Research Ethics
Research Involving Premature Infants: Timing Is Everything Leah R. Eisenberg, University of Arkansas for Medical Sciences Under what circumstances is it ethical to ask and allow parents to give permission for research on their newborn premature infant? Generally, parents can agree to enrollment in institutional review board (IRB)-approved clinical research as long as the infant is eligible for inclusion and the parents are willing and able to give permission. A high-quality permission process demands that the parents be provided with information about their child’s condition, why the infant is invited to join the study, the investigational procedures, and the risks, benefits, and alternatives to participation. Such data must be presented clearly and using language that the parents can understand. They must be given time to ask questions and to consider how they wish to proceed. Permission that is provided absent any one of these conditions, or that is the result of undue influence, is inadequate. It is therefore important to evaluate whether the role of the person obtaining permission influences the parent’s voluntariness or understanding. Research has shown that, in general, parents have a difficult time understanding details about the information presented on pediatric research consent forms (Flory and Emanuel 2004). Such difficulties are magnified when the child in question is a neonate in the first day of life, as the parents are still adjusting to having a child, learning about their child’s condition, and recovering from the birth itself (Ballard et al. 2004). In some instances, the infant may not be located in the same hospital where the birth occurred; the parents may have had to travel, and could be far from their support system. They will almost certainly be contending with a setting and medical team that are unfamiliar, yet they will still be striving to make decisions that they feel are best for their child. Thus, perhaps what is most important for this decision is whether the study is presented to the parents prenatally or postnatally. It is my contention that getting an expectant mother’s agreement to enroll her child in the clinical trial described here prior to giving birth is ethically acceptable, while postnatal permission obtained by the attending physician is not. In this case study, the protocol for enrollment required that someone other than the attending physician of record discuss potential enrollment with the parents. However, the principal investigator has learned that in at least one instance the attending was the study physician, and that another trial site was given IRB approval to allow an
attending to enroll infants when the hospital is shortstaffed. Prenatally, enrollment discussions could be handled by the study coordinator, once the mother’s obstetrician asked the mother whether she was interested in learning about the study. An advantage of speaking to the mother before the birth is that she and the study coordinator can talk during a relatively calm time, and the pregnant woman can be given some time to make her decision. As it is likely that the study coordinator would not be someone the expectant mother had dealt with before, it could be easier for the pregnant woman to appreciate the difference between her clinical care and the research study. She would see that she was not meeting with a physician, and that the interaction was different from what occurs at a typical prenatal appointment. There would be no examination, just a discussion about the study. The research team should always emphasize the experimental and voluntary nature of the trial when speaking with parents; the prenatal study setting would reinforce the separation between research and clinical care. Postnatal permission will necessarily take place in a higher stress environment. Parents will probably need extra time to take in all the information that is being presented to them then, but in reality they will receive less, because study enrollment must occur in the first 24 hours of life. If the study information is presented by a physician, it will be easy for parents to believe that they are being told to do something for the infant’s benefit (de Vries 2011). At that point in their infant’s life, they are meeting many new care providers, so they may not be able to identify their baby’s attending, or to differentiate the role of attending from that of study physician, particularly if one person is fulfilling both roles. Even if they are able to do so, they may falsely believe that study enrollment is an important piece of the infant’s clinical care (this is known as the therapeutic misconception). This all reinforces why postnatal enrollment by an attending, complicated as it is by exhaustion, time, worry, and faith in the physician, is the setting where there is the most risk for undue influence. That risk of permission, given without a clear understanding of the trial, outweighs potential benefits in this case, as data can still be obtained using infants for which prenatal permission was obtained. Does this mean all postnatal permission is unethical? No. It is important to recognize that improvements in care
Address correspondence to Leah R. Eisenberg, JD, MA, Assistant Professor Division of Medical Humanities Ethics Consultant, Arkansas Children’s Hospital UAMS College of Medicine 4301 W. Markham St., #646 Little Rock, AR 72205, USA. E-mail: [email protected]
April, Volume 15, Number 4, 2015
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The American Journal of Bioethics
for premature infants cannot be made without, at some point, trying them on premature infants. Prohibiting all postnatal study enrollment would greatly slow the pace of research, either because parents won’t give permission prenatally because they do not expect a premature infant, or because they were not invited to participate at that time. Infants born before 28 weeks of gestation often face a long and complicated medical course that can impact them during their whole lives. Research on neonates is therefore a necessity, and, as such, permission for such research will sometimes need to be obtained after birth. The question of whether it is ethical to allow postnatal parental permission must be considered on a study-by-study basis. However, study enrollment by a neonatal patient’s attending physician is never appropriate. The risk of the therapeutic misconception impacting the parents’ ability to give permission in a critical situation is too high. Furthermore, parents might give permission simply because they do not want to jeopardize their relationship with their child’s physician. It is also important to note that the methodology of the trial presented here makes postnatal permission especially problematic, because infants must be enrolled so soon after birth, when stress and chaos are often at their highest. Studies for which enrollment can come later not only allow parents time to adjust to life with a premature infant, but also present an opportunity for a study coordinator to visit with them in order to answer their questions and explain research participation.
