What is an institutional review board (IRB)?
The US Code of Federal Regulations addresses the protection of human subjects participating in clinical research and outlines the role of an IRB. An IRB is a group of individuals responsible for reviewing research studies to assess safety, privacy, and confidentiality concerns as they relate to the research that is being considered. The IRB also determines what information should be provided to the potential research participant and approves the informed consent form that is to be used before the study is started. The IRB can approve or modify studies to ensure that they include proper protections or disapprove any study that poses excess risk to a research participant. The main purpose of the IRB is to protect the rights and welfare of research participants who participate in research studies.
An IRB protects the rights and welfare of research participants by reviewing the protocol to make sure that:
- Risks to participants are minimized
- Risks are acceptable in light of the possible benefits
- The ICF is accurate and complete in describing the study and its risks and benefits
- The clinical research study is conducted in an ethical manner
- If the IRB believes that these conditions have been met, it may approve the study and allow it to begin
Who serves on an IRB?
According to the regulations, an IRB should have at least 5 members with varying backgrounds to ensure a sufficient review of the research studies. The IRB members are qualified based on their experience and expertise, and the IRB should be diverse in terms of race, gender, and cultural backgrounds. The IRB should also have at least 1 member who has scientific expertise and at least 1 member who does not have a scientific background. IRB members generally include health care personnel such as doctors, nurses, and pharmacists. The IRB also includes other members of the scientific community, non-scientists such as clergy or social workers, and community members (for Canadian research, a majority of members must be Canadian citizens).
What does an IRB review?
The IRB reviews research studies involving human subjects to ensure that the risks are appropriate in relation to the benefits and that there are safeguards in place to address risks encountered in the research. The regulations require an IRB to specifically review various aspects of a research study such as the study design, risk vs. benefit, the informed consent form and process, privacy protection, and confidentiality.
How often does your IRB meet?
Our US-based IRB meets daily (Monday through Friday). Our Canada-based IRB meets 3x weekly (Tuesday, Wednesday, Friday).
What type of research and therapeutic areas can your IRB review?
Our IRB oversight has included all major therapeutic areas and all phases of clinical research, including Phase I-IV IND studies, IDE studies, NIH/federally funded research, social science and behavioral studies, registry studies, retrospective chart reviews, and investigator-initiated studies.
What state/provincial laws should sponsors, CROs, and clinical investigators be familiar with that relate to the conduct of clinical trials?
Sponsors, CROs, and clinical investigators should be familiar with state/provincial laws where the research will be conducted, including:
- Age of adult consent/children’s assent
- Capacity to consent/legally authorized representatives
- HIV/STD reporting requirements
- Confidentiality of medical records
- Informed consent
- Clinical research
- Genetic research
- Referral fees and participant payment
- Recruitment methods
- Institutional review boards
- Investigational drugs
- Vulnerable subjects
- Medical practice and delegation of authority to perform procedures
What items can an IRB review by expedited review?
Per regulations, Advarra’s IRB can provide expedited review for:
- Research that presents no more than minimal risk. These categories are listed in OHRP Guidance; and
- “Minor changes” to previously approved research during the period (1 year or less) for which approval is granted.
Advarra reviews most new research site submissions, recruitment and study-related materials, as well as some amendments and new study submissions using expedited review.
If an IRB disapproves a study, can the sponsor/CRO or principal investigator submit the study to a second IRB?
Yes. However, the FDA states that the sponsor/CRO or investigator should inform the second IRB that another IRB previously disapproved the study.
What is the review timeline for submission of a new protocol?
Once your submission is complete, IRB review will occur within 4 business days. You will receive the IRB’s determination within 1-2 business days following the review.
What is the review timeline for submission of an additional investigator for a previously approved protocol?
An investigator’s submission is reviewed within 24 hours upon receipt of a complete submission. You can expect the outcome of the review 1-2 days after that.
What information should an independent, central IRB obtain about a research site?
Information includes the education and training of study personnel, the site’s history and experience in conducting clinical research, federal agency inspection reports, type of demographics the site will encounter, and safeguards for vulnerable subjects. In certain situations, the IRB may request that a site visit be conducted.
Does Advarra require qualifications of sub-investigators and personnel involved in the informed consent process plus the respective 1572 (if applicable) to be submitted?
No. Advarra only requires information on the principal investigator of the study and does not need the 1572 document (if applicable).
