Exempt research categories include:

1. Education Research
   1. This is a research activity conducted in established or commonly accepted educational practices (e.g., classroom, doctors office, professional meeting, church, support group,).
   2. This research involves normal educational practices that are not likely to adversely impact students’ opportunity to learn required educational content or the assessment of educators who provide instructions, such as an evaluation of an educational practice, or an assessment of program designed to assist instructors with classroom management.
   3. May include minors if it the research meets other criteria.
2. Interactions
   1. This research only includes interactions involving educational tests (e.g., aptitude, diagnostic, cognitive, or achievement), survey procedures, interview procedures, or observation of public behavior. This can include visual or auditory recordings.
   2. The research must protect privacy by:
      1. Recording the information in such a way that the identity of any participants cannot be ascertained readily (either directly or indirectly); OR
      2. Ensure that any disclosure of the responses outside the research would not reasonably place any participants in danger, facing criminal/civil liability, or be possibly damaging to the participants’ financial standing, employability, educational advancement, or reputation; OR
      3. Have other adequate provisions to protect the privacy of participants and to maintain the confidentiality of data.
   3. May include minors if it is limited to educational tests and observation of public behaviors where the investigator does not participate in the activity being observed.
3. Behavioral Interventions
   1. This can involve behavioral interventions in conjunction with the collection of information through verbal or written responses or audiovisual recording.
   2. Participants must all prospectively agree to the behavioral intervention/recording.
   3. Must be brief in duration, harmless, painless, not physically invasive, and not likely to have a significant adverse lasting impact on the participants (e.g., playing a game online, solving a puzzle under various levels of noise conditions, or decision-making such as dividing an amount of cash between themselves and another person).
      1. Brief in duration is intended to refer to the intervention as opposed to the intervention and the data collection activities together. To be brief in duration, the intervention should last a few minutes to a few hours. The entire time for the intervention should occur in a single day and not exceed a few hours in its entirety.
   4. The investigator has no reason to think the intervention will be embarrassing or offensive to participants.
   5. The research must protect privacy through:
      1. Recording the information in such a way that the identity of any participants cannot be ascertained readily (either directly or indirectly); OR
      2. Ensure that any disclosure of the responses outside the research would not reasonably place any participants in danger, facing criminal or civil liability, or be possibly damaging to the participants’ financial standing, employability, educational advancement, or reputation, OR
      3. Have other adequate provisions to protect the privacy of participants and to maintain the confidentiality of data.
   6. The research cannot involve deceiving the participants regarding the nature or purposes of the research unless the participant has been informed they will be unaware or misled regarding the nature and/or purpose of the research.
   7. Cannot include data gathering with devices (EEG, ECG, MRI, etc.).
4. Secondary Research Without Consent
   1. This is for research that involves the use of either identifiable private information or identifiable biospecimens.
   2. This information or biospecimens must meet one of the following criteria:
      1. Publicly available; OR
      2. Recorded in such a way that the identity of the participants cannot readily be ascertained, the investigator will not contact the participants, and the investigator will not re-identify the participants; OR
      3. Involves only information collection and analysis involving the investigator’s use of identifiable health information when the use is regulated under §§45 CFR 160 and 164, subparts A and E, for the purposes of “health care operations” or “research” as those terms are defined at 45 CFR §164.501 or for “public health activities and purposes” as described under 45 CFR §164.512(b).
      4. The research is conducted by, or on behalf of, a Federal department or agency using government-generated or government-collected information provided for non-research activities and meets specific criteria if there is identifiable information to be generated.
5. Federal Demonstration Projects
   1. This is research conducted or supported by a federal department or agency, or otherwise participant to the approval of Federal department or agency heads.
   2. The research or demonstration is designed to study, evaluate, improve, or otherwise examine public benefit or service programs, including procedures for obtaining benefits or services under those programs, possible changes in or alternatives to those programs or procedures, or possible changes in methods or levels of payment for benefits or services under those programs.
   3. The research or demonstration project will be published on a list of research and demonstration projects exempted under this category prior to commencing the research.
6. Taste and Food Research
   1. This category involves taste and food quality evaluation and consumer acceptance studies where wholesome foods without additives are consumed, or food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture.
7. Collection of Data for Secondary Research with Consent
   1. This requires limited IRB review, but WCG processes it through the exempt submission pathway.
   2. This category involves storage or maintenance of identifiable private information or identifiable biospecimens collected for either research studies other than the proposed research or non-research purposes for potential secondary research use.
   3. Must either:
      1. Make no changes to the way the identifiable private information or biospecimens are stored or maintained; OR
      2. Ensure adequate protections to protect the privacy of participants and to maintain the confidentiality of data.
   4. Legally effective informed consent must be obtained using a standard consenting process as described for research that requires IRB review.
   5. The consent document requires the following elements of consent: risks, benefits, confidentiality, investigator contact information, independent contact information, injury contact information, a statement that the research is voluntary, information about the right to refuse participation, information about how to withdraw consent, disclosure of what types of research will be done, disclosure of what interventions might be used, the duration of the research, details of the research, and any information about return of results.
      1. If appropriate, the consent will include a statement that the participant’s biospecimens may be used for commercial profit and whether or not the participant should expect to share in this commercial profit.
      2. If appropriate, whether the research will or might include whole genome sequencing.
   6. The consent must be documented in writing or documentation must be waived in accordance with 45 CFR §46.117.
8. Use of Data for Secondary Research with Consent
   1. Consent for the storage, maintenance, and secondary research use of the identifiable private information or identifiable biospecimens must have been obtained in a study that was reviewed in accordance with Category 7 above.
   2. The research must have adequate provisions to protect the privacy of participants and to maintain the confidentiality of data.
   3. The research must be within the scope of the consent.
   4. The investigator must not include returning individual research results to participants as part of the study plan.

