Informed consent must be documented by the use of a written informed consent form approved by the IRB and signed (including in an electronic format) by the participant or the participant’s legally authorized representative. A written copy must be provided to the person signing the informed consent form.
Because the signed document is a written record of the consent discussion
- The investigator must retain the original, signed document, and
- Each participant or legally authorized representative must be given a copy of the signed document.
Investigators can request a waiver by submitting a Waiver of Informed Consent Documentation form, justifying the request for waiver or alteration of the applicable federal requirements.
Documentation of consent cannot be waived for FDA-regulated research.
GINA is a federal law that prohibits discrimination in health coverage and employment based on genetic information. GINA defines genetic information as information about:
- An individual's genetic tests (including genetic tests done as part of a research study);
- Genetic tests of an individual's family members (defined as dependents and up to and including 4th degree relatives);
- Genetic tests of any fetus of an individual or family member who is a pregnant woman, and genetic tests of any embryo legally held by an individual or family member utilizing assisted reproductive technology;
- The manifestation of a disease or disorder in an individual's family members (family history); or
- Any request for, or receipt of, genetic services or participation in clinical research that includes genetic services (genetic testing, counseling, or education) by an individual or an individual's family members.
Genetic information does not include information about the sex or age of any individual.
GINA defines a genetic test as an analysis of human DNA, RNA, chromosomes, proteins, or metabolites that detect genotypes, mutations, or chromosomal changes. Under GINA, genetic tests do not include analyses of proteins or metabolites that are directly related to a manifested disease, disorder, or pathological condition that could reasonably be detected by a health care professional with appropriate training and expertise in the field of medicine involved.
When investigators develop consent processes and documents for genetic research, they should consider whether and how the protections provided by GINA should be reflected in the consent document's description of risks and provisions for assuring the confidentiality of the data.
Investigators must ensure that descriptions of the reasonably foreseeable risks of genetic research and any statements describing the extent to which confidentiality of records identifying the subject will be maintained do not overstate the protections provided by GINA (45 CFR 46.116(a)).
The GINA language that should be included as applicable can be found in the Sample Consent Form found on the Forms page of the UAB IRB website.
Background
There has been increasing concern in the biomedical community about the use of biological specimens obtained during clinical research. Current Federal regulations set out criteria for the use of participant specimens. These criteria include (1) participant specimens can only be used for research that is described in the protocol and consent; and (2) any new research use of identifiable specimens must be approved by the IRB. Furthermore, the National Bioethics Advisory Commission (NBAC), which was established by the President to make recommendations concerning bioethical issues arising from research on human biology and behavior, has released its recommendations on stored biological specimens.
Purpose
The following guide is provided for investigators who anticipate
- Using remnant (leftover) biological specimens that contain identifiers or are coded in any way that can be traced to the participant, or
- Taking extra biological specimens (in addition to what is needed for protocol-defined research), whether they are identifiable or anonymized.
These recommendations are based on current federal regulations and the NBAC recommendations.
Definitions
- Biological specimens:
- Tissues, bodily fluids (such as blood, saliva), and excreta (such as, stool and urine).
- Microbial organism specimens:
- Bacteria, fungi, virus and parasitic specimens that are stored in artificial culture or biological cell culture
- Identifiers:
- Data that directly identify the individual from whom a sample is obtained, such as, name, initials, Social Security Number, Hospital Patient Number, address, telephone number or a code number linking the individual to the data.
- Identifiable specimens:
- Biological specimens that are identified either directly or through a code. It is possible to determine the individual’s identity from the identifying information.
- Coded specimens:
- Biological specimens that are identified only by a code key that can be linked to the individual directly or through an intermediary (e.g., a repository). These are identifiable specimens.
- Anonymized specimens:
- Biological specimens that have been stripped of all identifiers (including codes) that would link directly to the individual. Please note that health and demographic data may be retained, such as height, weight, diagnosis, socio-ethnic group, zip code, etc.
Guidance
The IRB recommends that consent for retention and future use of biological specimen taken in conjunction with a clinical protocol be incorporated into the study consent form rather than being a separate consent document. As with any consent document, it must be reviewed and approved by the IRB before use. At the close of the study, these consents should be placed in a file and retained under lock by investigator/facility responsible for their use and maintained for at least two years after the last specimen has been used.
Anonymized biological specimens
Additional consent is not required for the use of biological specimens that have been anonymized. However, consent to obtain biological specimens is required if the specimens are being obtained outside of the study protocol or in addition to specimens obtained for study related purposes, even if these specimens are then anonymized.
Consenting Participants
It should be made clear to participants that they may refuse permission for future research use of their biological specimens without affecting their participation in the study or their care by the health provider. It should also be made clear to participants that they may change their mind and refuse to permit their specimens to be used at some time in the future.
Reconsenting Participants
By not requesting and obtaining proper consent from the participants at the time that the specimen is obtained, an investigator runs the risk of not being able to use valuable biological specimens later without re-consenting the participants—a procedure that may be problematic because it may be construed as a breach of confidentiality. If re-consenting a participant is planned, it is important to include in, preferably, the main protocol consent form rather than in a separate consent, permission to recontact the participant for future studies of stored biological specimens.
