Design and Conduct of the Research 

A decentralized trial can provide much-needed flexibility to participants, but as flexibility in data acquisition increases, variability in the data will also increase.

An example from the guidance includes using self-collected home spirometry measurements vs. in-office spirometry measurements. Participants may interpret instructions in unexpected ways leading them to perform the tests differently whereas a designated, trained healthcare provider could be trained to be more precise in administering the test. The benefit of home testing for recruitment and retention may still outweigh requiring participants to visit a clinic, but the increased variability in the data may require a larger sample size to demonstrate the same effect.

Remote Visits and Related Activities – Who Needs IRB Review?

A variety of alternatives to face-to-face study visits can make clinical trials more accessible to a wider demographic of participants. Telehealth visits are face-to-face visits under FDA regulations, not electronic communications. There may be challenges to overcome in ensuring participants have access to adequate technology and bandwidth for video conferencing. Any electronic visit notes would need to comply with 21 CFR Part 11. Additionally, at-home visits whether telehealth or with visiting health care providers (HCPs) may lead to privacy concerns depending on the participant’s living situation. Investigators should ensure that the participant has adequate privacy for discussions or in-home procedures.

Two of the most frequent questions IRBs get about remote visits and decentralized trial activities are: 

1. Who is the investigator? 
2. Which locations are research sites required to have IRB oversight?

According to the FDA guidance, investigators are personnel who contribute directly and significantly to the trial data and who must have detailed knowledge of the protocol, Investigator’s Brochure, or investigational product (IP), and sponsors should list them on the FDA 1572 form. The IRB would also consider these investigators or sub-investigators to be investigators whose activities require IRB review. If decentralized trials include the use of local HCPs to perform certain trial-related activities on a fee-for-service basis, and they are providing services they perform routinely in clinical practice, and do not require special knowledge of the protocol to perform them, then they are not considered investigators.

Because many sites and institutions receive federal funding, the Office for Human Research Protections (OHRP) guidance, “Determining When Institutions are Engaged in Research,” (the Engagement Guidance) may also be applicable for personnel at these locations.² The Engagement Guidance states that employees or agents who for the purpose of the research obtain the below, are engaged in research and need a Federal Wise Assurance (FWA) and IRB approval of their activities: 

1. Data about the subjects or the research through intervention or interaction with them.
2. Identifiable private information about the subjects of the research.
3. The informed consent of human subjects for the research.

Overall, the two guidance documents overlap, but there are a few areas of divergence. Administering an approved drug on label as part of a clinical trial might not require a local health care provider to be an investigator under the FDA guidance and regulations, but administering an approved drug might be engagement in research under the OHRP engagement guidance. For institutions that apply the common rule regulations to all research, these personnel should be investigators, and an IRB should oversee their research activities. Another area of discrepancy is around obtaining identifiable private information or identifiable biospecimens from a research participant. This activity alone might not make personnel an investigator under the FDA guidance, but it would under the OHRP guidance. These cases depend on the specifics of the situation, and investigators should reach out to their IRB office to discuss this to ensure all appropriate personnel have IRB oversight.

While local health care providers may not be investigators, the clinical trial investigators are responsible for ensuring local providers’ activities are in line with the protocol. Maintaining oversight and adequate supervision for providers who are not trial personnel can add additional complexity to managing a clinical trial. Investigators can address concerns about variability of data by communicating any specific protocol instructions for trial-related activities.

Digital Health Technologies

Decentralized trials may involve the use of digital health technologies (DHT) to measure clinical events and characteristics remotely. The FDA guidance references another FDA guidance, “Digital Health Technologies for Remote Acquisition in Clinical Investigations,” for a more detailed discussion around verifying and validating these technologies to be fit-for-purpose for the clinical trial. Additionally, the guidance instructs sponsors to consider whether DHT’s are suitable for use by the population being studied and to consider whether social or other barriers to the use of the technology could affect enrollment and persistence in the trial. Using familiar technology instead of a study-specific device can be a benefit to participants, but sponsors should ensure that participants who lack personal devices can still participate. WCG has additional resources related to digital health technology to support diversity in clinical trials in this Applied Clinical Trials article “Optimizing Technology Implementation to Improve Diversity in Clinical Research” and this WCG Talks Trials podcast episode, “Diversity & Inclusion with Technology in Decentralized Trials.”

