When submitting items to WIRB for review, is the use of the submission form required?
Yes, submission forms are required for initial review, change of prinicipal investigator, change in research, and subject recruitment requests. Each submission form lists the items required to accompany your request. Log on to Connexus (https://connexus.wcgclinical.com/) for convenient smartform submission or click "Download Forms" to access your desired form.
What is a Principal Investigator (PI)?
The PI is the named person who is responsible, under the regulations, for conduct of the research. WIRB prefers that only one investigator be named for this responsibility (Principal Investigator), but will allow a second person upon request (Co-Principal Investigator). Federal regulations do not recognize Co-Principal Investigators. Therefore, the Board approves the two investigators as if each is THE investigator and holds each individually responsible for the conduct of the entire study.
If there are multiple sub-investigators and/or sites, WIRB may require an explanation as to how the PI will personally conduct or oversee the research, as required under 21 CFR 50.3(d), 21 CFR 312.60, and Box 9 of the FDA Form 1572.
How do I submit a change of Principal Investigator (PI)?
WIRB requires written authorization of the change from several parties:
Please provide confirmation from the sponsor that the change is acceptable and has been approved. The sponsor is required to select investigators under 21 CFR 312.53(a).
The request should also be accompanied by:
A WIRB initial review submission form completed by the new PI
Documentation of the new investigator's qualifications to conduct the study (a CV and, when applicable, a professional license); and
A request to update the investigator information in the existing consent documents to reflect the new investigator information.
How will I receive documents from WIRB?
Your documents will be sent by email to the address(es) indicated in the WIRB initial review submission forms. Contact WIRB Client Services to request a change to the delivery method.
You can also access your approval documents and other research-related information 24 hours a day via WIRB's web portal called Connexus (https://connexus.wcgclinical.com).
What is a protocol?
The "protocol" is the written detailed description of the research project.
What is a research study?
The term "study" is used by WIRB to mean the combination of a particular research protocol and investigator.
What is a clinical trial?
The commonly used terms "research trial" and "clinical trial" generally refer to the overall research project at one or more investigator sites. WIRB does not use "trial" in consent forms because of possible misunderstanding by a lay reader.
What is a sponsor?
A sponsor is the company, person, agency, or other party that designs the research, typically funds the research, and bears the sponsor responsibilities under the regulations, but does not actually conduct the investigation.
If there is another IRB involved in my research, what are the options available for WIRB involvement in the oversight?
WIRB can engage in an agreement with another IRB to:
Provide complete dual oversight of research with another IRB, in which both IRBs provide initial and continuing review of all aspects of the research;
Provide split dual oversight of the research with another IRB, in which WIRB provides IRB oversight for specific physical locations, and an institutional IRB provides IRB oversight of the aspects of the study conducted at the institution; or
Assume jurisdiction from an existing institutional IRB for the review of a study or studies.
What is a waiver of consent and what criteria must my study meet if I request one?
For FDA regulated studies, waiver of consent must meet requirements of either 21 CFR 50.23 (a) - (c) (waiver of consent for individual emergency use) or 21 CFR 50.24 (emergency research without consent), or FDA guidance issued 04-25-2006 for In Vitro Diagnostic Device Study Using Leftover Human Specimens That Are Not Individually Identifiable.
For individual emergency waivers of consent, prospective IRB approval is not always necessary if a patient's life can be saved. See the FAQ below titled "What is the difference between "Emergency Use" and "Treatment Use," and how do I determine which situation I have?" for more information, or refer to 21 CFR 50.23 (a)-(c).
If you are requesting a waiver of consent and the research is not an FDA regulated study, then criteria from 45 CFR 46.116(d) must be met. WIRB applies this standard to all requests for waiver of consent for non-FDA regulated research.
The research involves no more than minimal risk to the subjects.
The waiver or alteration will not adversely affect the rights and welfare of the subjects.
The research could not practicably be carried out without the waiver or alteration.
Whenever appropriate, the subjects will be provided with additional pertinent information after participation.
What are WIRB's requirements for consent form signatures?
1. Subject Signatures
The subject must sign and date the consent form [21 CFR 50.27(a); 45 CFR 46.117(a), ICH 4.8.8].
WIRB may waive this requirement, when appropriate, under 21 CFR 56.109(c) or 45 CFR 46.117(c)(2), or when consent is entirely waived under 21 CFR 50.23, 21 CFR 50.24, or 45 CFR 46.116(d). Please see the WIRB FAQ on the Waiver of Documentation of Consent and Waiver of Consent. For requests for waiver of consent, and if you are a covered entity under HIPAA, please complete Request for Full Waiver Authorization Under HIPAA.
2. Signature of Person Who Conducted the Informed Consent Discussion
The person who conducts the informed consent discussion must sign and date the consent form (ICH 4.8.8).
3. Witness Signature
WIRB does not require a witness signature on the consent form, except in rare cases or as required by state or local law. However, WIRB will include a witness signature block at the request of the investigator or the sponsor. Because WIRB does not require a witness signature, WIRB does not have written procedures identifying who may serve as a witness. The investigator or the sponsor should have written procedures describing who may be a witness and what the witness signature signifies. If a witness signature block is included on the consent form, it must be signed for each consent form, unless the investigator or sponsor written procedures allow otherwise.
Does my study require a Certificate of Confidentiality, and if so, how do I obtain one?
WIRB’s Board requires a Certificate of Confidentiality (CoC) for certain types of research in order to provide the subjects with extra protection of their confidential information as defined in 45 CFR 46.111(a)(7) and 21 CFR 56.111(a)(7).
The determination to require a CoC is based on whether the research involves a subject population that might be prone to face legal or social harm by another’s discovery of private, confidential, or protected information, such as:
illegal behavior (e.g., crime, quasi-crime, supervision violation, contempt, child abuse, domestic violence, etc.);
illegal status (e.g., alien, child runaway, AWOL);
stigmatized behavior and/or diseases (e.g., HIV, alcoholism, drug abuse, mental illness);
embarrassing behavior (e.g., immoral behavior, sexual behavior);
discriminatory condition (e.g., employability, reputation, financial standing).
Listed below are links to helpful pages on the Office for Human Research Protection (OHRP) website and the National Institutes of Health (NIH) website. The pages provide information about acquiring a Certificate of Confidentiality.
http://grants2.nih.gov/grants/policy/coc/
http://grants.nih.gov/grants/policy/coc/contacts.htm
http://www.hhs.gov/ohrp/policy/certconf.html
What is a waiver of documentation of consent and what criteria must my study meet if I request one?
A waiver of documentation of consent is a waiver of the requirement for a signature on a consent form. The regulations allow the Board to approve this type of waiver if:
The research is of minimal risk and involves no procedures for which written consent is usually required; or
The only record linking the subject and the research would be the consent document and the principal risk of the research is the risk of breach of confidentiality.
Subjects enrolling in a study under this type of waiver must be provided with the elements of consent required by the regulations and subjects must consent to participate.
The Board will need to review the information that is provided to subjects to obtain consent to ensure that the required elements of consent are included in the consent discussion. Investigators requesting a waiver of documentation of consent must submit a written statement or script of this information for the Board’s review. A template “Information Sheet” is available on the Download Forms page.
How do I collect data on partners of subjects who become pregnant?
Many protocols now include instructions for investigators to collect data on the outcome of pregnancies that occur in partners of male subjects. WIRB follows 45 CFR 46, which defines research as use of private, identifiable information for research purposes. Because investigators would be obtaining private information from the pregnant partner and infant, the partner would be a subject in the research. Investigators must obtain consent from the pregnant partner before any data collection can occur, and WIRB requires a consent form to be submitted for these subjects if a pregnancy occurs.
If plans for obtaining consent from the pregnant partner (or a request for a consent waiver) are not submitted at initial review, the Board may approve the research, but send a letter reminding the investigator and sponsor that pregnant partners and their infants cannot be followed up on until WIRB approves a consent plan for them. Please note that no action is necessary until such time as a pregnancy occurs.
The letter will be accompanied by a sample consent form template that sites and sponsors may choose to use as a starting point for drafting a consent form for the pregnant partner. The template consent form is available on the Download Forms page. The template consent form cannot be used without WIRB approval.
What is the difference between “Emergency Use” and “Treatment Use,” and how do I determine which situation I have?
"Emergency Use” means the use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and where there is not sufficient time to obtain IRB approval, as stated in 21 CFR 56.102(d). Life-threatening, for the purposes of section 21 CFR 56.102(d), includes both life-threatening and severely debilitating conditions, as defined below:
Life-threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted, and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the subjects must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
Severely debilitating means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand, or foot, loss of hearing, paralysis, or stroke.
