I. What does informed consent mean in the human research context?
II. The Informed Consent Process
III. What are the basic elements of informed consent that are required in a written informed consent document and in most oral consent scripts?
IV. What are the informed consent documents that must be reviewed and approved by the IRB prior to use in a study?
A. Ethical Foundation
Informed consent is one of the primary ethical considerations in research involving human participants. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research describes the purpose of consent as the mechanism to ensure that participants understand the research study and voluntarily agree to participate. A copy of the Belmont Report may be found at the following site: http://www.hhs.gov/ohrp/humansubjects.
The PI and study team members should consider that consent is a process, and not just a form that potential study participants must sign.
B. Regulatory requirements for informed consent
There are federal requirements that mandate the type of consent that may be obtained, the elements that should be present in a written or oral consent explanation, and who may obtain and give consent for research purposes. Below is an outline of these requirements.
Federal Requirements: Informed consent must meet the regulatory requirements of the US Department of Health and Human Services (45 CFR 46.116) and the US Food and Drug Administration (21 CFR 50.20). Under these regulations, there are four general requirements for informed consent:
a) Consent Required: Investigators may involve human participants in research only with the consent of the participant or his/her legally authorized representative, unless the requirement for consent is waived. There are exceptions for waiver of consent, but waivers are highly regulated and must be justified. (see: http://irb.jhmi.edu/Guidelines/WaiverorAlterationofInformedConsent)
b) Voluntary Participation: The potential study participant must be given enough time to consider whether or not to participate in the research, and the possibility of coercion or undue influence should be minimized.
c) Understandable Language: Written or oral consent explanations must be in language understandable to the potential study participant or the individual’s legally authorized representative.
d) Waiver of Rights Prohibited: The consent (whether written or oral) may not include language through which the participant or their representative is made to waive the participant's legal rights or releases the investigator, the sponsor, the institution or its agents from liability for negligence.
A. What is meant by “informed consent process”?
Under the federal regulations, a PI must obtain “legally effective” informed consent in order to enroll a person into a research study. The “consent process” describes who will obtain informed consent and from whom, and when, where and how the consent process will take place. It also involves an assessment by the consent designee that the person providing informed consent understands what is being asked of him/her. Informed consent is legally effective if:
1. it is obtained from the subject or the subject’s legally authorized representative; and
2. it is documented in a manner that is consistent with the federal regulations on protection of human subjects (DHHS, FDA) and with the applicable laws of the jurisdiction in which the research is conducted, and
3. it is obtained under under circumstances that:
- provide the prospective subject or the legally authorized representative sufficient opportunity to consider whether to participate in the research;
- minimize the possibility of coercion or undue influence, and
- Respects the privacy of the potential participant by taking place in a setting that is not open to the public
The information provided should be in language that is understandable to the subject or the representative. No informed consent, whether oral or written, may include any exculpatory language (language that waives or appears to waive any of the participant’s legal rights, or releases or appears to release the investigator, the sponsor, the institution or its agents from liability for negligence).
The regulations provide two possible mechanisms for obtaining informed consent from a research participant:
- a process with consent documented by having the appropriate person sign a written IRB approved consent document, or
- an oral consent process that has been approved by the IRB.
B. Process for Obtaining Informed Consent Documentation
Generally, the IRB requires consent to be documented by a written consent form that includes all the required elements, and all appropriate optional elements, approved by the IRB prior to use. An IRB approved consent document will contain the date of IRB approval. Unless the need for consent is waived by the IRB, the written consent form must be reviewed with the participant (or the participant's representative), and signed and dated by the participant or the participant's representative before any research procedures (including screening) or research data collection can begin. The consent form should also be signed and dated by the individual who obtains the participant’s consent.
C. Oral Consent Process (waiver of documentation)
Oral consent must meet the regulatory requirements of DHHS (45 CFR 46.117) and FDA (21 CFR 56.109). An investigator may request that the IRB waive the requirement for written informed consent and approve instead an oral consent process for some or all potential research participants. The investigator should submit this request for oral consent with the e-IRB application and the investigator must include a script that the consent designee will use with participants. This script must include all the required consent elements and the elements required for HIPAA privacy authorization (when PHI is to be collected). If oral consent is obtained, the details about that consent (time, date, identity of consent designee) should be recorded in the study record by the consent designee. If the project involves clinical care, these details about the consent should be added to the clinical record.