Roles and Responsibilities

Sponsor

The DCT guidance confirms that responsibilities for oversight of a decentralized trial are the same as for any other clinical trial, but sponsors may need to oversee complex contracts if they are using local networks of clinics, pharmacies, or laboratories. Sponsors are responsible for maintaining records of these contracts and relationships. Additionally, data management plans should include a description of the data origin and flow from all sources to the sponsor and the methods and technologies used to collect trial data. Sponsors should also maintain a list of service providers for all steps in the data collection, handling, and management as well.

In the protocol, sponsors should describe the details of the DCT including how and where visits will take place, which activities study personnel vs. local HCP’s will perform, how they will manage study data and delivery of investigational products, and safety monitoring. As with any trial, sponsors should use a risk-based approach to monitor the study.

Investigator

Investigators are responsible for conducting the DCT, including overseeing any other personnel who work on the trial. If local HCPs conduct trial activities, then investigators are responsible for ensuring any delegated trial tasks are in adherence with the protocol and for ensuring data resulting from those tasks is complete and accurate. The investigator is also responsible for providing investigational products to participants, whether directly or through local HCPs and pharmacies. 

When trial personnel contribute directly to drug trial data, they are investigators or sub-investigators. Local HCPs, who are not investigators, do not need to be listed on the FDA 1572 form, and maintaining a log of local HCPs is not required. Investigators must maintain complete case histories which would include the name of the local HCP and the date of activities. For device trials, HCPs are not investigators and do not need to sign an agreement with the sponsor or to be listed in an Investigational Device Exemption (IDE) application. 

DCTs can involve the use of central laboratories and imaging centers for tests specific to the trial, and they can use samples collected remotely and then processed at local facilities if appropriate for the trial. For drug trials under an Investigational New Drug (IND) application, the investigator should list all clinical laboratory facilities on the FDA 1572 form, and for device trials, the investigator should identify clinical labs in the investigational plan.

In the case of an emergency, participants should seek help at their local health care facilities, and investigators should obtain consent to obtain reports regarding any incidents from the local provider.

Informed Consent – Who Can Obtain Informed Consent?

Informed consent is foundational to conducting ethical research, and IRBs review the consent process and consent documents. The guidance notes that consent discussions can take place in remote locations where the participant and investigator are not co-located, and the participant can document their consent electronically or on paper. Investigators can also delegate the informed consent discussion to qualified staff, but these staff must have detailed knowledge of the research, so local HCPs who are not investigators should not obtain informed consent. Participants must also be able to reach someone knowledgeable about the research if they have questions. The consent process should disclose specific details of the decentralized nature of the clinical trial – participants should know whether local HCPs will conduct trial activities and if any activities will take place in their homes. 

Summary

The guidance clarifies the roles of local service providers in decentralized trials. While the regulations governing clinical research apply to all trials, decentralized or not, there are novel considerations around how to balance the flexibility of local providers and at-home tasks with the increase in variability of the data this flexibility will introduce. Digital technologies have the potential to expand participation in research, but variability in access and comfort with technology may also lead to the potential exclusion of certain groups. Sponsors, investigators, and IRBs should approach decentralized trials with these complexities in mind.

References

1. Conducting Clinical Trials With Decentralized Elements | FDA
2. Determining When Institutions are Engaged in Research (January 13, 2009) | HHS.gov

The post Decentralized Trials: Thoughts for Sponsors, Investigators, and IRBs appeared first on WCG.

In this episode of WCG Talks Trials, host Kelly FitzGerald sits down with Dr. Currien MacDonald, medical chair director at WCG, and Sara Reed, a participant in two psychedelic clinical trials, to explore the evolving landscape of psychedelics research. Dr. MacDonald shares his expertise on the growing acceptance of psychedelics in clinical settings, recent FDA updates, and the inner workings of ongoing trials. Later, Sara provides a firsthand account of her experiences as a trial participant, offering unique insights into how psychedelics are being tested as potential therapeutic options. Tune in to learn more about aligning clinical practice with patient experience in this emerging field.