“Treatment Use” (a.k.a. “compassionate use”) is described in the regulations (21 CFR 312.34) as follows:
“During the clinical investigation of the drug, it may be appropriate to use the drug in the treatment of patients not in the clinical trials, in accordance with a treatment protocol or treatment IND. The purpose of this section is to facilitate the availability of promising new drugs to desperately ill patients as early in the drug development process as possible, before general marketing begins, and to obtain additional data on the drug’s safety and effectiveness…. Treatment use of an investigational drug is conditioned on the sponsor and investigators complying with the safeguards of the IND process, including the regulations governing informed consent (21 CFR part 50) and institutional review boards (21 CFR part 56) and the applicable provisions of part 312, including distribution of the drug through qualified experts, maintenance of adequate manufacturing facilities, and submission of IND safety reports.”
Please Note: Regulations require that an emergency use of a test article be reported to the IRB within five working days (21 CFR 56.104(c)). Consequently, you must report an emergency use to WIRB within five working days of its occurrence, even if you communicated with WIRB prior to the emergency use. You may use the form posted here to report the use to WIRB.
Are we required to obtain the consent of subjects who were originally enrolled as children, but have now reached the age where they can consent for themselves?
Yes. Unless consent has been waived, WIRB requires you to obtain the consent of subjects who reach the age of majority during the research. You may use the current WIRB-approved consent form to obtain their consent, or, if the approved consent form is not appropriate for doing so, you may download the consent addendum and present it, along with the current WIRB approved consent form, to the subject in order to obtain his/her consent.
If you use the addendum, please remove the statement from it regarding authorization to use and disclose information if the consent form signed by the parent/guardian did not include an authorization section.
You do not have to seek WIRB approval of the generic addendum before using it if you use it without alteration (besides removal of the authorization statement if appropriate as outlined above).
Why does WIRB require a corrective action plan with unanticipated problem reports?
Sites often ask why WIRB requires a corrective action plan with reports of unanticipated problems, since the regulations do not specifically require a corrective action plan.
An adverse event or protocol variance is considered to be an unanticipated problem if it suggests that the research places subjects or others at a greater risk of harm than was previously known or recognized. If this is the case, WIRB has an ethical responsibility to ensure a corrective action is proposed that will minimize the risk or at least inform subjects about the increased risk (so that they can make a decision about whether to continue to participate in the research). Possible actions taken to minimize the risk might include (but are not limited to) a change in the inclusion or exclusion criteria, addition of new safety monitoring, a change to the administrative processes at the site, or the addition of information about the increased risk to the consent form.
What is WIRB's policy regarding the Statement of Investigator, form FDA 1572?
Investigators are not required to submit a 1572 to WIRB, even when one is required by the FDA for the research being conducted. The FDA Information Sheet "Frequently Asked Questions - Statement of Investigator (Form FDA 1572)" defines the 1572 as:
An agreement signed by the investigator to provide certain information to the sponsor and assure that he/she will comply with FDA regulations related to the conduct of a clinical investigation of an investigational drug or biologic.
The same information sheet goes on to explain that:
The 1572 has two purposes: 1) to provide the sponsor with information about the investigator's qualifications and the clinical site that will enable the sponsor to establish and document that the investigator is qualified and the site is an appropriate location at which to conduct the clinical investigation, and 2) to inform the investigator of his/her obligations and obtain the investigator's commitment to follow pertinent FDA regulations.
For questions regarding completion of and requirements for a 1572, sites may refer to the guidance issued by FDA here: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM214282.pdf
What do I need to know about WIRB's relocation to Puyallup?
Effective December 6, 2013, WIRB’s offices are located at 1019 39th Ave SE, Puyallup, WA 98374.
- We have prepared an address change notification to subjects for sites to provide to all enrolled subjects. The notification is available on the WIRB web site and is also being sent to sites with change in research and continuing review approval documents.
- In existing, approved consent forms, WIRB is replacing its Olympia address with the Puyallup one when revisions are processed.
When WIRB issues a revised consent form, only the substantive issues in the consent form will determine whether the Board directs sites to re-consent all subjects using the revised consent form. The WIRB address change alone does not necessitate formally re-consenting all subjects if they are provided with the notification discussed in point 1 above.
Puyallup [pronounced pew-al-up] is located between Washington’s largest cities -- Olympia, Tacoma and Seattle -- and is within driving distance of several major colleges and universities. Our new, state-of-the-art facility is equipped with the latest technology, to enhance existing processes and improve efficiency.
Our drive for continuous improvement is eclipsed only by our commitment to provide you with the quality and service you deserve. As a client of WIRB, you should expect the gold-standard in ethical review. Should you have any questions, please contact us at 1-800-562-4789. As always, we thank you for your continued business and look forward to serving you in the future.
Do I need to revise my 1572 when WIRB is no longer in Olympia?
WIRB does not require sites to send in copies of its 1572 form.
Please consult your sponsor or CRO about whether it requires you to update your 1572 with our new address.
Please note that WIRB's OHRP/FDA IRB registration will reflect the new address when the move is effective.
When submitting items to WIRB for review, is the use of the submission form required?
WIRB requires that a completed initial review submission form be submitted with each initial review request and change of PI request. The form lists any additional materials items required.
Also posted on the website is a Change in Research Submission Form. Please use this form to submit changes in research and new or revised subject recruitment materials.
If you need help with any of the WIRB submission forms, please contact Client Services via e-mail at ClientServices@wirb.com or by calling 1-800-562-4789.
How does WIRB handle initial review of consent forms from affiliated institutions?
Multi-site protocols previously approved by WIRB:
If WIRB has previously approved the protocol, WIRB will be able to generate a consent form for you based on the previously approved consent form and site-specific information and institution-specific requirements. If so, you do not have to submit a consent form.
If your institution has language that is chosen by a checklist or other documentation such as cover letters or grants and contracts forms, it must be included with the application to WIRB as usual. WIRB will incorporate this language into the consent form that will be approved for you.
If your institution requires protocol-specific insertion of language to the text of the consent form, such as study visit durations or a listing of which procedures are standard care, clearly mark those changes on a copy of the WIRB-approved consent form. All other standard institution language will be incorporated by WIRB and does not need to be marked on the submitted consent form.
If your institution requires a pre-review of your application that includes a consent form, please contact WIRB to obtain a copy of the previously approved consent form to include for this review. Client Services can be reached by phone at 1-800-562-4789 or by email at ClientServices@wirb.com. The copy of the consent form that you receive will not include the institutional language requirements, but you do not have to incorporate this language yourself, because WIRB will do so as part of its review. If your institutional pre-review has any questions about this, please refer them to WIRB.
If WIRB has not previously approved the protocol, submit the sponsor’s template as a Microsoft Word compatible file (please contact Client Services if you need assistance with submitting in this format). There is no need to incorporate any institution-required language because WIRB will do so as part of its review, including information from the submission form and any language from a checklist or other documentation such as cover letters or grants and contracts forms.
If your institution requires protocol-specific insertion of language to the text of the consent form, such as study visit durations or a listing of which procedures are standard care, clearly mark those changes on the sponsor’s template in Microsoft Word compatible format. All other standard institution language will be incorporated by WIRB and does not need to be marked on the submitted consent form.
Single-site protocols:
Submit a consent form as a Microsoft Word compatible file that will be reviewed as new. Please make sure you have reviewed the information on this website on consent forms. You may also request to have WIRB write the consent form (extra fee applies). Please incorporate your institution-required language into the submitted consent form. Please contact your institutional department for the latest version of required language.
Can I submit a hand-written submission form?
As of January 1, 2011, WIRB does not accept hand-written initial review submission forms. Hand-written submissions have resulted in significant delays and miscommunications. You may contact Client Services at 1-800-562-4789 or ClientServices@wirb.com for help using the electronic copies of the submission form or the smart form.
How should consent forms be submitted?
Consent forms should be submitted in a Microsoft Word compatible format. This includes files with extensions .doc (Word 2003 and earlier), .docx (Word 2007 and 2010), and .rtf (Rich Text Format, available in most word processing programs). If you have received only a .pdf version from the sponsor, please attempt to get a Word version. Contact Client Services if you need any assistance with submitting your documents in this format.
What information is required when submitting advertisements to WIRB for review?
The WIRB Change in Research submission form should be used to submit recruitment materials for review after initial review of the research. The basic information required includes: investigator name, sponsor name, research protocol number, and the name of the person submitting. Ads must be submitted and approved by WIRB before they are used.
For best results, when submitting subject recruitment materials or other subject materials (diaries, questionnaires, etc.) that have been previously reviewed by WIRB, state in the cover letter which items have been previously reviewed by WIRB. WIRB support staff will provide the Board with information about the previous Board review, and the previous decision of the Board will be taken into account when the additional materials are reviewed.
If some recruitment will be done on a website, submit the recruitment portions of the website for WIRB review; do not submit the portions of the website that are not intended for subject recruitment.
Ads can be submitted via Connexus (https://connexus.wcgclinical.com), by sending email to ClientServices@wirb.com or via postal mail.
WIRB requires a copy of print ads as they will appear, to allow the Board to review the font size, font style, images, etc.
Advertisements that will be used by some or all participating investigators should be identified as such in the cover letter or submission form. Identifying shared advertisements as such will help ensure consistent review of ad materials for all participating sites.
