Informed Consent Toolkit

Research Researchers

According to the American Medical Association, informed consent is more than simply getting a patient to sign a written consent form. It is, instead, a process of communication between a patient and healthcare provider that ultimately results in the patient’s authorization or agreement to undergo a specific medical intervention or participate in a clinical trial. Informed consent is at the forefront of a battery of protections aimed to ensure that research participants are fully respected as human beings and made aware of the purpose, procedures, risks, and benefits of a study.

But what happens in the emergency care setting? When patients face time-sensitive and potentially life-threatening conditions, it may be impossible to achieve this level of understanding prior to medical interventions or study enrollments. This is especially true among pediatric patient populations: depending on their age, cognitive capabilities, and clinical conditions, children may be in no position to authorize potentially life-saving experimental treatments.

The result is that children experiencing health emergencies are rarely the subjects of research trials. This means that EMS procedures routinely practiced in the field may have little or no evidence base corroborating their efficacy; in fact, some may even present more risks than benefits to pediatric patients. In order to increase the scientific evidence behind emergency medical care, “exception from informed consent” becomes tantamount to research efforts.

This concept amounts to a waiver of the informed consent requirement under certain conditions when conducting clinical trials in the emergency setting. Patients may be eligible for exception: if their medical condition preclude assent, if the intervention must be administered before consent can be obtained from their legally authorized representative, and/or if it is not feasible to prospectively identify whether they are likely to become eligible for study participation.

EMSC National Resource Center

PECARN Primer: A Guide for Research Coordinators in the Pediatric Emergency Care Applied Research Network

Intended primarily for research coordinators and research assistants involved with PECARN, this primer includes a section on research ethics. Informed consent is one of the key concepts addressed, along with autonomy, non-maleficence, beneficence, and confidentiality. (November 2013)

American Academy of Pediatrics

Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations

This American Academy of Pediatrics (AAP) policy statement contains a section on emergency research. There, the Academy details the requirements for proceeding with research using the exception from informed consent. It also explains additional requirements for emergency research studies, such as the development and implementation of a plan for community consultation and public disclosure. (April 2010)

Columbia University Medical Center

PowerPoint presentation describing the history of exception from informed consent, federal regulations and responsibilities, ethical challenges, and community consultations.

National Institutes of Health

Research Involving Individuals with Questionable Capacity to Consent

The National Institutes of Health (NIH) created this resource in order to provide investigators and institutional review boards (IRBs) with points to consider (a) in fulfilling ethical and federal regulatory requirements to ensure the protection of the rights and welfare of research subjects who — due to impairments in their capacity to give informed consent — may be vulnerable to coercion or undue influence and (b) in maintaining appropriate awareness of the ethical challenges associated with research involving this vulnerable population. (Accessed July 2015)

Annotated Compendium of NIH Resources on Informed Consent

Developed by the NIH’s Clinical Research Policy Analysis and Coordination (CRpac) program, this compendium contains a comprehensive list of informed consent resources available online from the NIH’s various Institutes and Centers (ICs). Among the resources are informed consent templates, frequently asked questions, guidance created by specific ICs, and other relevant materials. (Accessed July 2015).

U.S. Department of Health and Human Services

Code of Federal Regulations (CFR) Title 45, Part 46

These federal regulations from the U.S. Department of Health and Human Services’ Code of Federal Regulations (CRF) ensure that the human subjects of behavioral and biomedical research receive the protections to which they are entitled, and aim to minimize risks. Within this document, HHS outlines general requirements for written informed consent (CRF Title 45, Part 46.116). (Accessed September 2013) The regulations also provide two subsections on exceptions to written consent: the Waiver or Alteration of Informed Consent Requirements (CFR Title 45 Part 46.116 (d)), and the Waiver for Written Documentation (45 CFR 46.117(c)). In addition, Subpart D of 45 CFR part 46 details additional protections for children participating in human subjects research. (Revised January 2009)

Code of Federal Regulations (CFR) Title 21, Chapter 1, Part 50

Title 21 (Foods and Drugs), Chapter 1 (Food and Drug Administration), Part 50 (Protection of Human Subjects) in the CFR contains a set of federal regulations that outline the general requirements for informed consent. Within these regulations, there are two sections pertaining to exceptions to informed consent: 21 CFR 50.23 — Exception from General Requirements (Emergency Use) and 21 CFR 50.24 — Exception from Informed Consent Requirements for Emergency Research. (April 2013)

U.S. Food and Drug Administration

Draft Guidance for IRBs, Clinical Investigators, and Sponsors: Exception from Informed Consent Requirements for Emergency Research

This guidance applies to research studies involving FDA regulated products (drugs, biological products, and medical devices). It assists sponsors, clinical investigators, and IRBs in the development and conduct of research in emergency settings when an exception from the informed consent requirements is requested under Title 21, Code of Federal Regulations, Section 50.24 (21 CFR 50.24) and understanding their responsibilities for communicating with, and submitting information to, the FDA. (July 2006)

Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Exception from Informed Consent Requirements for Emergency Research

This guidance was created to assist IRBs, clinical investigators, and sponsors in the “development, conduct, and oversight of investigators to determine the safety and effectiveness of FDA regulated products in emergency settings when an exception from the informed consent requirements is requested…” (April 2013)

Exception from Informed Consent in Emergency Research and Investigational Device Exemption

This resource provides guidance to clinical investigators on investigational device exemption (IDE) informed consent and includes a section on exception from informed consent (EFIC) delineating the responsibilities of the IRB and sponsor. This guidance explains the IDE application process for protocols using the EFIC regulation.