For all the reasons discussed here, the most ethical way to proceed with this trial is to seek prenatal permission. If enrollment numbers lag, postnatal enrollment can be considered, but a firm plan will need to be in place for getting a study staff member to speak to the family about participation, and for clearly highlighting the investigative nature of the trial before such enrollment can begin. Physicians involved in the infant’s clinical care, particularly the infant’s attending, should never be involved in trial enrollment. While improving care for premature infants is a goal everyone can agree upon, such improvements cannot come at the expense of ethical research conduct. &
REFERENCES Ballard, H. O., L. A. Shook, N. S. Desai, and K. J. S. Anand. 2004. Research and the validity of informed consent obtained in the perinatal period. Journal of Perinatology 24(7): 409–415. Available at: http://dx.doi.org/10.1038/sj.jp.7211142. de Vries, M. C. 2011. Ethical issues at the interface of clinical care and research practice in pediatric oncology: A narrative review of parents’ and physicians’ experiences. BMC Medical Ethics 12: 18. Flory, J., and E. Emanuel. 2004. Interventions to improve research participants’ understanding in informed consent for research: A systematic review. Journal of the American Medical Association 292 (13): 1593–1601. Available at: http://dx.doi.org/10.1001/ jama.292.13.1
Precluding Consent by Clinicians Who Are Both the Attending and the Investigator: An Outdated Shibboleth? Anita Shah, University of Washington School of Medicine Kathryn Porter, Seattle Children’s Research Institute Sandra Juul, University of Washington School of Medicine Benjamin S. Wilfond, Seattle Children’s Research Institute The question raised by this case about who should obtain parental permission can be clarified by considering four general requirements for informed consent: (1) Individuals must have the capacity to give consent; (2) the information must be disclosed; (3) the information must be understood; and (4) the decision must be voluntary (Faden and Beauchamp 1986). This case highlights challenges related to
two of these concepts: understanding and voluntariness. Specifically, does a parent’s ability to comprehend and give voluntary permission differ depending on whether such permission is obtained by the attending physician, a researcher, or a study coordinator? This research protocol utilized a standard approach of having a researcher not involved in the infant’s care obtain
Address correspondence to Benjamin S. Wilfond, Treuman Katz Center for Pediatric Bioethics, Seattle Children’s Research Institute, M/S JMB-6 , 1900 Ninth Ave, Seattle, WA 98101, USA. E-mail: [email protected]
80 ajob
April, Volume 15, Number 4, 2015
Copyright of American Journal of Bioethics is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Research Involving Premature Infants: Timing Is Everything Leah R. Eisenberg, University of Arkansas for Medical Sciences Under what circumstances is it ethical to ask and allow parents to give permission for research on their newborn premature infant? Generally, parents can agree to enrollment in institutional review board (IRB)-approved clinical research as long as the infant is eligible for inclusion and the parents are willing and able to give permission. A high-quality permission process demands that the parents be provided with information about their child’s condition, why the infant is invited to join the study, the investigational procedures, and the risks, benefits, and alternatives to participation. Such data must be presented clearly and using language that the parents can understand. They must be given time to ask questions and to consider how they wish to proceed. Permission that is provided absent any one of these conditions, or that is the result of undue influence, is inadequate. It is therefore important to evaluate whether the role of the person obtaining permission influences the parent’s voluntariness or understanding. Research has shown that, in general, parents have a difficult time understanding details about the information presented on pediatric research consent forms (Flory and Emanuel 2004). Such difficulties are magnified when the child in question is a neonate in the first day of life, as the parents are still adjusting to having a child, learning about their child’s condition, and recovering from the birth itself (Ballard et al. 2004). In some instances, the infant may not be located in the same hospital where the birth occurred; the parents may have had to travel, and could be far from their support system. They will almost certainly be contending with a setting and medical team that are unfamiliar, yet they will still be striving to make decisions that they feel are best for their child. Thus, perhaps what is most important for this decision is whether the study is presented to the parents prenatally or postnatally. It is my contention that getting an expectant mother’s agreement to enroll her child in the clinical trial described here prior to giving birth is ethically acceptable, while postnatal permission obtained by the attending physician is not. In this case study, the protocol for enrollment required that someone other than the attending physician of record discuss potential enrollment with the parents. However, the principal investigator has learned that in at least one instance the attending was the study physician, and that another trial site was given IRB approval to allow an