Click here for additional guidelines regarding subject recruitment materials submitted to WIRB.
Should I do anything differently if I am submitting audio and/or video recordings?
To avoid costly re-work, audio or video recordings should be submitted first as a script. When the script is approved by WIRB, it may then be used to make the final recording. The recording should then be submitted with a copy of the WIRB approved script for final review as a video tape, audio tape, CD, DVD, Windows Media file (.wm), etc. The audio or video ad is not approved for use until the final recording has been reviewed and approved by WIRB. The submitted audio or video recording is kept in the WIRB files; the recording is NOT returned to the site. Please be sure to retain a copy for use.
Can I make changes to an advertisement without resubmitting to WIRB?
Changes made to an advertisement may alter the effect of the advertisement on potential subjects (changes to pictures, font sizes, font types, etc.). WIRB must review anything that could alter the impact of what was previously reviewed, as required in 21 CFR 56.108(a)(4).
See Subject Recruitment Materials for more information about modifications to approved recruitment materials, or contact Client Services via email at clientservices@wirb.com or call 1-800-562-4789.
What if changes are desired in sponsor-approved language in a consent form?
Initial Review:
To request that WIRB consider at the time of initial review wording that differs from the sponsor's template consent form or the consent form already approved by WIRB (approved during WIRB's pre-review or approved for other sites), you have two options: 1) You may rewrite all or some of the consent form yourself and submit the changes clearly marked on the WIRB-approved copy of the consent form (or on the sponsor's template if no WIRB-approved version exists); or 2) You may send a cover letter communicating your concerns, and it will be used in the WIRB review and editing of the consent form.
After Initial Review:
To request changes to consent forms for approved research, WIRB requires a completed Change in Research Submission Form and either a copy of the current WIRB-approved consent form with proposed changes clearly marked, or the changes can be detailed in a document specifying the requested changes.
Proposed new changes may be submitted either on a copy of the current WIRB-approved consent form with new changes tracked in redlined format or handwritten on the form, OR the changes can be detailed in a document that indicates each change and the section of the consent form where the change should be made.
For more information on submitting consent form changes, please contact Client Services via email at ClientServices@wirb.com or by calling 1-800-562-4789.
How do I obtain informed consent from someone who speaks and understands English, but cannot read English?
Sometimes potential subjects speak and understand English, but cannot read due to blindness, illiteracy, or some other reason. These individuals may still participate in a research study as long as the Board has not excluded limited or non-readers and there is an impartial witness present for the consent process, in accordance with ICH 4.8.9, which states:
ICH 4.8.9 - If a subject is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion. After the written informed consent form and any other written information to be provided to subjects is read and explained to the subject or the subject's legally acceptable representative, and after the subject or the subject's legally acceptable representative has orally consented to the subject's participation in the trial and, if capable of doing so, has signed and personally dated the informed consent form, the witness should sign and personally date the consent form. By signing the consent form, the witness attests that the information in the consent form and any other written information was accurately explained to, and apparently understood by, the subject or the subject's legally acceptable representative and that informed consent was freely given by the subject or the subject's legally acceptable representative.
The definition of impartial witness is provided at ICH 1.26, which states:
ICH 1.26 Impartial Witness - A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject or the subject's legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject.
WIRB applies this provision of ICH to all research studies.
If an impartial witness signature block is not included on a consent form, and the site encounters a subject who speaks and understands English, but does not read English, please check to see if the protocol allows enrollment of limited or non-readers. If the protocol does not exclude them, download the WIRB standard impartial witness form from the Download Forms page of www.wirb.com to document the participation of an impartial witness in the consent process for the non-reader.
The impartial witness block may not be used to enroll subjects who speak a language other than English. WIRB requires that non-English speaking subjects sign a translated consent form. See the frequently asked question "How is consent obtained from a non-English speaking subject?" for more information.
Why did WIRB change the consent form?
WIRB makes changes to consent forms to ensure the content complies with our SOPs, is factually correct and conforms to the requirements of institutions and sponsors. In the "redline" version, the superscript numbers and Legend Reasons for Change provide information about why a change was made.
How will I receive documents from WIRB?
Your documents will be sent by email to the address(es) indicated in the WIRB initial review submission forms. Contact WIRB Client Services to request a change to the delivery method.
You can also access your approval documents and other research-related information 24 hours a day via WIRB's web portal called Connexus (https://connexus.wcgclinical.com). Click "LOGIN" in the upper right to set up an account.
If there is another IRB involved in my research, what are the options available for WIRB involvement in the oversight?
WIRB can engage in an agreement with another IRB to:
Provide complete dual oversight of research with another IRB, in which both IRBs provide initial and continuing review of all aspects of the research (for more information about dual oversight arrangements, see below);
Provide split dual oversight of the research with another IRB, in which WIRB provides IRB oversight for specific physical locations, and an institutional IRB provides IRB oversight of the aspects of the study conducted at the institution (for more information about split oversight arrangements, see below); or
Assume jurisdiction from an existing institutional IRB for the review of a study or studies (for more information about a local IRB waiving jurisdiction to WIRB, see below).
What is a waiver of consent and what criteria must my study meet if I request one?
For FDA regulated studies, waiver of consent must meet requirements of either 21 CFR 50.23 (a) - (c) (waiver of consent for individual emergency use) or 21 CFR 50.24 (emergency research without consent), or FDA guidance issued 04-25-2006 for In Vitro Diagnostic Device Study Using Leftover Human Specimens That Are Not Individually Identifiable.
For individual emergency waivers of consent, prospective IRB approval is not always necessary if a patient's life can be saved. See the frequently asked question below titled "What is the difference between "Emergency Use" and "Treatment Use," and how do I determine which situation I have?" for more information, or refer to 21 CFR 50.23 (a)-(c).
If you are requesting a waiver of consent and the research is not an FDA regulated study, then criteria from 45 CFR 46.116(d) must be met. WIRB applies this standard to all requests for waiver of consent for non-FDA regulated research.
The research involves no more than minimal risk to the subjects.
The waiver or alteration will not adversely affect the rights and welfare of the subjects.
The research could not practicably be carried out without the waiver or alteration.
Whenever appropriate, the subjects will be provided with additional pertinent information after participation.
What are WIRB's requirements for consent form signatures?
1. Subject Signatures
The subject must sign and date the consent form [21 CFR 50.27(a); 45 CFR 46.117(a), ICH 4.8.8].
WIRB may waive this requirement, when appropriate, under 21 CFR 56.109(c) or 45 CFR 46.117(c)(2), or when consent is entirely waived under 21 CFR 50.23, 21 CFR 50.24, or 45 CFR 46.116(d). Please see the WIRB FAQ on the Waiver of Documentation of Consent and Waiver of Consent.
2. Signature of Person Who conducted the Informed Consent Discussion
The person who conducts the informed consent discussion must sign and date the consent form (ICH 4.8.8).
3. Witness Signature
WIRB does not require a witness signature on the consent form, except in rare cases or as required by state or local law. However, WIRB will include a witness signature block at the request of the investigator or the sponsor. Because WIRB does not require a witness signature, WIRB does not have written procedures identifying who may serve as a witness. The investigator or the sponsor should have written procedures describing who may be a witness and what the witness signature signifies. If a witness signature block is included on the consent form, it must be signed for each consent form, unless the investigator or sponsor written procedures allow otherwise.
4. Signature of Impartial Witness
If a subject or a legally authorized representative (LAR) is unable to read because of blindness, illiteracy, or some other reason, an impartial witness should be present during the entire consent process, and should sign and date the consent form in compliance with ICH E6 4.8.9. The definition of an impartial witness is provided at ICH E6 1.26. In the absence of designated signature lines, download the WIRB standard impartial witness form from the Download Forms page of www.wirb.com.
An impartial witness' signature may not be used to attest to ad hoc translation of the consent into a language different than the language in which the consent form is written.
The impartial witness signature block should be left unsigned unless there is an impartial witness present for the consent process. Please see the Frequently Asked Question, "How do I obtain informed consent from someone who speaks and understands English, but cannot read English?" for further discussion of the impartial witness requirements.
5. Signature of Legally Authorized Representatives (LARs)
In research that allows the enrollment of adult subjects who are not legally competent, the consent form will include a signature block for an LAR. If an adult subject is not legally competent, an LAR must participate in the consent process, agree to the enrollment of the subject in the research, and sign the consent form. If the research allows the enrollment of adult subjects who are legally competent and subjects who are not legally competent, then the LAR signature block will be labeled, "when necessary." In this case, the LAR signature block should not be signed if the subject is legally competent. The LAR signature block will only be signed when the subject is not legally competent.