What documents are needed for initial site submissions?
A site application needs to be completed through the Advarra CIRBI® Platform. In the application, there will be areas where you can upload attachments, including the CV of the principal investigator and any FDA findings within the past 5 years that are required as part of the submission. There are other places where you can upload SOPs, site-specific ICF language, and any other supporting documents that may aid in the IRB’s review.
Must each research site submit an ICF?
Additional research sites conducting a protocol previously reviewed by the IRB are not required to submit a copy of the ICF. However, sites with institution-specific language are invited to provide their required text to Advarra with their site submission so that text can be appropriately incorporated into the ICF. Advarra will provide each approved research site with a site-specific ICF.
What could slow the approval process for my study or site?
- Incomplete Submission Documents: Please refer to the submission form to ensure you are submitting all required documents for the review of new studies and additional sites.
- Study Placed Missing Key Information: The IRB may identify areas of concern with the protocol and defer approval of a study or require modifications as part of the approval.
- Delays in Finalization of ICF: After formal IRB review, additional Advarra-internal or sponsor/CRO/institution review of the ICF may be required prior to finalization. Approval documents will not be sent to sites until the ICF is finalized.
- IRB Concerns With Site Submission Information: Upon review of additional sites conducting a previously approved protocol, the IRB may note an area of concern with the site’s responses on the submission documents. If concerns are noted or the compensation for participation information is unclear, an Advarra representative will contact the site. The site must provide satisfactory resolution of the identified issues before the approval process can be completed.
- Site-Specific ICF Revisions: If a site submits a request for additional site-specific revisions, an IRB member must review the requested revisions to determine their appropriateness. In some instances, approval from the sponsor/CRO may also be required.
What are the costs associated with IRB review?
Please request a fee schedule on the Contact Us page.
How are investigators, CROs, and sponsors informed of approvals or requests by the IRB?
Any time approval information is posted or there are additional requests from the IRB, you will be prompted by email notifications sent from the Advarra CIRBI Platform.
Will the IRB provide hard copies of documents?
No. All IRB documentation is electronically available through the Advarra CIRBI Platform.
How do I submit information to Advarra?
Advarra is a paperless IRB. All submissions, from the beginning of the study to the termination of a study, need to occur through the Advarra CIRBI Platform.
Do I have a point of contact for my study?
Yes. Advarra has a dedicated point of contact assigned to all your studies to ensure that any questions you have are rapidly addressed.
Does Advarra provide translation services?
Yes. Advarra can assist with certified translation using our approved vendor, or we can accept a valid certificate of translation. Please contact us for additional information.
Where do I go if I have questions about your online submission management system, CIRBI?
Please contact us.
What is an institutional biosafety committee (IBC)?
An institutional biosafety committee is a committee that reviews safety aspects of research involving engineered genetic material referred to as recombinant DNA or synthetic nucleic acid molecules (r/sNA). The committee’s review includes:
- Risks associated with genetic modifications and experimental procedures
- Occupational and environmental safety
The committee must be comprised of at least 5 members who collectively have the expertise to assess risks associated with the proposed recombinant DNA research. At least 2 members must be local community members not affiliated with the institution/site.
Each IBC is registered with the NIH Office of Science Policy. IBC registrations are updated annually. For more information, read our IBC 101 handout.
What does the IBC do?
The IBC is charged under the NIH Guidelines with assessing risks associated with research involving recombinant or synthetic nucleic acid (r/sNA) molecules. This includes:
- Assessing containment levels per NIH guidelines
- Evaluating the adequacy of facilities, equipment, personal protective equipment, SOPs, training, and waste disposal practices
- Inspecting facilities involved in conducting the research
- Conducting post-approval monitoring, including review of safety reports and incident reports
When is IBC review required?
NIH Guidelines require IBC review when:
- The research and development of an investigational product containing engineered genetic material was funded by NIH,
- The study is funded by NIH, or
- The research takes place at a site that has accepted any NIH funds
For clinical trials, IBC review takes place in addition to IRB review. Both committees focus on risk, but their purposes and mandates differ: While the IRB focuses on protecting the rights and welfare of human research participants, the IBC focuses on risks posed by recombinant DNA (genetically modified material) to study personnel, the community, and the environment.
Who serves on an IBC?
An IBC comprises:
- A minimum of 5 members who collectively have the expertise to assess the risks associated with the proposed recombinant DNA research.