The post Have a Safe Trip: Clinical and Patient Alignment in Research with Psychedelics appeared first on WCG.

When originally conceived, IRBs were assumed to be embedded in institutions.  The image that comes to mind of undue influence in this context is of a university president overruling the IRB and insisting on approval of research to support a star researcher or a wealthy and generous donor. Independent IRBs are private companies acting on behalf of independent clinics, research institutes, or academic institutions. While they are, perhaps, less likely to be unduly influenced by a university president, concerns have been raised about for-profit independent IRBs and whether they can remain truly independent from the company’s financial interests. 

At WCG we have a strong foundation of policies prohibiting undue influence of our IRBs, and that foundation supports a robust series of firewalls around the boards and committees including both our membership decisions and our culture. WCG’s flagship IRB was the first central IRB to receive accreditation by AAHRPP in 2003.

Policies

WCG enacted policies to protect the independence of our board by “walling” them off from the rest of the business. The heart of our undue influence policy is that “No individual in the organization may attempt to unduly influence the decisions of individuals involved in the oversight of research.”

The first wall insulates the IRB from business development activities of the company. Individuals engaged in business development are considered to have a conflict of interest with any related research. They may not discuss business matters with IRB members, and they may not participate in any way in the IRB review of that research. Examples of business development activities include: working in a booth at a trade show to solicit business, calling or meeting with potential clients to persuade them to use company services, and meeting with current clients to increase or expand their use of company services.  

The second wall is the protection from influence by other divisions of the company. Because WCG provides clinical trial services of various types, our undue influence policy requires any questions or comments from another part of the business about an IRB review to be routed to the chief compliance officer.  The chief compliance officer determines how and whether the questions or comments can be posed to the IRB review committees without jeopardizing their independence.

The third wall is comprised of the company staff. Staff may not communicate financial issues regarding specific research to individuals involved in the IRB review. Additionally, they may not answer questions from an individual involved in the IRB review about business issues when the answer might influence or appear to influence review decisions. No information related to the financial implications to WCG regarding its relationship with the sponsor is included in the materials the board receives.    

Finally, the fourth wall is the IRB members themselves. Individuals involved in IRB review are not allowed to ask questions about or engage in business development activities. While our IRB members may attend conferences, they will never be working in a trade booth or soliciting business.    

Membership

IRB regulations (45 CFR 46.107 and 21 CFR 56107) require that at least one member of the IRB is unaffiliated with the institution. WCG IRB unaffiliated members make up almost 2/3 of our IRB membership. In most meetings, unaffiliated members comprise the majority voting on whether to approve research. WCG IRB invests in recruiting, supporting, and training such a large proportion of unaffiliated members to support the independent nature of the IRB review. WCG also seeks to maintain a diverse membership on the IRB in as many dimensions as possible, including educational and professional backgrounds. Our primary board membership is made up of six scientific members and three non-scientific members. While we rely on our scientist members to provide the necessary expertise to understand the research under review, we rely on our board members without formal training in a scientific field to bring alternative viewpoints to the table. Every member undergoes training on conflicts of interest and company policies including undue influence annually.   

Culture

WCG IRB supports a culture of independence among our board members, and we communicate this via our policy governing committee review conduct. Our meeting chairs are expected to encourage IRB members to ask questions, speak their minds at every protocol review, share information that has not been discussed, listen, and learn from the group, respect dissenting opinions, and to think and vote independently.

WCG as a company values the IRB’s independence. Encouraging vigorous discussion in board meetings while operating efficiently requires our IRB Chairs to facilitate board members’ understanding of the material before them, to direct IRB member concerns to the criteria for approval, and to encourage and reward dissent when criteria for approval are not met. IRB Chairs also encourage our IRB members to use their unique perspective to contribute to IRB deliberations and ensure all IRB members know their opinions count. WCG has established policies in place to support the independence of our IRB, and WCG reinforces this perspective through our internal training, norms, and culture.

References

1. 45 CFR 46. https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46
2. 21 CFR 56. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-A/part-56
3. Association for the Accreditation of Human Research Protection Programs, Inc. https://www.aahrpp.org/resources/for-accreditation/instruments/evaluation-instrument-for-accreditation/Domain-I-Organization/standard-i-1/element-i.1.c

The post WCG’s Philosophy of Ethical 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.