Minors as Participants
If a parent or guardian on behalf of a minor child gave consent, the child participant as an adult may rescind the permission to use the identifiable biological specimens (just as adult participants could change their mind about use of their biological specimens). In the event that recontact is required for the research, the investigator would need to attempt to contact the child/now adult whose identifiable biological specimens were kept.
Research Populations
Special consideration should be given to the handling of the information obtained from research with biological specimens, even if not individually identified, in cases in which the participants’ socio-economic or ethnic community might be harmed by the disclosure of data for that community as a group (for example, a study linking incidence of a specific disease with participant zip codes, or with an ethnic group). A statement that there might be unintended harm to the individual or group as a result of disclosure of data or research results should be included in the Risk section of the supplemental consent.
Previously Collected Biological Specimens
If the investigator plans to use already collected identifiable biological specimens in research not specifically defined in the protocol, the investigator must consult with the IRB. If the IRB finds that an existing consent covers the intended research use, then further action may not be necessary. If there was no prior consent, or if the IRB finds that the consent does not cover the intended use, then consent must be obtained, or waived by the IRB, as appropriate.
Microbial Organisms Derived From Biological Specimens
No additional consent is required for microorganisms that are stored with no information that identifies the participant or link to an identified specimen after the study is completed. Permission to retain microorganisms with participant identifying information after the study is completed must be included in the consent form document. This includes organisms that are linked to identifiable specimens.
Storage of Biological Specimens
If no biological specimens are to be stored after a study is completed, then there needs to be a statement in both the protocol and informed consent that all biological specimens will be destroyed at the end of the study or at a specified time (e.g., after analysis).
If biological specimens are to be kept for non-protocol-defined research, the investigator should create a consent document covering each of the sections in the consent template attached. Samples of acceptable statements are included for each paragraph or section. At the very least, participants should be told:
- What kind of specimens will be collected and the means of collection.
- What type of research will be done with the specimens.
- Whether the biological specimens will be shared with other investigators,
- Whether biological specimens will be coded or anonymized (no way of tracing back to participant/uncoded or code destroyed).
- Whether the participant may be contacted for additional consent.
- How long, if known, the biological specimens will be stored. (Short-term: current protocol only or other current research; Long-term: future studies on disease or condition, repository, etc.).
- Foreseeable risks or benefits to participants in the collection, storage and subsequent research use of specimens.
- What will be done with the biological specimens if the participant refuses permission (“anonymized”—stripped of identifiers--or destroyed?).
- What will be done with the research results. (Research results should not be placed in the individual participant’s medical record.)
The IRB staff can assist in developing the consent if you call and schedule an appointment at least 1 week prior to the deadline for submission.
The IRB determines, for each protocol it reviews, which of the following elements and disclosures must be included in the informed consent process. Investigators can avoid delay in the review process by ensuring that all applicable items are included and reflect the latest institutional language.
Basic Elements
Each item listed must be included unless the IRB approves a waiver or alteration of informed consent.
- A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject’s participation, a description of the procedures to be followed, and identification of any procedures that are experimental;
- A description of any reasonably foreseeable risks or discomforts to the participant;
- A description of any benefits to the participant or to others that may reasonably be expected from the research;
- A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous to the participant;
- A statement describing the extent, if any, to which confidentiality of records identifying the participant will be maintained;
- For research involving more than minimal risk, an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what it consists of, or where further information may be obtained;
- The UAB statement must be included: “UAB has not provided for any payment if you are harmed as a result of taking part in this study. If such harm occurs, treatment will be provided. However, this treatment will not be provided free of charge.”
- If the research is sponsored, include whether or not the sponsor(s) will provide compensation for and/or pay for treatment of research-related injuries
- When the sponsor(s) will not provide compensation for or pay for treatment of research-related injuries, include the name of all sponsors in the UAB
- When the sponsor(s) will provide compensation for and/or pay for treatment of research-related injuries, include the specific language provided by the sponsor(s) regarding injury compensation. Note: The IRB must be provided with “sponsor verification” in the form of a letter signed by the sponsor(s) with the same wording given in the consent form, a model consent form included in the protocol and listed in the Table of Contents of the protocol with the same wording, or in the contract or agreement.
- An explanation of whom to contact for answers to pertinent questions about the research and research participants’ rights, and whom to contact in the event of a research-related injury to the participant;A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the participant is otherwise entitled, and the participant may discontinue participation at any time without penalty or loss of benefits to which the participant is otherwise entitled; and
- One of the following statements about any research that involves the collection of identifiable private information or identifiable biospecimens:
- A statement that identifiers might be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies or distributed to another investigator for future research studies without additional informed consent from the subject or the legally authorized representative, if this might be a possibility; or
- A statement that the participant’s information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies.
- For research involving UAB students or employees, the appropriate statement must be included (see Sample Informed Consent Document).
Disclosures
In seeking informed consent, the following information will be disclosed to the participant unless waived by the IRB:
- Only IRB-approved advertisements and recruitment materials.
- If applicable, relevant animal data and their significance should be explained to potential participants.
