搜索结果：Pediatric research

What do we mean by “assent” in the context of research involving children? Why do we obtain it? What is its purpose? Which children should be asked to assent? When should dissent be overridden? These are some of the questions regarding assent for pediatric research that remain under debate. In this month’s Pediatrics, Kimberly et al1 found wide variability in assent requirements, and perhaps such variability is expected when so many fundamental issues remain unresolved. In this commentary I present a brief review of the Kimberly et al findings, examine the foundation and justification for the assent requirement, summarize the debate over the appropriate age at which a child should be asked to assent, and illuminate controversies in both the information-delivery aspect of assent and the decision-making expectations. The commentary concludes with an assertion that our entire approach to assent is flawed and suggestions for the focus of future inquiry.Kimberly et al1 reviewed informed permission, assent, and consent documents for 3 multicenter clinical trials involving children. Standard informed-consent documents were submitted to institutional review boards (IRBs) at 55 separate institutions, and these IRBs required substantively different alterations. The Kimberly et al study focused on requirements for assent and the amount of compensation at participating institutions and found considerable variability in both arenas.As an example of the inconsistency seen in the assent requirements, the age at which IRBs required investigators to obtain assent varied greatly. For the hypertension study, the age at which assent was required ranged from 6 to 15 years; for the pain study, the range was 6 to 12 years; and for the respiratory-failure study, the range was 7 to 12 years (see Fig 2 in ref 1). Why some IRBs felt that it would be appropriate for a 6-year-old to provide assent and others felt that assent was not appropriate until the age of 15 is not apparent.The Belmont report2 outlines 3 fundamental ethical principles of research-subject protection: respect for persons, beneficence, and justice. The report goes on to clarify that “respect for persons incorporates at least two ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection. The principle of respect for persons thus divides into two separate moral requirements: the requirement to acknowledge autonomy and the requirement to protect those with diminished autonomy.”2This statement has been interpreted in 2 ways. On one hand, some argue that because more-mature adolescents have many of the qualities and mental capacities that we associate with autonomous agents, assent should be required only for these individuals. Younger children who are less cognitively advanced should be protected, which does not necessitate their assent for research participation.3On the other hand, some believe that the principle of respect for persons requires that all individuals, regardless of their cognitive ability, participate in decision-making to the extent that they are able. Although younger children are not developmentally capable of adult-like comprehension of complex study protocols, they are able to have some level of understanding. As such, even very young children should be involved in assent discussions.4 If seen as individuals with emerging autonomy and progressively increasing cognitive and emotional development, children should participate in all such discussions; however, the content and purpose of assent must vary depending on the child's developmental stage.The divergent interpretations discussed above have lead researchers and ethicists to disagree on the appropriate age at which assent should be sought. As an example of this controversy, Kimberly et al found that some IRBs required documentation of assent in children as young as 6, but others did not require documentation of assent in children under 15 for the same research protocol (see Fig 2 in ref 1).The debate over the proper age at which we ought to require assent has been raging since the publication of the Belmont report. In 1977, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (“the commission”) recommended that active affirmation should be required for all children over 7 and that the objection of a child of any age should be binding.5 The commission did note that a child's objection may be overridden when research holds out the prospect of direct benefit to participants that is important to the child's health or well-being and is available only in the context of research, and that assent should not be required from incapacitated children. Twenty years after the commission's statement, the American Academy of Pediatrics (AAP) continued to endorse using 7 as the age of assent.6Others, however, believe that requiring the assent of such young children is inappropriate and have argued that the age of assent should be raised significantly. When researchers view assent as a quasi-consent process, they necessarily focus on what children understand. Under such a model, researchers should not be compelled to obtain assent from children who are unable to attain some minimal level of comprehension. On the basis of empirical data of what children understand during assent discussions, some wish to raise the age of assent to as high as 14 years.3To provide guidance for investigators and create institutional norms, many IRBs have adopted strict age cutoffs for assent requirements. There is substantial variability, however, in the age of assent at different institutions.7 Although policies that create an institutional age of assent have their appeal, such systems often fail to address the nuances of the assent process. In addition, such policies may lead to decisions that seem to make little sense, such as requiring documentation of assent in a study of children with respiratory failure