The post What Is Exempt Research? appeared first on WCG.

The post What Is Expedited Review? appeared first on WCG.

Building Partnerships Toward Single IRB

On September 28, 2022, FDA published a proposed rule that if implemented would require any institution located in the United States to rely on review and approval of a single IRB for FDA-regulated cooperative research¹. If the proposed rule is implemented, having smooth processes for managing reliance agreements will become more important than ever. At WCG, we value our relationships with institutions, and recognize the difficulty in managing multiple IRB reliance agreements whether WCG is acting as a central or local IRB. SMART IRB is an NIH-funded initiative to facilitate IRB reliance agreements for multi-site studies². WCG has been a signatory to versions 1 and 2 of the SMART IRB agreement. WCG’s experience with SMART IRB is that it reduces the time and effort to establish an IRB reliance agreement. Participating in the SMART IRB community is one of the ways WCG has built partnerships with institutions as first NIH, then the Common Rule moved toward a single IRB model^3,4.

WCG Policy Changes to Support Rule Harmonization of Informed Consent Regulations

SMART IRB has proposed a revised version 3.0 of the SMART IRB agreement for which comments closed on February 15, 2024. One of the proposed requirements for signatories of SMART IRB is to apply the Common Rule standards to the review of all research, not just research subject to the Common Rule due to federal funding unless a different standard is agreed to by both parties. WCG is supportive of this proposed requirement and has already taken steps to align our policies with it. One impact WCG wishes to highlight for sponsors and institutions is the requirement for consent forms to include a key information section at the beginning of the informed consent document and to include additional disclosures in the consent form. We discuss the elements of the concise summary in more detail in the podcast below.

Revised Common Rule Consent Requirements

WCG has included the Common Rule informed consent requirements in our publicly available sample informed consent document since the revised Common Rule was implemented in 2019 because their inclusion facilitates understanding of the research by participants⁵. At that time, WCG made the decision not to require these additional sections unless it was specifically required. Since 2019, WCG has seen an increasing number of institutions and sponsors reflecting the revised Common Rule requirements in the informed consent documents submitted for review by WCG in all research, regardless of funding source. 