The IRB may approve a request for oral consent for non-FDA regulated studies under two circumstances:
- The only record linking the participant to the research would be the consent document and, the principal risk to the participant would be potential harm resulting from a breach of confidentiality. In this case, each participant will be asked if he/she wants documentation linking him/her to the research and the participant’s wishes will govern; or
- The research presents no more than minimal risk to the participants and involves no procedures for which written consent is normally required outside of the research context.
For FDA-regulated studies, waiver of documentation is only permitted if the JHM study presents no more than minimal risk (second bullet above).
If the IRB approves an oral consent process, the IRB may require the investigator to provide participants with a written statement regarding the research. Such a document requires IRB approval.
D. Describing the Informed Consent Process in a Research Application
i. Who may obtain informed consent?
The principal investigator for an IRB-approved research is ultimately responsible for the conduct of the study. Both the consent process and the consent form must be approved by the IRB. The principal investigator must ensure that informed consent from each potential research participant is:
1. obtained by an IRB approved consent designee, and
2. documented (if required) using the method approved by the IRB. Informed consent must be obtained before that participant takes part in any aspect of the research study, unless the IRB has approved a waiver of the requirement to obtain consent.
The principal investigator does not have to obtain the consent personally. Co-investigators or study team members listed on the IRB application form as a consent designee (or added to the study by an amendment) may obtain consent only after the approval of the IRB for each designee. Each individual who interacts with potential research participants to obtain consent must submit evidence of human participants compliance training to the IRB as part of the application process (https://secure.lwservers.net/default.cfm).
The principal investigator must confirm that he/she has trained the individuals who will be getting consent. Each of the consent designees must be knowledgeable about the study and must be capable of answering study-related questions posed by the potential participant.
Consent designees must be “unconflicted”; they may not have a financial or outside conflict of interest associated with the research activity. Investigators with conflicts of interest must report those conflicts to the Committee on Outside Interests (COI).
ii. When and where may informed consent be obtained?
The informed consent process description must include details about the timing and the place of informed consent. Depending on the type of study and the risk associated with it, participants should have adequate time to review the consent form, ask questions about the research, and consult with family, friends or others (if desired) before signing the consent form.
NOTE: Consent should not be solicited immediately before beginning an elective procedure or scheduled therapy because the participant will not have time to consider whether or not to participate.
Generally, for research approved by the JHM IRBs, the consent form should be signed and include date and time of signature by both the participant and the principal investigator (or consent designee) at the time that consent is obtained. If the study involves sending the consent form to the potential participant for review and signature, without a face to face interaction with the consent designee, the process should describe whether there will be a telephone call to the individual to answer questions, and an explanation of the differences in the dates of the signatures of the participant and consent designee.
iii. From whom may consent/assent be obtained?
One of the ethical principles described in the Belmont Report, “Respect for Persons”, provides that individuals should be treated as autonomous agents. This means that potential participants who are approached to volunteer to participate in a research study must be given sufficient information to allow them to make an informed decision about participation. In the US, adults (as defined by State law) may provide consent for themselves. In Maryland, adults are defined as persons age 18 or older.
A. Adults who Lack Capacity to Provide Informed Consent
One of the principles described in the Belmont Report is “respect for persons”, which we interpret to mean that individuals should be treated as autonomous agents with the right to make an informed, voluntary decision whether or not to participate in human research. Potential participants who are approached to volunteer to participate in a research study must be given sufficient information to allow them to make an informed decision about participation, and adequate time in which to consider that information. In the U.S., adults (as defined by State law) may provide consent for themselves. In Maryland, adults are defined as persons age 18 or older.
NOTE: Investigators who conduct research in which participants are recruited at sites outside of the State of Maryland must follow the law that applies in the local jurisdiction to determine who is an adult who may give legal consent, and how consent from adults who lack capacity should be obtained.
An exception to the general rule that an adult may consent for himself or herself applies when an adult is determined to lack capacity to give consent. “Lack of capacity” to provide consent is not the same as “incompetence”, and PIs of studies which seek to enroll adults who may lack capacity to make an informed decision must make clear in the eIRB application how capacity to provide informed consent will be assessed. If participants are expected to lose the ability to consent while the study progresses, explain procedures for reassessing the ability of participants to understand the protocol procedures and to provide ongoing informed consent.
Incompetence may be a temporary result of the participant's condition (e.g., the participant is unconscious or sedated) or may result from cognitive impairment produced by a disease or medical condition that impairs mental capacity. Whenever a participant lacks capacity to provide informed consent for him/herself, federal regulations require that the participant's legally authorized representative must give consent before the incapacitated person may participate in a research study.
A legally authorized representative means an individual or other entity authorized under state law to consent on behalf of the research participant. Maryland law does not specify who may consent to research participation on behalf of an incompetent adult; however, Maryland law does indicate who may consent to medical care on behalf of an incompetent adult.