who could not possibly participate in such discussions because of heavy sedation and mechanical ventilation.1 Although clear age cutoffs seem easier from the perspective of many researchers (“just tell me which kids need to sign their name on the form”), such policies fail to address the varied needs of children at different stages of development and may lead investigators to focus on assent forms rather than on the assent process.The appropriate content of assent conversations has also been debated. Some argue that the assent process should mirror the informed-consent process and that investigators should disclose all information that they would discuss with potential adult research participants. The commission stated: “Disclosure requirements for assent and permission are the same as those for informed consent.”5 In the research context, this would include disclosure of information including the purpose of the research, duration of the research project, research procedures, risks and discomforts, potential benefits, alternatives, level of confidentiality, contact information for persons who can answer additional questions or who can be contacted in the case of research-related injury, cost to participants, approximate target number of participants, and an explanation that the study is research rather than treatment and the voluntary nature of research participation.8 In research involving adults, part of the informed-consent discussion includes disclosure of the nature and amount of compensation given to research participants. In research involving children, however, the position of the AAP is that children should not be told about compensation until after study participation, because the promise of compensation might unduly influence the child's choice.6 Few IRBs follow the AAP recommendation, however, and authors have discussed some of the ethical difficulties of such a policy.9,10Conversely, the requirements for assent may be interpreted to be less robust that those of consent. Rather than encompassing all aspects of consent disclosure, assent can be taken to mean merely “helping the [child] achieve a developmentally appropriate awareness.”11 Such an interpretation might substantially limit the information discussed in the assent process depending on what the investigator or IRB believes is “developmentally appropriate” information. For example, in contrast to the informed-consent process, one quarter of IRBs do not require investigators to disclose to potential pediatric subjects those risks that are serious but rare.7 At a minimum, most agree that an assent discussion should contain at least an overview of the basic study procedures, a disclosure that participation is voluntary, and an explanation that what the child is being asked to agree to is research rather than medical care per se.To address the developmental differences within the pediatric population, some have proposed a more fluid approach to assent. Such a system would allow a range of definitions of assent. In young children, one could provide only minimal information and ask the child about their feelings regarding participation, whereas in more-mature adolescents the assent process could mimic informed consent.12,13 Such systems may address the broad range of potential pediatric research participants; however, they also may be seen as less practical, and researchers need guidance in implementing such a complex approach.The control over decision-making can similarly be interpreted to have substantively different meaning. Some contend that we ought require the active affirmation of a child before study enrollment,5,6 whereas others have argued that we should adopt a lack-of-dissent standard.3 Those who support the latter argue that most children are incapable of understanding research protocols sufficiently to qualify their assent as meaningful,3 whereas proponents of the former argue that there is value in the child's active assent even if all that the child understands is that he or she will have to endure some discomfort for the sake of helping others.4,12The finding by Kimberly et al of broad variability in assent documentation is noteworthy; however, because of the study design, the investigators were unable to scrutinize the assent conversations themselves. As in the case of informed consent, merely obtaining a signature on a piece of paper does not ensure that an appropriate discussion has occurred. Assent, like consent, requires an ongoing discussion that does not end after signing one's name.12Protecting children's rights, shielding them from harm, and fostering their emerging autonomy are laudable goals. The commission attempted to balance these ideals with the real benefit that some children receive from study participation. The recognition that children generally have a right to participate in decision-making that directly affects them was a major step forward in pediatric medicine and research.What seems to be lacking from the current discussion of assent requirements is the realization that just because children may have a right to participate, it does not imply that they have an obligation to do so. Particularly in the United States, there has been a major shift toward autonomous decision-making in adult medicine. Despite this trend, the medical community recognizes that when a patient chooses to be shielded from information, clinicians may need to respect such wishes.14 In the case of pediatric patients and potential pediatric research participants, it would seem reasonable that if a child does not want information, such wishes should be respected. Indeed, many children (including many adolescents) choose to defer to their parents when making such decisions and prefer to remain ignorant of many aspects of their disease and risks of study participation.15In addition, we seem to have lost sight of the social nature of a