On September 28, 2022, proposed changes to FDA informed consent requirements were published in the Federal Register. The changes incorporate the requirement to include a key information section in the informed consent document, to include similar new elements of consent as required by the Common Rule, and to include new definitions to support the new required elements. The policy changes WCG is making now will allow for a smooth transition for sponsors and institutions once the proposed rule is finalized.  

On February 29, 2024, FDA and OHRP published a draft guidance, Key Information and Facilitating Understanding in Informed Consent Guidance for Sponsors, Investigators, and Institutional Review Boards⁶. It notes FDA’s proposed regulations would require consent information to “begin with a concise and focused presentation of the key information that is most likely to assist a prospective subject or legally authorized representative in understanding the reasons why one might or might not want to participate in the research”, identical language as in the Common Rule.

Waiver of Informed Consent

On December 21, 2023, a final rule was issued by FDA to amend its regulations to allow for a waiver of consent for certain types of minimal risk research⁷. FDA had previously published its plan to exercise enforcement discretion for waivers of consent for minimal risk research in 2017. That guidance stated that FDA does not “intend to object to an IRB approving a consent procedure that does not include, or that alters some or all the element of informed consent set forth in 21 CFR 50.25,” as long as the IRB finds and documents that:

• The clinical investigation involves no more than minimal risk (as defined in 21 CFR 50.3(k) or 56.102(i)) to the subject.
• The waiver or alteration will not adversely affect the rights and welfare of the subjects.
• The clinical investigation could not practicably be carried out without the waiver or alteration.
• And whenever appropriate, the subjects will be provided with additional pertinent information after participation.

WCG has been following that guidance since 2017. With the publication of the new final rule on waivers of informed consent, the previous guidance is no longer valid, and FDA harmonized with the revised Common Rule criteria for a waiver of consent for minimal risk research. We discuss the criteria for a waiver of consent in the podcast below.

Summary

While change can be difficult to manage, the goal of harmonizing federal regulations for research with human subjects is to reduce the burden on institutions and sponsors to ensure valuable research developments reach the public efficiently and safely. Institutions and sponsors may have concerns about how the single-IRB mandate and the evolving informed consent requirements affect their research programs. We encourage you to reach out to ask questions. Our regulatory experts are ready and willing to provide guidance to you.

References:

1. https://www.federalregister.gov/documents/2022/09/28/2022-21089/institutional-review-boards-cooperative-research
2. https://smartirb.org/
3. Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research Notice Number: NOT-OD-16-094.  Release Date:  June 21, 2016. Effective Date: New Date – January 25, 2018 as per issuance of NOT-OD-17-076.
4. Title 45 Subtitle A Subchapter A Part 46  § 46.114 Cooperative research.
5. https://www.wcgclinical.com/wp-content/uploads/2020/08/WCG-Consent-Template-HRP-500.doc?v=1701459189
6. https://www.fda.gov/media/176663/download
7. https://www.federalregister.gov/documents/2022/09/28/2022-21089/institutional-review-boards-cooperative-research

The post How WCG Is Preparing for FDA Harmonization with the Common Rule appeared first on WCG.

If my study includes approved drugs, when do the risks of those drugs need to be disclosed in the consent form?

Response

The United States Department of Health and Human Services (HHS) and the U.S. Food and Drug Administration (FDA) regulations require that the study participant is provided with a “description of any reasonably foreseeable risks or discomforts to the subject;” (45CFR 46.116(a)(2)) (21 CFR 50.25(a)(2)) within the consent form.

Therefore, when the protocol “requires” a participant to begin taking a drug while on-study, even if it is an approved drug and/or is standard of care (SOC), the reasonably foreseeable risks of that drug are required to be disclosed in the consent form. The IRB typically defines “requires” based on how the protocol is written.