- At least 2 members who must be local community members who are not affiliated with the institution/site. The community members represent the interests of the community in regard to public health and protection of the environment.
The IBC must be able to provide documentation to the NIH Office of Science Policy that:
- The IBC has knowledge of local institutional characteristics — such as investigator training, laboratory conditions, and operating procedures; and
- An individual at the registering institution has the authority and responsibility to implement the IBC’s directives
This is accomplished through the IBC setup and registration process. Each IBC is registered with NIH, including member CVs. Registration is updated annually.
Advarra Accreditation and Compliance
Has your IRB ever been audited by the FDA, OHRP, or any other government agency?
Advarra has been audited, and our organization has had no FDA Form 483s issued in the past 10 years.
Is your IRB accredited?
Yes, Advarra has full accreditation with the Association of Human Research Protection Programs (AAHRPP) and has a long history of compliance excellence.
Is Advarra registered with the Office for Human Research Protections and FDA?
- US IRB Organization (IORG) Number: 0000635
- US IRB Registration Number: 00000971
- Canadian IRB Registration Numbers: 00000776 and 00005290
Please visit Accreditation and Compliance for more information.
Federally Funded Research/FWA
My study is federally funded. Does Advarra review federally funded studies?
Yes, Advarra’s IRB reviews federally funded studies.
How can I find my Federalwide assurance number?
Please visit the OHRP Federalwide Assurance (FWA) database and follow the instructions provided.
Does my Federalwide assurance number cover federally funded research only or is all of the non-exempt research at my site/institution covered by our Federalwide assurance?
Are IRBs required to have Federalwide Assurances?
No. Only institutions that receive federal funding for human subject research are required to have Federalwide assurances (FWAs) on file with the Office for Human Research Protections (OHRP). IRBs reviewing research must be registered with OHRP and FDA.
An FWA is a written document by which an institution agrees to comply with appropriate ethical standards and the standards set forth in the federal regulations at 45 CFR 46.
What is different about Department of Defense (DoD) research?
DoD follows the Common Rule; however, 32 CFR 219 adds other requirements. Each DoD component may apply different policies, such as the DoD Addendum to FWA required by the Navy, to address those requirements. Call Advarra, contact the funding point of contact, or reference the following websites for more information:
Note that other funding agencies may also have additional requirements.
What is a clinical study? Why are studies done?
Before a new treatment is approved and put on the market, it must undergo rigorous testing to ensure it is safe and effective. This testing is conducted as part of a clinical study, during which volunteers are given the prospective treatment — under strict guidelines and regulations that the researchers must follow. Besides safety and efficacy, clinical studies help researchers determine how much improvement the treatment offers participants, the proper dose and dosage form, how long the treatment takes to cause an improvement, and much more.
Without clinical research, there can be no new treatments. Clinical studies are essential to advance health care.
How are they organized?
Drug studies are done in steps or phases. Each phase looks at different questions:
- Phase I studies are largely nontherapeutic explorations of possible new drugs. As described by the FDA, Phase I studies aim to determine the metabolism and pharmacologic actions of a drug in humans; any side effects associated with increasing doses; and, if possible, early evidence of effectiveness. The studies often are “first-in-human,” that is, the first time anyone has received the drug. While some Phase I studies (notably oncology trials) recruit affected patients, most require healthy volunteers. In Phase I studies, the study medicine is administered to people for the first time. Only a small number of people (usually between 20 and 80) are part of Phase I studies. Phase I studies focus on the safety of the study medicine and how much medicine may be safe to take in future studies.
- Phase II trials follow a successful Phase I. In Phase II, researchers administer the drug to volunteers who have the disease or condition which the drug aims to treat, but these studies typically are not large enough to show whether the drug will be beneficial. Instead, Phase II studies provide additional safety data, and researchers can use the results to refine research questions, develop research methods, and design Phase III protocols. In Phase II studies, study doctors begin to look at the effect of the study medicine on disease and continue to study its safety. Usually between 100 and 300 people are in a Phase II study.
- Under the US FDA’s regulations for investigational new drugs (IND), Phase III tests the effectiveness of a new, experimental treatment. After Phases I and II gauge safety and dosages, Phase III assesses whether a product works. Phase III studies can involve 300 to 3,000 participants across numerous research sites and often have design complexities beyond their Phase I and Phase II predecessors. Phase III studies are done to better understand the effectiveness and safety of the study medicine or treatment. Phase III studies include large groups of people so that researchers can have a thorough understanding of the study medicine.
