The following Insight is a featured article from WCG’s 2025 Trends & Insights Report. If you would like to read more insights from this report, please click here.

The FDA has released a notice of proposed rulemaking to mandate that any institution located in the United States, participating in FDA-regulated cooperative research, must rely on a single Institutional Review Board (sIRB) for overseeing research conducted in the United States.  (See Institutional Review Boards; Cooperative Research (87 FR 58752)). The proposal aims to harmonize the FDA Institutional Review Board (IRB) regulations with the Federal Policy for the Protection of Human Subjects, known as the “Common Rule”, which currently requires a single IRB review for such research.    

The new FDA regulation will require that “Any institution located in the United States that is participating in cooperative research must rely upon approval by a single IRB for that portion of the research that is conducted in the United States.”     

To ensure the rule is comprehensive yet pragmatic, the FDA has proposed four exceptions to this requirement:  

1. Cooperative research for which more than a single IRB review is required by law (including tribal law passed by the official governing body of an American Indian or Alaska Native tribe);  
2. Cooperative research involving a highly specialized FDA-regulated medical product for which unique, localized expertise is required;  
3. Cooperative research on drugs exempt from an investigational new drug application, as outlined under § 312.2(b) of this chapter; or  
4. Cooperative research on medical devices that meets the abbreviated requirements under § 812.2(b) of this chapter or that meets the requirements for exempted investigations under § 812.2(c) of this chapter.    

When the FDA adopts this requirement, sponsors will be obligated to use a single IRB for U.S. sites. Previously, this approach was allowed, but not required. Many industry sponsors have voluntarily taken this approach for some time, so disruption at the sponsor level will be minimal. For institutions and investigators, the imposition of the single IRB requirement will likely require some modifications to standard operating procedures (SOPs) and resources in order to comply. Still, many have already taken these steps due to the previous adoption of the Common Rule requirement, thereby facilitating a smoother transition and promoting more harmonization as we move into 2025.  

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Revisiting the FDA’s Proposed Single IRB Mandate: Navigating Changes and Aligning for Success

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The post FDA’s Proposed Rule for Single IRB Review in Cooperative Research appeared first on WCG.

About the Webinar

This webinar is aimed at all stakeholders in clinical research, including sponsors, CROs, institutions, and sites. Our experts dive into the intricacies of the FDA’s proposed single Institutional Review Board (sIRB) Mandate, providing crucial insights and updates to ensure your organization remains compliant and efficient in multi-site clinical trials.

Topics covered include:

• Recap of the 2023 NPRMs: We start by revisiting the key points of the 2023 Notice of Proposed Rulemaking (NPRM), highlighting the proposed changes and their potential impact on clinical research stakeholders.
• Update on Changes: Get up-to-date with the latest developments surrounding the FDA’s proposed Single IRB Mandate. We explore what has changed since the NPRM and discuss how these changes may affect your organization’s operations and procedures.
• Demystifying the FDA: Ever wonder why FDA mandates seem to take forever to become final rules? We demystify this process, providing clarity on the intricacies and timelines involved in regulatory decision-making at the FDA.

Plus, our experts discuss why aligning to the sIRB mandate sooner rather than later is advantageous to accelerating your research. Don’t miss this opportunity to gain valuable insights and strategies for navigating the FDA’s proposed Single IRB Mandate. Watch the recording now to stay ahead in the ever-evolving landscape of clinical research compliance.

The post Revisiting the FDA’s Proposed Single IRB Mandate: Navigating Changes and Aligning for Success 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.

Appropriately compensating clinical trial participants lessens the financial burden placed on them by participation in research and increases the pool of possible contributors. As a result, sponsors can increase diversity in their clinical trials, and make sure that they are truly representative of the patient population. Compensation increases recruitment, allowing studies to be completed efficiently, saving time, money, and staff resources. It also recognizes participants for their contribution to advancing medical science.

