On Oct. 15, 2024, WCG experts Matthew Staves and Cristin MacDonald presented the webinar, “Maximizing the Power of Central IRBs Prior to the FDA’s sIRB Mandate.” The panelists provided an overview of the impending sIRB mandate, discussed strategies for streamlining clinical trial processes to meet the new requirements, and shared how the role of site selection fits into the picture. Live questions submitted by the audience were addressed, summarized below. 

1. When the sIRB becomes mandatory, how will WCG work with local IRBs? Is there no role for local IRBs? 

2. If a study currently utilizes a central IRB and local IRBs, do sponsors need to switch to an sIRB model once the sIRB mandate is implemented? 

3. Under the sIRB mandate, how will “local language” requirements of universities be handled? Or will the central IRB’s informed consent form (ICF) be the template? 

4. How will this impact ongoing studies, especially if the ongoing study is using multiple IRBs? 

5. Will non-federally funded studies need to utilize an sIRB when this transition happens? Specifically, will sponsor-funded studies be required to use an sIRB? 

6. How do we expect the sIRB requirement to impact sites using their local IRBs? 

7. Will the sIRB requirement be for just US sites or will there be a global impact? 

8. Will sponsors have to choose one central IRB? Or can they have more than one for a study? We currently have two central IRBs for one study. 

9. Will sites that like to use a local IRB still be able to require their local IRB to review prior to central IRB submission? Will reliance agreements still be required? 

10. What might IRB review/approval look like under the new rule? Is the expectation that local IRBs and other central IRBs may still exist in a multi-center study and the chosen central IRB will liaise between the sponsor or those IRBs? Or will there only be two layers: the sponsor and one central IRB? 

11. How will the sIRB mandate affect reliance agreements when you have an IRB for oversight? Will reliance agreements still be required for sites with local IRBs? 

12. What happens if sites still have local IRBs? 

13. Currently, if the sponsor requires an sIRB, and the site agrees to use the sIRB, some sites still use their local IRB after the sIRB approval. Doesn’t this create duplicative work and cause delays in study timelines? 

14. Are there penalties in place for sites that do not comply with the mandate? 

Looking Ahead 

Preparing now for the sIRB mandate enables you to maximize the benefits of a central IRB and avoid last-minute adjustments to meet the upcoming requirements. Understanding the process of identifying the right sites is essential for the success of your studies. Take proactive steps today to elevate clinical trial efficiency. 

Have more questions? Connect with a WCG expert. 

The post The Upcoming sIRB Mandate and the Critical Role of Site Selection: Your Questions Answered  appeared first on WCG.

About the Webinar:

As planning and coordination for 2023 is underway, it’s imperative that study Sponsors, CROs, principal investigators (PIs), and Institutional teams understand FDA’s recently released Notices of Proposed Rulemaking (NPRMs) and pediatric research guidance and their potential impacts on clinical research. In late 2022, the FDA released two NPRMs to help standardize and streamline clinical trials in the US.

These NPRMS cover two general categories relevant to research sites and sponsors:

• Single IRB Review for multisite trials
• New required elements of informed consent and informed consent document organization

FDA has also released a draft guidance that directs how IRBs should assess the relative risks and potential benefits of pediatric research, a process that differs from the same assessment in adults.

This webinar discusses the details of these three documents and outline the actions that need to be taken now to ensure utmost compliance and continued efficiency for trial stakeholders.

Frequently Asked Questions

Expand the sections below to read answers to common questions related to NPRMs.

Please note: The Notices of Proposed Rule-Making (NPRMs) and draft guidance do not represent final regulations or final guidance, and they may change during the finalization process, or not be released at all.  The information below is based on these proposed/draft documents, and may change. This content will be updated when new information becomes available. When these regulations and guidances are finalized, we expect to provide more information (webinars, etc.).

The post Understanding the FDA’s new proposed regulations on human subject research and their impact on your clinical trial plans appeared first on WCG.

