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]]>WCG IRB Review Process for a New Proposed Research Study:
Step 1: Initial administrative assessment
After WCG IRB receives a new proposed research study, a designated staff member will assess whether all required documents have been submitted. Missing or incomplete submissions lead to communication with the Investigator or sponsor until all the required documents are provided and the submission packet is ready to initiate the review process.
Step 2: Assessment of the overall risk and review level required
A designated reviewer will review the Protocol document and initial review submission form, to do a preliminary assessment of risk level. Reviewers follow the regulatory guidelines and guidance documents issued by both DHHS and FDA to make this determination.
Evaluation of the overall risk level is a critical step because this is a determinant of whether a study can be reviewed by an expedited (designated) review process or via a convened board meeting. Minimal risk research studies that fit into one of the nine categories described per 45 CFR 46.110 are directed to a designated reviewer, while greater than minimal risk studies and those that do not fit into a category are sent for review at a convened board meeting.
Step 3: Scheduling a new research study for a convened Board meeting
The study is assigned to a Board meeting with specific Board members assigned to present the protocol, consent form(s), and other documents associated with the study. The assignment is based on a board member’s qualifications, experience, and expertise. If necessary, an independent consultant with specialized expertise may also be assigned to facilitate the review process.
Step 4: Release of meeting agenda and start of pre-Board discussions and review process
Staff will inform the board members that their agenda and materials are available for review. Prior to the board meeting, the chair and the board members actively engage with each other to discuss the study and identify any issues or concerns. During this period the chair may also reach out to the Investigator or sponsor to resolve any identified issues and clarify queries raised by the board members that come up during their review. Additionally, the chair can utilize the expertise of WCG consultants, or other internal experts to facilitate the review process.
Step 5: Convened Board meeting
The board members, the chair, and administrative support staff meet at the scheduled time. Before the meeting starts, the chair ensures that all board members are present, and requests disclosure of any conflict of interests in the studies that will be reviewed in the meeting. Next, the chair confirms that a quorum has been established and starts the meeting. The studies listed in the agenda are systematically discussed one at a time.
For a new proposed research study, the assigned board member presents the study to the board. The presentation generally includes an overall summary of the study (purpose, scientific/medical merit, study design and population, objectives, and data collection and analysis), regulatory status of the investigational product (if applicable), a list of key findings, and any issues or concerns identified including any pending items that need to be addressed by the sponsor or investigator.
Next, the board member invites questions from the rest of the board members, and discussions are moderated by the chair. During the discussions, it is important to note that board members need not agree on the status of all the issues or concerns being discussed, disagreements and alternative ideas are welcome.
The consent form presenter then presents the consent form(s) with proposed revisions to the board. Another staff member will capture any additional revisions to the consent form(s) made during the meeting. The board’s objective is to ensure that the consent form(s) meets the guidelines as indicated in the regulations (21 CFR 50 and 45 CFR 46).
If any additional documents are provided in the submissions packet, such as advertisements, enrollment scripts, information sheets, questionnaires, or emergency cards, these are reviewed for their appropriateness.
The board member will conclude the presentation with a statement of whether they believe the study meets the regulatory criteria for approval. If the criteria are not met, a list of unresolved issues that may need to be addressed by the sponsor or investigator is generated.
An administrative staff member captures notes from the board’s discussions. After the meeting concludes, the notes are utilized to draft the official meeting minutes to capture the various discussion points for all reviewed research studies on the agenda.
Step 6: Board’s action on the new proposed research study
Most commonly, a new proposed research study may receive one of three types of Board action after board review: (1) if there are no pending issues identified, then the study is approved, (2) if there are pending issues that only require confirmation of board’s revisions to study documents or clear requests for modifications to the research, then the study is conditionally approved for confirmation or submission of the requested modifications or documents, or (3) the study is deferred when the issues significantly impact the criteria for approval, such as concerns regarding study design, potential safety issues, uncertainty regarding the investigational product, and when the consent form(s) require extensive revisions that cannot be made by the Board without input from the investigator or sponsor.