But how can sponsors strike the right balance between compensating research participants to achieve those benefits, while minimizing the potential for the payments to have an undue influence on their behavior?

The U.S. Food and Drug Administration (FDA) states that an investigator can only seek a person’s consent to join a clinical trial if the prospective participant has “sufficient opportunity to consider whether or not to participate” under circumstances that “minimize the possibility of coercion or undue influence.”¹ As coercion involves a threat of force, payments can never be coercive, but they could be unduly influential.

Primary concerns are that payments might interfere with participants’ ability to give voluntary informed consent, by encouraging them not to fully consider the risks, burdens, and discomforts associated with the research, or to ignore side effects during the trial due to their desire to complete the study and get paid.

Regulatory Guidance

Fortunately, the FDA has provided an Information Sheet on this topic,² and the U.S. Department of Health and Human Services’ (HHS’) Office for Human Research Protections (OHRP) has published responses to frequently asked questions.³ The Secretary’s Advisory Committee on Human Research Protections (SACHRP) has also provided some valuable recommendations.⁴ While this guidance is helpful, there are still circumstances in which Institutional Review Boards (IRBs) need to rely on their experience and good judgement to make the best decisions.

Recruitment Advertisements

It is generally acceptable for sites to state in clinical trial advertisements that people will be paid for participating and the amount. But the FDA guidance states that payments should look like the rest of the text and not be highlighted or in bold type.

Most clinical trial participant payments fall into one of four categories: reimbursement, compensation, bonus, or incentive.

Reimbursement

The FDA is generally comfortable with sponsors reimbursing clinical trial participants for costs they must incur. Its 2018 guidance states: “FDA does not consider reimbursement for travel expenses to and from the clinical trial site and associated costs such as airfare, parking, and lodging to raise issues regarding undue influence.” But it adds that “IRBs should be sensitive to whether other aspects of proposed payment for participation could present an undue influence.”

Reimbursement for some studies, particularly those for rare diseases, can involve substantial costs because they may require flying patients in from another country, include a one-week hotel stay, etc. If those costs were not covered, it could skew studies towards people with more resources because they could pay for themselves to get there, which is problematic from the justice perspective.

Compensation

Compensating participants for lost economic opportunities during a study is a little more complicated because participants’ income levels can vary significantly. IRBs typically require everyone to be paid the same amount, as a matter of equity. In multi-site trials, however, investigators are sometimes given the discretion to offer a payment that they feel is appropriate for their area, so the compensation in Alabama might be different from New York City due to differences in the relative cost of living.

Payments for participation are seen predominantly in studies for chronic conditions such as diabetes, obesity, or high blood pressure where people are not likely to suffer serious harm without the intervention. The payment is intended to compensate participants for the time and effort required to attend additional clinic visits outside the scope of their normal medical care.

Compensation in Phase 1 studies is generally higher than for later phase studies because it requires recruiting healthy individuals. It is more like a job for those participants than other types of research when the study drug is combined with medical care. Volunteers are typically required to spend the entire study confined to the Phase 1 Unit, so that researchers can better control their diet and other aspects of their environment. Compensation for Phase 1 studies usually works out to be about $10- $20 an hour. The only exception would be Phase 1 studies involving patients with cancer or another potentially deadly disease. Those studies generally do not pay for participation because they fall more in the clinical care continuum.

SACHRP suggests that payment for participation is prorated or evenly scheduled throughout the trial. For example, participants might get paid once a month or once every six months during a yearlong trial. Paying a participant when the study ends for the number of meetings attended or study visits completed is also considered acceptable.

To further counter undue influence concerns, SACHRP recommends that the IRB evaluates the risk-benefit ratio for the clinical trial, and the other IRB criteria for approval, before considering payment. Then, if the IRB considers that the study is acceptable, the money becomes less important because people cannot be drawn into a study that is not in their interest because the IRB has already deemed the risk-benefit ratio appropriate. In addition, the IRB will have determined that risks are minimized to the extent possible, and the research will provide benefit to society.

