Informed assent

The term informed assent describes the process whereby minors may agree to participate in clinical trials. It is similar to the process of informed consent in adults, however there remains some overlap between the terms. The term informed assent describes the process whereby minors may agree to participate in clinical trials. It is similar to the process of informed consent in adults, however there remains some overlap between the terms. In adult medical research, the term informed consent is used to describe a state whereby a competent individual, having been fully informed about the nature, benefits and risks of a clinical trial, agrees to their own participation. National authorities define certain populations as vulnerable and therefore unable to provide informed consent, such as those without the necessary cognitive, psychological, or social maturity to understand these benefits and risks. The oft-reported belief that minors (for the purposes of this discussion, read minors as persons under the age of 18 years) are considered a vulnerable population and therefore may not autonomously provide informed consent, is actually an oversimplification that does not always hold true. In fact, the requirements for children participating in clinical trials are somewhat indistinct, with freedom to vary both between countries and within countries. For this reason, two terms have sprung into existence: pediatric consent and pediatric assent. William G. Bartholome, MD, drafted the first statement for pediatric participation presented to the original American Academy of Pediatrics (AAP) Committee on Bioethics in 1985. The U.S. Food and Drug Administration encourages clinical trials in children in order to ensure the development of safe and effective pediatric medicines. According to the relevant Code of Federal Regulations (45 CFR 46, Subpart d), investigators wishing to conduct clinical trials in children in the United States are required to seek the permission of both parents and patients. This regulation defines informed assent as 'a child's affirmative agreement to participate in research' and stipulates that mere failure to object cannot, without affirmative agreement, be taken as assent. However, 45 CFR 46 does not specify an exact age at which informed assent must be obtained. Instead, it places responsibility for this determination with hospitals’ own Institutional Review Boards (IRBs). Increasingly, many such IRBs are adopting the ‘Rule of Sevens,’ which has formed part of common law for centuries and divides a child’s life into three sections: birth to seven, seven to fourteen, and fourteen to twenty one years old. Before 7 years old children are said to lack the cognitive development necessary for autonomous decision-making. At age 7 years children are considered able to distinguish right from wrong. Adolescents 14 years old and above are legally and socially accountable for their actions. Although not law, meaning physician can choose to ignore it, the rule of sevens is recommended by organizations including the American Academy of Pediatrics and in some areas, such as the state of California, has been written into local law. Unless a waiver is granted, the European Medicines Agency mandates that drug companies prepare Pediatric Investigation Plans (PIPs) and conduct clinical trials that will ensure their products are safe and effective in children. According to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Topic E11, Investigators wishing to conduct such trials within the European Union are required to seek the permission of both parents and patients. The recommendations of the Ethics Working Group of the Confederation of European Specialists in Paediatrics (CESP) places the onus of deciding at what age assent should be required is delegated on the Independent Ethical Committees for each study or individual healthcare institution, but a general convention has arisen to use the rough ‘rule of sevens’ described above. Generally, separate information and assent forms should be provided for the patient and their parents. According to CESP, child-focused forms should include all the elements and considerations generally required for seeking informed consent of competent adults. Additionally, it should conform to their intellectual capacity to understand the reason for the research and the risks therein, and the family should be given sufficient time and information to consider the pros and cons of their involvement. A child should also be aware they are able to withdraw willingly from the trial at any time. All this information must be presented in a style and format appropriate to the child's individual level of understanding. This means being tailored to the child’s age, social environment, psychological and intellectual maturity, hence specialist companies have arisen to serve the need of providing specialized pediatric study information.