Ethical and Regulatory Considerations in Drug Development for Intranasal Naloxone

This PowerPoint presentation describes how the EFIC regulation in a clinical trial is evaluated to ensure compliance with the FDA’s pediatric ethics regulations. This presentation describes a study designed to evaluate the efficacy of the use of intranasal Naloxone for the complete or partial reversal of narcotic depression as well community consultations which are a required component of conducting research using EFIC.

Pediatric Ethics web page

This page provides information on ethical issues related to the development and use of FDA-regulated products in infants, children, and adolescents. Resources on this page include an overview of the general application of FDA’s pediatric ethic regulations with clinical trials involving children, supporting podcasts, and presentations.

Transcript for Ethical and Regulatory Challenges in the Development of Pediatric Medical Countermeasures, February 15-16, 2012

The FDA’s Office of Pediatric Therapeutics held the public workshop “Ethical and Regulatory Challenges in the Development of Pediatric Medical Countermeasures” to provide a forum for careful consideration of scientific, ethical, and regulatory issues confronting FDA and other stakeholders in the area of medical countermeasures and public health preparedness.

U.S. Office for Human Research Protections

Informed Consent FAQs

These informed consent Frequently-Asked-Questions provide guidance that represents the Office of Human Research Protection’s (OHRP’s ) current thinking and recommendations on the topic. Some FAQs specifically address issues in child assent, in addition to exception from informed consent requirements. (February 2013)

Research Involving Children FAQs

This second set of FAQs from OHRP addresses special requirements, parental permission, and informed consent regulations and waivers as related to research involving children. (January 2011)

Institute of Medicine

Ethical Conduct of Clinical Research Involving Children

This Institute of Medicine Committee on Clinical Research Involving Children report examines research ethics as related to the policies and practices designed to protect the safety and well-being of children enrolled in clinical trials. Chapter 5, titled “Understanding and Agreeing to Children’s Participation in Research,” is specifically designed for parents and caregivers. (2004)

National Institutes of Health

Children’s Assent to Clinical Trial Participation

This guide is aimed at parents considering enrolling their children in a clinical trial. It discusses the issues surrounding a child’s agreement to participate in a research study, including parental involvement in the process, legal responsibilities, and when assent of the child is and is not necessary. (May 2005)

Children and Clinical Studies

Developed by the NIH National Heart, Lung, and Blood Institute (NHLBI), this website contains resources for parents and caregivers addressing the importance of research in kid and rights of families in studies. This website targets parents and caregivers with information explaining the importance of research children. Tools and resources are provided to families to ensure that they have reliable information to understand clinical studies including safety and protections.

The Children’s Oncology Group

Research web page

Although this site is intended to provide resources and tools for parents and children receiving treatment for cancer, there is a research section for families that provides information about clinical trials and the informed consent process.

Neurological Emergencies Treatment Trials Network

The Neurological Emergencies Treatment Trials (NETT) network, was created in 2007 by the National Institute of Neurological Disorders and Stroke (NINDS) to conduct large trials targeting injuries and illnesses that impact the brain, spinal cord, and peripheral nervous system. The NETT network consists of academic medical centers that coordinate research activities with aligning community hospitals and EMS systems. Since the goal of this Network is to study interventions during the initial phases of care following the injury or illness, trials will take place in the prehospital and emergency department settings. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) study, is the first trial from NETT that utilizes an EFIC regulation.

Patients suffering from status epilepticus are often unresponsive in the prehospital and/or emergency department setting. This trial was conducted in 17 academic medical centers and the purpose was to study the prehospital treatment of status epilepticus in adult and pediatric patients. This randomized, double blind, multicenter study compared two anti-seizure medications, midazolam and lorazepam, as well as the routes of administration (intravenous vs. intramuscular injection). (Accessed July 2015)

Community Partnerships for Ethical Research

This Richmond-based project aims to target minority, underserved, and vulnerable populations critical to research and understanding health disparities, yet historically mistrustful of participating in research studies. The Virginia Community University project team developed and evaluated a model of community participation intended to yield sustainable long-term research relationships with the community.

Sample Hospital Policies and Procedures for EFIC for Research in Emergency Setting

University of Tennessee Health Science Center’s Institutional Review Board Emergency Medicine Research Exemptions from Informed Consent Requirements

The University of Alabama