Those questions touch on an array of issues, and those issues have changed over the course of the pandemic. A few, however, have remained constant; for example, we continue to receive questions about informed consent.

As you already know, regulations require initial consent, and they require consent to changes that could affect a participant’s willingness to continue in the trial. However, the regulations don’t detail exactly how.

Conveying Information

New information can be presented in a multitude of formats:

• It could be a revised consent document. Sometimes, that is the most appropriate way to go about it–for instance, when there’s a significant number of changes throughout the originally approved consent form.
• In other cases, it could be an addendum to a consent form that narrowly focuses on the changes to a specific section, or maybe to the list of procedures that are happening.
• It could also be as simple as a memo, or a letter, or some other written communication sent to the participant.
• In some circumstances, it could be oral communication by phone or in person.
• The FDA is making its MyStudies app available to investigators as a free platform to obtain informed consent securely from participants for eligible clinical trials. It is available through both the Apple App store and the Google Play store.

All this is to say there are several completely appropriate ways to satisfy the requirement that don’t involve revising the consent form with the burden of having all sites re-consent participants.

From a regulatory standpoint, remote consent is permissible as long as consent is documented. If it is not possible to document in real time, use witnesses to confirm that the patient completed the consent process. So, our advice is to document everything.

Ideally, the approach will be the one easiest for the participant. According to the Secretary’s Advisory Committee on Human Research Protections (SACHRP), “When there is a need to present participants with new information, IRBs should encourage use of the least burdensome approach for the participant.”

Sometimes, that approach is digital.

E-signatures and E-consent

One of the most common questions we receive is: Does 21 CFR Part 11 apply to e-consent and e-signatures? The answer is “Yes.” The FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency  states that “systems used to generate electronic signatures… including informed consent documents, during the COVID-19 public health emergency must comply with the requirements outlined in FDA regulations at 21 CFR part 11.”

21 CFR Part 11 compliance dictates that those companies who use electronic systems for document and signature control must provide assurance that the electronic documents are authentic.

What does this mean? It means you need to have the right tools for e-consent. Many of the tools that are available for electronic signature fail to comply with Part 11. For instance, Adobe, DocuSign and similar e-signature products have both Part 11- and non-Part 11-compliant versions.

Get Approval

Regardless of delivery format, any written communication intended for participants to explain study changes or new procedures requires IRB approval; ICH-GCP guidelines are quite clear about that. Moreover, based on our interpretation of FDA regulations, we believe that changing the method from a paper consent to electronic also requires IRB review. But we also believe IRBs need to consider what the sponsor, the principal investigator or the site thinks is a compelling way to convey this information.

Document, Communicate and Stay Nimble

The COVID-19 pandemic has forced everyone involved in the clinical trial enterprise to be more agile, including IRBs and regulators. In fact, regulators, including the US FDA and the Office of Human Research Protections (OHRP), have been very responsive. For example, the FDA quickly set up a dedicated email address for COVID-19 questions: Clinicaltrialconduct-COVID19@fda.hhs.gov.

Likewise, IRBs must allow sites to be nimble. The philosophy of the WCG IRBs–and, we hope, the philosophy of IRBs everywhere–is that the regulations provide us with a great deal of latitude and now is not a time for IRBs to be afraid to use it. No IRB should be a roadblock to making changes that are scientifically valid, ethically appropriate and maximize safety.

Sometimes a site or sponsor may need to make an immediate change for the best interest of those involved in the research. Modifications made without IRB approval must be submitted as soon as possible–ideally, within five days. Of course, the pandemic doesn’t give carte blanche to implementing changes without IRB approval.

We’re all playing this by ear, in many ways. So, I would say be vigilant, continue to communicate, document everything, and when in doubt–again–reach out to your IRB and even to the FDA and say, “What do we need to be doing here that we haven’t thought of?” It is better to ask too many questions than too few.

Answers to frequently asked questions related to research and COVID, as well as information to the previously discussed OHRP and FDA guidance, are available at WWW.WCGCLINICAL.COM/COVID-19/FAQS/.