- Also known as post-marketing or surveillance studies, Phase IV research gathers additional information about a drug’s long-term effects. Phase IV studies are done with medicines or treatments that can be prescribed for patients. Phase IV studies are conducted for many reasons, including to find out more about the safety of the medicine or to see how it works for other diseases. The FDA can require Phase IV studies as part of its approval to monitor for any rare or long-term adverse effects in a much larger patient population.
How are study participants protected?
Clinical studies and the study doctors who work in them are regulated by the US government. The law requires that every study be reviewed by an independent group of scientists and community members, whose job is to make sure that the study is as safe for the volunteers as possible. This group is called an institutional review board or IRB.
You might consider volunteering for an IRB — these boards need community members and always need help to review studies. The IRB looks at the plan for the study (called the research protocol) before anyone can join the study. They may ask for changes in the study to make it safer for the people who participate. The IRB also looks at the participants’ confidentiality and privacy. If you join a study, measures must be in place to protect your private health information as well as your name and contact information. Your information will not be in any of the reports about the study. If new information that may be important to you and your decision about the study — especially information about safety — is discovered during the research, you will be informed.
Why join a study?
People have many reasons for joining a study. Some people like the feeling that, by joining, they are helping make new treatments available for all. They may feel that they are helping to improve medical care for the next generation. Many studies include health education and medical tests, which some people like to have and join a study for this reason. Some studies need participants who are suffering from a disease or condition. In these cases, these people often participate in hopes of finding a better treatment.
What are the risks?
A study medicine is an untested or limited tested medicine. Clinical studies are done to test the study medicine or treatment. It is important to talk to your doctor and the study doctor about the study. Ask them what is known and what risks they see. And, when you have asked them all your questions, ask them what else you should ask.
All medicines have unpleasant side effects. Some people may experience the side effects, and others may not. Ask the study doctor about the kinds of side effects that may happen in the study.
The study likely will require appointments with the study doctor. Make sure that the schedule is convenient for you. If it isn’t convenient, ask the study doctor if it can be more flexible. These appointments are important for checking the effects of the study medicine on your health. Additionally, some studies may require overnight stays. Rest assured, researchers are required by law to tell what is required before you agree to participate.
What are placebos?
A placebo is an inactive substance. Studies use placebos to compare against a drug or treatment to check the effectiveness of that drug or treatment.
What are combination products?
If a proposed treatment has both a drug (or biologic) and device component, the FDA may consider it a combination product.
Examples of possible combination products are asthma inhalers, drug delivery patches, collagen implants, and drug-eluting stents. The FDA may decide to treat a combination product as a drug or as a device, and that determination will affect the IRB submission.
How do I decide?
Talk with the study doctor and with your own doctor. Ask the study doctor to explain the study — including any details you would like to know. Be certain you ask all your questions. The study staff want you to feel comfortable with the study. Here are some questions you may want to ask:
- What will I have to do in the study?
- How long will it last?
- How many times will I have to come for study appointments?
- How long will the study appointments last?
- Who will be watching out for my health?
- What are the risks in the study?
- Will my transportation and parking be reimbursed?
Again, once you have asked every question you have, ask the study doctor what else you should ask.
What is informed consent?
The US government oversees medical studies that include people. One law ensures that no person can be forced to be in a clinical study or join against his or her will. Another law requires researchers to make sure that the people who join understand what to expect. Any person who joins a research study must consent to join, and that consent must be “informed.”
The study staff or doctor will give you an informed consent form to explain the study. Please take your time to read and understand it and be sure to ask about anything you don’t understand. If you like, you may take it home and have a family member or your doctor look at the form. If you decide to join the study, the study staff or doctor will ask you to sign the form to show that you understand what has been explained about the study. You will also be given a copy of the informed consent form to take home and keep.
Everyone who joins a clinical study has responsibilities to the study. These are some of the important responsibilities that study volunteers have:
- Come to the study appointments on time. If you have a conflict, please call and reschedule.
- You may be asked to take a medication or fill out forms at home. Please try to do this on schedule and follow the study doctor’s instructions.
- Always try to be honest when answering questions. If you had a headache, it is important for the study staff to know. If you don’t feel better, tell them. They want to know the truth. Ask the study staff what other responsibilities you may have in the study.
