Newborn subjects, vulnerable families
IRBs’ challenge: Truly informed consent
They’re among the most vulnerable research subjects — newborn babies, born with problems, spending the first days of their lives in neonatal intensive care units.
Their parents are vulnerable, too. After sometimes traumatic deliveries, mothers are exhausted, and perhaps on medication. Fathers are frantic with worry about both mother and baby.
Some question whether it’s even possible to get true informed consent for research under those circumstances.
Recent studies bear out the fact that the stress of making decisions for a newborn can impair parents’ abilities to understand and remember what they’re agreeing to. A study last year indicated that a substantial percentage of parents who had agreed to allow their children to be part of one neonatal research project didn’t fully understand the study. Some didn’t even remember allowing their child to be enrolled.
"We know the literature tells us that parents are very unlikely to be able to make a true informed consent at all," says Lisa Golec, RTT, BSc, MHSM, clinical research coordinator for the NICU at Sunny-brook and Women’s College Health Centre in Toronto. "But we also know that we need to do research. Research is how we provide the care that we can provide for these babies. Research is what has given us the technologies and therapeutics to provide the exceptional care that we can to the point that we are saving 24-weekers."
The challenge, for investigators and in turn, for IRBs, is to figure out ways to do the most necessary neonatal research while providing sufficient safeguards to tiny patients and maximizing their parents’ ability to understand and consent.
Golec and others involved in neonatal research say that’s possible through a combination of respect for traumatized families, seeking input from the entire care giving team, a truly comprehensible informed consent document and frequent checks to ensure that parents understand the research and still agree to it.
Parents don’t remember details of study
The study, published last year in the Journal of Perinatology, looked at newborns in the NICU at the University of Kentucky Medical Center in Lexington who had been enrolled in the NEOPAIN study, a multicenter trial that evaluated the effects of morphine infusions in newborns who were on mechanical ventilation.1
Researchers surveyed parents who had signed consent forms, and whose children had survived to discharge. Parents were asked about their memories of the informed consent process, as well as their understanding of the NEOPAIN study itself.
Five of the 64 parents contacted (7.8%) had no memory of the study or of signing a consent form. Of the remaining parents, 40 (68%) recalled the purpose of the study. Most parents (95%) who knew the purpose of the NEOPAIN study could describe its possible benefits, but only two (5%) remembered any potential risks.2
A total of 14 parents (37.5%) didn’t know they had the right to withdraw their child from the study at any time.
Those results don’t surprise Golec.
"Happens all the time," she says. "[Parents are] getting pummeled with information, they’re getting to know the unit, they’re seeing all this equipment they’ve never seen before. They’re trying to digest all this and they’re recovering and they’re exhausted and they’re emotionally fraught. Who can remember everything they’re given?"
Mothers have been through labor, in some cases, labor with serious complications, and often are receiving pain medications or magnesium sulfate, which is often used for toxemia. Even without medication, new mothers often are subject to short-term memory loss, says Lori Shook, MD, a neonatologist at the University of Kentucky Medical Center who co-authored the study surveying parents of NEOPAIN babies.
"They may be answering you, they may be signing things; and 10 minutes later, they may have no idea what you’re talking about," Shook says. "That’s something you really have to be on the lookout for as a researcher and from the IRB perspective."
A model for protecting families
Fathers are contending with their own anxieties regarding the health of the mother and the baby. A surprising finding in the University of Kentucky study was that despite medications, mothers generally remembered the details of the study in which their babies were enrolled better than fathers did, Shook says.2
"Our hypothesis was that the dads would probably be better to approach for this type of thing in that situation, but they really aren’t," she says. "We actually had a father who was a physician give consent. And he swore up and down he knew everything about it, and he got every answer wrong."
Time often is a crucial, complicating factor in neonatal research requiring that parents be approached only hours after their baby is born, at a time when they’re just dealing with the shock of having a sick baby and are least able to process the information.
Shook says one current study being conducted in the NICU at her institution requires that babies be enrolled and on the study drug by 12 hours after beginning ventilation.
And Golec notes that because the research population in question is so small, families often are approached multiple times in the first several days of life to inquire about enrolling their child in various studies.
So how do IRBs balance the urgent need for neonatal research with the real vulnerabilities of both the babies and the parents who must make decisions for them?
Golec has proposed an optimal model for research recruitment in the NICU, based on many of the practices in place at her institution. Among her suggestions for IRBs considering research in the NICU:
- Ask who will be approaching parents to gain consent. Golec says the chair of Sunnybrook’s research ethics board (REB, the Canadian version of an IRB) believes it to be a conflict of interest for a principal investigator to approach a family for research, and prefers that someone such as a research coordinator make the inquiry.