For the purpose of determining who may serve as a legally authorized representative of an incompetent adult, investigators should follow the Maryland law applicable to surrogate decision-making for health care. This law specifies that the following categories of persons, in the specified order of priority, may make health care decisions for the incompetent adult: (1) a health care agent appointed by the adult before becoming incompetent; (2) a legal guardian appointed by the court; (3) a spouse; (4) an adult child; (5) a parent; (6) an adult sibling; or (7) a friend or other relative. For individuals who know that they may lose capacity to provide consent during the course of the study, PIs should provide participants the opportunity to appoint a “research agent” who may provide consent on the participant’s behalf after the participant loses capacity to consent for him/herself.
B. Other vulnerable adult populations:
The JHM IRB recognizes that the ability of adult populations to give voluntary informed consent may be compromised by circumstance. Those circumstances range from economic or educational disadvantage, physical handicap, sedation, and drug abuse to the terminally ill. The protocol should take into account any of these issues and address them in the consent process.
C. Pregnant Women, Fetuses, Neonates
Under the federal regulations, there are special conditions if pregnant women, fetuses or neonates will be involved in the research. ( Note: “Neonates” are newborns who are not viable or whose viability is uncertain; healthy newborns are “children” under the regulations.) The conditions are listed at (45 CFR Subpart B). The pregnant woman must give her informed consent, and, if the research holds out the prospect of direct benefit only to the fetus, then the father must also give informed consent (unless he is unable to consent because of unavailability, incompetence, temporary incapacity, or the pregnancy resulted from rape or incest). Each individual providing consent must be informed of the impact of the research on the fetus.
D. Non-English Speakers
See the guidance at: http://irb.jhmi.edu/Guidelines/nonenglishconsent.html.
In Maryland, anyone under 18 years of age, with few exceptions, is considered a child. The Federal regulations require that any person, including a child, who participates in research must do so voluntarily. Generally speaking, the investigator must ask for the assent of the child to participate, and permission (informed consent) from the child's parents.
A. Parental Permission: The investigator must ask permission of the child's parents before enrolling the child in a study. Usually that means having the parent sign an informed consent document that looks like the typical adult research consent form. Permission must be documented, in writing, unless the IRB waives this requirement.
a) For studies involving minimal risk, or more than minimal risk with the prospect of direct benefit to the child, the IRB may find that the permission of one parent is sufficient for enrollment in the research project. Otherwise, the permission of both parents is required unless one parent is deceased, unknown, incompetent, or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child.
b) For a minor increase over minimal risk studies that offer no prospect of direct benefit to the child, both parents must give permission unless one parent is deceased, unknown, incompetent, or not reasonably available or when only one parent has legal custody for the child.
Exception to Requirement for Parental Permission: The IRB could waive parental permission if the protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the participants (for example, abused or neglected children). If the IRB waives permission in this instance, another appropriate mechanism for protecting the children who will be participants in the study must be substituted, and the waiver must not be inconsistent with Federal, state or local law.
B. Child's Assent: A child whose age, maturity, and psychological state make it possible for him or her to make an independent decision to participate in a study must have the chance to give assent. Assent should be an ongoing dialogue between the investigator and the participant. It also should be documented unless the IRB waives that requirement.
The investigator should give the child:
- An explanation of the research procedures in language appropriate to that child
- A description of any risks, discomforts, or inconveniences that the child might experience; and
- Assurance that the child can withdraw from the study at any time.
C. How should a PI describe the assent process in the IRB application?
a) Explain who will discuss the study with the child: The IRB will want to know that the person discussing the study with the child is experienced with the consent process and will make the assessment as to the child’s capacity to make an independent decision. This assessment must consider the child’s age, maturity, psychological and emotional state.
b) Explain what information will be discussed with the child: The IRB will want to see a script of the language the researcher will use in the discussion. The wording should capture the essential elements in age-appropriate language.
c) Explain whether you plan: (1) to use an assent statement in the parental permission form or (2) to use a separate assent form. If you choose option (1) the assent statement in the parental consent should state, “This project has been explained to my child in my presence and in language he/she can understand. He/she has been encouraged to ask questions now and in the future about the research study.” If you choose option (2), a sample assent form is available on the IRB website at : http://irb.jhmi.edu/Forms/researchassent.rtf
D. Waiver of Assent
The IRB may consider waiver of assent requirements under the following regulatory criteria:
a) The child is incapable of providing or communicating assent;
b) The study intervention offers the prospect of direct benefit to the child that is only available through research;
c) The study is conducted by, or subject to the approval of, public officials and concerns public service programs and could not be carried out without the waiver; or
d) The research involves no more than minimal risk, the waiver will not hurt the rights and welfare of the participants, the research would be impracticable without the waiver, and when appropriate additional information will be provided to the children.