child's life. Children are not autonomous individuals, devoid of social context. Indeed, family and other social interactions are often central to a child's understanding of his or her experiences, and any policy that is blind to the social characteristics of children will not serve them well. The assent process must be flexible enough to allow for different models of communication in different families and should support the relationships within the family.12,16 In discussing research with terminally ill children, Bluebond-Langner et al note: “If important decisions have not been the child's to make in the past, this is not the time to change that by seeking the child's assent.”15 They argue further that “[c]hildren respect and act to preserve the social order of their families. Regulations that do not take these realities into account are not useful in facilitating children's involvement in decision-making or in fostering whatever autonomy they possess. They may, in fact, if enthusiastically applied, do harm.”15Until we are able to develop a concept of assent that is child-focused, we will be unable to reach consensus. Assent policies must be rigid enough to provide protection and respect for children yet flexible enough to allow for varied cognitive and emotional levels and to appropriately address the diverse preferences of our potential pediatric research subjects.Before we are able to agree on (1) the appropriate elements of assent conversations, (2) whether lack of dissent is adequate to protect children's interests, and (3) at what age ought investigators obtain a child's assent, we first must recognize that different children will have different needs and desires. Any policy must address these differences if it is to adequately serve children. This is not to say that parents should be free to keep their children in the dark without just cause; rather, I argue that the child should direct his or her own level of involvement. Some children may wish to hear all aspects of study protocols, whereas others may prefer to remain absent from such conversations. Some children may wish to be active participants in the decision-making process, whereas others may be more comfortable deferring to their parents. Respecting children's rights and treating them with respect requires allowing them to participate to the extent to which they feel most comfortable.An Institute of Medicine report stresses that “[g]uidance and education for investigators and members of institutional review boards should make clear that federal regulations allow discretion—based on children's developmental maturity—about the way in which information is presented to children and the manner in which assent is documented. Investigators and institutional review board members should apply that knowledge in determining what procedures will best serve the goals of assent for particular research protocols and populations. (Recommendation 5.7)”12 This recommendation is admirable; however, I would argue that such determinations should be based not only on the child's developmental maturity but also on his or her personal wishes.Research on children's abilities to provide assent that is akin to an adult's consent has focused on what aspects of research protocols children are able to understand.17 Capacity to consent to research participation, however, encompasses 4 elements: (1) the ability to understand the research protocol (including risk, benefits, purpose of research, the differences between research and clinical care, and the voluntary nature of participation); (2) the ability to grasp the ramifications of study participation and the capacity to appreciate how one's own life and medical care might be affected by study participation; (3) the ability to reason through a choice regarding whether to participate; and (4) the ability to make a choice and state it clearly.18 Future studies must build on previous work and provide a clearer picture of children's abilities to understand research protocols at different developmental and chronological ages. Research must also address, however, children's abilities in these other aspects of capacity (ie, appreciation, reasoning, and choice-making). This information will not dictate assent requirements; however, such knowledge is necessary to inform the pediatric-research community.Although there is much to be learned by studying permission and assent documents, we must illuminate the conversations themselves. Although the forms are an important part of the permission-and-assent process, they are merely one aspect. Additional work must focus on how best to present information to children so that they are able to choose how much information they require and investigators can learn how best to educate their young potential research subjects. Research should also assess optimal settings and timing for delivery of information. Where should such discussions take place? Who should be present (parents, investigators, child psychologists, child-life specialists, etc)? How far in advance should children be told of study procedures (eg, should one wait until the last minute to tell a young child that he or she will be giving a blood sample)?Finally, investigators and IRBs should clearly decide before study recruitment whether the assent of children is necessary for a particular protocol and to what extent a child's objection to participation will be honored. Because it is inappropriate to solicit a child's opinion when his or her views will not be weighed seriously,11 investigators should not mislead potential research subjects by asking for their opinions when their dissent will not be honored. Integrity, honesty, and clarity are paramount in physician-patient and investigator-subject relationships regardless of age.This work was supported by a grant from the Greenwall Foundation Faculty Scholars Program in Bioethics.