The post Informed Consent: An IRB Perspective on Navigating the New Normal appeared first on WCG.

The first set of recommendations, which were approved in July 2019, address concerns that arise when sponsors and investigators want to offer payments to research participants. SACHRP was asked to examine this issue following the January 2018 update to the FDA Information Sheet Payment and Reimbursement to Research Subjects  in which the FDA clarified that reimbursement of expenses incurred due to research participation were acceptable and did not raise ethical concerns.

In their recommendations, SACHRP notes that payments to participants can take on many forms – reimbursement for out of pocket expenses, compensation, tokens of appreciation, and incentive – and that most of them should not present concerns of undue influence on participants.

In the context of incentive payments, where there is the potential for undue inducement, SACHRP recommends that the regulators “acknowledge that concerns about incentive payments that may be unduly influential can be managed without necessarily lowering or eliminating them.” The recommendation identify five considerations for IRBs when evaluating the acceptability of incentive payments:

• Their responsibility to approve research only when risks are reasonable in relation to benefits to participants and/or society;
• The possibility that incentive payments will compromise the informed consent process;
• Steps that can be taken to support autonomous decision-making in those contexts;
• Tradeoffs that may be associated with restricting incentive payments and how that may affect achieving adequate recruitment; and
• How similar payment might be viewed outside the research setting.

The second set of recommendations that were approved by SACHRP on October 16^th examine research studies that ask potential research participants to bear some or all of the costs of the research.  Anecdotally, IRBs are seeing an up-tick in the frequency of such submissions, with many of them being in the area of regenerative medicine. Earlier this year, the FDA targeted some of these studies and warned consumers to be wary of unproven therapies. While some of these are examples of investigator-initiated, unfunded research, there are also reports of entities using this mechanism to provide unproven therapies without having to market a product in a way that would require FDA oversight.

The recommendations also note that there is an increase in the use of crowd-funding mechanisms that have not been previously contemplated by IRBs or regulators. Although the FDA regulations do address charging participants for investigational drugs and biologics (21 CFR 312.8), and investigational devices (21 CFR 812.7), they did not contemplate a scenario where the ability to charge study participants might be exploited to take advantage of individuals who are both desperate for an effective therapy and have the ability to manage significant out of pocket costs.

SACHRP’s recommendations conclude with a list of questions that can serve as a starting point for prospective subjects who are contemplating such research, and also the IRBs that review proposals that require participants to pay for access to the experimental intervention.  These questions include:

• Who has reviewed this research and said it is OK to do?  Has there been ethical and scientific review of the research?
• Why do the researchers think that what is being tested might help people like me? What do they think it might do, if it works?
• Has it been tested before? If so, how many people has it been tested on?
• Why am I being asked to pay to join this research?
• How much will the researchers charge me to be in this research?
• What exactly will I be paying for (eg., diagnostic tests, the study intervention)?
• What are some reasons I might be willing to pay to join this research? What are some reasons I might not be willing to pay to join this research?
• Besides the people like me who join this research, are any other people or groups also paying for this research? If so, what exactly are they paying for?
• If I am injured, who will pay for the treatment of that injury?
• When will I be expected to pay?  If paid in installments, what happens if a payment it missed?
• If I quit the research, will I get any of my money back?
• If the researchers make me leave the research, will I get any of my money back?
• What other costs might I have to pay if I join this research?
• Will being in this research affect my health insurance coverage? Will my health insurance cover any part of what I am being charged for this research?

Ultimately, IRBs need to proceed in a careful and deliberate manner when considering the intersection between research, payments and participants.

The post An Overview of the Recent SACHRP Recommendations Around Payments in Clinical Research appeared first on WCG.

This guidance, which was issued in draft form in August 2016, marks another step towards the more complete harmonization of the OHRP and FDA regulations.

What is the guidance?