"In the NICU, it’s frequent that a PI would be an attending physician, so you can see where the conflict would come in," Golec says. "How likely are [the parents] to want to say no, knowing full well that you’re the attending and you’re taking care of their 24-weeker?"
- Ask for input from bedside staff. Golec says caregivers in the NICU are notoriously fiercely protective of the families and establish strong bonds of trust. As a clinical research coordinator, she often consults with them regarding which families are good candidates to approach, or regarding families who previously may have agreed to research but later seem not to understand it.
At Sunnybrook, bedside staff are involved in research projects from the beginning. They’re given the opportunity to review the proposal before submission to the REB, and to give their input. Golec says they often make suggestions that can lead to changes in the protocol.
"As a researcher, I may think I’ve thought out every possible nuance of the study, and then they’ll say, Don’t you think that’s a lot of blood to take?’ and the researcher will say You know, I never thought about that,’" she says. "As a researcher, you become so hyperfocused that sometimes you miss things and it’s always nice to have somebody who comes in who’s subjective."
The researcher also is required to do multiple inservice programs with the bedside staff just before enrollment in the study begins, so that the staff can answer families’ questions. This type of approach could lead to families better understanding the study, Golec notes.
- Require an informed consent process that gives families as much time as possible to deliberate. Parents need time to discuss the study with each other, and if possible with other family members, clergy or friends, Golec says.
"I think we need to look at the process of consent as being continuous in nature," she says. "It’s not just a single moment in time when you go and talk to somebody; it’s touching base with them again."
- Ensure informed consent documents are understandable. While this should be a requirement for all research, it’s especially important when asking consent of parents who are in a vulnerable state, Golec says.
"For parents of neonates, we know they don’t remember — they don’t remember participating in a study, they don’t remember saying yes," she says. "Would they be more likely to remember if they weren’t just scanning something that didn’t really make a lot of sense to them because the verbiage was so advanced?"
Golec says Toronto is a highly diverse city, so her health center’s NICU sees parents from varying cultural and educational backgrounds. Too often, she points out, the informed consent forms she sees are written too high an educational level and contain too much jargon.
Teenaged decision makers
Shook agrees, noting that many parents of premature infants are themselves only in their teens.
"Had they not just had a baby, they wouldn’t be able to really consent for themselves, and now suddenly because they’ve had a baby, they’re considered emancipated and able to do that," she says. "If you plan to include emancipated minors in a study, things have to be written well enough so that they can understand them. Are you really explaining them in a way that a 13-year-old can understand?"
Shook also suggests that parents can be approached to begin the consent process before labor, when they’re more likely to be able to understand what’s being said.
Researchers at her institution often check in with obstetricians to see if there are mothers admitted who are expected to go into labor soon with babies who have problems. The researcher may or may not attempt to get a signed consent form beforehand, but will talk with the parents to begin the process of informing them about the study.
At the University of Texas Health Science Center at Houston, the IRB employs another method that can be used to ensure better understanding of research in the NICU, reports Paula Knudson, the center’s special advisor for research involving human subjects.
A research intermediary, who is hired by the IRB and reports to it, can be assigned when the IRB approves a protocol that it believes requires special attention.
While the intermediary is not part of the initial consent process, she is notified as soon as someone from that protocol has signed a consent form, Knudson says.
"She immediately goes to talk with them, and she ascertains whether there is real comprehension about the study," she says. "It’s before the intervention begins, if we have that luxury, and it provides a liaison between the families and the research staff for questions that come up."
If the intermediary believes that the family doesn’t understand the study or wants to withdraw, she can make sure that happens, Knudson says. "It’s not something she does easily, but if they really feel differently about it, or feel obligated in some way to be part of the study, we make it possible for them to come out gracefully."
Knudson contends that because it’s so difficult to get true informed consent from parents of newborns, neonatologists should petition to be able to use a waiver of consent, similar to how it is used in emergency medicine.
"I think there are ways we could manage this," she says. "IRBs should assist neonatologists in petitioning for inclusion in this waiver of consent. But it has to come from the neonatologists. They have to say, There’s work we’re not able to do, and we need to do it in order to determine what really works for these babies.’"
1. Ballard H, Shook L, Desai N, et al. Neonatal research and the validity of informed consent obtained in the perinatal period. J Perinatol 2004; 24(7):409-15.
2. Golec L, Gibbins S, Dunn M, et al. Informed consent in the NICU setting: An ethically optimal model for research solicitation. J Perinatol 2004; 24(12):783-91.