Generally, the presenter makes the motion for one of the above-noted actions, another member seconds the motion, and the chair calls on all the board members to cast their vote. A board member may vote in favor, against, or may abstain from voting. The voting is tallied, and a simple majority of favorable votes results in an official board action. This completes the initial review of a new proposed research study to the WCG IRB.
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]]>The post What Is Assent, When Provided by an Adult Participant Lacking Capacity? And What Are WCG’s Expectations and the Investigator’s Responsibilities? appeared first on WCG.
]]>What is assent, when provided by an adult participant lacking capacity? What are WCG’s expectations and the investigator’s responsibilities, when the IRB Board provides assent instructions for adult participants who lack capacity to consent for themselves?
Background
The term “assent” is often misinterpreted by stakeholders who are involved in the conduct of clinical research studies because it is commonly only associated with seeking affirmative permission from capable children as stated in U.S. federal regulations related to Protection of Human Subjects (21 CFR 50.3(n) and 45 CFR 46.402(b)).
However, an adult participant who lacks full capacity may still be able to be cognitively engaged in the consent discussion. They can also provide their assent to participate in the research study. Therefore, assent can be broadly interpreted as an affirmative agreement by either children or adults lacking capacity who have that capability.
Response
The Board will provide assent instructions for the adult participants who lack capacity to consent for themselves and may require the investigator to obtain and document their assent, like with children. WCG’s IRB expects the investigator to involve both the participant and the appointed Legally Authorized Representative in the consent discussion. During the consent process, the investigator should holistically evaluate the participant’s engagement by assessing their cognitive presence, non-verbal facial and body gestures, any evidence of understanding, and subtle emotional reactions. Furthermore, to respect the participant’s autonomy, the investigator should also encourage the participant to communicate via common gestures, such as head-nodding, lifting arm to seek clarification or stop the discussion, and thumbs-up or down movements to engage with the investigator. However, the investigator is not limited to these techniques but may incorporate any reasonable methods including the help of others who have expertise in communicating with the participant.
After the consent discussion, the person obtaining assent will document the discussion as directed by the assent instructions. A participant’s rights and welfare are best protected when the investigator engages with the participant to the extent they are able, which is an on-going process throughout the study.
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]]>Research submission/protocols are deferred when the Board is unable to determine that the regulatory criteria for approval are met (21 CFR§56.111 and 45 CFR§46.111). The institutional review board (IRB) needs adequate information to fulfill its regulatory responsibilities and to ensure that the rights and welfare of human subjects are protected. WCG’s IRB has identified two broad types of deficiencies which frequently lead to the IRB’s inability to determine the Criteria for Approval are met:
- Regulatory status of the test article(s) is/are not provided, and
- Submitted protocol information is incomplete.
Insufficient Regulatory Status Information
The first category includes missing or insufficient regulatory status information about the test article utilized such as: drugs, vaccines, biologics, medical devices, combination products, dietary supplements, or human cells, tissue, and cellular and tissue-based products (HCT/Ps).
Submissions Involving Drugs, Vaccines or Biologics That Do Not Have an IND from FDA
If an investigational drug, vaccine, or biologic is being evaluated for safety and efficacy, the study requires an investigational new drug (IND) application from the U.S. Food and Drug Administration (FDA) or an exemption.
The sponsor should provide the IRB with the IND number on a sponsor document, e.g., the protocol or a separate sponsor letter, an FDA letter with the IND number, or documentation from FDA that an IND is not needed. If the sponsor believes an IND application is not required, documentation of the rationale for not needing an IND, and the regulatory status that should be applied, is also needed.
Instructions for applying for an IND can be found here. In brief, complete a 1571, append the protocol, and if applicable, provide a rationale for not needing an IND, and submit that to FDA. By law, when a 1571 is submitted, FDA must respond within 30 days with a decision. Applying for an IND does not imply that an IND will be issued. FDA does not issue INDs if they are not necessary. If FDA determines that the research does not need an IND, FDA will issue a statement to that effect. If FDA considers an IND necessary, they may issue an IND or follow up for more information.
Submissions Involving a Medical Device
If a medical device is being evaluated in the research and is FDA approved (has a PMA #), cleared (has a 510k #), or is a Class I or Class II device exempted from pre-market review, and is being used in the research in a way that matches the indications on the FDA documentation, please provide the approval/exemption information.