Everyone who joins a clinical study has rights. Ask the study staff about your rights in the study. The informed consent form will also tell you about your rights. Some important rights are:
- You do not have to join a study.
- If you join, you can change your mind. You may leave a study at any time.
- You have a right to ask questions and have them answered to your satisfaction.
- Some studies reimburse volunteers for their time and transportation costs.
- You have a right to confidentiality and privacy. Your name and contact information will not be on any study report.
You may have questions about a specific study, an injury that you think might be related to research, the instructions you received, or a payment. Ask the study doctor or staff all your questions. If you have questions about your rights, or if you have complaints, you can also contact the IRB listed on your copy of the informed consent form.
How do I learn more?
Below are links you can visit for more information about clinical studies:
- The Center for Information and Study on Clinical Research Participation is a nonprofit organization that works to help the public understand clinical research. ciscrp.org
To find lists of US clinical research studies:
- Clinical studies are listed on a website run by the US government. You can use this site to find a study. clinicaltrials.gov
- The National Cancer Institute lists cancer studies on its site. cancer.gov/clinicaltrials
- The US Department of Veterans Affairs also works to educate veterans about clinical studies. research.va.gov/default.cfm
- The National Health Council is a group that works to improve health across the country. Its membership represents a breadth of disease-specific participant advocacy groups. nationalhealthcouncil.org
To find lists of Canadian clinical research studies:
- Health Canada’s Clinical Trial Database provides a public listing of Phase I, II, and III clinical trials. https://health-products.canada.ca/ctdb-bdec/index-eng.jsp
- Health Canada encourages sponsors to register studies on ClinicalTrials.gov (run by US NIH). https://clinicaltrials.gov/
- The Canadian Institute for Military and Veteran Health Research (CIMVHR) works to educate veterans about clinical studies and research. https://www.cimvhr.ca/
Most medical schools offer information on clinical studies. You can also find information about research studies by searching the web for the participant support groups that meet your specific needs.
What is HIPAA?
The Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule imposes important privacy and security requirements on investigators, research organizations, and institutions that qualify as “covered entities.” Before an investigator at a covered entity can use or disclose anyone’s protected health information (PHI) for research, the investigator must either:
- Obtain the participant’s written authorization to use or disclose PHI; or
- Receive a waiver for the need of authorization.
Can HIPAA be waived?
The HIPAA Privacy Act authorizes IRBs to approve waivers to some research-related requirements. Advarra can consider and approve any 1 of the 3 HIPAA waivers for research:
- Partial Waiver: For example, an investigator may wish to use existing PHI to contact potential participants or collect and record PHI via telephone screens before potential research participants visit the research site
- Complete Waiver: For example, an investigator may ask to access PHI contained in patient medical charts for a retrospective chart review study without contacting the patients
- Alteration: For example, an investigator or sponsor with a waiver of a documentation of consent also would like to waive the requirement for a signed HIPAA authorization
How should I incorporate HIPAA requirements into my ICF?
Advarra prefers that ICFs include language that satisfies HIPAA standards rather than a stand-alone HIPAA document.
Does Advarra provide sites with approved HIV consents when HIV testing is explicitly required by the protocol or when the protocol allows for HIV testing at the investigator’s discretion?
No. It is Advarra’s expectation that the principal investigator will assume the responsibility of being aware of and ensuring compliance with state/provincial laws and/or regulations regarding HIV testing when HIV testing is explicitly required by the protocol or when the protocol allows for HIV testing at the investigator’s discretion. Advarra recommends that Canadian sites consult with their provinces’ health officials and/or legal counsel to assist in determining the provinces’ laws and/or regulations pertaining to HIV testing. Advarra recommends that US sites consult with their states’ department of health and/or legal counsel to assist in determining the states’ laws and/or regulations pertaining to HIV testing.
If a site intends to use a separate consent to obtain consent for HIV testing as part of a study, is it necessary to submit that consent to Advarra for review and approval?
No. This is not necessary as long as the separate consent does not contain study-specific information.
Who has to sign and date the informed consent form (ICF)?
The subject or the subject’s legally authorized representative (LAR) and the person conducting the consent discussion and, if applicable, an impartial witness must sign and date the ICF.
Can a research site use a screening consent for screening tests and procedures prior to having subjects sign a study-specific ICF?
Yes. A screening consent may be used only for minor screening procedures, such as a physical exam, blood draw, chest X-ray, or medical history. If a potential subject qualifies after the screening procedures, a study-specific ICF must be given to the subject.
