This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Collection of data for this study will be limited to the use of non-invasive, non-painful procedures routinely employed in clinical practice. In addition, we will rely on interviews and surveys of the pediatric patients and their parents or legal guardians.Recent government policy has been developed aimed at increasing participation of children in clinical research [National Institutes of Health (1998, March 6). NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects. Bethsda, MD]. The policy and guidelines mandate that children must be included in all human subject research unless there are scientific and ethical reasons not to include them. Because of their physical, cognitive, and emotional developmental level, children are recognized as vulnerable subjects and special ethical and regulatory considerations are involved when investigators design and IRBs review research involving children. Although research on vulnerable populations is regulated in part with a threshold for permissible risk, the degree of risk premissible remains controversial. Some institutions are not supportive of studies in which healthy children are subjected to even minimal risks from non-therapeutic procedures, even with their assent and consent of their parents/legal guardians.Federal regulations permit the following four categories of research involving children: (1) research that does not involve greater than minimal risk to children; (2) research involving greater than minimal risk but presenting the prospect of direct benefit to the individual child-subject; (3) research involving greater than minimal risk and no prospect of benefit to the individual child-subject; and (4) research not otherwise approvable under one of the above categories but that the IRB determines will present a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health and welfare of children. According to these regulations, research involving non-therapeutic procedures, interventions that are used only to answer the scientific questions of a trial, can be permitted even if they pose greater than minimal risk and offer no benefit to the subject. However, these procedures remain ethically problematic because, while necessary to generate knowledge, they pose risks to participants without the prospect of direct benefit.With this general guidance, it is the obligation of individual IRBs to determine qualitatively, based on a risk-benefit calculus, whether a non-therapeutic study involving children is acceptable. Although venipuncture is the most common invasive procedure performed on children for non-therapeutic reasons, little, if any, systematic information is available on the effects of venipuncture. Thus no empirical evidence exists, to facilitate an assessment of the risks involved or to support judgment about whether the risks are ethically acceptable (minimal or greater than minimal). Quantification of the degree of risk associated with non-therapeutic venipuncture will aid in such decision-making and adherence to NIH guidelines. Identification of degree of risk will also ensure compliance with the mandate in the International Ethical Guidelines for Biomedical Research Involving Human Subjects to assure a low risk-benefit ratio when performing non-therapeutic research in children [International Ethical Guidelines for Biomedical Research Involving Human Subjects. (1993). Geneva, Switzerland: The Council for International Organizations of Medical Sciences (CIOMC)].Based on our clinical experience with childrenb undergoing non-therapeutic procedures as participants in clinical studies, we believe that children who voluntarily enroll in studies do not experience inappropriate levels of risk associated with study participation. In order to evaluate the validity of our experience, we want to examine the actual incidence of risks, particularly with regard to the subject's experience of pain and emotional distress associated with venipuncture. Children over the age of 7 years are generally capable of understanding the purpose of the research and capable of deciding if they want to participate [Glants, LH. (1996). Conducting research with children: legal and ethical issues. Journal of the American Academy of Child & Adolescent Psychiatry, 35, 1283-1291.]. One older study, examining venipuncture in normal children for research purposes, demonstrated that the majority of parents reported their children as experiencing minimal physical effects and that the venipuncture hurt a little or not at all [Smith, M. (1985). Taking blood from children causes no more than minimal harm. Journal of Medical Ethics, 11, 127-231.]. A similar study examining the risk of venipuncture in preschool children demonstrated comparable findings [Lau, Y-L. (1992). Parental perception of the effect of venipuncture in preschool children in non-therapeutic research. Journal of Paediatric Child Health, 28, 294-296.]. Conclusions based on parental perception were that: children felt more confident when going to have another blood sample taken (83%, 77.9%, in Smith and Lau respectively) and when seeing a doctor/dentist (40.1%, 40.1%), children did not feel upset after the venipuncture (92%, 87%), and children described the actual blood taking as hurting a little (55%, 67.3%) or not at all (38%, 22.8%). Both studies have been criticized for examining the effects of venipuncture by means of a parental questionnaire long after blood sampling was conducted (18 months and 1 month, respectively).Unlike the studies mentioned above, our intention is to conduct a prospective study examining the level of risk associated with venipuncture by means of physiologic measures as well as direct assessment of pain intensity and emotional distress. The prospective methodology should yield more accurate results, not subject to potential distortion of the event that occurs with retrospective investigation, e.g., either minimizing or maximizing the risks/psychological responses/outcomes.The goal of this study is to determine the level of risk associated with venipuncture in children. The risks involved with venipuncture include physical pain, emotional distress, bleeding/bruising, and to a lesser degree, infection and nerve damage. Outcome measures in this study include verbal ratings of pain and emotional distress, physiologic response measures, and parent or legal guardian report of residual physical symptoms. Analysis of outcome measures will quantify presence and magnitude of harm or discomfort associated with venipuncture, allowing for evaluation of degree of risk.Although the venipuncture is not being performed for this study, the risk associated with venipuncture is the major variable of interest and the focus of this study. The study team must address the outcomes of venipuncture in order to assess the risks associated with it. It will be important to document adverse events or perceptions of adverse events that may be associated with venipuncture to determine whether risks accrue after patients leave the clinic setting.
Showing the most recent 10 out of 1825 publications