6. Assent of Children
When research includes children, WIRB follows the regulations for the inclusion of children in research, found at 45 CFR 46, Subpart D, and 21 CFR 50 Subpart D. As part of these regulations, WIRB requires assent from children as required under 45 CFR 46.408 and 21 CFR 50.55. These regulations require that children assent to participation in research unless they lack the mental capacity or unless there is a prospect of direct benefit that is not available outside of the research. WIRB generally finds that children seven years of age and older have the capacity to assent. The child's assent may be documented on the consent form in a variety of ways. The WIRB consent form will include instructions for the documentation of assent. The WIRB Certificate of Approval will note that assent is required.
7. Assent of Adults Incapable of Consent
When research includes legally cognitively impaired adults, WIRB will determine whether the assent of the cognitively impaired adults is required. ICH 4.8.12 requires that when a research study includes subjects who can only be enrolled in the study by a legally authorized representative, "the subject should be informed about the trial to the extent compatible with the subject's understanding and, if capable, the subject should sign and personally date the written consent form." For research involving this study population, WIRB generally includes the following signature block to document that assent was obtained by a representative of the study:
For subjects who have a legally authorized representative, I confirm that I have explained the study to the extent compatible with the subject's understanding, and that the subject has agreed to be in the study.
Signature of Person Conducting Assent Discussion
If the subject is unable to assent at all due to incapacity, the person conducting the assent should still sign this block to indicate that an attempt was made to obtain the subject's assent.
8. Signature of Principal Investigator
As of June 19, 2001, WIRB does not require an investigator's signature on the consent form; however, if a consent form is submitted with an investigator signature line, WIRB will not remove it. If an investigator signature line is on the consent form, the investigator or an "equally qualified" sub-investigator must sign the consent form. WIRB does not require that the investigator signature be dated the same as the subject signature.
Why is there a signature block for the person who conducted the consent discussion?
WIRB will automatically include a signature block to be signed by "the person who conducted the informed consent discussion," in compliance with ICH 4.8.8. WIRB does not include a witness signature block unless requested by the site or sponsor.
How do I consent a cognitively impaired subject?
FDA regulation 21 CFR § 50.20 and HHS regulation 45 CFR 46.116 state that:
No investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative.
If an adult subject is not medically capable and/or legally competent to consent to participate in a study, the federal regulations require that a legally authorized representative consent for the subject. The definition of “legally authorized representative,” as described in FDA 21 CFR § 50.3 and HHS 45 CFR 102(c) is:
An individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research.
The applicable law is the law of the state, as well as any other local law. Thus, the definition of “legally authorized representative” will be determined by state law or other local law. If a subject is medically incapable and/or legally incompetent, then a legally authorized representative, as determined under state or local law, must consent on the subject’s behalf. The Office for Human Research Protections (OHRP) has determined that state laws addressing consent for treatment decisions concerning the same procedures involved in the research are an acceptable basis for determining who may serve as a “legally authorized representative.”
For questions regarding the legal status of an individual subject and the applicability of local law to an individual subject’s enrollment in research, contact a healthcare attorney admitted to the bar in that state. Sites should be aware that changes in statutes and regulations occur frequently, and that court decisions may determine or change the interpretation of such statutes and regulations. Legal counsel should always be consulted to determine the current state of applicable law.
What is a legally authorized representative (LAR)?
FDA regulation 21 CFR § 50.20 and HHS regulation 45 CFR 46.116 state that:
No investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative.
If an adult subject is not medically capable and/or legally competent to consent to participate in a study, the federal regulations require that a legally authorized representative consent for the subject. The definition of “legally authorized representative,” as described in FDA 21 CFR § 50.3 and HHS 45 CFR 102(c) is:
An individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject’s participation in the procedure(s) involved in the research.
The applicable law is the law of the state, as well as any other local law. Thus, the definition of “legally authorized representative” will be determined by state law or other local law. If a subject is medically incapable and/or legally incompetent, then a legally authorized representative, as determined under state or local law, must consent on the subject’s behalf. The Office for Human Research Protections (OHRP) has determined that state laws addressing consent for treatment decisions concerning the same procedures involved in the research are an acceptable basis for determining who may serve as a “legally authorized representative.”
For questions regarding the legal status of an individual subject and the applicability of local law to an individual subject’s enrollment in research, contact a healthcare attorney admitted to the bar in that state. Sites should be aware that changes in statutes and regulations occur frequently, and that court decisions may determine or change the interpretation of such statutes and regulations. Legal counsel should always be consulted to determine the current state of applicable law.
How is consent obtained from a non-English speaking subject?
WIRB requires that non-English speaking subjects sign the current WIRB-approved translated consent form. An ad hoc oral translation of the consent form is not acceptable. WIRB's Translations department can arrange to have a WIRB-approved consent form or subject material translated into any language, or the site/sponsor can submit to WIRB a translated document along with a signed translator certification statement for verification and approval. Specific submission requirements may be obtained from the WIRB Translations department.
You must also explain your plans for 1) conducting the consent discussion in the language understandable to the subject, and for 2) ongoing communication with the subject throughout the research and in case of emergency.
For example, your site might indicate “At least one member of the research team is fluent in the language that will be used for communication, and that research staff member(s) will be available during emergencies,” “The research team has 24-hour access to a translation service with sufficient medical expertise to discuss the research in this study,” or provide another appropriate plan.
Please provide these plans each time you request a translation into a new language for a particular study. Your translation requests may be delayed if you have not already provided an acceptable language-specific and research-specific plan.
Information about use of the short form consent process when a current WIRB approved version of the consent form is not readily available in the language the subjects speaks is available in the WIRB Guide for Researchers
My site is in California, but the contents of the California Experimental Subjects’ Bill of Rights don’t apply to my research project. Can I ask WIRB to omit the Bill from my approved consent form?
Yes, WIRB will consider omitting the Bill from your approved consent form. Sites that believe the Bill is not applicable to their research and that desire to see it omitted from their consent form can submit a change in research request. WIRB review fees apply for requests submitted as changes in research.
As of June 1, 2010, the California Experimental Subject's Bill of Rights is not included in the approved consent form. However, consent forms continue to contain a reference to it ("If you agree to be in this study, you will receive a signed and dated copy of this consent form and the Experimental Subject's Bill of Rights for your records"), and it continues to be provided to California sites with the Initial Review approval documents.
The text of the applicable California law can be found in the California Health and Safety code, section 24174.
Does my study require a Certificate of Confidentiality, and if so, how do I obtain one?
WIRB’s Board requires a Certificate of Confidentiality (CoC) for certain types of research in order to provide the subjects with extra protection of their confidential information as defined in 45 CFR 46.111(a)(7) and 21 CFR 56.111(a)(7).
The determination to require a CoC is based on whether the research involves a subject population that might be prone to face legal or social harm by another’s discovery of private, confidential, or protected information, such as:
illegal behavior (e.g., crime, quasi-crime, supervision violation, contempt, child abuse, domestic violence, etc.);
illegal status (e.g., alien, child runaway, AWOL);
stigmatized behavior and/or diseases (e.g., HIV, alcoholism, drug abuse, mental illness);
embarrassing behavior (e.g., immoral behavior, sexual behavior);
discriminatory condition (e.g., employability, reputation, financial standing).
Listed below are links to helpful pages on the Office for Human Research Protection (OHRP) website and the National Institutes of Health (NIH) website. The pages provide information about acquiring a Certificate of Confidentiality.
http://grants2.nih.gov/grants/policy/coc/
http://grants.nih.gov/grants/policy/coc/contacts.htm
http://www.hhs.gov/ohrp/policy/certconf.html
What is a waiver of documentation of consent and what criteria must my study meet if I request one?
A waiver of documentation of consent is a waiver of the requirement for a signature on a consent form. The regulations allow the Board to approve this type of waiver if:
The research is minimal risk and involves no procedures for which written consent is usually required; or
The only record linking the subject and the research would be the consent document and the principal risk of the research is the risk of breach of confidentiality.
Subjects enrolling in a study under this type of waiver must be provided with the elements of consent required by the regulations and subjects must consent to participate.
The Board will need to review the information that is provided to subjects to obtain consent to ensure that the required elements of consent are included in the consent discussion. Investigators requesting a waiver of documentation of consent must submit a written statement or script of this information for the Board’s review. A template “Information Sheet” is available on the Download Forms page.
How do I collect data on partners of subjects who become pregnant?
Many protocols now include instructions for investigators to collect data on the outcome of pregnancies that occur in partners of male subjects. WIRB follows 45 CFR 46, which defines research as use of private, identifiable information for research purposes. Because investigators would be obtaining private information from the pregnant partner and infant, the partner would be a subject in the research. Investigators must obtain consent from the pregnant partner before any data collection can occur, and WIRB requires a consent form to be submitted for these subjects if a pregnancy occurs.
If plans for obtaining consent from the pregnant partner (or a request for a consent waiver) are not submitted at initial review, the Board may approve the research, but send a letter reminding the investigator and sponsor that pregnant partners and their infants cannot be followed—up until WIRB approves a consent plan for them. Please note that no action is necessary until such time as a pregnancy occurs.
The letter will be accompanied by a sample consent form template that sites and sponsors may choose to use as a starting point for drafting a consent form for the pregnant partner. The template consent form is available on the Download Forms page. The template consent form cannot be used without WIRB approval.