NOTE: The federal regulations have additional restrictions on research activities in which children who are wards of the state or any other agency/institution may participate; contact the IRB to discuss these restrictions if your study involves these children.
E. Children who are Minors and are Wards of the State
Minors who are wards of the state, including those placed in foster care, may participate in research if investigators obtain the consent of the State official responsible for that child. Each jurisdiction has its own policies and processes. See: http://irb.jhmi.edu/Guidelines/fosterchildren.html.
F. Minors who may Consent as Adults
In certain situations, minors are not treated as “children” and may consent to research on their own, without parental permission. Those circumstances are explained in the Guidance, Informed Consent for Children in Research Studies at: http://irb.jhmi.edu/Guidelines/Informed_Consent_Minors.
iv. How does an investigator know if a participant understands the information in the consent form?
In order for participation in a study to be truly voluntary, the participant must understand what he or she is agreeing to do. The investigator must present the information to the participant in a way that is understandable to that participant, and then assess whether the participant did, indeed, understand the information. This part of the process is very important, because it lasts throughout the time that the participant is in the study. The investigator must make sure that the participant understands all the important elements of the consent form at the time the consent form is signed, and, all during the research study. The participant must understand that participation is voluntary and that he or she can withdraw from the study at any time.
The Johns Hopkins Medicine Institutional Review Boards require investigators to include the consent requirements established by DHHS (45 CFR 46.116) and FDA regulations (21 CFR 50.20). These include the following eight required elements:
1a) A statement that the study involves research;
1b) An explanation of the purposes of the research;
1c) The expected duration of the participant's participation;
1d) A description of the procedures to be followed;
1e) Identification of any procedures which are experimental;
2) A description of any reasonably foreseeable risks or discomforts to the participant;
3) A description of any benefits to the participant or to others which may reasonably be expected from the research;
4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the participant;
5a) A statement describing the extent, if any, to which confidentiality of records identifying the participant will be maintained;
5b) If the research is subject to FDA regulation, a statement that notes the possibility that the FDA may inspect study records (Research is FDA regulated if it involves the use of any drugs or medical devices other than the use of approved drugs and medical devices in the course of medical practice, or if the data will be submitted to or held for inspection by the FDA.)
6a) For research involving more than minimal risk, an explanation as to whether any compensation is available;
6b) An explanation as to whether any medical treatments are available if injury occurs;
6c) If so, what they consist of, or where further information may be obtained;
7a) An explanation of whom to contact for answers to pertinent questions about the research and research participants' rights;
7b) Whom to contact in the event of a research-related injury to the participant;
8a) A statement that participation is voluntary;
8b) A statement that refusal to participate will involve no penalty or loss of benefits to which the participant is otherwise entitled; and
8c) A statement that the participant may discontinue participation at any time without penalty or loss of benefits to which the participant is otherwise entitled.
In addition, the consent document may contain the following items when appropriate:
1a) A statement that the particular treatment or procedure may involve risks to the participant which are currently unforeseeable;
1b) If the participant is or may become pregnant, a statement that the particular treatment or procedure may involve risks to the embryo or fetus which are currently unforeseeable;
2) Anticipated circumstances under which the participant's participation may be terminated by the investigator without regard to the participant's consent;
3) Any additional costs to the participant that may result from participation in the research;
4) If this is a clinical trial, a statement that the research will be entered into the clinical trials.gov website;
5a) The consequences of a participant's decision to withdraw from the research;
5b) Procedures for orderly termination of participation by the participant;
6) A statement that significant new findings developed during the course of the research which may relate to the participant's willingness to continue participation will be provided to the participant;
7) The approximate number of participants involved in the study.
Some elements (both required and optional) are included in the preprinted "boilerplate" text of the JHM IRB template consent form. The investigator is expected to be familiar with this standard text and not duplicate items when preparing a consent form for the IRB's review.
In addition, the HIPAA authorization for use and disclosure of health information is included in the "boilerplate" text on the JHM IRB consent form template. HIPAA, which took effect on April 14, 2003, requires a participant's prior written authorization before his or her identifiable health information can be used or disclosed by “covered entities” (which includes many Hopkins institutions).
