- Purpose and Applicability
- Regulatory Oversight
- Exempt Research
- Consent Overview
- The Key Information Requirement
- Identifying and Describing Reasonably Foreseeable Risks in Research
- Protected and Vulnerable Populations
- Diminished or Fluctuating Consent Capacity and Use of a Legally Authorized Representative (LAR)
- Subjects with Comprehension Barriers (e.g., language, literacy, visual impairment) or Who Cannot Write or Speak
- Anticipated involvement of subjects with limited English proficiency
- Unexpected involvement of subjects with limited English proficiency
- Subjects with low literacy
- Subjects with visual impairments
- Subjects who cannot write a signature on a consent form
- Electronic Consent
- Documentation of Consent
- Reconsent and Ongoing Subject Communication
- Related Materials
- Regulatory References
- Version Table
Purpose and Applicability
This guidance provides researchers, the Human Subjects Division (HSD), and the UW Institutional Review Boards (IRBs) with an overview of the requirements and best practices for obtaining regulatorily compliant and meaningful consent, parental permission, and assent for participation in research. This information applies to:
- All research reviewed by the UW IRB, including non-UW institutions and sites for which the UW IRB is providing review.
- UW research reviewed by an external (non-UW) IRB.
- UW research determined to be exempt or reviewed by the Limited IRB process (except as indicated below regarding specific requirements). (Details: GUIDANCE Exempt Research and SOP Limited IRB Review)
The following specialized consent-related topics are covered elsewhere:
- Exception from Informed Consent (SUPPLEMENT EFIC), which may be appropriate when the time frame between recruiting and study procedures is too short for obtaining consent (e.g., emergency medicine studies).
- Emergency or Compassionate Use of investigational drugs or devices for clinical care (not research) (Single Patient Emergency or Compassionate Use).
- Clinical use of Humanitarian Use Devices.
Informed consent for research must be legally effective and obtained before the subject can participate in any study-related activities. It should include an active process of sharing information between the researcher and potential subject and an affirmative agreement by the subject that they want to participate. The concept of “implied” or “passive” consent (e.g., parental permission is assumed unless the parent “opts out” of their child’s participation in the research) does not meet the requirements for informed consent for research. Informed consent serves to:
- provide sufficient details about the study so prospective subjects can make an informed decision about whether to participate;
- facilitate understanding of what has been disclosed; and
- promote voluntariness about whether to participate.
Consent method. The method by which consent is obtained depends on the specifics of the study and the regulations that govern the research. When documentation of consent can be waived, researchers have greater flexibility in the ways in which they can design the consent process. For example, it may be appropriate to conduct an oral consent process without providing the subjects with printed consent materials if the study is a low risk, one-time interview with adults. If subjects will participate in the study remotely (e.g., low risk computer surveys) then providing the subjects with an electronic information statement would be appropriate. Regardless of the method used (e.g., oral, electronic, in-person), consent processes must include all the applicable regulatory requirements (Regulatory Oversight) unless the IRB determines any requirements can be waived.
Assent is obtained from subjects who are unable to provide legally-effective informed consent on their own behalf because they are minors or have diminished decision-making capacity. Subjects who have the cognitive capability may provide their assent to participate and a parent/guardian or legally-authorized representative (LAR) may provide consent on behalf of the subject. Alternatively, assent, LAR consent, and/or parental permission may be waived by the IRB. Failure to object should not be equated with an active willingness to participate. See the section on Assent for more information.
Subject. Unless otherwise indicated, in this guidance the term “subject” refers to: the subject, the parent(s) or guardian of a minor subject, and the LAR for a decisionally-impaired adult subject.
Recruitment. Advertisements, announcements, social media (e.g., Facebook, Twitter) postings, and other recruitment processes and materials are generally considered to be part of the consent process.
Which regulations apply?
Consent requirements may vary depending on the subject population, federal regulations, state laws, international laws, and institutional polices that apply to the research.
Federal agency consent requirements
It is HSD policy to voluntarily apply the Common Rule (45 CFR 46) consent regulations to all research reviewed by the UW IRB except as described in the HSD Flexibility Policy (GUIDANCE Authority and Responsibilities of HSD and UW IRB), in addition to other applicable requirements. The WORKSHEET Consent Requirements and Waivers provides a summary of the required general characteristics and elements of consent as well as the criteria for waiving required elements and documentation of consent for the Common Rule, FDA, and other federal regulatory agencies (e.g., Department of Justice). That worksheet also lists the consent requirements for federally-designated protected populations (i.e., pregnant women and neonates, prisoners, children).
State or other local law
State laws in the jurisdiction where the research is being conducted may affect the consent process (e.g., mandatory reporting; age of majority). See GUIDANCE Human Subjects Regulations, GUIDANCE Mandatory State Reporting, and the section on legally authorized representative consent for details. Researchers are responsible for identifying applicable state or other local laws when the research is conducted outside of Washington State, including internationally (see OHRP webpage for international research).
HSD policies related to consent can be found in the WORKSHEET Consent Requirements and Waivers and throughout this guidance.
HSD does not apply consent regulations to research that is determined to be exempt from IRB review. Nor does HSD review and approve consent plans and consent materials for exempt research. Researchers are still responsible for protecting the rights and the welfare of subjects in their research and for providing subjects with information about the research prior to their agreement to participate. See the section on Information for subjects in the GUIDANCE Exempt Research for full details.
More on The Purpose of Consent
An effective consent process provides the information that a reasonable person would want to have, in a transparent way, so that the prospective subjects are in control of their decision to provide authorization (or not) to participate, based on whether their own values and opinions align with those of the research, and considering the risks and benefits from their individual perspectives.
Most research generates knowledge to promote a common good. It is often funded by public sources and is increasingly integrated into health care delivery systems. In addition to the value of consent to the individual, there is a social value to establishing effective and ethical consent processes and norms to ensure accountability of the research enterprise.
More on Facilitating Informed Decision-Making
Information provided during consent should emphasize the Key Information that is most likely to assist the particular subject population with making a decision about whether to participate in research. This means that the consent process and/or form does not necessarily need to include a detailed description of every procedure the enrolled subject would undergo. Rather, it should emphasize the information that will be most influential for enrollment decisions. Subjects can be provided with tables or supplemental information sheets with additional study details after the enrollment decision has been made.
Consent information must be presented in a way that facilitates comprehension. This means providing consent information in a logical sequence and in a way that allows for real-time review during discussion between study staff and the prospective subject. Providing context that is meaningful and language that is familiar and at an appropriate reading level for the particular subject population will make the content easier for subjects to understand.
More on Written Consent Materials
Written consent materials should be presented from the perspective of the subject and what it would mean to them to participate (e.g., the pros and cons, and whys and why nots of the many aspects of the study). When consent information is provided in writing, understanding may be facilitated by breaking up dense text with sectioning, pictures, icons, schematic diagrams of study design, or putting information in side-by-side comparison tables. Headings should be subject-focused rather than regulations-focused. For example, depending on the study and population-specifics, information about risks and benefits, time commitments, and certain procedures may be appropriate under the headings, “Why I may want to participate” and, “Why I may not want to participate”. As described in Consideration 2, the consent form does not need to include every procedure the subject would undergo and should instead focus on the procedures and other information that would be most likely to influence the subject’s decision about whether to enroll in the study.
More on The Consent Process
The presentation and discussion of consent information, as well as the consent form itself, are single elements of the overall consent process. Decision-making by prospective subjects typically begins with the information presented in recruitment materials and in initial discussions with study staff, well before the consent form is presented. This information may be equally or more influential in final decision-making as the consent form. Post-enrollment communication, such as answering subject questions and providing them with relevant new information, is also part of the consent process, because subjects consider throughout a study whether they wish to continue their participation. The continued education and engagement of subjects throughout the research process is vital. In addition, it is a way to demonstrate respect and gratitude for their contribution and to maintain trust. Finally, the initial consent procedure may need to be repeated or supplemented if relevant new information becomes available or if the study involves a lengthy commitment from subjects.
More on Coercion, Undue Influence, Diminished Consent Capacity, and Vulnerable Populations
Federal regulations identify pregnant women*, prisoners, and children as Protected Populations and specify additional protections and consent requirements for them. However, these additional required protections may not be enough to ensure consent comprehension and voluntary participation for these groups. Other populations are also vulnerable to undue influence or coercion. Similar protections may be appropriate for them. These additional safeguards must be considered throughout the vulnerable subject’s participation in the study (i.e., recruitment, obtaining consent, and after enrollment).
*Pregnant women are not designated as a vulnerable population in the Common Rule or FDA regulations. However, there are additional regulatory requirements for enrolling this population for research funded or supported by the agencies that signed Subpart B. See Protected and Vulnerable Populations for additional discussion.
The Key Information Requirement
The Key Information requirement and its purpose
The Common Rule requires that informed consent must begin with a concise and focused presentation of Key Information that is most likely to assist prospective subjects or their representatives in understanding the reasons why they might or might not want to participate in the research. The Key Information must be organized and presented in a way that facilitates comprehension. Although a Key Information section may serve as an abstract or executive summary for a longer consent form, that is not its primary function.