What is the difference between “Emergency Use” and “Treatment Use,” and how do I determine which situation I have?
“Emergency Use” means the use of a test article on a human subject in a life-threatening situation in which no standard acceptable treatment is available, and where there is not sufficient time to obtain IRB approval, as stated in 21 CFR 56.102(d). Life-threatening, for the purposes of section 21 CFR 56.102(d), includes both life-threatening and severely debilitating conditions, as defined below:
Life-threatening means diseases or conditions where the likelihood of death is high unless the course of the disease is interrupted, and diseases or conditions with potentially fatal outcomes, where the end point of clinical trial analysis is survival. The criteria for life-threatening do not require the condition to be immediately life-threatening or to immediately result in death. Rather, the subjects must be in a life-threatening situation requiring intervention before review at a convened meeting of the IRB is feasible.
Severely debilitating means diseases or conditions that cause major irreversible morbidity. Examples of severely debilitating conditions include blindness, loss of arm, leg, hand, or foot, loss of hearing, paralysis, or stroke.
“Treatment Use” (a.k.a. “compassionate use”) is described in the regulations (21 CFR 312.34) as follows:
“During the clinical investigation of the drug, it may be appropriate to use the drug in the treatment of patients not in the clinical trials, in accordance with a treatment protocol or treatment IND. The purpose of this section is to facilitate the availability of promising new drugs to desperately ill patients as early in the drug development process as possible, before general marketing begins, and to obtain additional data on the drug’s safety and effectiveness…. Treatment use of an investigational drug is conditioned on the sponsor and investigators complying with the safeguards of the IND process, including the regulations governing informed consent (21 CFR part 50) and institutional review boards (21 CFR part 56) and the applicable provisions of part 312, including distribution of the drug through qualified experts, maintenance of adequate manufacturing facilities, and submission of IND safety reports.”
Please Note: Regulations require that an emergency use of a test article be reported to the IRB within five working days (21 CFR 56.104(c)). Consequently, you must report an emergency use to WIRB within five working days of its occurrence, even if you communicated with WIRB prior to the emergency use. You may use the form posted here to report the use to WIRB.
What is WIRB's policy regarding the Statement of Investigator, form FDA 1572?
Investigators are not required to submit a 1572 to WIRB, even when one is required by the FDA for the research being conducted. The FDA Information Sheet "Frequently Asked Questions - Statement of Investigator (Form FDA 1572)" defines the 1572 as:
An agreement signed by the investigator to provide certain information to the sponsor and assure that he/she will comply with FDA regulations related to the conduct of a clinical investigation of an investigational drug or biologic.
The same information sheet goes on to explain that:
The 1572 has two purposes: 1) to provide the sponsor with information about the investigator's qualifications and the clinical site that will enable the sponsor to establish and document that the investigator is qualified and the site is an appropriate location at which to conduct the clinical investigation, and 2) to inform the investigator of his/her obligations and obtain the investigator's commitment to follow pertinent FDA regulations.
For questions regarding completion of and requirements for a 1572, sites may refer to the guidance issued by FDA here: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM214282.pdf
When submitting items to WIRB for review, is the use of the submission form required?
WIRB requires that a completed initial review submission form be submitted with each initial review request and change of principal investigator request. The form lists what additional documentation may also be required.
Also posted on the website is a Change in Research Submission Form. Please use this form (either the "smart form" version or a paper version) to submit changes in research and new or revised subject recruitment materials.
If you need help with any of the WIRB submission forms, please contact Client Services via e-mail at ClientServices@wirb.com, or by calling 1-800-562-4789.
How do I submit a change of Principal Investigator (PI)?
WIRB requires written authorization of the change from several parties:
Please provide confirmation from the sponsor that the change is acceptable and has been approved. The sponsor is required to select investigators under 21 CFR 312.53(a).
In addition to the sponsor authorization of the change, the request should also be accompanied by:
1. A WIRB initial review submission form completed by the new PI.
2. Documentation of the new investigator's qualifications to conduct the study (a CV and, when applicable, a professional license).
3. A request to update the investigator information in the existing consent documents to reflect the new investigator information.
Can I submit a hand-written submission form?
As of January 1, 2011, WIRB does not accept hand-written initial review submission forms. Hand-written submissions have resulted in significant delays and miscommunications. You may contact Client Services at 1-800-562-4789 or ClientServices@wirb.com, for help using the electronic copies of the submission form or the smart form.
How should consent forms be submitted?
Consent forms should be submitted in a Microsoft Word compatible format. This includes files with extensions .doc (Word 2003 and earlier), .docx (Word 2007 and 2010), and .rtf (Rich Text Format, available in most word processing programs). If you have received only a .pdf version from the sponsor, please attempt to get a Word version. Contact Client Services if you need any assistance with submitting your documents in this format.
What information is required when submitting advertisements to WIRB for review?
WIRB will need the name and title of each person involved in the conduct of the research (those members of the study team who have contact with subjects or distribute study articles), a description of the role of each study member, and a curriculum vitae for each sub-investigator. WIRB's initial review submission forms provide a space for sites to list the names, titles, and duties of the study staff.
WIRB must be assured that the investigator can personally oversee the conduct of the research and the protection of human subjects (21 CFR 50.3(d)).
WIRB will need to know the number of sub-investigators. Possible relevant information includes whether the PI holds periodic meetings, whether all of the sub-investigators are on rotation at a clinic, whether multiple specialties are represented, and if written procedures exist for the conduct of research.
WIRB will need to know some basic information about each site. The initial review submission form solicits this information for the first site; when more than one site will be used, WIRB requires a completed "Additional Sites Listing" form for each additional site.
How will I be notified of my ad's approval?
Ads are approved in one of two ways: "As Submitted" (no changes) or "As Modified." Board-directed changes are indicated on the ad returned with the certificate of approval.
Ads submitted with the protocol and consent form at the time of initial review will be returned in the initial approval packet. Approved ad(s) will be listed on the certificate of approval, and show any changes required by WIRB. (Prior to 2013, acceptable audio and video scripts were found "approvable" and stamped as such; "approvable" scripts were not listed on the certificate of approval; currently they are approved, but audio and video materials may not be used until after the audio or video recording has been reviewed by the Board.)
WIRB does not routinely apply approval stamps to approved advertisements. The Certificate of Approval listing approval of the ad is documentation of WIRB's review and approval of the advertisement.
Should I do anything differently if I am submitting audio and/or video recordings?
To avoid costly re-work, audio or video recordings should be submitted first as a script. When the script is approved by WIRB, it may then be used to make the final recording. The recording should then be submitted with a copy of the WIRB approved script for final review as a video tape, audio tape, CD, DVD, Windows Media file (.wm), etc. The audio or video ad is not approved for use until the final recording has been reviewed and approved by WIRB. The submitted audio or video recording is kept in the WIRB files; the recording is NOT returned to the site. Please be sure to retain a copy for use.
Can I make changes to an advertisement without resubmitting to WIRB?
Changes made to an advertisement may alter the effect of the advertisement on potential subjects (changes to pictures, font sizes, font types, etc.). WIRB must review anything that could alter the impact of what was previously reviewed, as required in 21 CFR 56.108(a)(4).
See also the Subject Recruitment Materials section of this website for more information about modifications to approved recruitment materials, or contact Client Services via e-mail at ClientServices@wirb.com, or call 1-800-562-4789.
What if changes are desired in sponsor-approved language in a consent form?
Initial Review:
To request that WIRB consider at the time of initial review wording that differs from the sponsor's template consent form or the consent form already approved by WIRB (approved during WIRB's pre-review or approved for other sites), you have two options: 1) You may rewrite all or some of the consent form yourself and submit the changes clearly marked on the WIRB-approved copy of the consent form (or on the sponsor's template if no WIRB-approved version exists), or 2) You may send a cover letter communicating your concerns, and it will be used in the WIRB review and editing of the consent form.
After Initial Review:
To request changes to consent forms for approved research, WIRB requires a completed Change in Research submission form and either a copy of the current WIRB-approved consent form with proposed changes clearly marked, or the changes can be detailed in a document specifying the requested changes.
Proposed new changes may be submitted either on a copy of the current WIRB-approved consent form with new changes tracked in redlined format or handwritten on the form, OR the changes can be detailed in a document that indicates each change and the section of the consent form where the change should be made.
For more information on submitting consent form changes, please contact Client Services via e-mail at ClientServices@wirb.com, or by calling 1-800-562-4789.
Why did WIRB change the consent form?
WIRB makes changes to consent forms to to ensure the content complies with our SOPs, is factually correct, and conforms to the requirements of institutions and sponsors. In the "redline" version, the superscript numbers and Legend Reasons for Change provide information about why a change was made.
What are WIRB's requirements for consent form signatures?
1. Subject Signatures
The subject must sign and date the consent form [21 CFR 50.27(a); 45 CFR 46.117(a), ICH 4.8.8].
