were asked to enroll their children. They spoke about their need to quickly learn about their child’s diagnosis and prognosis while attempting to navigate the NICU and understand proposed research. Parents’ concerns for their children’s survival and the foreign surroundings of the NICU understandably contributed to the parents’ confusion about research, and it is not surprising that the hospitalization of a sick child became blurred with the research protocol. Confusion for a few parents came with misunderstandings about the entirety of the research. Pamela, a mother asked to enroll her prematurely born child in a moderate-risk study, said, ‘I did not know, or maybe I didn’t hear her say it was a study. And I actually signed while she talked real fast and then left. And I remember thinking, wait, what are we doing now?’

Vulnerability

Vulnerability was the second theme that emerged in this the study. The parents voiced perceptions of their own vulnerability, acknowledged other parents’ susceptibility, and showed vulnerability through their misunderstandings of their children’s research protocols. Brian, a father whose child participated in moderate-risk research, noted, ‘My mind was a little bit screwy the whole time he was there.’ Thomas, another father of a child who participated in neonatal research, observed that he often ‘nodd(ed) his head without really understanding’ the research.

All of the parents stated that they enrolled their children in clinical research to help them. Steven said, ‘I feel that it’s the only reason my son is alive… and there wasn’t any other choice.’ Sandra, the mother of prematurely born twins, pointed to parents’ vulnerability when their children are critically ill: ‘You’re in a situation where you’re like, ok, my baby is sick, and I want everything done… I was doing anything I can to help my children.’ The parents’ beliefs in the value of research enrollment for the prematurely born children were confirmed when they witnessed visible improvement in their children’s medical status. For example, some attributed positive changes in lung function and vital signs to the research protocols. This was despite the fact that the child might have been in a non-intervention control group.

The parents had varying perceptions of the risks in neonatal research. Parents identified the risks, discounted the risks or did not find them relevant to their situation. For example, parents of children diagnosed prenatally with birth defects recognized the possible risks verbalized by professionals and integrated them into their beliefs about whether to consent to a clinical trial. Two parents reported that these risks were emphasized repeatedly and influenced them to decline enrollment.

Some parents of neonates with other conditions either discounted the risks of research or did not believe them to be applicable to their own situation. Parents stated that they knew the neonatal research entailed risk to their children, but believed these research risks were insignificant when compared to their children’s poor health status. Cynthia, the mother of a prematurely born child, said, ‘They approached me about a research study, and all I heard was that… it could only help him… it would be for the well-being of my child… to give him a chance at life.’ This mother said that the only risk would have arisen if she had declined to enroll him.

When parents were asked how they would advise other parents making decisions about research, every one of these parents spoke about how important it is to weigh the risks and benefits of the research. However, despite their stated concerns about possible pain caused by the protocols, only parents contemplating enrollment in the fetal intervention protocol elaborated on risk potential. The concept of risk in the abstract was important to the parents of prematurely born children, but actual risk in their individual situation was not tangible for them.

Taking responsibility for a decision about research was felt by all to be a parental duty, yet it was difficult for many of them to do that. Parents spoke about their fears of making the wrong decision about neonatal research enrollment. Their concerns were assuaged, however, when the infants’ progress met parents’ expectations about research enrollment. When parents saw noticeable improvement in their children during or shortly after the research protocols were complete, they were able to state categorically that they had made the right decision. Only Laura and Thomas, the parents of a child in a study of surfactant, expressed lingering doubts about their daughter’s research enrollment. These parents questioned why their daughter still required home oxygen administration when it had been their understanding that the purpose of the study in which she was enrolled was to prevent long-term lung problems. Both said they ‘probably’ would make the same decision if asked to do so again, but they had reservations about the study since the outcome was not what they had expected.

Situational vulnerability for parents resulted from the circumstances of their child’s critical illness. Parents felt vulnerable because of the unfamiliar and frightening conditions in which they found themselves. Part of the vulnerability mentioned by some of the parents was their roles as parents in the NICU. Steven, a Caucasian man with a graduate school education, spoke of his perceptions about being the father of a premature infant, and how those perceptions may have colored his decision-making about research enrollment.

You’ve already… f___ up as a parent because you had this child early. That’s the big major thing that you’ve already messed up on. Second of all, as a kind of punitive measure for your inability to be a parent, you are now with your child in a hospital under observation.

Laura and Amy both referred to their children’s health-care providers as the children’s guardians as long as the infants were ‘on life support of any kind.’ Amy noted her difficulty in refusing a moderate-risk study for one of her daughters: ‘You don’t want to piss off the doctor.’ These mothers both recognized, however, that decisions made about research and treatment would affect the families because once the infants were discharged, the parents were the ones who had to live with the results of decisions made in the NICU.

Parents also recognized that other parents were susceptible to harm because of their life circumstances or their children’s illnesses. These parents commonly voiced unease about others’ potential lack of strength or resources to handle situations similar to their own. Sandra, for example, questioned whether someone without her medical background as a health professional would be comfortable withdrawing her child from a research protocol. Todd said that only people with great fortitude could handle the responsibility of caring for a child with birth defects or making research decisions on the child’s behalf.