When is Key Information required?
All consent-related materials must include Key Information if the study meets these criteria:
- The study is non-exempt human subjects research reviewed by the UW IRB (per HSD policy, it does not matter whether the Common Rule governs the study); and
- The IRB has not fully waived the requirement to obtain consent; and
- The study is fully or conditionally approved by the IRB on or after January 21, 2019 (the date when this regulatory requirement was enacted).
- This includes consent forms, online or paper information statements, e-consent information, the short form consent process, oral consent with no written component, parental permission, and LAR consent.
The Common Rule does not require Key Information in assent forms for children and decisionally-impaired adults, however, it is HSD policy to require Key Information when assent forms have more than 2000 words.
Consent materials must have a distinct Key Information section when they are more than 2,000 words (not counting any signatures sections; approximately 5 pages; single-spaced; 1-inch margins). It is HSD policy to consider shorter documents (less than 2000 words) to have met the requirement to present Key Information in a concise and focused manner because of their short length. However, the IRB has the authority to require a separate Key Information section if appropriate.
There is no specific information that must be included in the Key Information. The appropriate information depends on the nature of the study, nature of the subject population, and on the other information presented as part of the consent process and/or form. Federal guidance stresses that the Key Information should be meaningful within the context of the study and has therefore avoided strictly defining what information should be included. However, the guidance does generally expect that Key Information include a concise explanation of the following elements:
Key Information elements
- voluntary consent is being sought for research;
- research purpose, expected duration of participation, and procedures;
- the most important, reasonably foreseeable risks or discomforts*;
- reasonably expected benefits to the subjects or others; and
- appropriate alternative procedures or courses of treatment, if any.
*Risks and discomforts in Key Information should be described with the study context and subject perspective in mind. For example, if the most important risks associated with the study are from a blood draw, these risks should be described in Key Information. However, if a blood draw is only one of many procedures and the other study procedures are associated with more significant risks to subjects, then information about the blood draw may be left out of Key Information and instead described in a more detailed Risks section later in the consent process or form.
HSD tip. For most biomedical studies, information about compensation for injury, specific protections for privacy and confidentiality, and how data and specimens will be shared and stored does not need to be in the Key Information. Such information can be described elsewhere in the consent form or process.
Primary factor: the subject population. Key information is intended to be the information that is most likely to assist the specific subject population (e.g., end-stage cancer patients; first-year college students; parents of toddlers with autism; prisoners). Identifying this information is the responsibility of the researcher. This may mean that the researcher needs to consult with publications about research subjects’ preferences, disease-focused nonprofit groups, patient interest groups, or other researchers/study staff with experience with the specific population. It may also involve directly consulting selected members of the study population.
When writing Key Information, consider the following questions:
Questions to consider
- What are the main reasons a subject will want to join, or not join, this study?
- What is the research question the study is trying to answer and why is it relevant to the prospective subject?
- What aspects of research participation in this study are likely to be unfamiliar to a prospective subject, diverge from a subject’s expectations, or require special attention?
- What information about the subject is being collected as part of this research?
- What are the types of activities (procedures) that subjects will do in the research?
- What impact will participating in this research have on the subject outside of the research? For example, will it reduce options for standard treatments?
- How will their experience as a research subject in this study differ from treatment they might receive as a patient outside of the study?
- In what ways is this research novel?
- What is the anticipated time commitment for the subject?
Relationship to the rest of the consent form/materials. A Key Information section may appropriately include a summary of relevant pieces of information that are then explained in greater detail later in the consent form or process. However, information that is fully described in the Key Information section does not need to be repeated later in the form or process. Similarly, if the Key Information section includes any of the elements of consent described in the WORKSHEET Consent Requirements and Waivers, those elements do not need to be repeated later in the form or consent process. See the document, EXAMPLE Key Information).
Structure and presentation
The Key Information may be in a separate document or in the beginning of the consent form, but it must be presented to subjects at the beginning of the consent process. The Key Information requirement applies to the consent process as a whole – not simply to consent documents. In other words, there is flexibility in how the presentation of Key Information is structured if it is organized and presented in a way that facilitates comprehension for prospective subjects.
In most cases, when there is a separate Key Information section, it will be relatively short compared to the rest of the consent document or process. For example, complicated clinical trials involving high risk procedures typically involve consent forms of more than 20 pages. In these cases, the federal agencies expect that the Key Information section would be no more than a few pages. However, those agencies have also stressed that the section should be meaningful within the context of the study and have therefore purposely avoided specifying length requirements. See EXAMPLE Key Information.
Identifying and Describing Reasonably Foreseeable Risks in Research
A workable definition of ‘reasonably foreseeable’ is required to ensure that a description of any reasonably foreseeable risks or discomforts to the subject are presented to a potential research participant as part of the informed consent process (45 CFR 46. 116 (b) (2); 21 CFR 50.25(a)(2)). This is particularly relevant for risks associated with drugs, devices, or complex procedures where the number of risks may be large, and inclusion of all possible risks may detract from an individual’s ability to consider those risks that are relevant to their decision to participate in the research.
The following definition, built upon FDA guidance and SACHRP guidance, should be used to help evaluate which risks are reasonably foreseeable and, therefore, should be included in the consent form or included as part of the informed consent process.
Reasonably Foreseeable Risks
Reasonably foreseeable risks are those risks that a reasonable person in the target population would find meaningful to their decision to participate in the research. This should include (but not be limited to) any of the following: (a) risks that are more likely to occur; (b) risks that are serious; OR (c) risks that the research is evaluating and that an individual would not otherwise be exposed to if they were to decide not to participate in the research.
(a) “More likely to occur” are risks that are frequent/common or very frequent/very common as described in the table below. Risks expected or known to be very frequent/very common or frequent/common should generally be included in the consent form and/or consent process. The IRB can always exclude frequent/very frequent risks that don’t apply to the target population (for example the study includes an adverse drug reaction with acetaminophen but subjects taking acetaminophen are excluded from participating). Conversely, the IRB can require the inclusion of infrequent, rare, or very rare risks that don’t otherwise meet the overall definition above if they determine the target population would find them meaningful to their decision to participate in the research (e.g., rare permanent teeth discoloration).
We recognize that in some cases, there is no written source or data (e.g., drug Investigator Brochure or package insert) to rely on when determining frequency of risks. In those instances, the expert judgement of the researcher, or relevant published literature, would need to be applied when determining frequency. The IRB, in their review, would have the opportunity to check these assumptions.
|Group Descriptor||Frequency Rate||Percentage|
|very frequent/very common||>1 in 10||10% or higher|
|frequent/common||1 in 100 to 1 in 10||1-10%|
|infrequent/uncommon||1 in 1,000 to 1 in 100||0.1-1%|
|rare||1 in 10,000 to 1 in 1,000||0.01-0.1%|
|very rare||<1 in 10,000||<0.01%|
Table adapted from the Council for International Organizations of Medical Sciences and FDA prescription drug labeling guidance.
(b) “Serious” are risks that fall under the FDA’s definition of a Serious Adverse Event (i.e., anything that would result in death, be life-threatening, would require hospitalization to treat, could cause disability/permanent damage, cause birth defects, require an intervention to prevent permanent impairment or damage or other important medical events). For a full description of the definition, visit this FDA webpage. These risks should generally be included regardless of the potential frequency of occurrence. As with ‘more likely to occur’ the IRB has discretion to leave out serious risks that are not relevant to a particular population, may be theoretical or unsupported by the data, or would detract from a participant’s understanding of the more significant risks associated with the primary aim(s) of the research.
- A drug can be life threatening to children under 5 years of age, but all children are excluded from participating in the study
- A researcher proposes including Stevens-Johnson syndrome (SJS) as a possible risk of the study but there has been no incident of SJS to date
- A study of a novel diabetes drug involves routine blood draws with use of topical lidocaine to numb the area of the needlestick but the very rare risk of anaphylaxis from the lidocaine is excluded (i.e., inclusion is not relevant to a reasonable person’s meaningful decision to participate in the research.
(c) “Risks that the research is evaluating.” If researchers design and conduct a study for the purpose of evaluating a particular risk then the research risk being evaluated has been recognized as a sufficiently possible outcome to be considered “reasonably foreseeable” and should be disclosed to prospective subjects (adapted from OHRP Comparative Effectiveness Guidance).
A researcher may suspect a new study drug might cause slightly increased blood sugar levels. There is no prior evidence of this, and they think it’s very unlikely (so it doesn’t trigger inclusion based on frequency), and it doesn’t meet the ‘serious’ criteria for inclusion in the consent. However, they are planning to actively monitor subject blood glucose levels throughout the study and intervene when appropriate. This would be an example where we would expect the researcher to include risks of increased blood sugar levels in the consent form.