BACKGROUND: Pediatric prehospital research has been limited, but work in this area is starting to increase particularly with the growth of pediatric-specific research endeavors. Given the increased interest in pediatric prehospital research, there is a need to identify specific research priorities that incorporate the perspective of prehospital providers and other emergency medical services (EMS) stakeholders. OBJECTIVES: To develop a list of specific research priorities that is relevant, specific, and important to the practice of pediatric prehospital care. METHODS: Three independent committees of EMS providers and researchers were recruited. Each committee developed a list of research topics. These topics were collated and used to initiate a modified Delphi process for developing consensus on a list of research priorities. Participants were the committee members. Topics approved by 80% were retained as research priorities. Topics that were rejected by more than 50% were eliminated. The remaining topics were modified and included on subsequent surveys. Each survey allowed respondents to add additional topics. The surveys were continued until all topics were either successfully retained or rejected and no new topics were suggested. RESULTS: Fifty topics were identified by the three independent committees. These topics were included on the initial electronic survey. There were 5 subsequent surveys. At the completion of the final survey a total of 29 research priorities were identified. These research priorities covered the following study areas: airway management, asthma, cardiac arrest, pain, patient-family interaction, resource utilization, seizure, sepsis, spinal immobilization, toxicology, trauma, training and competency, and vascular access. The research priorities were very specific. For example, under airway the priorities were: "identify the optimal device for effectively managing the airway in the prehospital setting" and "identify the optimal airway management device for specific disease processes." CONCLUSION: This project developed a list of relevant, specific, and important research priorities for pediatric prehospital care. Some similarities exist between this project and prior research agendas but this list represents a current, more specific research agenda and reflects the opinions of working EMS providers, researchers, and leaders. KEY WORDS: emergency medical technician; research; emergency medical services; priorities.

<h3>Importance</h3> Many medicines prescribed to children have not been studied or formally approved for pediatric use. The Pediatric Research Equity Act of 2003 authorized the US Food and Drug Administration (FDA) to require pediatric clinical studies. <h3>Objective</h3> To evaluate the characteristics, completion rate, and transparency of study design and results for mandatory pediatric postmarketing studies required under the Pediatric Research Equity Act. <h3>Design and Setting</h3> A retrospective cohort study was conducted of pediatric postmarketing studies required for new drugs and new indications approved by the FDA between January 1, 2007, and December 31, 2014, with follow-up through December 1, 2017. Information on the status, design, and results of pediatric studies was obtained from publicly available FDA databases and ClinicalTrials.gov, direct communication with the FDA, and searches of MEDLINE, EMBASE, and Web of Science for peer-reviewed publications. <h3>Main Outcomes and Measures</h3> Characteristics and transparency of pediatric studies, results reporting (in ClinicalTrials.gov, peer-reviewed literature, or FDA documents), and availability of pediatric information in drug labels. Rates and times to study completion were evaluated using Cox proportional hazards regression models. <h3>Results</h3> Between 2007 and 2014, the FDA approved 114 new drugs and new indications for already approved drugs that were subject to Pediatric Research Equity Act requirements. These drugs were associated with 222 required pediatric postmarketing clinical studies. Overall, 75 pediatric studies (33.8%) were completed as of December 1, 2017. The rates of completion were significantly lower for efficacy studies (38 of 132 [28.8%]) compared with pharmacokinetic studies (19 of 34 [55.9%]; adjusted hazard ratio, 0.31; 95% CI, 0.12-0.82). Information on randomization, blinding, comparator, end point, and study size could not be identified for 74 studies (33.3%), and no reason for discontinuation was provided for 29 of the 42 discontinued studies (69.0%). Among the completed studies, the results were reported for 57 (76.0%). At the time of approval, 18 of 114 drug approvals (15.8%) had any pediatric efficacy, safety, or dosing information in their labels. After a median duration of follow-up of 6.8 years (interquartile range, 4.7-9.1 years), 47 of 114 of drug labels (41.2%) had any pediatric information. <h3>Conclusions and Relevance</h3> Only 33.8% of mandatory pediatric postmarketing studies have been completed after a median follow-up of 6.8 years, and most drug labels do not include information important for pediatric use. To improve evidence-based prescribing of medicines to children, more timely completion of pediatric drug studies is needed.