With four pages of guidance and a nine-page checklist, the goal of the document is to assist staff at institutions and IRBs who are responsible for preparing and maintaining written procedures including standard operating procedures (SOPs) and policies. The guidance notes that “OHRP and FDA believe that when institutions and IRBs develop and follow clear written procedures, there is an increased likelihood that the rights and welfare of human subjects will be protected.”

People are often surprised to learn that the regulations governing IRBs require only seven specific written procedures. Both the HHS regulations at 45 CFR 46.103(b)(4) and (5) and the FDA regulations at 21 CFR 56.108(a) and (b) state that IRBs must follow written procedures for the following functions and operations:

1. conducting initial and continuing review of research and for reporting IRB findings and actions to the investigator and the institution;
2. determining which projects require review more often than annually and determining which projects need verification from sources other than the investigator that no material changes have occurred since previous IRB review;
3. ensuring prompt reporting to the IRB of proposedchanges in a research activity;
4. ensuring that changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval except where necessary to eliminate apparent immediate hazards to the human subjects
5. ensuring prompt reporting to the IRB, appropriate institutional officials, and, as applicable, any department or agency head, OHRP, and/or FDA of any unanticipated problems involving risks to human subjects or others;
6. ensuring prompt reporting to the IRB, appropriate institutional officials, and, as applicable, any department or agency head, OHRP, and/or FDA of any unanticipated problems involving risks to subjects or others;
7. ensuring prompt reporting to the IRB, appropriate institutional officials, and, as applicable, any department or agency head, OHRP, and/or FDA of any instance of serious or continuing noncompliance with the applicable HHS and/or FDA regulations, or the requirements or determinations of the IRB, and any suspension or termination of IRB approval; and
8. ensuring prompt reporting to the IRB, appropriate institutional officials, and, as applicable, any department or agency head, OHRP, and/or FDA of any suspension or termination of IRB approval.

While these are the only specifically-required written procedures, there are other IRB activities that require findings and determinations for which the underlying regulations do not explicitly require the IRB to follow a written procedure, such as the requirement that IRBs determine that proposed research meets the criteria for a waiver of documentation of informed consent. Many IRBs have additional procedures for these processes as well. Finally, the Association for the Accreditation of Human Research Protection Programs (AAHRPP) will also have additional procedures that are required in order for IRBs to achieve and maintain AAHRPP accreditation.

What does this mean?

There are several ways in which the new guidance is helpful to IRBs.

• The guidance is clear regarding what items are required by the regulations versus recommended by FDA/OHRP. In response to the 2016 draft version of the guidance, the HHS Secretary’s Advisory Committee on Human Research Protections (SACHRP) recommended that final guidance be clear on this point.
• FDA/OHRP also clarify that the regulations provide a great deal of flexibility in how IRBs choose to format their written procedures and how much detail to include. With this in mind, an IRB can define their written procedures to include traditional documents such as policies and SOPs, but can also include other types of controlled documents including work instructions, checklists, and other tools that guide IRB members and staff in fulfilling regulatory expectations.

With these clarifications in the guidance, the written procedures checklist that forms the bulk of the guidance is a helpful tool that IRBs can use to evaluate their written procedures. The checklist provides extensive recommendations regarding what information could be considered for inclusion within the required seven written procedures. It also goes beyond the required procedures to include recommendations for written procedures in additional areas of relevance to the IRB. Section V of the checklist, Additional Topics the Institution/IRB May Consider provides suggestions for what might be included in written procedures in numerous areas including IRB membership and IRB records.

The checklist should serve as a useful tool for IRBs and institutions that want to ensure that they have covered not only the minimal regulatory requirements, but that are interested in creating and maintaining a comprehensive set of written procedures that reflect best practices for IRBs.

References:

1. U.S. Department of Health and Human Services and the Office for Human Research Protections (OHRP). Institutional Review Board (IRB) Written Procedures: Guidance for Institutions and IRBs. https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM512761.pdf. Accessed June 20, 2018.

The post Written Procedures for IRBs: What Does the New Final Guidance from FDA and OHRP Mean to You? appeared first on WCG.

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