WIRB may waive this requirement, when appropriate, under 21 CFR 56.109(c) or 45 CFR 46.117(c)(2), or when consent is entirely waived under 21 CFR 50.23, 21 CFR 50.24, or 45 CFR 46.116(d). Please see the WIRB FAQ on the Waiver of Documentation of Consent and Waiver of Consent. For requests for waiver of consent, and if you are a covered entity under HIPAA, please complete Request for Full Waiver Authorization Under HIPAA.
2. Signature of Person Who Conducted the Informed Consent Discussion
The person who conducts the informed consent discussion must sign and date the consent form (ICH 4.8.8).
3. Witness Signature
WIRB does not require a witness signature on the consent form, except in rare cases or as required by state or local law. However, WIRB will include a witness signature block at the request of the investigator or the sponsor. Because WIRB does not require a witness signature, WIRB does not have written procedures identifying who may serve as a witness. The investigator or the sponsor should have written procedures describing who may be a witness and what the witness signature signifies. If a witness signature block is included on the consent form, it must be signed for each consent form, unless the investigator or sponsor written procedures allow otherwise.
4. Signature of Impartial Witness
A subject or a legally authorized representative (LAR) may be unable to read because of blindness, illiteracy, or some other reason. Unless consent has been waived or the protocol excludes enrollment of limited readers or non-readers, involve an impartial witness in the consent process when enrolling limited or non-readers and document the participation of the impartial witness (in compliance with ICH E6 4.8.9) using the designated signature lines on the WIRB-approved consent form. In the absence of designated signature lines, download the WIRB standard impartial witness form from www.wirb.com. . The definition of an impartial witness is provided at ICH E6 1.26.
An impartial witness's signature may not be used to attest to ad hoc translation of the consent into a language different than the language in which the consent form is written.
The impartial witness signature block should be left unsigned unless there is an impartial witness present for the consent process. Please see the frequently asked question, "How do I obtain informed consent from someone who speaks and
Why is there a signature block for the person who conducted the consent discussion?
WIRB will automatically include a signature block to be signed by "the person who conducted the informed consent discussion," in compliance with ICH 4.8.8. WIRB does not include a witness signature block unless requested by the site or sponsor.
My site is in California, but the contents of the California Experimental Subjects’ Bill of Rights don’t apply to my research project. Can I ask WIRB to omit the Bill from my approved consent form?
Yes, WIRB will consider omitting the Bill from your approved consent form. Sites that believe the Bill is not applicable to their research and that desire to see it omitted from their consent form can submit a change in research request. WIRB review fees apply for requests submitted as changes in research.
As of June 1, 2010, the California Experimental Subject's Bill of Rights is not included in the approved consent form. However consent forms continue to contain a reference to it ("If you agree to be in this study, you will receive a signed and dated copy of this consent form and the Experimental Subject's Bill of Rights for your records"), and it continues to be provided to California sites with the initial review approval documents.
The text of the applicable California law can be found in the California Health and Safety code Section 24174.
My HUD is not research; how do I fill out the WIRB Continuing Review Report Form?
Humanitarian Use Devices (HUDs) are approved devices whose use must comply with 21 CFR 814, Subpart H “Humanitarian Use Devices,” and 21 CFR Part 803, “Medical Device Reporting.” Federal regulation 21 CFR 814.124 requires IRB review and approval of use of the device.
WIRB requires all approved, active sites to provide progress reports at least annually (21 CFR § 56.109(f)). Continuing Review Report Forms are sent to sites approximately two weeks before their due date.
WIRB understands that some of the questions on its Continuing Review Report Form are not pertinent to the use of a HUD according to its approved labeling and indication(s) to treat or diagnose patients, but you must complete the applicable questions and mark the rest “NA.” See this sample form indicating which questions can routinely be marked “NA.” If your use of the HUD qualifies as research (investigational use or clinical investigation of a HUD), you cannot mark the blanks “NA.”
In situations where progress reports are not returned with accurate information in a timely manner, federal regulations grant the Board authority to suspend or terminate approval of the use of the device at the site (21 CFR § 56.113).
If the Board takes action to suspend approval for use of a HUD at your site, you would not be allowed to use the HUD on any new patients until the Board receives the information it requires and votes to lift the suspension.
Therefore, it is imperative that you submit the accurate and complete continuing review reports by the due date stated on the form.
The FDA guidance on Humanitarian Use Devices is available here:http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm110194.htm
Humanitarian Use Devices (HUDs) are approved devices whose use must comply with 21 CFR 814, Subpart H “Humanitarian Use Devices,” and 21 CFR Part 803, “Medical Device Reporting.” Federal Regulation 21 CFR 814.124 requires IRB review and approval of use of the device.
WIRB requires all approved, active sites provide progress reports at least annually (21 CFR § 56.109(f)). Continuing Review Report Forms are sent to sites approximately two weeks before their due date.
WIRB understands that some of the questions on its Continuing Review Report Form are not pertinent to the use of a HUD according to its approved labeling and indication(s) to treat or diagnose patients, but you must complete the applicable questions and mark the rest “NA.” See the document below for a sample form indicating which questions can routinely be marked “NA.” If your use of the HUD qualifies as research (investigational use or clinical investigation of a HUD), you cannot mark the blanks “NA.”
PDF Version
In situations where progress reports are not returned with accurate information in a timely manner, Federal Regulations grant the Board authority to suspend or terminate approval of the use of the device at the site (21 CFR § 56.113).
If the Board takes action to suspend approval for use of a HUD at your site, you would not be allowed to use the HUD on any new patients until the Board receives the information it requires and votes to lift the suspension.
Therefore, it is imperative that you submit the accurate and complete continuing review reports by the due date stated on the form.
The FDA guidance on Humanitarian Use Devices is available here:
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm110194.htm
Are we required to obtain the consent of subjects who were originally enrolled as children, but have now reached the age where they can consent for themselves?
Yes. Unless consent has been waived, WIRB requires you to obtain the consent of subjects who reach the age of majority during the research. You may use the current WIRB-approved consent form to obtain their consent, or, if the approved consent form is not appropriate for doing so, you may download the consent addendum and present it, along with the current WIRB approved consent form, to the subject in order to obtain his/her consent.
If you use the addendum below, please remove the statement from it regarding authorization to use and disclose information if the consent form signed by the parent/guardian did not include an authorization section.
You do not have to seek WIRB approval of the generic addendum before using it if you use it without alteration (besides removal of the authorization statement if appropriate as outlined above).
Why does WIRB require a corrective action plan with unanticipated problem reports?
Sites often ask why WIRB requires a corrective action plan with reports of unanticipated problems, since the regulations do not specifically require a corrective action plan.
An adverse event or protocol variance is considered to be an unanticipated problem if it suggests that the research places subjects or others at a greater risk of harm than was previously known or recognized. If this is the case, WIRB has an ethical responsibility to ensure a corrective action is proposed that will minimize the risk or at least inform subjects about the increased risk (so that they can make a decision about whether to continue to participate in the research). Possible actions taken to minimize the risk might include (but are not limited to) a change in the inclusion or exclusion criteria, addition of new safety monitoring, a change to the administrative processes at the site, or the addition of information about the increased risk to the consent form.
The PI is unexpectedly no longer able to oversee the study. What do I do?
WIRB must be assured that the investigator can personally oversee the conduct of the research and the protection of human subjects [21 CFR 56.102 (h); for Canadian investigators: Part C Division 5 of the Food and Drug Regulations, Part 4 of the Natural Health Products Regulations (if applicable), Medical Devices Regulations (if applicable)].
As soon as possible, WIRB will need either a study closure request from the site, or a submission of a new PI for the Board’s review. As with any unanticipated research-related event, please submit this information within 10 days of the investigator’s departure from the study.
Provide the following information with your submission:
- When did the PI leave this study?
- Why did the PI leave this study?
- Who has provided oversight in the PI's absence?
- Have there been any subject safety concerns during the PI's absence?
How does WIRB handle initial review of consent forms from affiliated institutions?
Multi-site protocols previously approved by WIRB:
If WIRB has previously approved the protocol, WIRB will be able generate a consent form for you based on the previously approved consent form and site-specific information and institution-specific requirements. If so, you do not have to submit a consent form.
If your institution has language that is chosen by a checklist or other documentation such as cover letters or grants and contracts forms, it must be included with the application to WIRB as usual. WIRB will incorporate this language into the consent form that will be approved for you.
If your institution requires protocol-specific insertion of language to the text of the consent form, such as study visit durations or a listing of which procedures are standard care, clearly mark those changes on a copy of the WIRB-approved consent form. All other standard institution language will be incorporated by WIRB and does not need to be marked on the submitted consent form.
If your institution requires a pre-review of your application that includes a consent form, please contact WIRB to obtain a copy of the previously approved consent form to include for this review. Client Services can be reached by phone at 1-800-562-4789 or by e-mail at ClientServices@wirb.com. The copy of the consent form that you receive will not include the institutional language requirements, but you do not have to incorporate this language yourself, because WIRB will do so as part of its review. If your institutional pre-review has any questions about this, please refer them to WIRB.