Completion Bonuses & Incentive Payments

Most of the unease relating to payments pertains to bonuses or participants receiving extra money at the end of a study for completing it. There are concerns that that payment structure might encourage a participant to stay in a study after they have had an adverse event or are experiencing a side effect of the drug because they are reluctant to lose the extra payment for the visits they have completed or miss the big bonus at the end of the study if they drop out. This is one of the remaining areas where concern exists at SACHRP and in IRBs about undue influence.

A small bonus payment is acceptable under the FDA guidance, but it does not give an actual figure or range for that payment. In practice, up to about 25% of the amount that the participant would be paid can generally be held over as a bonus. But anything more than 25% will raise eyebrows with an IRB. When pay is weighted too much toward completing the study, that is when it becomes inappropriate and potentially unduly influential.

SACHRP recommends keeping the level of financial and non-financial incentives low for clinical trials. Non-financial incentives might include entertainment, hairdresser appointments or a massage for participants in a Phase 1 study who must remain onsite for several weeks.

Another way to reduce the risk of introducing any undue influence with these benefits is to ensure that they are clearly described, without any exaggeration, in the consent documents. Situations in which a participant will receive only a partial payment, or no payment should be described there. The payment schedule should also be clearly stipulated. If the study involves six visits, and a participant drops out after three visits, they will often want to be paid right away for the three visits. However, many sites wait until the study ends to pay everyone because it is more efficient from an administrative standpoint. Payments may be prorated throughout the study but not paid until the end. It is important to set expectations appropriately in the consent document.

Conclusion

It is acceptable to pay people to participate in clinical trials because they are making sacrifices to join research studies for the good of others. With careful consideration, it is possible to reimburse their costs, and compensate them for their time, effort, and other burdens without posing undue influence on their decisions. The IRB’s objective review of the consent documents helps to ensure that occurs.

References

1. FDA regulations 21 CFR Part 50.20. Definition of informed consent: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=50.20
2. FDA Payment and Reimbursement to Research Subjects information Sheet. January 2018:
   https://www.fda.gov/regulatory-information/search-fda-guidance documents/payment-and-reimbursement- research-subjects
3. OHRP FAQs:
   https://www.hhs.gov/ohrp/regulations-and-policy/guidance/faq/informed-consent/index.html
4. SACHRP recommendations:
   https://www.hhs.gov/ohrp/sachrp-committee/recommendations/attachment-a-september-30-2019/index.html

The post The IRB’s Perspective: Determining Optimal Compensation for Clinical Trial Participants appeared first on WCG.

Question:  Is there a specific regulation that you can direct me to regarding the specific rules that outline compensating a physician for referring a patient to our site for recruiting of a study?
– Regulatory Affairs Professional, CRO

Response: 

WCG IRB does not allow referral fees (offering or accepting payment for referring patients to research studies, sometimes referred to as “finder’s fees”) for medical professionals or research staff. This is in accordance with the American Medical Association Code of Medical Ethics which states, “Offering or accepting payment for referring patients to research studies (finder’s fees) is also unethical.” Some states have laws that ban such practices.  However, it is acceptable to reimburse for activities directly related to performance of the research and at a rate not exceeding the fair-market value for the level of activity performed.  These kinds of activities might include chart review to find eligible subjects.

The post May I pay a physician for referring a patient to our study? appeared first on WCG.

Our phase I informed consent document (ICF) is very specific in terms of the types of analyses that will be completed from the blood draw specimens that are collected from our subjects. It recently came to our attention that sites were collecting samples for a particular assay on days that were not noted in the ICF. So, the subjects consented to blood draws for “general health” but not for the performance of the assay on those particular days. We have since revised the ICF by adding a statement that the assay will also be performed on those specific days. May we perform the assay and retain the data for those samples we received before we revised the ICF?
– Director, Clinical Compliance, Pharmaceutical Company

Response:

The deviation from the approved protocol as described is a minor error with no substantive subject rights or safety issues. While the reporting requirements for this type of error may vary across IRB, we suggest that as a first step, you make a note to file describing the deviation and the corrective actions. 