If a specific drug and dose is required by the protocol, the risks must be disclosed to participants. If the protocol requires a drug “or equivalent” to be administered (e.g., “prednisone or equivalent corticosteroid”), then the risks that would cover the equivalent drugs (e.g., corticosteroid drugs) should be described. If the protocol design includes “Investigator choice” but that choice is limited by the protocol, then the risks are required.

It is important to note that when the risks are required to be disclosed, they must be disclosed within the consent form [45 CFR 46.117(b)(1), 21 CFR 50.27(a)(1)]. It is not sufficient to direct participants to the package labeling for a drug instead of adding the risks to the consent form.

Study designs often compare SOC drugs with investigational drugs. In a design where participants will be placed in one group or the other as part of the research, the risks of the drugs in each group must be disclosed in the consent form. Other study designs require that all participants start on SOC for research purposes, and then some of the participants are administered an investigational drug. Because the SOC is a requirement of the protocol, the risks must be disclosed. However, if participants will just continue the SOC they already started prior to the research and the SOC is maintained independent of the research, then the risks of the SOC are not research risks and not required to be disclosed.

According to Informed Consent Guidance for IRBs, Clinical Investigators, and Sponsors (Aug 2023), “For clinical investigations involving the comparison of an investigational product to one or more standards of care, it may be acceptable to describe the more common and significant risks and discomforts of the standard of care in the informed consent form and provide additional risk information, as appropriate, as part of the consent discussion.”

Other studies are designed to evaluate one or more SOCs (“comparative effectiveness”). Even in these studies, the risks of a specific SOC being evaluated are risks of research if (1) a standard of care that at least some of the individual participants will be assigned to receive will be different from the standard of care that they would have received if they were not participating in the study, and (2) there might be different risks associated with those standards of care. Therefore, in such studies, the risks of each SOC being evaluated are considered risks of the research and must be disclosed in the consent form.

Finally, in addition to evaluating drugs as comparators, many study designs often also include pre-medications, prophylaxis, and rescue medications as part of the protocol. If they are required, even for a limited period, the risks should be described in the consent form. If they are not required, and are only recommended, optional, or given at the discretion of the research staff, then the risks are not required.

The post If My Study Includes Approved Drugs, When Do the Risks of Those Drugs Need to Be Disclosed in the Consent Form? appeared first on WCG.

If a study is closed, when do study related activities require IRB review and approval?

-Program Director, CRO

Response:

After IRB oversight has been closed out, sponsors or research sites may need to conduct after-study activities which may or may not require IRB approval. Once a study is closed with the IRB, some study related activities can occur without IRB approval, while some require IRB approval and the study to be re-opened.

What after-study activities require review and approval?

• Collection of new adverse event information or follow-up information from subject(s) for research purposes, for example, interviewing subjects or sending additional questionnaires or obtaining new feedback from use of investigational products.
• Collection of new data such as review of medical records when obtaining new data related the study.
• Formal distribution of treatment randomization assignment and/or unblinding information to subjects through written means (e.g., letter).
• Any study interventions.

What after-study activities do not require IRB review and approval?

• Review of study records if obtaining or verifying data that had already been collected prior to study conclusion unless the research is federally funded. If the research is federally funded the study would need to be re-opened until data analysis is complete.
• Informal distribution of treatment randomization assignment and/or unblinding/blinding information to subjects (e.g., phone call).
• Return of study results. This information can be shared in any format, including written.

The post Post Study Activities Requiring IRB Review appeared first on WCG.

What are the WCG IRB requirements for notification of study closure at the research site? Specifically, does the close out visit need to have taken place before submission?

– Director, CRO

Response:

There is no regulatory or WCG IRB requirement for the closeout visit to take place before notifying the IRB of the study closure at a research site.