Risk statements in consent forms should be simplified such that the information included is understandable and relevant to the subject population. Detailed descriptions of all potential risks are counterproductive if they do not provide potential subjects with useful information and may inadvertently distract subjects from relevant data. (SACHRP recommendations)
For minimal risk procedures, risks or burdens that are immaterial or obvious to potential participants need not be explicitly addressed in the consent form or dialogue. For example, participants need not be told that needle sticks can cause minor pain or that surveys can be boring. There is also no need to specifically state the absence of risk where none exists. (SACHRP recommendations)
Applying the Guidance – Examples
A particular condition has several treatment options, but an individual’s response to the treatment can be highly variable and unpredictable. Many patients undergo a trial-and-error period until they find a treatment plan that is effective for them. The purpose of this study is to identify biomarkers that may help predict a response to a specific drug in individuals diagnosed with the condition. The drug is an FDA-approved drug for the treatment of this condition and is frequently used in clinical care. A revised package insert includes three new post-market risks.
- risk of serious infection (12%)
- diarrhea (5.3%)
- mild back pain (0.5%)
Should these risks be added to the consent form/process as reasonably foreseeable risks?
Serious infections are very frequent according to the investigator’s brochure. Diarrhea is a frequent risk according to the investigator’s brochure. Therefore, both serious infections and diarrhea meet the definition of a reasonably foreseeable risk as they are risks that are more likely to occur.
Risk of mild back pain does not meet definition of a reasonably foreseeable risk because it is not more likely to occur, nor is it serious or being evaluated by the study.
The risks of serious infection and diarrhea need to be added to the consent form/process.
The study aims to optimize the imaging of abdominal organs with a contrast enhanced ultrasound comparing clinical ultrasounds with research ultrasounds. Study procedures include a contrast-enhanced ultrasound using a contrast agent (FDA approved). This procedure adds approximately 15 additional minutes to the patient’s standard of care ultrasound. Although rare, the contrast agent does have a risk of severe allergic reaction.
Should this risk be added to the consent form/process as a reasonably foreseeable risk?
Severe allergic reaction is a rare risk and is therefore not more likely to occur. However, severe allergic reaction meets the definition of a serious risk as it could be life threatening.
Yes, the risk of severe (life-threatening) allergic reaction should be added to the consent form.
The purpose of this study is to investigate the safety and effectiveness of long-term treatment using either a combination of drugs or a single drug to prevent subjects acquiring HIV in subjects who are HIV negative.The investigator brochure lists three rare but serious risks for the drug combination that are not currently in the consent form (viral resistant mutations, interstitial nephritis, and immune reconstitution syndrome) that exclusively affect HIV positive individuals.
Should these risks be added to the consent form/process as reasonably foreseeable risks?
These are risks associated with taking the drug if HIV positive, however, the study is excluding HIV positive subjects and regularly testing subjects for HIV transmission.
No, these risks do not need to be added to the consent form.
When to Describe Risks for Studies Evaluating Medically Recognized Standards of Care
It can be difficult to determine which risks to include in the consent form when the research involves medically recognized standards of care procedures or treatments in addition to, or instead of, any investigational procedures or treatments.
In general, the reasonably foreseeable risks associated with a standard of care procedure or treatment should be described in the consent form when:
- the standard care procedure or treatment is required solely for research purposes;
- the research design dictates the procedure or treatment that will be provided to the subject;
- the research design restricts the ability of the subject or the subject’s care provider to choose the procedure or treatment that will be provided to the subject.
The examples below illustrate how to identify: (1) which risks are research risks and should be described in the consent process/form; and (2) which risks are not research risks and should not be described in the consent process/form. Additional information can be found in the OHRP draft Guidance, “Disclosing Reasonably Foreseeable Risks in Research Evaluating Standards of Care”.
Example 1 - biomedical
A physician researcher plans to compare the effects of two different FDA-approved vascular stents on oxygen flow in patients with significantly blocked arteries that are life-threatening and for whom the only appropriate clinical treatment is implantation of a vascular stent.
The risks associated with each of the two stents are research risks and must be included in the consent process/form. There are many stents that a physician could use, but the research protocol is restricting the physician’s (and subject’s) choice to the two that are the focus of the study.
Not research risks
The risks associated with the surgery, including the surgical procedures, general anesthesia, and any angiography with radio-opaque dyes performed during the surgery to verify the placement and efficacy of the stent are not different than they would be if the patient were not enrolled in the research and should not be included in the consent process/form.
Example 2 - biomedical
A physician researcher at a local clinic plans to do a research study with patients who have been recently diagnosed with osteoporosis and who require treatment. The physician wants to compare the effects of two different FDA-approved estrogens on the osteoporosis. As part of clinical care, the physician normally does a DEXA scan to measure bone density before beginning any osteoporosis treatment, and then repeats the DEXA scan after one year to see whether the treatment is having any beneficial effects.
The physician will randomly assign each subject to one of two FDA-approved estrogen treatments for osteoporosis.
The risks associated with the two estrogen treatments are research risks and must be included in the consent process/form. The choice of how the osteoporosis will be treated has been restricted by the research design (to the two estrogens).
Not Research Risks
The risks associated with the two DEXA scans are not research risks because the physician obtains DEXA scans for all of their patients being treated for osteoporosis, not just those who are in the research study.
The physician is interested in the effects of the two FDA-approved estrogens. However, they will prescribe osteoporosis treatment to all of their patients based solely on clinical factors. The treatment could be one of many estrogens (including the two they are interested in), or one of many bisphosphonate drugs. For example, patients who are breast cancer survivors would receive a bisphosphonate drug instead of estrogen because of the effects of estrogens on the growth of some types of cancer cells. Per the physician’s normal clinical procedures, they will do DEXA scans on all their patients before they begin any treatment and after one year on the treatment.
Not Research Risks
None of the risks associated with the two estrogen treatments and none of the risks associated with the DEXA scans are research risks because they are not dictated by the research protocol.
Example 3 - behavioral
A university has counseling services available for students who engage in binge alcohol drinking. The counseling always includes two educational sessions, followed by sessions based on one of several widely accepted approaches to reducing binge drinking. All students fill out a series of standard validated questionnaires about drinking behavior and attitudes before and after they receive counseling.
A psychologist at the counseling center is interested in comparing the effectiveness of two of these approaches: a short series of motivational interviews versus participation in a weekly cognitive-behavioral group session.
Each student who agrees to participate in the research will have the two educational sessions and will then be randomly assigned to either the motivational interviews or the cognitive-behavioral group. The psychologist will use the results of the clinic’s pre/post questionnaires to assess the two approaches.
The risks associated with motivational interview and the cognitive-behavioral group are research risks and must be described in the consent process/form. the choice of counseling techniques is being dictated by the research design. The confidentiality risks associated with the questionnaire for research purposes are research risks and must be described in the consent form.
Not Research Risks
The risks associated with the educational session are not research risks because all students who come into the counseling center participate in those sessions whether or not they are in the research study.
Each psychologist at the counseling center works with their student clients to decide which approach is best suited to the student’s circumstances. Students who join the cognitive-behavioral group or who undergo the motivational interview approach are referred to the psychologist researcher before they begin counseling. The psychologist researcher gives those students a series of questionnaires about depression, social anxiety, and stress coping strategies before and after they receive the counseling. The psychologist researcher also obtains the results of their standard clinic questionnaires.
The risks associated with the research questionnaires (depression, social anxiety, stress coping strategies) and with research use of the standard clinic questionnaires are research risks and must be described in the consent process/form.
Not Research Risks
None of the risks associated with the two counseling approaches or with administration of the standard clinic questionnaires are research risks.
Protected and Vulnerable Populations
Undue influence and coercion
Human subjects regulations require that the consent process minimizes the possibility of undue influence or coercion and notes that some populations of subjects are considered especially vulnerable. The regulations designate three “protected populations” (pregnant women, prisoners, children) that each have additional required protections. Other vulnerable groups may also require additional protections against the potential for coercion or undue influence.
Undue influence may occur through an excessive offer of something valuable or desirable that influences decision-making in inappropriate ways. Undue influence is often scrutinized by the IRB when subjects will receive significant payment for participation (see GUIDANCE Subject Payment). There are other situations when concerns about undue influence may arise. Federal regulatory guidance concedes that there is no bright line between mere influence and undue influence and so it is up to the IRB to make that distinction.
A study benefit might raise concerns about undue influence when it is likely to: 1) inhibit a potential subject’s adequate consideration of, and reflection about, important study features such as risks, burdens, and discomforts; or 2) impair a potential subject’s understanding of the research and their participation in it.
Minimizing the potential for undue influence or coercion. It is important to remember that the IRB is tasked with minimizing, not eliminating the possibility of undue influence or coercion. Whether a subject may be vulnerable to being unduly influenced or coerced to participate in research is contextual and dependent upon the individual subject’s situation, yet the IRB approves research on a population-level.