- FDA SR Device PMA Database
- FDA NSR Device 510K Database
- FDA Device Search
- FDA Medical Device Databases
- Class I and Class II Exempt Device listing
If your device meets another exemption under the investigational device exemption (IDE) regulations, please provide a rationale for why your device qualifies as IDE exempt.
Otherwise, if the device is investigational, the IRB must make specific determinations related to the risk of the device and whether an IDE or abbreviated IDE is required. You can either propose with a rationale why the device meets the abbreviated IDE requirements as the use does not present a significant risk, or obtain documentation from FDA.
There are two ways to ask FDA about potential or planned medical device studies. The first is to complete a study risk determination request through the Q-submission program. The FDA will give written documentation if they determine the study does or does not need an IDE. The other way is to apply for an IDE. By law, when an application is submitted, FDA must respond within 30 days with a decision. Applying for an IDE does not imply that an IDE will be issued. FDA does not issue IDEs if they are not necessary. If FDA determines that it is a nonsignificant risk device study, FDA will issue a statement to that effect. FDA may issue an IDE or follow up for questions.
Additional information to provide related to specific types of products:
- For investigational combination products, provide an FDA letter for the test articles with the IND or IDE number.
- For HCT/Ps, consult the following FDA guidance’s to ensure that your product is regulated solely as a Section 361 HCT/P product and meets all the criteria stated in 21 CFR 1271.10(a) (1) to (4) as explained in the two guidance’s below. Provide a rationale either in the protocol or a separate memo for how the test article meets all the requirements of Section 361 as stated in 21 CFR 1271.10(a) (1) to (4).
- If your test article will be studied as a food or dietary supplement, provide supporting evidence from literature that the test article has been classified as GRAS (Generally Recognized as Safe) as appropriate. Refer to the guidance and search the FDA database for GRAS articles. Please include GRAS rationale and clearly stated claims in the protocol.
- For dietary supplements, identify whether it is a new or previously known ingredient. Clearly state any structure/function claim in the research objectives or whether a structure/function claim is not valid with a rationale. If you make claims in the protocol that the supplement or food prevents, mitigates, or treats a disease, the IRB will consider the test article to meet the definition of a drug which could lead to a deferral if you do not have an IND.
Insufficient Protocol Information
The second category includes protocols that are missing important information or are inadequately described. The following are some examples of common issues and how to resolve them:
- The protocol is written in a manner which leads to confusion between research procedures required by the protocol and those that will occur regardless of the research. Access WCG’s whitepaper “Is This an Interventional Clinical Trial or Observational Study? How- and Why- It Is Important to Write Protocols That Make This Distinction Clear.” While this paper is oriented toward the two extremes of clinical trial and registry, the information is broadly applicable.
- The protocol lacks key elements. Access WCG’s whitepaper “Drafting a Research Plan for IRB Review and Research Conduct: Information That Must Be Included in a Clinical Trial Protocol.” While oriented to clinical trials, this information applies to all research studies. Another good resource with both clinical and non-clinical protocol templates is NIH.
- This includes scenarios where inclusion/exclusion criteria are incomplete, or do not address certain potentially vulnerable populations.
- The submitted protocol is labelled as a draft. The IRB requires final versions be submitted for review. Check to ensure there is no watermark or other indication the protocol is a draft. Also, ensure the final version submitted contains no redlining. While a separate redlined version is useful when there have been modifications, a final non-redlined version is needed for approval.
What Should I Do If My Research Submission/Protocol Is Deferred?
- Review the Board’s concern, and if unclear, discuss via telephone or schedule a meeting with the Chair listed in the Certificate of Action for contact.
- Address the Regulatory status of the test article, including provision of any FDA communication.
- Revise the protocol as needed to clearly distinguish research and non-research procedures.
- Clearly identify study population, especially any vulnerable population.
- If general concerns regarding protocol content and format are raised, please refer to the whitepapers noted above.
- Learn more about the submission process for IRB review and the Board’s determinations here.
- Contact our client care team to help with the submission process:
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