If you wish to test the samples collected prior to the approval of the modification to the ICF, you should consider reporting the event to the IRB as a protocol deviation along with a request to use the specimens and data and then retain the IRB communications in your regulatory binder.

The post How do I handle a deviation in the use of blood specimens collected outside the timeframe? appeared first on WCG.

A subject in a clinical trial signed the informed consent document but did not sign the HIPAA authorization. Does this failure to obtain the subject’s signature need to be reported to the IRB or can the missing signature just be documented in a Note to File?

– Project Manager, Device Company

Response: 

Under the HIPAA Privacy Rule, an individual’s signed authorization allows the use or disclosure of the subject’s protected health information collected during the clinical trial. HIPAA authorizations for research can be either embedded within the research consent form or be separate from the research consent form. When they are separate, an IRB may review the HIPAA authorization but does not have to do so. 

If the authorization has been reviewed and approved by the IRB, whether embedded or separate, then the failure to have the authorization signed should be reported to the IRB as noncompliance. However, if the IRB did not review the authorization, then the failure to have the authorization signed should be reported to the privacy officer or other institutional office of the covered entity.

The post How should a site document a missing signature on a HIPAA authorization form? appeared first on WCG.

Question:

May the inventor of a new therapy using gene editing technology also be the principal investigator of the study and owner of the clinical trial site conducting the clinical trials? It seems that there could be an ethical issue if the principal investigator has a proprietary or equity interest in new therapy.
– Clinical trial site

Answer:

In answering this question, we are assuming that there is no federal funding such as an NIH grant involved.  Under the FDA regulations, certain conflicts of interest will need to be reported to FDA in accordance with 21 CFR 54.  The FDA, through guidance, encourages sponsors with certain conflicts of interest to work with the FDA prior to the start of the study to “minimize any potential bias.”

In addition, most IRBs will ask about conflict of interest as part of their submission requirements.  An IRB is likely to find that this type of financial conflict would need to either be controlled or eliminated, but that will depend on many factors such as the level of risk to the human subjects and the potential for bias allowed by the study design. 

The post How should we handle financial conflicts of interest in FDA-regulated clinical trials? appeared first on WCG.

Studies show that most clinical trial participants want to know what was learned from their involvement. A growing number of sponsors are implementing plans to deliver plain language summaries to trial participants.  

Read this white paper, co-authored by the Center for Information and Study of Clinical Research Participation (CISCRP) to learn about the current best practices for the content and preparation of plain language summaries, and the current guidance for how sponsors should work with Institutional Review Boards (IRBs) which have oversight of the clinical trials for which the summaries are provided.

 

The post Returning Study Results to Research Participants appeared first on WCG.

The technological leap and informational explosion of biomarker and genetic mutation tests raises complex issues for the conduct of FDA-regulated clinical investigations.

Since a buccal swab, tissue, or blood sample can provide data that determines a person’s eligibility or assignment in a clinical trial, it is critical that the results of these tests be accurate. And sometimes, ensuring the accuracy of this crucial data requires research into the test that produces it.

When biomarker or mutation testing is part of a clinical trial protocol, the sponsor and Institutional Review Board (IRB) must make a determination as to whether the testing (and testing device) itself is investigational, and sometimes the answer to this question comes as a surprise to sponsors.

This paper discusses the roles of the FDA, sponsor and IRB in determining when biomarker testing, conducted as part of a clinical investigation, is considered FDA-regulated medical device research.

Background: FDA’s Authority

The post Under the Microscope: Biomarker and Diagnostic Tests as FDA-Regulated Devices appeared first on WCG.