Coercion occurs when an overt or implicit threat of harm is intentionally presented by one person to another to obtain compliance. Prior to implementation of human subjects research regulations, there were many instances of subjects being coerced into research. Regulatory protections and IRB oversight have reduced the likelihood of coercion in research, but it is still something researchers and the IRB should be cautious about, particularly when researchers are in a position of power over subjects (e.g., physician and patient or professor and student).
There will be some situations where identification of the potential for unduly influencing a subject group or groups will be clear, as will the steps for minimizing that potential. For example, when there are power dynamics involved (e.g., professor/student; supervisor/employee), it may be appropriate to ensure the consent process is conducted by someone outside the power dynamic. It may also be important to ensure that the person in power is not aware of which of their students, supervisees, etc. participated and which did not. For many other situations, rather than trying to anticipate what might be unduly influential for every individual subject, the IRB should make use of existing minimization tools including some of the other regulatory consent requirements and protections that have been described in this guidance. These include ensuring that:
- subjects have adequate time to consider and discuss participation prior to giving consent; and
- consent processes and materials are understandable and include Key Information in sufficient detail for the specific subject population to be able to make an informed decision about participation.
The IRB should pay particular attention to the way a study’s benefits are described. Known benefits should be accurately described and not exaggerated. Potential or uncertain benefits should be described clearly as to what is known about the uncertainty or likelihood of the potential benefits. A meaningful consent process enables prospective subjects to decline participation in research that they judge to be harmful or inappropriate according to their own interests, values, and obligations.
Examples of undue influence and coercion adapted from an Advarra IRB blog post:
Examples of Undue Influence and Coercion
Children are a federally designated “protected population” with additional regulatory protections and requirements described in Subpart D of the Common Rule. When children participate in research, parent/guardian permission and child assent are sought rather than consent.
See GUIDANCE Involvement of Children in Research for a discussion of who qualifies as a child. See the assent section of this guidance for details about when assent must be obtained and for guidance about designing the assent process and form.
Definitions. Permission is the agreement of parent(s) or guardian(s) to a child’s participation in research. A parent is defined as the child’s biological or adoptive parent and a guardian is an individual who is authorized under applicable State or local law to consent on behalf of the child to general medical care. In general, one or both parents or guardians must be provided with the same information that is provided during an adult consent process, unless the regulatory criteria are met for waiving permission or waiving or altering elements of permission (WORKSHEET Children).
One or two parent permission. The permission of one or both parents may be required depending on the children’s risk level category as determined by the IRB (GUIDANCE Involvement of Children in Research; WORKSHEET Children).
Waivers and alterations. Parental permission can be waived or altered, and documentation of permission can be waived, under the same criteria for waiving or altering consent and consent documentation. [For FDA-regulated research, parental permission can only be waived under the minimal risk criteria.] See WORKSHEET Children for a full description of waiver criteria.
Pregnant women and neonates
Pregnant women and neonates are a federally designated “protected population” with additional regulatory requirements and protections described in Subpart B of the Common Rule. However, bioethicists now tend to view pregnant subjects as a complex or special rather than vulnerable population, because pregnancy itself does not impair a subject’s ability to comprehend an informed consent process. Some research with pregnant women may have additional complexities such as weighing the risks and benefits of both the pregnant woman and the fetus or mitigating risk of exploitation in some specific contexts. However, these potential complexities are dependent upon the specific research design and are not necessarily applicable to all studies enrolling pregnant women. It is noteworthy that, in the 2018 revision to the Common Rule, pregnant women were removed as an example of a population that is potentially vulnerable to coercion or undue influence. Subpart B consent requirements for pregnant women and neonates are listed in the WORKSHEET Pregnant Women and WORKSHEET Neonates.
Prisoners are a federally designated “protected population” with additional regulatory requirements and protections described in Subpart C of the Common Rule (GUIDANCE Prisoners). These protections, and restrictions about the types of research in which prisoners may participate, were put into place to prevent a return to past research practices that exploited prisoners by exposing them to an unfair burden of risks, coercive and unduly influential enrollment practices, and an absence of informed consent procedures. However, these same protections can unfortunately restrict prisoners’ autonomy to independently weigh what risks they are willing to assume and possibly limit their access to potentially beneficial research.
Designing consent with prisoners. Poor reading and communication skills tend to be more common in prison populations (Committee on Ethical Considerations for Revisions to DHHS Regulations for Protecting Prisoners in Research, 2006). This creates challenges for obtaining informed consent because the process typically relies heavily on written materials. For example, it has been shown that undue influence was significantly higher among prisoners with lower educational attainment and those who had spent a longer time in prison (Ravi et al., 2018). This makes it particularly important that the Key Information about a study be tailored to the prisoner population and communicated in language that is understandable to them. Allowing adequate time during the consent process for discussion and opportunities for the subject to ask questions becomes extremely important when enrolling prisoners. Providing a clear and accurate description of confidentiality measures should also be discussed in detail, given the confidentiality limits that may exist in prisons because of institutional policies. As is noted in Consent Consideration # 5, with the appropriate protections in place, prisoners may still be able to take advantage of opportunities to share in the risks and benefits of research.
Assent is a subject’s affirmative agreement to participate in research. It must be accompanied by parent/guardian permission or the consent of a legally authorized representative (see Use of a LAR). Alternatively, assent, LAR consent, and/or parental permission may be waived the the IRB. It is HSD policy that researchers must obtain assent from subjects who are minors or decisionally-impaired adults, when the individuals are capable of providing assent and when it is appropriate to do so. Researchers who do not plan to obtain assent from these subjects must provide the IRB with justification about why obtaining assent is not appropriate.
Assent determinations. The IRB must determine whether the prospective subjects are capable of providing assent and, if they are, whether the proposed assent process is adequate for helping subjects decide whether they want to participate in the research (WORKSHEET Consent Requirements and Waivers). If the IRB determines that assent is possible, the IRB may nonetheless waive the assent requirement under the same criteria for waiving consent (WORKSHEET Consent Requirements and Waivers). These determinations will depend on several factors including the age, maturity of a minor, psychological state, and/or cognitive capabilities of the prospective subjects. The decision may apply to all subjects in the study or may differ by individual subject or group of subjects.
Assent requirements. Researchers are asked to describe their plans (if any) for obtaining and documenting assent in the IRB application. The assent process and any materials should provide information that is relevant for the subject population considering their capacity for comprehension and the research procedures. There is no regulatory requirement to provide all the standard elements of consent during the assent process. There is also no requirement to document assent with an assent form, although researchers should have some way of recording that they obtained assent.
Assent outcomes. Potential subjects may express an active willingness to participate, may simply fail to object, or may dissent (express unwillingness to participate). Failure to object should not be equated with an active willingness to participate. In general, dissent should be respected. A disagreement between a parent(s)/LAR and the potential participant may arise for many reasons and every effort should be made to reach consensus between the parent(s)/LAR and potential participant. However, the IRB may allow the parent(s)/LAR wishes to prevail over the potential participant’s dissent when the potential participant may directly benefit from the research. In these cases, it may be more appropriate to waive assent, rather than ask the subject and then not take their wishes into account. A potential participant’s assent cannot override a “no” from a parent or LAR unless the IRB has waived the requirement for parental permission or completely waived consent.
Design. When designing the assent process and, if applicable, assent form, researchers should consider the nature of the research as well as the age, maturity, and psychological state of the children. When the research involves adolescents whose capacity to understand resembles that of adults, the assent procedure and form would be similar to one designed for adults. In some cases it may be appropriate to use a single form to obtain both parental permission and child assent. For younger children, researchers should focus the assent process and information on the aspects of the research that the children would be mostly likely to understand and be interested in. This would likely be a short description of what the experience would be like, how long it would take, and whether there would be any pain or discomfort as a result of participating. For studies that span several age groups, it may be necessary to design multiple assent procedures and/or forms based on the comprehension capability of the different groups.
Longitudinal research and children who reach the age of majority. The assent process should be viewed as ongoing throughout the duration of the research. If a subject enrolls in research at a young age and remains enrolled for many years, it may be necessary to re-assent as the child’s capacity to understand increases. If the child reaches the legal age of consent while enrolled, the regulations about child participants no longer apply. In these cases, unless the IRB has waived the requirement, the researcher must obtain legally effective research consent from the now-adult subject for any ongoing interactions or interventions or continued analysis of identifiable specimens or data.
Diminished or Fluctuating Consent Capacity and use of a Legally Authorized Representative (LAR)
Presumption of capacity to consent
Individuals who have reached the age of legal consent in the jurisdiction in which the research is being conducted are presumed to have capacity to give informed consent for research. In the absence of indications to the contrary (e.g., a diagnosis of advanced dementia; impaired decision-making ability due to a stroke in specific brain areas), such capacity can be assumed without further evaluation of documentation unless required by the IRB.