WCG IRB considers the study open at a site until a study closure report is received. A study closure report may be submitted when all participants have finished all protocol related interventions, interactions, final visits and follow-up (including collection of data) and the sponsor confirms the site can be closed.

Although not required, many sponsors will complete the close out visit before confirming the site can close out the research with the IRB to ensure they have continued oversight if anything further is needed. 

Also note that if the study is federally funded and conducted under a Federalwide Assurance, the study must remain open until no additional identifiable private information about the participants is being obtained; and all data analysis at the site is complete.

The post What are the requirements for notifications of study closure at research sites? appeared first on WCG.

Can a company’s electronic health record (EHR) database be mined to identify potential subjects for a clinical trial? Can the information be used to contact them via phone, email, or text to recruit subjects?
– CEO, Pharma

Answer:

Note that the answer to this question presumes that the company in question is a covered entity under the HIPAA Privacy Rule.

The US Department of Health and Human Services has directly addressed this issue in an FAQ related to use of patient data protected by the HIPAA Privacy Rule. (Can the preparatory research provision of the HIPAA Privacy Rule at 45 CFR 164.512(i)(1)(ii) be used to recruit individuals into a research study? | HHS.gov).

Mining of patient data from EHR’s to both screen and recruit subjects for research is a tool frequently used in many research studies.  The requirements to obtain and use patient data from an EHR will depend on whether the researchers are employees of the company or not.

Under the preparatory to research provision, if the researcher is an employee of the company, data from the EHR may be mined to identify and contact patients who may qualify for the research. However, protected health information may not be disclosed outside the covered entity.

If the researcher is not an employee of the company or, if the researcher is an employee, but wants to transfer or disclose the patient’s protected health information outside the company, approval of a partial waiver of authorization by an IRB or Privacy Board is required.

If the recruitment activity falls within the preparatory to research provision or a partial waiver of authorization is approved, the researcher may contact prospective subjects through the indicated recruitment methods. However, prior to communicating with subjects, the researcher should work with the IRB to determine if the phone script, text script or template email requires IRB review and approval.

The post Can you use patient Electronic Health Records to identify and recruit subjects? appeared first on WCG.

Can you share what type of documentation or rationale may be needed to justify an Investigational New Drug (IND) exemption with an IRB? We’ve read the FDA guidelines and fit within the exemption criteria as stated but want to be prepared for our IRB review. Specifically, we are working with commercially available and legally marketed cannabinoids, which may have their own unique considerations.
—Director, Biopharmaceutical Sponsor

Response:

For purposes of this answer, it is presumed that you have already determined that the product in question is a drug, and that the research constitutes a clinical investigation as defined by FDA regulations, and laid out in FDA guidance titled “Investigational New Drug Applications (INDs) – Determining Whether Human Research Studies Can Be Conducted Without an IND,” and that the criteria you are looking for an IND exempt determination are those within 21 CFR 312.2(b)(1).

Once those determinations have been made, then the IRB must determine if the product meets the requirements within the regulation. Some of the criteria are not within the IRB’s purview for determination, specifically items (i), (ii) and (v) of 21 CFR 312.2(b)(1) are items that are solely under the control of the sponsor and we expect the content of those to be pre-determined by the sponsor to be met. In addition, criteria (iv) is satisfied by the fact that the study has been submitted for review by the IRB, presuming the submission is complete, the standard criteria for approval are met, and an appropriate consent form or waiver of consent request are also submitted.

This leaves the IRB with needing to have sufficient information to affirm that the product is lawfully marketed within the United States and that the criteria within item (iii) are met: The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product.

In regard to the confirmation that the product is lawfully marketed within the United States, generally just the product name is sufficient, as the IRB can confirm drug approvals on the FDA’s approved drugs database. However, if the product is marketed in any other way outside of a standard FDA approval, additional documentation of the product’s marketing status should be submitted.

