Ethical Conduct of Clinical Research Involving Children
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《新英格兰医药杂志》
This report from the Institute of Medicine Committee on Clinical Research Involving Children comprehensively discusses the conflicting objectives of scientific research that involves children: ensuring that children benefit from the progress in medical care made possible by such research while minimizing the risks from their participation. It is divided into eight sections that review the need for and challenges of clinical research involving children and the existing regulatory framework for protecting children who participate in research. The requirements of both parental consent and children's assent to participate are described in detail, as are the appropriate risk–benefit ratios. Important issues such as the ethics of payments for children's participation in clinical research are described fully.
The report is both welcome and timely. Many have pointed out repeatedly that children have not shared equally with adults in biomedical advances. The impetus for the report was the concern that clinical research involving children should be expanded but that the system for protecting children participating in such research should be strengthened. The Best Pharmaceuticals for Children Act of 2002 charged the Institute of Medicine with preparing a report that reviewed federal regulations that govern research involving children and that made recommendations about desirable practices in such research.
In evaluating potential harm or discomfort, the terms "minimal risks" or "minor increase over minimal risks" are used. Investigators and institutional review boards (IRBs) have struggled with the most appropriate interpretation of these terms, which has led to inconsistencies among IRB members and between one IRB and another. This report suggests that risks be weighed in relation to the normal experiences of average, healthy children as encountered in their daily lives or as experienced in routine physical or psychological examinations or tests. Chapter 4 contains useful discussions and illustrations of both types of research, but we are never told why risks that are more than minimal should be allowed in pediatric nontherapeutic research, especially since the United States is one of the few countries that do permit such research. Phase 1 trials, which can involve substantial risks and little prospect of direct benefit, seem particularly problematic in the case of pediatric research. This report briefly suggests that since data on adults are usually available, such trials can be designed to be ethically acceptable. Further elaboration on and examples of these specially designed studies would have been helpful.
One of the most important recommendations made by the panel is that the IRB that reviews pediatric research protocols should have adequate expertise in the area of child health and research, which is defined as having at least three such experts present as members or alternates during meetings in which such research protocols are reviewed. The report suggests that IRBs should design procedures that are sensitive to educational, cultural, or other differences when they are seeking parental permission for a child's participation in research. It would have been helpful for the committee to provide examples from existing studies that others could emulate.
The report supports the current practice of seeking assent from children as young as six or seven years of age. At the same time, in chapter 5, a substantial amount of developmental information is presented that shows that children below 12 or 13 years of age lack certain cognitive skills that are crucial for meaningful agreement to participate in research. It would have been useful for the authors to incorporate a more detailed discussion of the practice of seeking assent from these younger children.
The report does not merely stress the need to protect children from being exploited in research but correctly emphasizes the ethical importance of such pediatric research. An appropriate balancing of these two values is clearly required. A more detailed discussion of this delicate issue would have been helpful, particularly reflections about when research with adult subjects should precede pediatric research and when the two types of research should be carried out concurrently. This is a crucial issue in the formulation of Food and Drug Administration policy, as emphasized in chapter 2.
The committee should be commended on its willingness to make important recommendations on difficult issues. The report contains a wealth of information and suggestions for all who are concerned with clinical research that involves children, and it should receive wide dissemination and discussion.
Ralph D. Feigin, M.D.
Baruch Brody, Ph.D.
Baylor College of Medicine
Houston, TX 77030
bbrody@bcm.tmc.edu(Edited by Marilyn J. Fiel)
The report is both welcome and timely. Many have pointed out repeatedly that children have not shared equally with adults in biomedical advances. The impetus for the report was the concern that clinical research involving children should be expanded but that the system for protecting children participating in such research should be strengthened. The Best Pharmaceuticals for Children Act of 2002 charged the Institute of Medicine with preparing a report that reviewed federal regulations that govern research involving children and that made recommendations about desirable practices in such research.
In evaluating potential harm or discomfort, the terms "minimal risks" or "minor increase over minimal risks" are used. Investigators and institutional review boards (IRBs) have struggled with the most appropriate interpretation of these terms, which has led to inconsistencies among IRB members and between one IRB and another. This report suggests that risks be weighed in relation to the normal experiences of average, healthy children as encountered in their daily lives or as experienced in routine physical or psychological examinations or tests. Chapter 4 contains useful discussions and illustrations of both types of research, but we are never told why risks that are more than minimal should be allowed in pediatric nontherapeutic research, especially since the United States is one of the few countries that do permit such research. Phase 1 trials, which can involve substantial risks and little prospect of direct benefit, seem particularly problematic in the case of pediatric research. This report briefly suggests that since data on adults are usually available, such trials can be designed to be ethically acceptable. Further elaboration on and examples of these specially designed studies would have been helpful.
One of the most important recommendations made by the panel is that the IRB that reviews pediatric research protocols should have adequate expertise in the area of child health and research, which is defined as having at least three such experts present as members or alternates during meetings in which such research protocols are reviewed. The report suggests that IRBs should design procedures that are sensitive to educational, cultural, or other differences when they are seeking parental permission for a child's participation in research. It would have been helpful for the committee to provide examples from existing studies that others could emulate.
The report supports the current practice of seeking assent from children as young as six or seven years of age. At the same time, in chapter 5, a substantial amount of developmental information is presented that shows that children below 12 or 13 years of age lack certain cognitive skills that are crucial for meaningful agreement to participate in research. It would have been useful for the authors to incorporate a more detailed discussion of the practice of seeking assent from these younger children.
The report does not merely stress the need to protect children from being exploited in research but correctly emphasizes the ethical importance of such pediatric research. An appropriate balancing of these two values is clearly required. A more detailed discussion of this delicate issue would have been helpful, particularly reflections about when research with adult subjects should precede pediatric research and when the two types of research should be carried out concurrently. This is a crucial issue in the formulation of Food and Drug Administration policy, as emphasized in chapter 2.
The committee should be commended on its willingness to make important recommendations on difficult issues. The report contains a wealth of information and suggestions for all who are concerned with clinical research that involves children, and it should receive wide dissemination and discussion.
Ralph D. Feigin, M.D.
Baruch Brody, Ph.D.
Baylor College of Medicine
Houston, TX 77030
bbrody@bcm.tmc.edu(Edited by Marilyn J. Fiel)