Control

A third theme that emerged from the data was control. When parents recognized what little power they had over the circumstances of their child’s illness and the NICU environment, they attempted to exert control. The category ‘control of decision’ reflected parents’ understanding of their right to permit or decline their children’s research enrollment. Factors influencing this sense of control included the time parents believed they had to make a decision, gathering information and active participation.

One factor influencing parents’ perceived control over the decision about their children’s research participation was the time they believed they had to make a decision. When parents believed they were not being rushed into a decision, they felt less manipulated and were more likely to consider options and, in most instances, to enroll. Steven noted, ‘If you feel rushed, you feel that they’re trying to put something over on you.’ Todd, who considered research enrollment for his daughter diagnosed prenatally with birth defects, did not feel he had enough time for careful decision-making. He and his wife did not consent to enrollment because ‘they felt a little pressure and that added to us saying no, because we didn’t have more time to evaluate.’ Time perception was a relative concept and not an objective measure. There was no appreciable difference between the time this family had to make an enrollment choice and the time other parents had to decide on fetal surgery, and yet they perceived insufficient time to make an informed decision.

Another means by which parents gained control over the decision about research was by gathering information. All of the parents looked for corroboration of their understanding of the research. Being up front with the parents with information allowed them the sense of being in control of an otherwise uncontrollable situation. Sandra said that the researcher’s willingness to take the time to explain the study in the language that parents could understand overcomes the possible concern that the researcher might be trying to ‘flim-flam you… and practice on your baby.’ Knowledge about potential risks and benefits of research participation is thus not only a requirement of ethical research, but also a necessity for parents’ satisfaction in the process of decision-making.

A few parents, some of those who were offered prenatal research enrollment, found making the choice about neonatal research too much to assume. Todd, who refused to enroll his daughter in the study involving possible fetal interventions, said that trying to make the decision was ‘overwhelming and almost felt like we were playing God.’ Nonetheless, all the parents in the study exhibited control over their decisions, whether they perceived it or not, through refusing enrollment in research, withdrawal of their children from research or continued enrollment based on the parent’s interpretation of the child’s clinical progress.

Actively participating in the care of their children through research participation was one way that many parents gained control of the situation involving their critically ill child. Julie noted that when she and her husband learned about the research involving birth defects, for the first time since prenatal diagnosis they were able to be ‘in the driver’s seat… and do something to help our daughter… although we couldn’t change things, we were able to make decisions… (and) we didn’t have that helpless feeling.’ Cynthia, mother of a prematurely born child, compared passing up the prospect of possible therapeutic research with her child to parental negligence: ‘If your child started choking, would you just sit there and not do anything or would you try to help your child?’ Maria, mother of a prematurely born child, said she ‘felt empower(ed) that we were doing something good for our child.’ In this sense, research provided a way for some parents to take action influencing the health outcomes, (which they previously had seen no prospect of shaping), for their children.

One of the principal reasons for parents’ feelings of control was their perceived ability to help other parents faced with similar decisions. Lori, the mother of a prematurely born child, said that she had enrolled her son in a moderate-risk study primarily to help other children: ‘I didn’t know if he was going to make it. But I thought to myself, at least, you know, maybe through him I could help somebody else if he doesn’t…’.

Discussion

Parents’ descriptions of enrolling their neonates in clinical research are consistent with naturalistic decision making (NDM), a theoretical framework stating that decisions are influenced by personal circumstances and are made in changing contexts.¹⁸ Researchers have recognized that the classic decision-making models (for example, Janis and Mann’s conflict model of decision making), do not aid in understanding how decisions are made in actual situations. Decisions made by parents to enroll their neonates in research trials typify NDM since they are distinguished by ‘time pressure, uncertainty… high personal stakes and other complexities that characterize decision making in real world settings’.¹⁹ These decisions do not consist of distinct individual events or processes but are dynamic and include contextual understandings surrounding the decision process.²⁰ Much like Carol Gilligan has demonstrated in her work including In a Different Voice, moral decisions are made by individuals within an intricate network of interdependent relationships. Context and responsibility to specific others are crucial to decision making. Current work carried out by NDM researchers indicates that traditional means for understanding a person’s enrollment decision in research (for example, based on demographics of race, ethnicity or socioeconomic status), misses key elements in understanding decisions made about research. Namely, persons choose research enrollment based on demographic characteristics in addition to their understandings of the research environment and their individual perceptions of the situation. Parents’ perceptions developed through a dynamic process of meaning-making based on their beliefs about themselves and their neonates. The processes involved making sense of the chaos they perceived in the environment and their own vulnerability, through taking control of their situation.