In regards to information to support that criteria within item (iii) are met, generally the IRB can utilize the approved package labeling for drugs that appear on the FDA’s approved drugs database and determine if the use(s) in the proposed study are within the approved labeling, and if not, if the IRB believes that the criteria in item (iii) are met. However, if the use(s) within the proposed study are outside of the approved labeling, it would be helpful to the IRB if the submission contained a justification as to why the criteria in item (iii) are met. The justification should provide specific information about the potential risks and acceptability of the risk in the population to be studied. A change to the route of administration or population, such as pediatrics, may necessarily require FDA review. In addition, if the product does not appear on the FDA’s approved drugs database, then additional information, similar to FDA approved product labeling, would need to be submitted regarding what the product is lawfully marketed for, in addition to justification why the criteria in section (iii) are met.

The post What documentation needs to be submitted to the IRB for an IND exemption request? appeared first on WCG.

We obtained parental informed consent for a 16-year-old subject to participate in a migraine clinical trial. Does the parent need to accompany the child at each research visit? Based on the parent’s work schedule, the parent may not always be available to accompany the child.
– Director of Research, Primary Care Practice

Response:

The IRB would not be involved in this decision so long as the parent has given permission/consent to participate in the study. This kind of medical care decision is best left to the prudent judgement of the PI and the parents, with the child.

From an IRB perspective, the site would have to be careful to alert parents if there are protocol amendments that require reconsent and to communicate to the parents any new information that could possibly change the willingness of the parents to allow their child’s participation in the study.

The post Do parents need to accompany adolescents at each research-related office visit? appeared first on WCG.

Is it mandatory to update the consent form during a yearly Investigator Brochure update (when the safety updates were already shared with sites via Dear Investigator letters), or can the updates wait until the next protocol amendment that requires a consent form update?
– Study Lead at a Large Biopharma

Response:

The answer to this question largely depends on what new information is contained within the Investigator’s Brochure update.  When the new information is significant, such as new risk or safety information, then the start of the answer to this question is in 21 CFR 50.25(b)(5), which states that “significant new findings developed during the course of the research which may relate to the subject’s willingness to continue participation will be provided to the subject.”

The question is when, and how. These aspects were addressed by the Secretary’s Advisory Committee on Human Research Protections (SACHRP) in their recently published recommendation titled “New Information Provided to Previously Enrolled Research Subjects.” In this recommendation, SACHRP notes that consent is an ongoing process and that “in some research studies, circumstances arise in which new information becomes available that needs to be shared with subjects as part of this ongoing consent process.”

As noted in the SACHRP recommendation, there is no regulatory requirement that states that the new information must be added to the consent form, and subjects thereafter re-consent to participation in the research. However, when the information is significant, it must be communicated to subjects, which can be done in several different ways. It may be by providing the information verbally to subjects and documenting the discussion in the research record, or the use of a consent form addendum. However, modification to the existing consent form and re-consent of subjects is often a best practice.

A few key points to consider when determining when and how to provide significant new information to research subjects:

• Subjects should be provided significant new information as soon as possible
• The significant new information will also need to be provided to new subjects that enroll in the research if the study is still open to enrollment
• It is appropriate to document, by a research record note or consent form (including addendum), that the subjects received the information and thereafter still agree to participation in the research

Given these points, when there is significant new information that has been provided to investigator’s via a Dear Investigator Letter, the most prudent time to provide information to subjects is upon provision of the Dear Investigator Letter, rather than waiting until the time of updating the Investigator’s Brochure.  If the Consent Form has not yet been updated by the time the Investigator’s Brochure has been updated, it would be appropriate to update the Consent Form at that time, rather than waiting until there is a protocol amendment necessitating further consent form updates.

 [LA2]https://www.hhs.gov/ohrp/sachrp-committee/recommendations/april-7-2020-attachment-a/index.html

The post Should Consent Form updates be aligned with Investigator Brochure updates, or wait for next Protocol amendment? appeared first on WCG.