Why might the IRB request modifications of the ICF?
Under federal regulations, the IRB has the authority to request modifications to the submitted ICF. The IRB may seek modified language to ensure that the document includes the required elements of informed consent. The IRB may also suggest changes to an ICF to make it easier to read and/or be more understandable to a study subject.
Can I receive an electronic copy of the informed consent form (ICF)?
Advarra’s CIRBI Platform provides a downloadable PDF version(s) of the study’s ICF. If a sponsor or CRO is obtaining a translated consent(s) for its sites, Advarra will send a Microsoft Word document version of the ICF upon request. After approval documents have been sent to the appropriate parties, Advarra provides the sponsor/CRO with the electronic version of the ICF, with Track Changes enabled, for future revisions due to amendments, etc.
How does Advarra evaluate compensation for subjects participating in research?
Compensation is evaluated by the IRB on a study-by-study basis. Please review the schedule of visits outlined in the protocol before deciding compensation amounts. Compensation should be pro-rated and based on time and inconvenience to the subject. See FDA Guidance on Paying Research Subjects.
Does a study being conducted in a hospital have to be reviewed by the hospital's IRB?
No, it does not. The hospital can assign jurisdiction to another IRB, but it must be done in writing.
How will Advarra interact with my local IRB or research office?
Advarra will work closely with the institution to ensure that institutional requirements (informed consent language, reporting requirements, etc.) are appropriately addressed. Additionally, Advarra can provide the local IRB/research office with access to all approval documents via the Advarra CIRBI Platform. Other support and training services are also available.
How does Advarra ensure that it provides meaningful consideration of relevant local factors for communities from which research subjects will be drawn?
Advarra relies on the documentation provided by the institution regarding local considerations. Additionally, the IRB composition represents a diverse spectrum of expertise and perspectives that contribute to a thoughtful and meaningful review for the protection of human subjects.
Do I need to submit an IRB Authorization Agreement?
If the research being proposed is either federally funded, or the current FWA covers all research conducted at your institution (regardless of funding), an IRB Authorization Agreement or other formal agreement must be included in the submission or on file with Advarra.
When am I required to submit a Study Status Report?
Sponsors and CROs are required to submit continuing review approximately 6 to 8 weeks prior to the expiration of the study to allow adequate time for IRB review of the study. Sites (or sponsors/CROs on behalf of sites) are required to submit a periodic review at least 4 weeks prior to the site’s expiration date.
Is a sponsor/CRO closeout visit required prior to submitting a Final Report or Routine Termination to Advarra?
Advarra does not require a sponsor/CRO closeout visit prior to receiving a Final Report. However, please verify with the sponsor/CRO whether your site can be closed with the IRB prior to submitting your Final Report/Routine Termination to Advarra.
Pediatric and Adolescent Research
Can a child join a study?
Yes. Children can join studies, and they have an important role to help improve health care.
What should I do if someone asks me to consider a study for my child?
Talk to your child’s doctor. No one knows your child’s health better than his or her doctor. If your child’s doctor is not the study doctor, he or she may want to consult with the study doctor. Get all the information you need to help you decide whether the study may be a good idea for your child.
Where do I go if I am looking for a study for my child?
Ask your doctor. Search the internet. If your child has a chronic or serious disease, you may be able to find information from a support group for that disease.
Will my child be safe in a study?
Government regulations require that studies including children receive special scrutiny. The IRB will carefully evaluate a study of children to assess the risks compared to potential benefits.
What else should I consider?
Ask your child. Explain the reasons for the study and what he or she will have to do. If you have questions, ask the study doctor, and ask him or her to speak with both you and your child. If your child doesn’t want to be in the study, don’t try to persuade him or her. No one should ever feel forced to join a study — including your child.
What is a child's assent? Is it required under FDA regulations?
In pediatric studies, the investigator must obtain, in addition to written permission from the child subject’s parent(s) or legal guardian, the child’s affirmative agreement or “assent” before the child may participate in the study. (A child’s mere failure to object is not assent.) Assent must be obtained from children who are capable of understanding the concepts involved in the research and should usually be obtained from any child with an intellectual age of 7 years or more. Thus, in addition to explaining the study to the parents, the investigator must explain the purpose, risks, and benefits to the child at a level appropriate to the child’s intellectual age, and the child must affirmatively agree to participate. Under the FDA regulations, the IRB must determine that adequate provisions are made for soliciting the assent of the children when, in the judgment of the IRB, the children are capable of providing assent.