Nature of decision-making impairments
Decision-making impairments may be permanent, temporary, progressive, or fluctuating. Also, the capacity to consent is protocol-specific and situation-specific. For example, an individual may have the capacity to make the research participation decision for a low-risk study in usual circumstances but not have the capacity in a stressful situation to understand and evaluate a high-risk study. In other words, the presence of a cognitive impairment or cognitive-state-altering circumstances does not necessarily mean that the person is incapable of an informed consent decision. However, the IRB will expect the researcher to assess the impact of the circumstances on the person’s decision-making ability about the specific participation decision.
If an adult’s capacity to consent is reduced, then they can participate in the research only if a legally-authorized representative (LAR) provides consent on their behalf. In addition, researchers must obtain some type of assent from the subject, when the individuals are capable of providing assent (see assent). A careful balance of the Belmont Ethical Principles is vital to enrolling subjects with diminished consent capacity. So long as the additional protections afforded by LAR consent are in place to offset the subject’s diminished autonomy, it is possible that individuals with reduced consent capacity can still participate in research.
Who can be a LAR is determined by the laws of the jurisdiction in which the research is conducted. There are no Washington State laws that directly address the use of LARs in research. However, Washington State law RCW 7.70.65 defines who may serve as a LAR for providing informed consent for health care. Established legal opinion has determined that it is appropriate to apply this definition of LAR for research consent as well.
For information about who can be LAR for a minor, see the section on Parent/Guardian Permission in Protected and Vulnerable Populations and RCW 7.70.65(2) which describes the somewhat different requirements for an LAR for minors in Washington State, when the parents are not available.
Washington State Law about who can be a LAR for an adult
A LAR for an adult must be a member of one of the following classes of persons in the following order or priority:
- The appointed guardian
- An individual, if any, to whom the person has given a durable power of attorney that encompasses the authority to make health care decisions
- Spouse or state-registered domestic partner
- Children, if they are at least 18 years old
- Adult siblings
- Adult grandchildren, who are familiar with the person
- Adult nieces and nephews, who are familiar with the person
- An adult who meets all of the following criteria:
- Has exhibited special care and concern for the person
- Is familiar with the person’s personal values
- Is reasonably available to make health care (and research) decisions
- Is not any of the following: a physician for the person; an employee of the person; the owner, administrator, or employee of a health care facility, nursing home, or long-term care facility where the person resides or receives care; or a person who receives compensation to provide care to the person
- Provides the following declaration, which is effective for up to 6 months, signed and dated under penalty of perjury, that recites facts and circumstances demonstrating that they are familiar with the person and that they:
- Meet the requirements described above
- Are a close friend of the person
- Are willing and able to become involved in the person’s healthcare (or research participation)
- Have maintained such regular contact with the person as to be familiar with the person’s activities, health, personal values and morals, and
- Are not aware of a person in a higher priority class willing and able to provide informed consent on behalf of the person.
Availability. If reasonable efforts to locate and secure consent from a competent person in the first of succeeding class are unsuccessful, then consent may be given by any person in the next class in order of descending priority.
Disagreement among possible LARs. No LAR may provide consent on behalf of the person if:
- A person of higher priority has refused to give consent, or
- There are two or more individuals in the same class and the decision is not unanimous among all available members of that class.
Decision-making standard. The LAR must decide in good faith whether the person would consent to the research. If this is not possible, the LAR should consider the person’s best interests.
IRB approval and authority
Prior IRB approval of using LARs to obtain consent is not required by federal regulations. However, the IRB has the authority to limit, or explicitly not allow the use of LARs to obtain consent when such limits or prohibition is appropriate for a specific study.
Subjects with Comprehension Barriers (e.g., language, literacy, visual impairment) or Who Cannot Write or Speak
Researchers may encounter individuals who are interested in participating in research and have the cognitive ability to consent on their own behalf, but who have limited ability to understand or read consent information presented in English, or to sign a consent form.
The consent process for these individuals must meet the same regulatory requirements as for any other consent process. This includes the requirement for consent information to be presented in a language that is understandable to the subject. The researcher may need to take additional steps to ensure the subject comprehends the consent process, has adequate opportunity to ask questions, and voluntarily agrees to participate. Accommodations to the consent form or process will be specific to the needs of the particular subject(s).
The IRB must approve the consent plan, including the process that will be used to ensure that oral and written information will be in a language understandable to subjects throughout the study and at an appropriate reading and comprehension level. The IRB has the authority to require revisions or additions to the consent process to ensure that all subjects are adequately informed and are providing truly voluntary consent.
In keeping with the Belmont Principle of Justice that selection of subjects should be equitable in terms of fairly distributing the risks and benefits of research, researchers should carefully consider the purpose of the research and the scientific question when considering the inclusion and exclusion of these subject populations. This is particularly important when the study may offer significant benefit to the individual subjects or subject population.
Anticipated involvement of subjects with limited English proficiency
For research intended, or likely, to involve subjects who are not fluent in English, researchers are responsible for ensuring all consent information and materials are presented in a language understandable by the subjects and in a way that accurately conveys the information. Remembering that consent is a process, researchers must have a plan for ongoing communication between the research team and the subjects throughout their participation in the research.
Interpretation. Researchers must describe in their IRB application how and when interpretation will be provided and the qualifications of the interpreter(s) (e.g., certifications, experience, familiarity with research-related vocabulary in English and the target language). If no member of the research team is fluent in the subjects’ language, interpretation services should be made available throughout the course of the research.
When working with interpreters, consider the following:
- If the subject’s family members or friends will be asked to serve as interpreter, the researcher should think carefully about privacy and confidentiality issues, particularly for research that involves health or other sensitive topics. They should also ensure that the interpreter will accurately convey the information (e.g., Are they capable of interpreting complicated biomedical information?).
- It is almost never appropriate to use children as interpreters. Exceptions may rarely be allowed when the children are considered adults in the local setting, the risks are low, there are no alternatives, and there are no potential conflicts of interest.
- Researchers should discuss the consent process, including the HSD Consent Considerations, with interpreters before conducting consent. For example, how will the researcher and interpreter determine whether the subject truly understands the consent information?
Translation. Researchers must describe in the IRB application how translations will be obtained for consent and all study materials that will be presented to subjects (e.g., surveys). The qualifications of the translator must also be described. Translated documents must be: 1) linguistically accurate; 2) at an appropriate reading level for the participant population; and 3) culturally sensitive for the locale in which they will be used. The IRB review focuses on whether the translation method is appropriate rather than approving the translated text.
- Translated materials that must be provided to the IRB. It is HSD policy that researchers obtain and provide the IRB with translations for all consent materials that will be provided to the subject in written or electronic form. The IRB may request translated versions of any other materials.
- The IRB will request that researchers fill out the form, TEMPLATE Translation Attestation for studies that are greater than minimal risk or if they otherwise deem it necessary. Researchers should only submit this form in response to a request from the IRB.
- Who does the translation? HSD does not require researchers to use a specific translation service.
Possible translation services
- The American Translators Association maintains two online directories: Directory of Translation and Interpreting Services (by individual); Directory of Translation and Interpretation companies. http://www.atanet.org/onlinedirectories/
- Dynamic Language. UW Medicine uses and recommends this local translation service, which is experienced in working with UW researchers (including biomedical researchers) and with invoicing to UW budgets.
- Native speakers who have demonstrated proficiency in English, including knowledgeable members of the research team, academics at other institutions, bi-lingual tribal leaders, etc.
- Graduate students or instructors in foreign language programs.
Unexpected involvement of subjects with limited English proficiency
The regulations allow an alternative method of obtaining and documenting consent called short form consent. This method is intended to be used only for the infrequent and unanticipated enrollment of an individual with limited English proficiency in a study for which no consent form in the subject’s language has been prepared and there is insufficient time and opportunity to obtain an appropriate written translation of the IRB-approved English consent forms.
Short form consent requirements
- Short form written consent form. This generic document states that the required elements of consent (unless waived by the IRB) have been presented to the subject in the subject’s language, with Key Information being presented first. The short form written consent form must be translated into the subject’s language so that literate subjects have the opportunity to read it. A pre-approved English version of the generic short form consent form is posted on the HSD website [TEMPLATE Consent Form, Short (English)]. The short form written consent form is signed by the subject and a witness. A copy of the form is provided to the subject.
- Summary document. The IRB must approve a written summary of the information that will be said to the subject during the consent process. This summary is almost always the English version of the consent form. The summary document is signed by the witness and the person obtaining consent. A copy of the form is provided to the subject.
- Witness. The short form process requires a witness to the oral presentation of the consent information and the subject’s voluntary participation. The witness must be impartial (i.e., not a member of the research team), an adult, and fluent in both English and the subject’s primary language. If the interpreter is not a member of the research team, they may serve as the witness.
Subjects with low literacy
It is HSD policy to generally apply the guidelines described in the FDA Guidance on Informed Consent when enrolling subjects who are illiterate or who have low literacy.
- Consent materials are read to the subject in the presence of an impartial witness who observes the entire consent process.
- Sufficient time is allowed for questions to ensure subject comprehension.