About this episode:

The episode of WCG Talks Trials, hosted by Kelly Fitzgerald, Executive IRB Chair and Vice President of IBC Affairs at WCG, dives into the topic of diversity and inclusion with technology in decentralized clinical trials (DCTs). The episode explores the transformative opportunities that DCTs present for addressing diversity gaps in clinical research. The discussion features a panel of experts, including Otis Johnson, former Chief Diversity, Inclusion, and Sustainability Officer at Clario; Archana Sah, a seasoned clinical development leader with a focus on oncology and healthcare technology; and Ken McCann, a physician with a background in pediatrics and a keen interest in social determinants of health. The panelists share insights on how DCTs can improve accessibility, overcome barriers, and enhance representation in clinical trials, emphasizing the potential for these trials to be a game-changer in making clinical research more equitable and inclusive. 

Moderator & Speakers:

Archana Sah, MS (Pharm.), PMP

Otis Johnson, PhD, MPA

Ken McCann, MD

Kelly FitzGerald, PhD, CIP

IRB Executive Chair and VP IBC Affairs

The post Diversity & Inclusion with Technology in Decentralized Trials appeared first on WCG.

About this episode:

Join WCG Talks Trials podcast host Kelly Fitzgerald, PhD, in a riveting dialogue with guest expert Currien MacDonald, MD, as they unravel the nuances of “Psychedelics in Research: Ethical and Medical Perspectives.”

Dr. MacDonald, with a solid foundation in family medicine and clinical trials administration, guides listeners through a grounded exploration of psychedelic substances. In this episode, they demystify the realm of psychedelics, encompassing both dissociative and classic varieties, such as LSD and MDMA.

As the conversation delves into ongoing research, the potential applications of these compounds in treating mental health challenges like depression, anxiety, and post-traumatic stress disorder come to the fore. The dialogue doesn’t shy away from probing the ethical dimensions surrounding psychedelic research, addressing concerns about study design, potential abuse, and the intricate balance between benefits and risks. This insightful podcast offers an engaging journey into the evolving field of psychedelic research, shedding light on its medical potential and the ethical considerations that guide its path.

Speakers:

• Kelly Fitzgerald, PhD, IRB Executive Chair and VP IBC Affairs
• Currien MacDonald, MD, CIP, IRB Chair, WCG IRB

Episode Transcript

Kelly: I’m here today speaking with Dr. Currian McDonald. We’re going to be speaking about psychedelics and research today. After graduating top of his class from the University of Minnesota Medical School, Dr. McDonald completed a family medicine residency program as chief resident. He then delivered primary care for five years in San Diego, California.

After that period, he served as a medical consultant to the University of California, San Diego, on a groundbreaking prisoner health care reform project. He has been with WCG for over 10 years, and he has completed certification programs and clinical trials administration and medical acupuncture. He’s also a certified IRB professional with Primer, the National Organization for the Protection of Human Subjects in Research.

In addition, Dr. McDonald’s a member of the American Academy of Family Physicians, the American Medical Association, and the American Medical Writers Association.

We’re here today to talk about clinical research with psychedelic drugs. FDA published its first draft guidance on this topic in June in response to an increasing interest in clinical trials of psychedelic drugs to treat a range of diseases. So, Currien, when we hear someone say psychedelics, what types of drugs are they talking about?

Currien: It’s a great question, Kelly, and really important when we start to look into this to be clear about what we’re talking about. In the kind of general term, psychedelics are anything that produce this psycho emotional or dissociative state, kind of your hallucinogen is another term that’s commonly gone with it.

However, that’s not the best scientific term. There’s a number of terms that are better and psychedelics are ones that go with. A either disassociative or an increased associative emotional state, sometimes enacted genes or pathogens are used with these because they have someone connect more deeply with themselves and more deeply with someone else.

They act in a certain place in the brain rather. Dr scientific key. And that’s why they’re kind of lumped together. However, the mechanism of actions and. The specific drugs being studied mechanisms are different enough to think that this is not one thing, but actually very multiple things with the multiple different kinds of mechanisms and things to worry about.