The second question on the submission form deals with consent form choices. You should mark the first box (“If one is available, I would like to use the previously approved WIRB consent form…”) in most cases for previously approved multi-site protocols, unless the study does not require a consent form, in which case mark the last box (“I am not requesting approval of a consent form…”) and indicate the reason.
or
You require protocol-specific changes to the language, in which case mark the second box (“I would like the Board to consider text that differs…”) and provide a copy of the WIRB-approved consent form with only those changes marked.
Multi-site protocols NOT previously approved by WIRB:
If WIRB has not previously approved the protocol, submit the sponsor’s template as a Microsoft Word compatible file (please contact Client Services if you need assistance with submitting in this format). There is no need to incorporate any institution-required language because WIRB will do so as part of its review, including information from the submission form and any language from a checklist or other documentation such as cover letters or grants and contracts forms.
If your institution requires protocol-specific insertion of language to the text of the consent form, such as study visit durations or a listing of which procedures are standard care, clearly mark those changes on the sponsor’s template in Microsoft Word compatible format. All other standard institution language will be incorporated by WIRB and does not need to be marked on the submitted consent form.
Mark the third box (“This is a new protocol or…”) in question 2 of the submission form.
Single-site protocols:
Submit a consent form as a Microsoft Word compatible file that will be reviewed as new. Mark the third box (“This is a new protocol or…”) in question 2 of the submission form. Please make sure you have reviewed the information on this website regarding consent forms. You may also request to have WIRB write the consent form (extra fee applies). Please incorporate your institution-required language into the submitted consent form. Please contact your institutional department for the latest version of required language.
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How should consent forms be submitted?
Consent forms should be submitted in a Microsoft Word compatible format. This includes files with extensions .doc (Word 2003 and earlier), .docx (Word 2007 and 2010), and .rtf (Rich Text Format, available in most word processing programs). If you have received only a .pdf version from the sponsor, please attempt to get a Word version. Contact Client Services if you need any assistance with submitting your documents in this format.
What if changes are desired in sponsor-approved language in a consent form?
Initial Review:
To request that WIRB consider at the time of initial review wording that differs from the sponsor's template consent form or the consent form already approved by WIRB (approved during WIRB's pre-review or approved for other sites), you have two options: 1) You may rewrite all or some of the consent form yourself and submit the changes clearly marked on the WIRB-approved copy of the consent form (or on the sponsor's template if no WIRB-approved version exists), or 2) You may send a cover letter communicating your concerns, and it will be used in the WIRB review and editing of the consent form.
After Initial Review:
To request changes to consent forms for approved research, WIRB requires a completed Change in Research and Subject Recruitment Submission Form (either a "smart form" version or a paper version) and either a copy of the current WIRB-approved consent form with proposed changes clearly marked, or the changes can be detailed in a document specifying the requested changes.
Proposed new changes may be submitted either on a copy of the current WIRB-approved consent form with new changes tracked in redlined format or handwritten on the form, OR the changes can be detailed in a document that indicates each change and the section of the consent form where the change should be made.
For more information on submitting consent form changes, please contact Client Services via e-mail at ClientServices@wirb.com or by calling 1-800-562-4789.
How do I obtain informed consent from someone who speaks and understands English, but cannot read English?
Sometimes potential subjects speak and understand English, but cannot read due to blindness, illiteracy, or some other reason. These individuals may still participate in a research study as long as the Board has not excluded limited or non-readers and there is an impartial witness present for the consent process, in accordance with ICH 4.8.9, which states:
ICH 4.8.9 - If a subject is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion. After the written informed consent form and any other written information to be provided to subjects is read and explained to the subject or the subject's legally acceptable representative, and after the subject or the subject's legally acceptable representative has orally consented to the subject's participation in the trial and, if capable of doing so, has signed and personally dated the informed consent form, the witness should sign and personally date the consent form. By signing the consent form, the witness attests that the information in the consent form and any other written information was accurately explained to, and apparently understood by, the subject or the subject's legally acceptable representative and that informed consent was freely given by the subject or the subject's legally acceptable representative.
The definition of impartial witness is provided at ICH 1.26, which states:
ICH 1.26 Impartial Witness - A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject or the subject's legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject.
WIRB applies this provision of ICH to all research studies.
If an impartial witness signature block is not included on a consent form, and the site encounters a subject who speaks and understands English, but does not read English, please check to see if the protocol allows enrollment of limited or non-readers. If the protocol does not exclude them, download the WIRB standard impartial witness form from the Download Forms page of www.wirb.com to document the participation of an impartial witness in the consent process for the non-reader.
The impartial witness block may not be used to enroll subjects who speak a language other than English. WIRB requires that non-English speaking subjects sign a translated consent form. See the frequently asked question "How is consent obtained from a non-English speaking subject?" for more information.
Why did WIRB change the consent form?
WIRB makes changes to consent forms to meet regulatory requirements, improve the readability, and to be consistent with information in the protocol. In the "redline" version, the superscript numbers and Legend Reasons for Change provide information about why a change was made.
What is a waiver of consent and what criteria must my study meet if I request one?
For FDA-regulated studies, waiver of consent must meet requirements of either 21 CFR 50.23 (a) - (c) (waiver of consent for individual emergency use) or 21 CFR 50.24 (emergency research without consent), or FDA guidance issued 04-25-2006 for In Vitro Diagnostic Device Study Using Leftover Human Specimens That Are Not Individually Identifiable.
For individual emergency waivers of consent, prospective IRB approval is not always necessary if a patient's life can be saved. See the frequently asked question below titled "What is the difference between "Emergency Use" and "Treatment Use," and how do I determine which situation I have?" for more information, or refer to 21 CFR 50.23 (a)-(c).
If you are requesting a waiver of consent and the research is not an FDA-regulated study, then criteria from 45 CFR 46.116(d) must be met. WIRB applies this standard to all requests for waiver of consent for non-FDA-regulated research.
The research involves no more than minimal risk to the subjects.
The waiver or alteration will not adversely affect the rights and welfare of the subjects.
The research could not practicably be carried out without the waiver or alteration.
Whenever appropriate, the subjects will be provided with additional pertinent information after participation.
If you are a covered entity under HIPAA, please complete Request for Full Waiver Authorization Under HIPAA.
What are WIRB's requirements for consent form signatures?
1. Subject Signatures
The subject must sign and date the consent form [21 CFR 50.27(a); 45 CFR 46.117(a), ICH 4.8.8].
WIRB may waive this requirement, when appropriate, under 21 CFR 56.109(c) or 45 CFR 46.117(c)(2), or when consent is entirely waived under 21 CFR 50.23, 21 CFR 50.24, or 45 CFR 46.116(d). Please see the WIRB FAQ on the Waiver of Documentation of Consent and Waiver of Consent. For requests for waiver of consent, and if you are a covered entity under HIPAA, please complete the WIRB form "Request for Full Waiver of Authorization under HIPAA."
2. Signature of Person Who conducted the Informed Consent Discussion
The person who conducts the informed consent discussion must sign and date the consent form (ICH 4.8.8).
3. Witness Signature
WIRB does not require a witness signature on the consent form, except in rare cases or as required by state or local law. However, WIRB will include a witness signature block at the request of the investigator or the sponsor. Because WIRB does not require a witness signature, WIRB does not have written procedures identifying who may serve as a witness. The investigator or the sponsor should have written procedures describing who may be a witness and what the witness signature signifies. If a witness signature block is included on the consent form, it must be signed for each consent form, unless the investigator or sponsor written procedures allow otherwise.
4. Signature of Impartial Witness
If a subject or a legally authorized representative (LAR) is unable to read because of blindness, illiteracy, or some other reason, an impartial witness should be present during the entire consent process, and should sign and date the consent form in compliance with ICH E6 4.8.9. The definition of an impartial witness is provided at ICH E6 1.26. In the absence of designated signature lines, download the WIRB standard impartial witness form from the Download Forms page of www.wirb.com.
An impartial witness' signature may not be used to attest to ad hoc translation of the consent into a language different than the language in which the consent form is written.
The impartial witness signature block should be left unsigned unless there is an impartial witness present for the consent process. Please see the Frequently Asked Question, "How do I obtain informed consent from someone who speaks and understands English, but cannot read English?" for further discussion of the impartial witness requirements.
5. Signature of Legally Authorized Representatives (LARs)
In research that allows the enrollment of adult subjects who are not legally competent, the consent form will include a signature block for an LAR. If an adult subject is not legally competent, an LAR must participate in the consent process, agree to the enrollment of the subject in the research, and sign the consent form. If the research allows the enrollment of adult subjects who are legally competent and subjects who are not legally competent, then the LAR signature block will be labeled, "when necessary." In this case, the LAR signature block should not be signed if the subject is legally competent. The LAR signature block will only be signed when the subject is not legally competent.