- Researchers may consider using a video or audio recording of the consent process as part of documenting consent. If the consent process is not captured by audio or video, the researcher should create a written description of how the consent information was communicated to the subject and how the researcher ensured the subject’s questions were answered.
- If the IRB did not waive documentation of consent, the subject documents their willingness to participate by signing, or marking an X, on the consent form. The witness and the researcher should also sign and date the form. On rare occasions, the IRB may approve a process that involves reading the consent form to the subject and noting the consent in some official record that is not part of the research records (e.g., the subject’s medical record).
Subjects with visual impairments
The consenting process described above for illiterate individuals may be used, but it is preferable to provide the subjects with an electronic copy of the materials which can then be examined by using an electronic device (e.g., computer) with a screen reader. In general, the use of Braille-based materials is discouraged.
Subjects who cannot write a signature on a consent form
A subject may be unable to physically sign a consent form due to some impairment (e.g., injury to hands). in these cases, the subject may “sign” the form by marking an X on the signature line. An impartial witness should witness the mark and sign the form. If the subject cannot use their hands at all, the IRB will consider alternative methods of documenting consent.
Electronic informed consent (“e-consent”) refers to the use of electronic systems and processes that employ some type of electronic media (including text, graphics, audio, video, podcasts, passive and interactive websites, biological recognition devices, card readers, etc.) to convey consent information and/or to document informed consent. These may be used in place of, or in combination with, paper-based consent methods.
Paper vs. e-consent – choosing the appropriate method
E-consent processes are invaluable when it is not possible to have an in-person interaction with a subject. E-consent can take many different forms including, consent information or documents that are delivered electronically (e.g., email, text message); passive or interactive websites; social media platforms; audio; video; podcasts; or any combination of these. E-consent may also be useful and appropriate for in-person consent interactions. For example, a consent form may be emailed in advance to a potential subject, followed by an in-person meeting in which the study is discussed, after which an electronic signature is obtained.
E-consent allows for using images, animations, embedded comprehension checks, and other technological tools that can improve consent comprehension. However, there are also potential limitations to using e-consent. The subject population will require infrastructure (e.g., reliable internet connection), hardware (e.g., smartphone, computer), and technological experience in order to benefit from the potential advantages of e-consent.
When choosing whether to employ paper-based consent or e-consent, it is important to understand the needs and capabilities of the subject population(s). To ensure subject comprehension, it might be necessary to provide consent using a combination of both paper-based and electronic methods.
Facilitating comprehension and the opportunity to consider participation
When consent is not an “in-person” process, the researcher and the IRB must consider how subjects will be provided with an opportunity to ask questions and have the research team answer them (if appropriate) and/or whether alternative ways of facilitating comprehension may be appropriate. For example, this may be accomplished through telephone calls, electronic messaging (examples: email, text messages), video conferencing, live chat, or other methods. Regardless of the subject’s location, there may also be optional information (for example, hyperlinks or help text) embedded in the electronically delivered material to aid in comprehension of key study elements. Similarly, subjects may be asked questions embedded during the electronic process to gauge their comprehension.
Regulatory requirements for e-consent
Electronic delivery of consent information must meet the same human subjects regulatory requirements as paper-based delivery of the information. This includes ensuring the information is accessible by subjects for the duration of the research and is easily retrievable for auditors and monitors.
FDA-regulated research. Use of electronic systems, archiving, and retention of consent materials must meet the FDA “Part 11” requirements. The Part 11 regulations are separate from the FDA’s human subject regulations and have nothing to do with IRB review and approval. Part 11 compliance is the responsibility of the researcher.
- The Part 11 requirements are outlined in the FDA Guidance for Industry: Part 11, Electronic Records; Electronic Signatures – Scope and Application (September 2003).
- The UW-ITHS-supported non-mobile version of REDCap meets the FDA’s Part 11 electronic system requirements. However, to fully comply with Part 11, researchers must also implement all other procedural requirements for Part 11 (e.g., limiting system access to only authorized users).
Electronic Documentation of Consent (e-signature)
Documentation of Consent
Documentation of Consent. Prior to initiating any research activities, including screening procedures or extracting information from records, federal regulations require that the subject sign the IRB-approved consent form and that a copy of the consent form be provided to the subject. HSD considers it best practice for the subject to receive a copy of the consent form that they have signed and dated, but it is not a regulatory requirement.
Waiver of documentation of consent. Alternatively, the IRB may grant a waiver of documentation of consent if the criteria are met (WORKSHEET Consent Requirements and Waivers). Most minimal risk studies will qualify for a waiver of documentation of consent. If a waiver is granted, none of the requirements listed below in this section apply to the study.
Researchers must provide the IRB with a written description of what subjects will be told during the consent process, even if consent will not be documented (i.e., no consent form). The process and information presented must include the required characteristics and elements of consent as described in the WORKSHEET Consent Requirements and Waivers. HSD recommends, and the IRB may require, that researchers provide subjects with a written description of the consent information (e.g., information statement) even when a waiver of consent documentation has been granted (i.e., no consent form).
Subject. The subject is required to sign and date the consent form to document that all their questions have been answered and they agree to participate in the research.
When a legally authorized representative (LAR) or parent/guardian provides consent, the subject’s name should be printed on the subject’s signature line. Ideally there should be a designated line for the LAR or parent/guardian signature and date, but this information can be added anywhere in the signature area of the consent form. The LAR or parent/guardian name and relationship to the subject should also be recorded in the signature area.
Researcher. It is HSD policy that for greater than minimal risk research, the consent form must contain the legible name of the person who obtained consent from the subject. The person’s signature is not required. The name may be placed on the consent form in advance of the consenting interaction. It is best practice to date the form at the time when consent is obtained. By placing their name on the consent form, the researcher is confirming that they provided the subject with information about the study, that the subject was given sufficient time to consider participation, that the researcher answered all the subject’s questions, and that the subject indicated they understood the nature of the study, including the risks and benefits of participating.
Exception: If the consent form is being used as the “summary document” when using the short form consent process, the researcher must provide a signature on the consent form. See short form consent.
Witness. Witness signatures are required by federal regulations in limited circumstances (e.g., when using short form consent) or may be required by the IRB to ensure an adequate informed consent process. A witness signature documents that the requirements for consent have been satisfied and that consent was voluntarily given by the subject.
Verification of identity
This refers to the process for confirming that the individual who provided the signature is the subject. This can be accomplished in a number of ways such as: the research team visually witnesses the signature; subjects share some form of official identification with the research team (e.g., scanned copy or digital photo); the subject answers security questions (similar to questions sometimes used by banks).
- General principle. A signature that is personally witnessed by a member of the study team, either in-person or visually using a video conferencing service (e.g., Zoom, Facetime, Skype) is generally considered sufficient verification and documentation of a subject’s identity. In all other circumstances, federal Common Rule guidance encourages researchers and the IRB to apply a risk-based approach to determine if more formal verification is required. For example, how likely is it that someone other than the subject would provide the consent and signature, and how risky would that be to the actual subject and to the integrity of the study?
- Examples where more formal verification might be appropriate include: 1) a study that involves giving alcohol to subjects (verify age); 2) a longitudinal study where it is necessary to ensure that the same person is providing information over time; and 3) a study involving access to sensitive data such as a person’s mental health or sexually-transmitted infection (STI) records.
- FDA-regulated research. The FDA requires verification of identity when electronic signatures (per the FDA definition of e-signature) are used to document consent. See Approvable Methods for Obtaining Electronic Signature for details but briefly:
- UW eSignature (DocuSign) is not valid for FDA-regulated research; and
- FDA considered the UW ITHS REDCap signature tool a “hand-written” signature so the identity verification requirements do not apply.
- Handwritten signature using a permanent method (e.g., ballpoint pen).
- Electronic signature (e.g., REDCap or DocuSign).
- Other formats. See Subjects With Comprehension Barriers or Who Cannot Write or Speak for alternative formats.
Approvable methods for obtaining handwritten signatures
- The subject signs the consent form in the presence of the researcher. The research may begin immediately.
- The subject receives the consent form by mail or email, the consent discussion occurs by phone or video, the subject signs the form and texts or emails a photo of the signature to the researcher, and the subject mails the signed consent form to the researcher. The research may begin as soon as the researcher receives the photo of the signature.
- The IRB may approve other methods so long as they meet regulatory requirements and are consistent with any applicable local law.
Approvable methods for obtaining electronic signatures
There are many electronic alternatives to a handwritten signature, including: electronic signatures using tools such as DocuSign or REDCap; digital signatures; computer-readable ID cards; biometrics; or username and password combinations. See HSD’s tutorial, Electronic Consent: What You Need to Know for an overview.
There are two electronic signature tools that have been vetted by the UW and its legal counsel as meeting the federal and Washington State definitions of a “legally valid” electronic signature. Review the INSTRUCTIONS UW E-Signature Tools for more information on how to use these tools.
- UW ITHS REDCap is a tool provided and supported by the UW Institute of Translational Health Sciences (ITHS).