OBJECTIVE: Payment to subjects for participation in research is reportedly common, but no published data documents the nature of this practice. Institutional review boards (IRBs) are responsible for ensuring both the safety and voluntary participation of research subjects, yet guidance from federal and expert pediatric sources regarding appropriate payment approaches is conflicting. Ethical issues of payment for participation of adult versus pediatric research subjects may differ. This empirical study sought to examine current payment practices for participation in pediatric research as reported by IRBs. DESIGN: An 18-question survey regarding payment practices for participation in pediatric research was sent to IRB chairs at member institutions of the National Association of Children's Hospitals and Related Institutions, and to a systematic random sample of IRB chairs listed with the Office for Protection From Research Risks. Descriptive, nonparametric, and qualitative analyses were used to describe institution types, payment practices, and correlations among responses. RESULTS: Data from 128 institutions that conduct pediatric research revealed that payment for participation in pediatric research was allowed by 66% of responding institutions, and practices varied widely among institutions. Most responding IRBs that allowed payment required disclosure of payment before enrollment (during the consent process), following federal guidelines more closely than American Academy of Pediatrics guidelines. An IRB's perception of potential benefits or harms of a study correlated with the amount of payment approved. CONCLUSIONS: IRBs must balance the need to recruit pediatric research subjects against the risk of undue influence during the recruitment process. Federal guidelines and expert pediatric opinion differ in recommendations regarding payment; responding IRBs appeared to follow federal guidelines more closely than guidelines proposed by the American Academy of Pediatrics.

Pediatricians play a key role in advancing child health research to best attain and improve the physical, mental, and social health and well-being of all infants, children, adolescents, and young adults. Child health presents unique issues that require investigators who specialize in pediatric research. In addition, the scope of the pediatric research enterprise is transdisciplinary and includes the full spectrum of basic science, translational, community-based, health services, and child health policy research. Although most pediatricians do not directly engage in research, knowledge of research methodologies and approaches promotes critical evaluation of scientific literature, the practice of evidence-based medicine, and advocacy for evidence-based child health policy. This statement includes specific recommendations to promote further research education and support at all levels of pediatric training, from premedical to continuing medical education, as well as recommendations to increase support and mentorship for research activities. Pediatric research is crucial to the American Academy of Pediatrics' goal of improving the health of all children. The American Academy of Pediatrics continues to promote and encourage efforts to facilitate the creation of new knowledge and ways to reduce barriers experienced by trainees, practitioners, and academic faculty pursuing research.

OBJECTIVES: To describe the establishment of a national pediatric primary care research network to improve children's health care-Pediatric Research in Office Settings (PROS), and to evaluate the network's progress toward achieving its objectives. SETTING: Pediatric practices in all 50 states and Puerto Rico. PARTICIPANTS: Approximately 1400 pediatric practitioners from more than 470 practices. RESULTS: Beginning in 1986, a core of volunteer pediatrician coordinators from participating American Academy of Pediatrics chapters were identified to oversee local PROS efforts, represent practitioners, and inform the development of proposed research studies. PROS subsequently recruited practitioners from around the country, building a research infrastructure and a system of collaboration between the practitioners, research staff at the AAP, and investigative teams at academic institutions. This PROS collaboration has developed and conducted 10 primary care research studies that have added to the knowledge base of pediatric primary care. CONCLUSIONS: PROS has accomplished two of its initial objectives-development of a structure and process for pediatric practice-based research and provision of research experience to practitioners. Successful and consistent achievement of a third objective-meaningful dissemination of study results to relevant audiences-will depend on meeting several challenges.