6. Assent of Children
When research includes children, WIRB follows the regulations for the inclusion of children in research, found at 45 CFR 46, Subpart D, and 21 CFR 50 Subpart D. As part of these regulations, WIRB requires assent from children as required under 45 CFR 46.408 and 21 CFR 50.55. These regulations require that children assent to participation in research unless they lack the mental capacity or unless there is a prospect of direct benefit that is not available outside of the research. WIRB generally finds that children seven years of age and older have the capacity to assent. The child's assent may be documented on the consent form in a variety of ways. The WIRB consent form will include instructions for the documentation of assent. The WIRB Certificate of Approval will note that assent is required.
7. Assent of Adults Incapable of Consent
When research includes legally cognitively impaired adults, WIRB will determine whether the assent of the cognitively impaired adults is required. ICH 4.8.12 requires that when a research study includes subjects who can only be enrolled in the study by a legally authorized representative, "the subject should be informed about the trial to the extent compatible with the subject's understanding and, if capable, the subject should sign and personally date the written consent form." For research involving this study population, WIRB generally includes the following signature block to document that assent was obtained by a representative of the study:
For subjects who have a legally authorized representative, I confirm that I have explained the study to the extent compatible with the subject's understanding, and that the subject has agreed to be in the study.
Signature of Person Conducting Assent Discussion
If the subject is unable to assent at all due to incapacity, the person conducting the assent should still sign this block to indicate that an attempt was made to obtain the subject's assent.
8. Signature of Principal Investigator
As of June 19, 2001, WIRB does not require an investigator's signature on the consent form; however, if a consent form is submitted with an investigator signature line, WIRB will not remove it. If an investigator signature line is on the consent form, the investigator or an "equally qualified" sub-investigator must sign the consent form. WIRB does not require that the investigator signature be dated the same as the subject signature.
Why is there a signature block for the person who conducted the consent discussion?
WIRB will automatically include a signature block to be signed by "the person who conducted the informed consent discussion" in compliance with ICH 4.8.8. WIRB does not include a witness signature block unless requested by the site or sponsor.
How do I consent a cognitively impaired subject?
If adult subjects do not have the capacity to consent, WIRB expects that consent will be obtained from a legally authorized representative (LAR), and that the assent of the subject will be obtained to the extent compatible with their capacity.
How is consent obtained from a non-English speaking subject?
WIRB requires that non-English speaking subjects sign a WIRB-approved translated consent form. An ad hoc oral translation of the consent form is not acceptable. WIRB's Translations department can arrange to have a WIRB-approved consent form or subject material translated into any language, or the site/sponsor can submit to WIRB a translated document along with a signed translator certification statement for verification and approval. Specific submission requirements may be obtained from the WIRB Translations department.
You must also explain your plans for 1) conducting the consent discussion in the language understandable to the subject, and for 2) ongoing communication with the subject throughout the research and in case of emergency.
For example, your site might indicate “At least one member of the research team is fluent in the language that will be used for communication, and that research staff member(s) will be available during emergencies,” “The research team has 24-hour access to a translation service with sufficient medical expertise to discuss the research in this study,” or provide another appropriate plan.
Please provide these plans each time you request a translation into a new language for a particular study. Your translation requests may be delayed if you have not already provided an acceptable language-specific and research-specific plan.
My site is in California, but the contents of the California Experimental Subjects’ Bill of Rights don’t apply to my research project. Can I ask WIRB to omit the Bill from my approved consent form?
Yes, WIRB will consider omitting the Bill from your approved consent form. Sites that believe the Bill is not applicable to their research and that desire to see it omitted from their consent form can submit a change in research request. WIRB review fees apply for requests submitted as changes in research.
As of June 1, 2010, the California Experimental Subject's Bill of Rights is not included in the approved consent form. However, consent forms continue to contain a reference to it ("If you agree to be in this study, you will receive a signed and dated copy of this consent form and the Experimental Subject's Bill of Rights for your records"), and it continues to be provided to California sites with the initial review approval documents.
The text of the applicable California law can be found in the California Health and Safety code Section 24174.
What is a waiver of documentation of consent and what criteria must my study meet if I request one?
A waiver of documentation of consent is a waiver of the requirement for a signature on a consent form. The regulations allow the Board to approve this type of waiver if:
The research is minimal risk and involves no procedures for which written consent is usually required; or
The only record linking the subject and the research would be the consent document and the principal risk of the research is the risk of breach of confidentiality.
Subjects enrolling in a study under this type of waiver must be provided with the elements of consent required by the regulations and subjects must consent to participate.
The Board will need to review the information that is provided to subjects to obtain consent to ensure that the required elements of consent are included in the consent discussion. Investigators requesting a waiver of documentation of consent must submit a written statement or script of this information for the Board’s review. A template “Information Sheet” is available on the Download Forms page.
How do I collect data on partners of subjects who become pregnant?
Many protocols now include instructions for investigators to collect data on the outcome of pregnancies that occur in partners of male subjects. WIRB follows 45 CFR 46, which defines research as use of private, identifiable information for research purposes. Becaise investigators would be obtaining private information from the pregnant partner and infant, the partner would be a subject in the research. Investigators must obtain consent from the pregnant partner before any data collection can occur, and WIRB requires a consent form to be submitted for these subjects if a pregnancy occurs.
If plans for obtaining consent from the pregnant partner (or a request for a consent waiver) are not submitted at initial review, the Board may approve the research, but send a letter reminding the investigator and sponsor that pregnant partners and their infants cannot be followed up on until WIRB approves a consent plan for them. Please note that no action is necessary until such time as a pregnancy occurs.
The letter will be accompanied by a sample consent form template that sites and sponsors may choose to use as a starting point for drafting a consent form for the pregnant partner. The template consent form is available on the Download Forms page. The template consent form cannot be used without WIRB approval.
Are we required to obtain the consent of subjects who were originally enrolled as children, but have now reached the age where they can consent for themselves?
Yes. Unless consent has been waived, WIRB requires you to obtain the consent of subjects who reach the age of majority during the research. You may use the current WIRB-approved consent form to obtain their consent, or, if the approved consent form is not appropriate for doing so, you may download the consent addendum and present it, along with the current WIRB approved consent form, to the subject in order to obtain his/her consent.
If you use the addendum below, please remove the statement from it regarding authorization to use and disclose information if the consent form signed by the parent/guardian did not include an authorization section.
You do not have to seek WIRB approval of the generic addendum before using it if you use it without alteration (besides removal of the authorization statement if appropriate as outlined above).
What if the Board didn’t require all subjects be re-consented, but the site would like to re-consent all subjects?
If the site is not required by the Board to re-consent all subjects, the site is still free to do so.
What if I received two changes to the consent form recently and each accompanying Certificate of Approval provided different re-consenting instructions?
The Board expects you to apply the more strict of the two sets of instructions. For example, if the first consent form change included updated risk information and was accompanied by instructions to re-consent all subjects, and the subsequent consent form change was the addition of a new site and the Board directed that the revised consent form only be presented to new subjects, the site is still expected to provide the updated risk information to all subjects using the most current version of the consent form.
What if I disagree with the Board’s re-consent instructions?
If you disagree with the Board’s re-consent instructions, you may PROMPTLY contact WIRB and ask for a reconsideration; however, we advise you not to delay complying with the Board's instructions.
How does WIRB handle the requirement for clinicaltrials.gov text in consent forms?
As of March 7, 2012, consent forms for
certain types of research must include a new element. Federal regulation 21 CFR 50.25(c) states:
“When seeking informed consent for
applicable clinical trials, as defined in 42 U.S.C. 282(j)(1)(A), the following
statement shall be provided to each clinical trial subject in informed consent
documents and processes. This will notify the clinical trial subject that
clinical trial information has been or will be submitted for inclusion in the
clinical trial registry databank under paragraph (j) of section 402 of the
Public Health Service Act. The statement is: "A description of this clinical trial will be available
on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will
not include information that can identify you. At most, the Web site will
include a summary of the results. You can search this Web site at any time."
Because not
all research reviewed by WIRB will need to have the statement referenced above
in consent forms, we are in the process of updating our initial review
submission forms with the following new question:
Is this research an “applicable clinical trial” that must be
registered on ClinicalTrials.gov? yes no
If yes, effective
March 7, 2012, the consent form must include the following statement (verbatim)
“A
description of this clinical trial will be available on http://www.ClinicalTrials.gov , as required by
U.S. Law. This Web site will not include information that can identify you. At
most, the Web site will include a summary of the results. You can search this
Web site at any time."
For
more information see Federal Register: January 4, 2011 (Volume 76, Number 2) Page
256-270
When the
question is answered “yes,” WIRB will include the required statement in the
consent form if it is not already there.
If the
question is answered “no”, WIRB will not include the required statement, but
will not remove it when it is in the submitted consent forms.
If you are
not sure how to answer the question, please consult with your sponsor.
Existing
approved consent forms will not be modified to include the statement unless
WIRB receives a request to add it.