The parents interviewed for this study belonged to a group for whom informed parental permission should have been most effective. The term ‘parental permission’ is often used in place of informed consent for pediatric research as only those persons with decisional capacity and legal empowerment can give their informed consent.²¹ In many instances, however, parents could not articulate significant aspects about the research protocols in which their children were enrolled nor did they express reservations about their confusion. The majority of the parents believed that the enrollment of their children in clinical research was for the specific purpose of helping the children, and they expressed satisfaction with their decisions. All parents who enrolled their children in moderate-risk research did so expressly to improve their children’s health outcomes. Although the thought of research risk was important to parents of prematurely born children in an abstract sense, the parents did not find the concept applicable to their own situation. Consequently, the parents were vulnerable to expectations that their children’s participation in research would ensure their children’s well being. Future research is needed to answer questions about whether the psychological health of the family is affected by parents’ choices about their children’s research participation.

Although many of the parents were confused about research and they acknowledged the stress surrounding their child’s NICU admission, these parents believed that they were capable of making responsible decisions. Most welcomed input from trusted professionals, but all thought decisions made about their child’s participation in research should remain within the parents’ purview. The parents did not want the health-care professionals to make these decisions for them. This finding echoes previous research with parents of children asked to participate in clinical research.^4,22 Ultimately, the beliefs that these parents expressed about making the right decisions for their child give credence to the view that the decision about research participation should remain with parents of the neonate.

As Zupancic et al.³ and Burgess et al.¹ found in their survey research, parents stressed the importance of examining the risks and benefits of potential research involving their children. This study, however, allowed for more comprehensive questioning about parents’ reasons for enrollment and found that although parents frequently articulated the words risk and benefit, they could not explain what those risks or benefits might be. When parents are asked about their reasons for declining or consenting to their child’s research, terms such as ‘risk/benefit’ may be easier to put into words than contextual elements of ‘NICU environment’ and ‘fear for child’s survival’ though these seem to have played a more significant role for parents in this study. Decision-making researchers note, for example, ‘The things we can most easily verbalize may not be the things we care most about. So, if forced to verbalize, we may distort the significance of easily verbalized dimensions of the decision’ (Schwartz B, 2006, personal communication).²³

In the study by Snowdon et al.⁶ many of the parents whose child received ECMO said that their child had been randomized to experimental care based on the child’s condition and needs. Similarly, in this study, parents of children involved in research of respiratory medications believed that their children had received the medication, even though the study was blinded, because their child was sick enough to warrant the intervention. These children may not, in fact, have received the study medication but the parents did not know this.

Most parents in the study said that they had decided about enrollment within an hour or less after first discussing the research with the investigator. Nearly all of these parents were subsequently advised by investigators to take more time to reach a final decision. These findings are similar to the results of a study by Snowdon et al,²⁴ who discovered that parents did not view swift decision-making as problematic. Parents made their decisions about research fairly rapidly, and although many would have appreciated more time, most parents perceived a great necessity to make a decision about research quickly. Although some may describe parents’ rapid decisions as worrisome, research in the field of decision-making supports the idea that their decisions were not made injudiciously.²⁵ NDM, unlike classic decision-making theory, is able to incorporate, (and embrace as relevant), factors such as emotion that impact decisions. If the parent of a critically ill child is concerned primarily or exclusively with the child’s survival, evaluating concepts such as risks or benefits of research may not be a priority; emotional, affective elements will take precedence with the consideration of the decision. Decision-making researchers have demonstrated that decisions based on emotion, affective features and hypervigilance, which are contextual elements present when parents are making decisions about clinical research, are not necessarily dysfunctional.^26–30

The primary implication for practice is to support parents’ attempts to make sense of their critically ill child’s research participation. Parents who disclosed their attempts at feigning understanding, especially early in their children’s hospitalization, needed health-care professionals to consistently reinforce the information given, with frequent discussions. The fact that parents relied primarily on what they were told rather than on what was in written consent forms speaks to the need for open communication with families, and a process to ensure that parents understand the research in which they enroll their children. Work by Penticuff and Arheart³¹ suggests that interventions such as ‘infant progress charts’ maintained by parents and care-planning meetings with parents and health-care professionals may improve NICU parents’ understanding of their children’s clinical progress. These types of interventions may also aid parents’ understandings of neonatal research.

This study had several limitations. Although attempts were made to obtain a diverse sample, the final sample was a well-educated group of parents. Nonetheless, parents who had graduate school education often expressed beliefs similar to those of parents with high school diplomas. The rate of refusals to response of initial recruiting efforts is unknown, but the consent rate with personal invitation by GCRC nurses was 100%. This finding suggests a way to recruit in future research to increase representation.

It is no surprise that mothers and fathers find the NICU a terrifying place to begin their parenting. Parents had worries for the survival of their newborn coupled with the overriding fear that they would make a decision about research that would negatively impact their child’s health. The parents interviewed for the study believed that they played active roles in ensuring their children’s health by giving the children an opportunity to participate in clinical research or by protecting them from possible research harms. Nonetheless, parents’ control over decisions made about their children’s research participation came through struggles with chaos and vulnerability.