Can a child's assent ever be waived?
Yes, assent may be waived if the IRB determines:
- (a) that the capability of some or all of the children is so limited that they cannot reasonably be consulted; or
- (b) the research presents a prospect of direct benefit that is important to the health or well-being of the child or children and is available only in the context of the research study.
The IRB may also waive assent of children who are capable of assenting if:
- (a) the clinical investigation involves no more than minimal risk to the subjects; and
- (b) the waiver will not adversely affect the rights and welfare of the subjects; and
- (c) the clinical investigation could not practicably be carried out without the waiver; and
- (d) when appropriate, the children will be provided with additional pertinent information after participation.
State-Specific Research Requirements
What state-specific research requirements should researchers be aware of?
Various states have specific research-related requirements. Advarra is familiar with these requirements and will work with you to help ensure compliance.
Can Advarra provide a copy of the California Experimental Research Subject's Bill of Rights?
Yes, English and a variety of translated versions of the California Bill of Rights are available for download on Advarra’s CIRBI Platform. For additional languages, please contact Translations.
Does Advarra require the California Experimental Research Subject's Bill of Rights to be signed?
California’s “Protection of Human Subjects in Medical Experimentation Act” and California Health and Safety Code, Section 24173(a) require that the California Experimental Subject’s Bill of Rights be given to subjects prior to conducting the initial protocol-specific consent process and that it is signed and dated.
For more information, please visit the California Informed Consent Guidelines, the California Experimental Subject’s Bill of Rights, and California’s Health and Safety Code, Section 24172 and 24173.
Does a California Experimental Research Subject's Bill of Rights need to be signed again when a consent form is revised?
No. It only needs to be provided and signed at the time of initial consent, prior to conducting the initial protocol-specific consent process.
Does California have requirements for informed consent forms?
Yes, the requirements are for HIPAA authorizations.
According to the Confidentiality of Medical Information Act, California Civil Code Section 56.11 (b), the authorization must be clearly separate from any other language present on the same page and executed by a signature which serves no other purpose than to execute the authorization. Additionally, the HIPAA authorization must be presented in 14 point font.
In order to satisfy the California requirements and maintain a consistent document for all states, please consider placing the HIPAA authorization at the end of the consent with its own signature lines and in 14 point font.
An expiration date of 50 years is also required. Advarra suggests the following text: “Your HIPAA authorization will expire 50 years from the date you sign it unless you revoke (cancel or withdraw) it sooner.”
What are the differences between a legally authorized representative (LAR) and a caregiver?
A LAR “stands in the shoes” of the decisionally impaired person and makes decisions on his or her behalf. Who may act as a LAR varies with the law of the state/province in which the research is being conducted. Therefore, the research staff should be familiar with its own state/provincial law in this area.
A research study may require the involvement of the subject’s caregiver. The caregiver may or may not be the subject’s LAR. It is the investigator’s responsibility to determine if the caregiver has the authority to act as a decisionally impaired subject’s LAR under his or her state’s/province’s law.
Can informed consent be obtained from a legally authorized representative (LAR) over the telephone?
A verbal approval does not satisfy the requirement for a signed consent, as outlined in 21 CFR 50.27(a). However, it is acceptable to send the ICF to the LAR by email or other means, and conduct the consent interview by telephone when the LAR can read the consent as it is discussed. If the LAR agrees, he or she can sign and return the signed ICF to the clinical investigator.
Are all clinical trials registered on ClinicalTrials.gov?
No. Only “applicable” clinical trials require registration. See ClinicalTrials.gov FAQs for the definition of which trials require registration and which trials are generally excluded from registration.
For a ClinicalTrials.gov registration, what information should I enter about Advarra?
When registering study at ClinicalTrials.gov, Advarra suggests the following responses:
- Board Approval – select one of the following as applicable
- Request not yet submitted
- Submitted, pending
- Submitted, approved
- Submitted, exempt
- Submitted, denied
- Submission not required
- Approval Number – Enter the Advarra approval date (mm/dd/yyyy)
- Board Name – Advarra
- Board Affiliation – Independent
- Board Contact – 410.884.2900
For more information, please refer to item #4 on the ClinicalTrials.gov Definitions page.