attending to enroll infants when the hospital is shortstaffed. Prenatally, enrollment discussions could be handled by the study coordinator, once the mother’s obstetrician asked the mother whether she was interested in learning about the study. An advantage of speaking to the mother before the birth is that she and the study coordinator can talk during a relatively calm time, and the pregnant woman can be given some time to make her decision. As it is likely that the study coordinator would not be someone the expectant mother had dealt with before, it could be easier for the pregnant woman to appreciate the difference between her clinical care and the research study. She would see that she was not meeting with a physician, and that the interaction was different from what occurs at a typical prenatal appointment. There would be no examination, just a discussion about the study. The research team should always emphasize the experimental and voluntary nature of the trial when speaking with parents; the prenatal study setting would reinforce the separation between research and clinical care. Postnatal permission will necessarily take place in a higher stress environment. Parents will probably need extra time to take in all the information that is being presented to them then, but in reality they will receive less, because study enrollment must occur in the first 24 hours of life. If the study information is presented by a physician, it will be easy for parents to believe that they are being told to do something for the infant’s benefit (de Vries 2011). At that point in their infant’s life, they are meeting many new care providers, so they may not be able to identify their baby’s attending, or to differentiate the role of attending from that of study physician, particularly if one person is fulfilling both roles. Even if they are able to do so, they may falsely believe that study enrollment is an important piece of the infant’s clinical care (this is known as the therapeutic misconception). This all reinforces why postnatal enrollment by an attending, complicated as it is by exhaustion, time, worry, and faith in the physician, is the setting where there is the most risk for undue influence. That risk of permission, given without a clear understanding of the trial, outweighs potential benefits in this case, as data can still be obtained using infants for which prenatal permission was obtained. Does this mean all postnatal permission is unethical? No. It is important to recognize that improvements in care
Address correspondence to Leah R. Eisenberg, JD, MA, Assistant Professor Division of Medical Humanities Ethics Consultant, Arkansas Children’s Hospital UAMS College of Medicine 4301 W. Markham St., #646 Little Rock, AR 72205, USA. E-mail: [email protected]
April, Volume 15, Number 4, 2015
ajob 79
The American Journal of Bioethics
for premature infants cannot be made without, at some point, trying them on premature infants. Prohibiting all postnatal study enrollment would greatly slow the pace of research, either because parents won’t give permission prenatally because they do not expect a premature infant, or because they were not invited to participate at that time. Infants born before 28 weeks of gestation often face a long and complicated medical course that can impact them during their whole lives. Research on neonates is therefore a necessity, and, as such, permission for such research will sometimes need to be obtained after birth. The question of whether it is ethical to allow postnatal parental permission must be considered on a study-by-study basis. However, study enrollment by a neonatal patient’s attending physician is never appropriate. The risk of the therapeutic misconception impacting the parents’ ability to give permission in a critical situation is too high. Furthermore, parents might give permission simply because they do not want to jeopardize their relationship with their child’s physician. It is also important to note that the methodology of the trial presented here makes postnatal permission especially problematic, because infants must be enrolled so soon after birth, when stress and chaos are often at their highest. Studies for which enrollment can come later not only allow parents time to adjust to life with a premature infant, but also present an opportunity for a study coordinator to visit with them in order to answer their questions and explain research participation.
For all the reasons discussed here, the most ethical way to proceed with this trial is to seek prenatal permission. If enrollment numbers lag, postnatal enrollment can be considered, but a firm plan will need to be in place for getting a study staff member to speak to the family about participation, and for clearly highlighting the investigative nature of the trial before such enrollment can begin. Physicians involved in the infant’s clinical care, particularly the infant’s attending, should never be involved in trial enrollment. While improving care for premature infants is a goal everyone can agree upon, such improvements cannot come at the expense of ethical research conduct. &
REFERENCES Ballard, H. O., L. A. Shook, N. S. Desai, and K. J. S. Anand. 2004. Research and the validity of informed consent obtained in the perinatal period. Journal of Perinatology 24(7): 409–415. Available at: http://dx.doi.org/10.1038/sj.jp.7211142. de Vries, M. C. 2011. Ethical issues at the interface of clinical care and research practice in pediatric oncology: A narrative review of parents’ and physicians’ experiences. BMC Medical Ethics 12: 18. Flory, J., and E. Emanuel. 2004. Interventions to improve research participants’ understanding in informed consent for research: A systematic review. Journal of the American Medical Association 292 (13): 1593–1601. Available at: http://dx.doi.org/10.1001/ jama.292.13.1
Precluding Consent by Clinicians Who Are Both the Attending and the Investigator: An Outdated Shibboleth? Anita Shah, University of Washington School of Medicine Kathryn Porter, Seattle Children’s Research Institute Sandra Juul, University of Washington School of Medicine Benjamin S. Wilfond, Seattle Children’s Research Institute The question raised by this case about who should obtain parental permission can be clarified by considering four general requirements for informed consent: (1) Individuals must have the capacity to give consent; (2) the information must be disclosed; (3) the information must be understood; and (4) the decision must be voluntary (Faden and Beauchamp 1986). This case highlights challenges related to
two of these concepts: understanding and voluntariness. Specifically, does a parent’s ability to comprehend and give voluntary permission differ depending on whether such permission is obtained by the attending physician, a researcher, or a study coordinator? This research protocol utilized a standard approach of having a researcher not involved in the infant’s care obtain
Address correspondence to Benjamin S. Wilfond, Treuman Katz Center for Pediatric Bioethics, Seattle Children’s Research Institute, M/S JMB-6 , 1900 Ninth Ave, Seattle, WA 98101, USA. E-mail: [email protected]
80 ajob
April, Volume 15, Number 4, 2015
Copyright of American Journal of Bioethics is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