For right now, since it’s rather the infancy of their being studied, calling them psychedelics as anything kind of that produces these states and is on the classes that we know about of either classic psychedelics like LSD. Or a classic antigen like M D M A are kind of good places to talk about them.

At first, I’ll leave dissociative drugs as kind of on the borderline. Those are important because there are known drugs that we currently are using that are very much like psychedelics in our arm, our arm medical armamentarium, the drugs that doctors commonly use. For current things you can think of general anesthesia, for example, as being something that’s used in this or.

Something used for a medical procedure. Okay.

Kelly: All right. So, have any of these psychedelic drugs been approved for treatments of disease yet?

Currien: That’s a great question, and that goes to, again, what do you call a psychedelic? Because we have dissociative drugs that we use very commonly some classic drugs that have been used in these areas.

So, for example, you can even think of propofol drug. It’s rather just an amnestic. So it’s dissociating you from yourself or you have the classic one, which is ketamine, which on the street is special case. So it kind of goes more towards a classic psychedelic. That’s approved both for anesthesia and also has been recently approved for depression in that specific way.

So depending on which you use, you use it for, it might be more psychedelic or less psychedelic, depending on how you’re using. It’s a very interesting question. Okay, and so sorry to answer your question directly ketamine and as ketamine are approved for anesthesia or depression treatments, respectively.

However, many people use ketamine off label because it is an approved drug and it’s cheaper than as ketamine, which is approved for that other indication, but it’s the same drug basically.

Kelly: And are they using it off label for these purposes or other purposes in addition?

Currien: Great question. Off label for the treatment of depression, which would be acceptable medically, generally medically, and off label uses are acceptable medically.

You can use it off label for a lot of other things. You can use it without a prescription if you happen to get it illegally for recreational use as well. And that is an abuse sidetrack that probably will come up later as we talk about these terms.

Kelly: Okay, and do you know what types of studies are currently underway for new therapeutic indications for these types of drugs?

Currien: This is a huge and such a great question. It depends on what you mean by studies and therapeutic indications. These drugs are very old. They’re used in a lot of kind of cultural experiences as well, and they have been around for a while illegally and have been brought into hard for a while. They’re being researched for kind of I want to actually now publish and let people know they can use it or perhaps get approval to use these drugs in a regular way is where the studies are going now, and the potential from these drugs is absolutely astronomical.

It is a new kind of way to get into the very powerful area of the human brain and includes things like major depressive disorder. We already mentioned with the approved drug, but the abuses, it’s kind of somewhat ironic to think of these drugs as being very good against alcohol abuse and tobacco addiction research.

I think they Actually gave a grant for these drugs to be used in tobacco addiction research, because it’s that you think that ones should be kind of simple, and it’s still not. But these seem to work well in that area. Cancer related anxiety, depression, kind of a coming to group with the end of life is another area that is a huge need, but.

Nothing else really can go there. Obsessive compulsive disorder is another one that is just not pharmacologically able to be treated right now, but this has a way to perhaps bridge that gap again. Eating disorders, very similarly, very large unmet need with no medical intervention. And even something as simple as post traumatic stress disorder, which has some drugs that kind of work and some therapy aspects that kind of work, but it’s still really very drastically unmet need.

The part of the reason the question is so interesting is because. We don’t understand the drugs and we don’t understand the brain. And so there’s this untapped potential that really is huge for something that needs study, desperately needs study.

Kelly: And so what are the hypotheses about why these particular drugs would be useful in treating these challenging diseases?

Currien: Again, I hate to say brilliant question all the time, but you’re just brilliant. These questions are brilliant. The idea is that because of their unique mechanism of action, it’s not terribly unique. They go through a pathway that we know works in, for example, depressions, and a lot of the run of the mill We know they work kinds of serotonin drugs in depression.

These work through a lot of them are through a similar pathway. Recently, we found out that the way we thought they work. These classic depression bugs is not the way they work, but they still work. We know that for sure. So it really calls in a. Brings to for the idea that we’re not exactly sure how all of these things go together to think your brain is as simple as kind of on off switch or simple things like that is obviously not true.