- An explanation of measures to prevent pregnancy that should be taken while in the study, if applicable.
- A statement that notes the possibility that specific entities (e.g., UAB IRB, OHRP, FDA and foreign regulatory agencies, if appropriate) may inspect the research records.
- A statement that any reportable diseases/conditions detected during the research will be reported to the county or state health department:
- Where HIV testing is conducted, individuals whose test results are associated with personal identifiers must be informed of their own test results and provided the opportunity to receive appropriate counseling before and after the testing;
- Where other protocol testing for reportable diseases is conducted, individuals will be informed of the results and told where to obtain counseling and referred to their primary care physician or the state health department.
- Where drug screening is conducted, participants will be told that the results may exclude them from the study or if the information in the opinion of the investigator poses significant harm to the participant or risks to others that the results of the drug testing will be reportable to a third party.
- Where DNA/genetic testing is conducted as part of the study, this information should be clearly stated and the testing will be limited to the disease under study or for other disease with the participants' permission.
- When any other applicable federal, state, or local laws, require additional information to be disclosed to the proper authorities in cases such as:
- child abuse and neglect;
- elder abuse and neglect.
- When a participant is the first one to undergo a new procedure, this information should be clearly stated.
- For research involving collection of biological or tissue specimens in conjunction with a clinical protocol:
- A statement on retention and future use of biological or tissue specimens within the body of the study consent documents rather than a separate informed consent document including the following choices:
- Limiting use for specified diseases;
- Allowing unlimited use;
- Contacting participants prior to use;
- Option not to allow use of specimens for future research.
- A statement clearly noting that participants may refuse permission for future research use of their biological specimens without affecting their participation in the study or their care by the health provider.
- A statement that participants may change their mind and refuse to permit their specimens to be used at some time in the future to the extent their specimens are identifiable.
- A statement on retention and future use of biological or tissue specimens within the body of the study consent documents rather than a separate informed consent document including the following choices:
Additional Elements
One or more of the following elements of information, when appropriate, shall also be provided to each participant or the legally authorized representative:
- A statement that the particular treatment or procedure may involve risks to the participant (or to the embryo or fetus, if the participant is or may become pregnant), that are currently unforeseeable. Examples of when the IRB requires this element are:
- Phase I or II clinical investigations;
- Experimental procedures or treatments with limited available data on risks.
- Anticipated circumstances under which the participant’s participation may be terminated by the investigator without regard to the participant’s or legally authorized representative’s consent. Examples of when the IRB requires this element are:
- If the sponsor may stop the study;
- If the investigator reserves discretion to remove the participant from the study;
- If the investigator may remove the participant from the study should the investigator determine it is in the best interest of the participant; or
- If the participant does not follow study instructions.
- Any additional costs to the participant that may result from participation in the research. Examples of when the IRB requires this element are:
- If study procedures result in potential billing to the participant or third party payers;
- If participants may have out-of-pocket costs from participation in the research (e.g., parking, meals, transportation); or
- If a possibility exists that a study drug become commercially available and no longer provided at no cost to the participant.
- The consequences of a participant’s decision to withdraw from the research and procedures for orderly termination of participation by the participant. Examples of when the IRB requires this element are:
- If drug dose tapering is required and has risks to participants;
- When a follow-up visit or testing is required for safety reasons.
- A statement that significant new findings developed during the course of the research that may relate to the participant’s willingness to continue participation will be provided to the participant.
- The approximate number of participants involved in the study. The IRB generally requires this element with respect to the number of participants locally and, if applicable, nationally.
- A statement that the participant’s biospecimens (even if identifiers are removed) may be used for commercial profit and whether the subject will or will not share in this commercial profit.
- A statement regarding whether clinically relevant results, including individual research results, will be disclosed to subjects, and if so, under what conditions.
- For research involving biospecimens, whether the research will (if known) or might include whole genome sequencing (i.e., sequencing of a human germline or somatic specimen with the intent to generate the genome or exome sequence of that specimen).
Broad Consent
Elements of broad consent for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens.
UAB is not adopting broad consent at this time.
Other Information in the Informed Consent
Other information that should be included as applicable can be found in the Sample Consent Form found on the Forms page of the UAB IRB website
When applicable, one or more of the following elements of information shall also be provided to each participant:
- Disclosure or non-disclosure of particular studies presented in the planned project. For example, the informed consent for a research study might advise patients in the following way: Over the course of this trial, routine healthcare information, such as [name of test] results and standard blood tests, will be obtained and kept in your medical record.
The results of these tests may be available to you from your healthcare provider. In addition, trial investigators may collect certain data that are not routine healthcare information, including [for example, assay results name of tests]; these are new [definition] of uncertain significance. The results of these tests will not be released to you.
- Special considerations for children should be addressed explicitly with language such as “parent or legally authorized representative has a right to look at the child’s data.”
- Most research data derived from tissue specimens has not been validated for clinical decision-making and should not be disclosed to the participant under most circumstances. In contrast, aggregate data should be made available to research participants when appropriate or if requested (Proceedings of the Confidentiality, Data Security and Cancer Research Workshop, Bethesda, MD, December 1-2, 1999).