- NOTE: The ITHS REDCap Mobile software application does not support a “legally valid” electronic signature under federal and Washington State law.
- UW eSignatures (DocuSign) is an electronic signatures service provider, centrally managed and supported by UW-IT.
- DocuSign is not valid for FDA-regulated research (see FDA-Regulated research under Requirements specific to electronic consent documentation).
Using a non-UW installation of REDCap may be permitted, so long as it meets all of the requirements outlined in the SUPPLEMENT Other REDCap Installation and a copy is provided with the IRB application.
Using an e-signature method not vetted by the UW is permitted on a case-by-case basis. The researcher must provide (as part of their Zipline application) a signed TEMPLATE Other E-signature Attestation Letter confirming the signature system meets all the applicable e-signature laws in the jurisdiction where the signature will be obtained and follows best practices for technical security. This letter must be signed by the Chief Information Officer, Chief Information Security Officer, or other individual at the company/institution with sufficient authority and subject matter expertise to make the above attestation. HSD and the UW will not vet other e-signature methods.
Regulatory requirements. Electronic documentation of consent must meet the same requirements as for handwritten signatures in addition to the following requirements that are specific to electronic consent documentation:
Requirements that are specific to electronic consent documentation
- Legally effective electronic signature. The signature method must be consistent with general laws about electronic signatures in the jurisdiction in which the research will be conducted. Only UW eSignatures (DocuSign) and UW ITHS REDCap have been vetted as meeting U.S. federal and Washington State requirements. HSD cannot advise researchers about the legality of other e-signature methods.
- Additional required consent/HIPAA authorization information. Washington State and federal e-signature laws require specific information to be provided to subjects when signatures are obtained electronically or through capture of a handwritten signature as an electronic record. These requirements are listed in the WORKSHEET Consent Requirements and Waivers. These requirements also apply to e-signature for HIPAA authorizations, read the GUIDANCE HIPAA for more information.
It is HSD’s general expectation that this additional required information is provided in the consent form(s) and HIPAA authorization (if applicable). In rare instances, HSD may permit the required information to be communicated to study participants via an alternative method. For example, a UW researcher participates in a multicenter trial using an external IRB and there may be no UW-site-specific form that can include this information. Any alternative method of providing this additional required information must still provide the information: 1) in writing; 2) prior to obtaining documentation of informed consent or authorization (e-signature); 3) in a manner that allows the participant to print, access it at a later date, or otherwise retain a copy in some fashion.
- FDA-regulated research. The key issues to consider are (a) the FDA’s definition of “electronic signature”; (b) the general Part 11 regulations about electronic systems; and (c) whether verification of the subject’s identity is required.
- UW e-Signature (DocuSign) is not allowed because DocuSign at the UW is not compliant with the FDA Part 11 regulations.
- UW ITHS REDCap is allowed because it is meets the FDA’s Part 11 electronic system requirements. FDA considers documentation of consent using REDCap to be a handwritten signature captured as an electronic record rather than a true electronic signature. While the FDA e-signature subject identity verification requirements do not apply, researchers are encouraged to document how identity is confirmed in case of an FDA audit.
- Other e-signature tools must be considered against the three key issues named above.
HSD and/or IRB approval. It is HSD policy that that IRB approval must be obtained in advance for the use of any e-signature or electronic signature capture system (e.g., DocuSign, UW ITHS REDCap).
- HIPAA authorization. Both DocuSign and the UW ITHS REDCap system (and equivalent, IRB-approved non-UW REDCap systems) may be used to obtain HIPAA authorization for access to PHI at UW Medicine and Seattle Children’s. E-signatures captured in any other systems are not acceptable. The authorization form must contain the electronic signature-specific consent elements as listed in the WORKSHEET Consent Requirements and Waivers. For authorization to obtain/access PHI at any other HIPAA-covered institution, consult that institution’s privacy and/or health records information office.
- Review by an external IRB. It is HSD policy that UW research that is being reviewed by an external IRB instead of the UW IRB must obtain HSD concurrence before implementing the use of e-signatures for consent and/or HIPAA authorization. This is accomplished by answering the e-signature questions in the REQUEST External IRB Review form and, if applicable, uploading the SUPPLEMENT Other REDCap Installation or TEMPLATE Other E-signature Attestation Letter to the Local Site Documents SmartForm in Zipline.
- International research. Other countries may have their own laws regarding the legal validity of an e-signature and what methods of capture are acceptable. It is the researcher’s responsibility to be aware of and comply with these laws. See online resources such as DocuSign eSignature Legality Guide. This resource is published by DocuSign and is informational only. HSD cannot guarantee that it remains current and accurate. Collaborating partners and experts in the target country(ies) may also be consulted.
The UW IRB system (“Zipline”) automatically places a watermark on consent forms when IRB approval is granted. It is best practice (but not required) for researchers to use the Zipline watermarked version of the consent form. Any non-watermarked version used must match exactly the content and format of the IRB-approved watermarked version.
Records retention and access
The original signed consent form, regardless of format (e.g., paper, electronic) is considered a research record and federal regulations require researchers to retain consent forms for a minimum of three years after completion of the research. Washington State records retention periods are much longer (see UW Records Management website).
Signed consent materials must be easily retrievable for auditors and monitors.
Reconsent and Ongoing Subject Communication
Throughout the course of a study, subjects may need to be informed about new information or consent may need to be revisited due to fluctuating decision-making capacity [see Diminished or Fluctuating Consent Capacity and use of a Legally Authorized Representative (LAR)] or because a child subject has reached the age of majority (see Children under Protected and Vulnerable Populations). In these situations, it is important for subjects to be able to reaffirm their willingness to participate in research.
The regulations do not provide details about how new information should be provided and do not specifically mention “reconsent”, although the Secretary’s Advisory Committee on Human Research Protections (SACHRP) provides recommendations on reconsent. Ultimately, it is up to the IRB to determine whether reconsent is required and to identify the most appropriate method for communicating new or revised information. In making this determination, the IRB should consider:
- Study status (procedures: not yet begun; ongoing; limited to long-term follow-up; complete)
- Time sensitivity of the information
- Magnitude of the changes and their likelihood to influence a subject’s decision to continue participation
Methods for providing new information to subjects. These methods are based on the SACHRP recommendations and an article from WCG IRB. The UW IRB may consider alternative methods.
Verbal discussion. This method may be appropriate for communicating information that: (1) is simple; (2) does not change the individual subject’s anticipated risks or benefits; (3) is not likely to affect a subject’s willingness to continue participation; and (4) does not require documentation that subjects are willing to remain in the study.
- Eliminating certain procedures from a study visit
- Payment method being changed from cash to a gift card
- A verbal discussion may be the first step for time sensitive information that should be shared immediately with subjects while a written notification (e.g., consent addendum; revised consent form) is being prepared
Letter or email. Sending the new information in a letter or by email may be appropriate when: (1) the information is easy to understand; (2) the information is not likely to affect a subject’s willingness to participate; and (3) it is important for subjects to have the information in writing for future reference.
- A new questionnaire is being added to the weekly battery of measures that subjects complete that does not change the type of scope of questions that were already being asked and is estimated to increase participation time by about 5-7 minutes each week
- A confidentiality breach is described in a Report of New Information (RNI). This risk is already described in the consent form but as part of the corrective action plan, the IRB determines that subjects should be informed of the breach.
- Informing subjects that there is a new principal investigator
- Informing subjects that they can use a commercial lab for blood draws
Consent addendum. This method may be appropriate for complicated or important information that requires consent because it (1) may impact a subject’s willingness to continue participation; but (2) does not require a full reconsent and review of the entire study. An addendum tends to be the least burdensome for subjects as it allows them to focus on the new information as they consider whether they want to continue participation. For this reason, HSD recommends the use of a consent addendum, rather than a re-review of the entire consent form, for most situations.
- A modification to add a new battery of measures is submitted; the new measures include sensitive mental health topics that subjects did not previously consent to
- The researchers want to add a new genetic analysis to the samples already being collected for the study
- New research-related risks are identified or there is an increase in the frequency or magnitude of previously described risks
- A decrease in anticipated benefits to subjects is identified
- New or alternative therapies are identified (e.g., FDA approval of a new drug or device for the condition under study) or there is a change on the impact of participation on alternative therapies [e.g., the investigational drug or device reduces the effectiveness of alternative treatment(s)]
- When a study includes online or in-app check-ins, a consent refresher or informing subjects about changes to the research can occur electronically with a checkbox or other method for the subject to confirm they wish to continue participation
Reconsent. This method requires the most time and effort and should be used when (1) there is no time sensitivity; and (2) the new information is complicated and/or affects many aspects of the study. A full reconsent is required when a LAR consent or parental permission is being replaced by the subject consenting on their own behalf.
- Subjects are moving into a new phase of the study with very different procedures
- Many changes are being made to the study
- A subject enrolled with parental permission as a minor reaches the age of majority and must provide adult consent
- Changes in the cognitive functioning, mental health, or physical health of the subject have occurred over the course of the research and the subject can replace LAR consent with consent on their own behalf
- There is a significant delay between providing consent and beginning the study
- Subjects are enrolled in a longitudinal study and a consent refresher may be appropriate even if procedures have not changed
- There are concerns about the way in which consent has been obtained (e.g., the wrong version of the consent form was used; study staff have not been appropriately trained in obtaining consent)
Study status. In many cases, multiple approaches will be required depending on where subjects are in the course of the study. For example, if new risks are identified for a study in which enrollment is ongoing, it might be appropriate to provide subjects who have already been enrolled with an addendum while also updating the consent form for subjects who have not yet been enrolled.
Revised consent form. Changes to the consent form do not necessarily require researchers to inform all enrolled subjects. Researchers should use the information in this guidance to assess the new/revised information and determine what, if any, method should be used to inform subjects of new information and/or obtain reconsent. Note that some sponsors or funders may require a full reconsent for any change to the consent form. In these cases, HSD defers to the sponsor/funder.
Waiver of documentation of consent. The IRB should assess the criteria for waiving documentation of consent when reconsent is being obtained whether it is an addendum, or full consent, or some alternative method.
- New risk information alters the IRB’s previous determination that the study is no greater than minimal risk and waiver of documented consent. The IRB requires a full reconsent for all enrolled subjects including obtaining documentation.
- A new genetic analysis is presented to subjects in the form of an addendum. Although the overall study is greater than minimal risk and requires documentation of consent, the new component is minimal risk, so the IRB waives documentation of consent for the addendum.
Other Consent Materials
EXAMPLE Key Information
GUIDANCE Consent Elements for Externally Reviewed Studies
INSTRUCTIONS UW E-Signature Tools
TEMPLATE Consent Form, Short (English)
TEMPLATE Translation Attestation
TUTORIAL Electronic Consent: What You Need to Know
WORKSHEET Consent Requirements and Waivers
Help Materials for HSD Staff and IRB Members
SOP Consent [HSD staff and IRB member access only]
WORKSHEET Consent Review for IRB Members [HSD staff and IRB member access only]
Other Materials Referenced in this Guidance
CHECKLIST Exception from Informed Consent
GLOSSARY Capacity to Consent
GLOSSARY Exempt Research
GLOSSARY Legally Authorized Representative
GLOSSARY Legally Effective Research Consent
GUIDANCE Authority and Responsibilities of HSD and UW IRB
GUIDANCE The Belmont Report
GUIDANCE Exempt Research
GUIDANCE Humanitarian Use Devices (HUDs)
GUIDANCE Human Subjects Regulations
GUIDANCE Involvement of Children in Research
GUIDANCE Mandatory State Reporting
GUIDANCE Subject Payment
REQUEST External IRB Review
SOP Limited IRB Review
SUPPLEMENT Other REDCap Installation
TEMPLATE Other E-signature Attestation Letter
WEBPAGE Is the UW IRB the Right IRB?
WEBPAGE Single Patient Emergency or Compassionate Use
WORKSHEET Pregnant Women
- 45 CFR 46.116 [pre-2018 requirements and 2018 requirements]
- 45 CFR 46.117 [pre-2018 requirements and 2018 requirements]
- 45 CFR 46.204 – .205
- 45 CFR 46.305
- 45 CFR 46.408
- 21 CFR 11
- 21 CFR 50.20
- 21 CFR 50.27
- 21 CFR 56.109
- 21 CFR 50, Part D
- OHRP Draft Guidance on Disclosing Reasonably Foreseeble Risks in Research Evaluating Standards of Care, 2014
- OHRP, Guidance on Institutional Review Board Review of Clinical Trial Websites; September 20, 2005.
- OHRP Guidance Documents on Informed Consent, from the OHRP website https://www.hhs.gov/ohrp/regulations-and-policy/guidance/informed-consent/index.html
- OHRP, “Obtaining and Documenting Informed Consent of Subjects Who Do Not Speak English”, memorandum; November 9, 1995.
- OHRP, “Simplifying Informed Consent”, webinar https://www.hhs.gov/ohrp/education-and-outreach/online-education/videos/simplifying-informed-consent-ohrp
- FDA, Guide to Informed Consent Information Sheet, July, 2014
- FDA and OHRP Guidance, “Use of Electronic Informed Consent: Questions and Answers”, December, 2016
- FDA Guidance, “Adverse Reactions Section of Labeling for Human Prescription Drug and Biological Products – Content and Format” January 2006
- FDA Guidance, “Part 11, Electronic Records: Electronic Signatures – Scope and Application”, August 2003
- FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency (updated July 2, 2020)
- FDA. “Guidance for Industry. E6 Good Clinical Practice: Consolidated Guidance”, April 1996, section 4.8.9.
- FDA – Reporting Serious Problems to FDA, “What is a Serious Adverse Event?”, 2016
- Meeting of the Secretary’s Advisory Committee on Human Research Protections, Key Information videotape, July 10-11, 2018
- SACHRP Recommendations, “Attachment A – Addressing Ethical Concerns Regarding Offers of Payment to Research Participants”, October 18, 2019
- SACHRP Recommendations, “Attachment A – Guidance on Applying the Regulatory Requirements for Research Consent Forms: What Should and Should Not be Included?”, July 2011
- SACHRP Recommendations, “Attachment A – Recommended Guidance on Minimal Risk Research and Informed Consent”, 2015
- SACHRP Recommendations, “Attachment A1 – Reconsent Appendix 1. New Information Provided to Previously Enrolled Subjects”, May 4, 2020
- SACHRP Recommendations, “Attachment A2 – Reconsent Appendix 2. Additional Information Scenarios and Suggested Options”, May 4, 2020
- SACHRP Recommendations, “Attachment A – SACHRP Commentary on the FDA Draft Guidance Entitled, ‘Informed Consent Information Sheet; Guidance for IRBs, Clinical Investigators and Sponsors’”, February 11, 2015
- • CIOMS III – Core Clinical Safety Information, “Guidelines for Preparing Core Clinical-Safety Information on Drugs”, 1995
- 15 U.W. Code Chapter 96 – The Electronic Signatures in Global and National Commerce Act (E-Sign Act)
- National Conference of Commissioners of Uniform State Laws, Uniform Electronic Transactions Act (UETA), (1999)
- Revised Code of Washington (RCW) Chapter 19.360, Electronic Signatures and Records
- Chapter 1.80 Revised Code of Washington (RCW) Uniform Electronic Transactions Act (Washington’s adoption of UETA)
- Committee On Ethical Considerations for Revisions to DHHS Regulations for Protecting Prisoners in Research, “Ethical Considerations for Research Involving Prisoners” (2006)
- Dickert et al., “Reframing Consent for Clinical Research: A Function-Based Approach”. American Journal of Bioethics, 17:12, 3-11 (2017)
- Dickert et al., “Partnering with Patients to Bridge Gaps in Consent for Acute Care Research”. The American Journal of Bioethics, 20(5), 7-17 (2020)
- Gelinas, L. “The Many Faces of ‘Coercion’ and ‘Undue Influence'”. Advarra Blog, Dec 2, 2020 https://www.advarra.com/blog/the-many-faces-of-coercion-and-undue-influence/
- Kraft et al., “Comprehension and Choice Under the Revised Common Rule: Improving Informed Consent by Offering Reasons Why Some Enroll in Research and Others Do Not”. The American Journal of Bioethics, 17:7, 53-55 (2017)
- Ravi et al., “Financial Payments for Participating in Research while Incarcerated: Attitudes of Prisoners”. IRB Ethics & Human Research, 40:6, 1-6 (2018)
- The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, April 18, 1979
- The PHASES Working Group, Pregnancy and HIV/AIDS: Seeking Equitable Study, “Ending the evidence gap for pregnant women around HIV and co-infections: A call to action” (2020)
- WCG IRB Insights, “Providing Research Participants with New Information: Is ‘Re-Consent’ Always Necessary?” https://www.wcgirb.com/insights/providing-research-participants-with-new-information-is-re-consent-always-necessary/
- Wilfond and Kraft, “Attending to the Interrelatedness of the Functions of Consent”. The American Journal of Bioethics, 17:12, 12-13 (2017)
Open the accordion below for version changes to this guidance.
|Version Number||Posted Date||Implementation Date||Change Notes|
|1.8||01.26.2023||01.26.2023||Add new section: Identifying and Describing Reasonably Foreseeable Risks in Research|
|1.7||12.29.2022||12.29.2022||Revise reference from GUIDANCE Electronic Consent Signatures to INSTRUCTIONS UW E-Signature Tools|
|1.6||08.15.2022||08.15.2022||Remove reference to SCCA|
|1.5||08.04.2022||08.04.2022||Add example of undue influence considerations when power dynamics are involved|
|1.4||04.28.2022||04.28.2022||Add section describing requirements for exempt studies|
|Previous versions||For older versions: HSD staff see the SharePoint Document Library; Others – contact email@example.com.|
Key words: Consent