What makes them so unique and so potentially powerful as they work in a different way. That is this disassociative or associative actions. We know the. Mental process that produces it. We know the anatomical structures that go to it. We have an understanding of some of the chemical compounds that are in it.

And so it’s an area that we could understand if we researched it and have a theory to drive a hypothesis that would drive in a clinical outcome. Right now, we just aren’t touching at all. And so that’s why they’re extremely exciting is because they’re like a new class of drug, like a new antibiotic that goes and kills bacteria in a way.

We’ve never seen before. That’s why kind of it’s exciting.

Kelly: Okay. So there’s a lot of potential here, but it would take controlled clinical trials to get at these mechanisms as opposed to doing sort of natural history studies of people who are already using them and then seeing how they respond.

Currien: Absolutely. Absolutely.

Kelly: What characteristics of psychedelics make them particularly risky in these types of environments?

Currien: And that is the flip side of power is power is dangerous. So anything that’s exciting and has a potential for really cracking open your brain and getting to a root cause is cracking open your brain and can have risks.

There’s several kinds of risks, especially for this kind of a drug, like an antibiotic. You’re not really worried about things such as abuse or dependency or them being taken. And like, Ketamine has a control. And esketamine has a control. Aspect to them, because they can be used as drugs of abuse.

Antibiotics don’t go that way. These certainly lend themselves to. We know that they have come out of a culture and have a history that goes with them of being used for recreational purposes and can be potentially abused. So there’s that part of it. The fact that if I know that the drug you prescribed for me works, and I can get it.

Without a prescription from my neighborhood dealer makes it also a different kind of a danger and having these kind of drugs available that then you have just the standard risks of side effects. We always talk about the side effects of abuse, but there’s also other ones to any chemical that works, works in different ways.

For example, the same kind of neural network in your brain is in your intestines. And so there’s a potential for these having kind of serious intestinal problems, especially when you start dealing with people who have intestinal disorders, then there’s the risk of on target effects. If they work really well for having you make close connections with your therapist and the drug wears off and you go home and getting a really bad Fight or car accident or something, then you’re going to have that same open connection to be available.

And so there may be problems with that and telling someone. Well, we’re going to give you this medicine. Then you’re going to stay in my clinic for 5 hours. That doesn’t really work. That’s a risk for use of. Well, maybe we can do it over the phone and that’s good enough. Maybe again. Need a lot of more study about this, how, what dose is appropriate, et cetera.

And then the last risk that goes with that are regulatory risks, kind of the flip side of back to the front of all right, these are potentially now becoming legal. There’s a problem with that, especially when I’m saying, okay, this thing is a drug, but it’s being used in ceremonial aspects right now without any regulation.

And to be clear that we’re not trying to regulate. This culture ceremonies, we’re just trying to regulate the abuse of this drug, which happens to be the same thing that y’all use. And that’s another really important thing to consider. I consider it a risk as something just to be aware of. Again, we’re kind of dovetailing on that, the power and the risk.

It’s not something to be afraid of. It’s something to be aware of so we can appropriately study it, learn how to minimize risks and maximize benefits, get the best from the power that we have. Same way that we do for electricity, right? It’s a very powerful thing, but don’t let it just wiggle around in your street in the rainstorm.

Kelly: All right, so we know there’s a potential for abuse because these are drugs that are used for recreational purposes. How much do we know about their abuse potential compared to other drugs such as oxycodone or and how would we study that? How would we do a good study?

Currien: I’m not going to say brilliant question. I won’t. It’s a very good question. However, we don’t know very well. FDA does have pretty clear general guidelines about what they would want to see for ensuring that the abuse potential of whatever is being studied is studied appropriately. That is in their job to ensure that drugs are safe and effective when used in general.

They’re going to want to have labeling and restrictions on them to maximize them. The benefits and minimize the risk. So they do have some guidance in there right now. I think we’re starting with. I would say nothing because it’s so mixed. Regular users say there’s very little to zero abuse potential while critics say there’s a very high abuse potential because.

Well, people get into trouble with them. It’s a little bit of a chicken egg because if they were legal and use, would you get into trouble with them anymore? