Informed assent
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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 Informed consent is a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatme ...
in adults, however there remains some overlap between the terms.


Background

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 Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
, 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.


Geographic variation


In United States

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 The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
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 In the law of the United States, the ''Code of Federal Regulations'' (''CFR'') is the codification of the general and permanent regulations promulgated by the executive departments and agencies of the federal government of the United States. ...
(45 CFR 46, Subpart d), investigators wishing to conduct clinical trials in children in the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
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 An institutional review board (IRB), also known as an independent ethics committee (IEC), ethical review board (ERB), or research ethics board (REB), is a committee that applies research ethics by reviewing the methods proposed for research to ens ...
(IRBs). Increasingly, many such IRBs are adopting the ‘
Rule of Sevens The rule of sevens, in English common law, establishes three age brackets for determining a young person's capacity to be responsible for torts and crimes. Children under the age of seven cannot be held to have capacity, while there is a rebuttab ...
,’ which has formed part of
common law In law, common law (also known as judicial precedent, judge-made law, or case law) is the body of law created by judges and similar quasi-judicial tribunals by virtue of being stated in written opinions."The common law is not a brooding omnipresen ...
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 The American Academy of Pediatrics (AAP) is an American professional association of pediatricians, headquartered in Itasca, Illinois. It maintains its Department of Federal Affairs office in Washington, D.C. Background The Academy was founded ...
and in some areas, such as the state of California, has been written into local law.


In European Union

Unless a waiver is granted, the
European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...
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.


Format and content

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.


Non-assent and controversy

Although the premise of pediatric consent using the rule of sevens is widely used and recognized as a practicable and ethical solution, it is not difficult to cite instances where it should not or has not applied, for example: # A child under 7 years old who is vehemently uncooperative with an aspect of a trial (such as a painful or uncomfortable assessment) may be removed from the trial by an investigator, i.e. be privilege to dissent. # A child over 7 years old who declines treatment for a devastating childhood illness and is therefore in mortal danger, might have their dissent overridden and have treatment forced upon them. # A child over 14 years old may be able to provide their own informed consent, independent of their parents. The legal precedent is that as an
emancipated minor Emancipation of minors is a legal mechanism by which a minor before attaining the age of majority is freed from control by their parents or guardians, and the parents or guardians are freed from responsibility for their child. Minors are norm ...
they may consent to any medical procedure they see fit (E.g., Carter v. Cangello, 105 Cal App 3d 348, 164 Cal Rptr 361, 1980; Lacey v. Laird, 139 NE 2d 25, Ohio 1956) # A child who does not wish to undergo treatment, and nor do their parents wish treatment for them, may be ordered to do so by the courts under child neglect laws. There have been instances where the failure to obtain proper assent (or even parental consent) has been directly opposed to the interests of the patient. In late 2000, the ''
Washington Post ''The Washington Post'' (also known as the ''Post'' and, informally, ''WaPo'') is an American daily newspaper published in Washington, D.C. It is the most widely circulated newspaper within the Washington metropolitan area and has a large nati ...
'' broke the story of a 10-year-old girl who died during a meningitis clinical study conducted in Kano, Nigeria, by the drug giant
Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer ...
. The story described the slow death of the girl while researchers, who were testing Pfizer’s antibiotic Trovan (
trovafloxacin Trovafloxacin (sold as Trovan by Pfizer and Turvel by Laboratorios Almirall) is a broad spectrum antibiotic that inhibits the uncoiling of supercoiled DNA in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It wa ...
), monitored her dying without modifying her treatment. The Post also alleged other such corporation-sponsored experiments “in Africa, Asia, Eastern Europe, and Latin America” that were “poorly regulated,” “dominated by private interests” and “far too often betray” their promises to research subjects and consumers. The trial was performed without informed consent. Initially, Pfizer successfully argued in court both that there was no international norm requiring its physicians to obtain informed consent for clinical trials and that any lawsuit brought against them relating to the trial should be tried in Nigerian courts, not U.S. courts. Pfizer abandoned this second claim in 2006, when a Nigerian Ministry of Health internal report was made public that concluded the study violated Nigerian law, the
Declaration of Helsinki The Declaration of Helsinki (DoH, fi, Helsingin julistus, sv, Helsingforsdeklarationen) is a set of ethical principles regarding human experimentation developed originally in 1964 for the medical community by the World Medical Association (WMA) ...
, and the United Nations' Convention on the Rights of the Child. The Nigerian government then filed both criminal and civil lawsuits against Pfizer in Nigeria. A settlement in this case has reportedly been reached, but the details of the agreement have not yet been made public. The Nigerian families have also gone to the U.S. Court of Appeals for the Second Circuit, winning the right to have the case tried in a US court. The central allegation is that “Pfizer, working in partnership with the Nigerian government, failed to secure the informed consent of either the children or their guardians and specifically failed to disclose or explain the experimental nature of the study or the serious risks involved” or to inform them that alternative treatment proven to be effective was immediately available from
Médecins sans Frontières (MSF; pronounced ), also known as Doctors Without Borders, is a humanitarian medical non-governmental organisation (NGO) or charity of French origin known for its projects in conflict zones and in countries affected by endemic diseases. M ...
at the same facility.


References


External links

* http://www.aap.org * https://web.archive.org/web/20130813023943/http://childmedicinesresearchinfo.com/ * https://web.archive.org/web/20120425092953/http://www.trialobytes.com/ {{Medical ethics Clinical research Legal terminology Human subject research Autonomy Clinical research ethics