The IRB must review all materials associated with obtaining informed consent. The IRB provides the following templates to document consent and/or assent:
- HIPAA Combined Informed Consent/Authorization Template
- HIPAA Combined Parental Informed Consent/Authorization Template
- Human Pluripotent Stem Cell Research Consent Form Template
- Oral Consent Script
- Research Assent Form for Children
- Oral Assent Form Script
- Telephone Screening Script
- Johns Hopkins/King Khaled Eye Specialist Hospital Informed Consent Template
- Short Form Consent for non-English speakers
Please note: DHHS and FDA consider recruitment materials to be part of the consent process. As such, recruitment materials require IRB review or approval before they are used.
HIPAA Combined Informed Consent/Authorization Template
This form is used for most research studies. The only time it would not be used is when an Oral Consent Script will be the only consent process is approved by the IRB. For some international studies, the JHM IRB may approve a consent form on a template approved by the local institutional review board.
HIPAA Combined Parental Informed Consent/Authorization Template
This template is used when ALL study participants will be under 18 years of age and parent/legally authorized representative consent is required.
Human Pluripotent Stem Cell Research Consent Form Template
This form is used for research using human materials to create pluripotent stem cells and/or to create human gametes and embryos.
Oral Consent Scripts
This form will be used if the IRB determines that the study meets the criteria for waiver of consent documentation, and that oral consent is appropriate. The investigator must submit a script of what the consent designee will say when talking about the study with a potential participant. The script must include the 8 required elements, plus any of the optional elements that seem appropriate for the study. The oral consent script may be used when obtaining informed consent in person, or may be used over the telephone.
The IRB has posted on its website an oral consent script template to guide investigators.
Oral Assent Form Script
The investigator will include an assent script for studies where children will receive an oral explanation of the study.
Research Assent Form for Children
The investigator will include the Research Assent Form for Children for studies where children will be given a written explanation of the study. The child will sign the Research Assent Form and will be given a copy.
Note: For studies that include children from a wide age range, it is possible that the investigator will use both the Oral Assent Form Script and the Research Assent Form for Children.
If telephone screening will be part of a research study’s recruitment process, a Telephone Screening Script must be included in the protocol application to the JHM IRB. Potential research participants must be informed of their privacy rights. The Telephone Screening Script includes a HIPAA privacy statement.
The script should contain the questions that the study team member will ask the potential research participant. The script should make clear to the potential research participant if:
- Their PHI will be recorded;
- Who might have access to the PHI and for what purpose;
- Whether the PI will keep the PHI if the person does not enroll in the study or is determined to not be eligible for the study; and,
- If applicable, at what point the PHI will be destroyed.
The script should also make clear that although the study team will use its best efforts to keep the information confidential, there is no guarantee.
A telephone script may ask the potential research participant’s permission to retain the information collected during the call in a recruitment database. The script should also make clear the potential research participant’s right to cancel the authorization at any time, and should provide information about how to do this.
The IRB must review and approve a phone screening script before it is used. The PI should submit a HIPAA Form 4, Application for IRB Waiver of Privacy Authorization when he/she wishes to collect screening information by phone. The waiver, if approved, will allow the PI to obtain the PHI over the telephone without obtaining a signed HIPAA authorization form required by law.
Johns Hopkins/King Khaled Eye Specialist Hospital Informed Consent Template
This form will be used for research studies being reviewed by the JHM IRB and conducted at the King Khaled Eye Specialist Hospital in Saudi Arabia.
Short Form Consent for non-English speakers
A short form may be used when the majority of study participants are English speakers, but there may be an occasional person who will not be able to understand the consent form written in English. . In this instance, the short form in the participant’s language can be used to obtain consent, thereby ensuring equal access for potential subjects. The short form documents that the elements of informed consent required by 45CFR46.116 have been presented and are understood by the participant or partcipant’s legally authorized representative.
What are the required signatures with short forms?
- Study participant must sign the short form consent.
- Witness must sign the short form consent and the approved JHM IRB full English version consent form.
- Consent designee must sign the approved JHM IRB full English version consent form.
HELPFUL HINT: Each person should sign the consent forms they understand. The non-English speaking participant signs the short form consent in their language. The consent designee signs the English version full consent. The witness understands both languages, so signs both.
The JHM IRB has approved translations of the short form document in several languages. These approved translations are posted on the IRB website. If you require a short form consent in a different language, you must have the English version short form translated into the required language and submit it, along with a Certificate of Translation to the JHM IRB for approval. Information about available services for translating the short form consent can be found at the following website http://www.hopkinsmedicine.org/stlm/translating.html or by contacting the Johns Hopkins Language Access Services at 410-614-4685. There is a fee for this service.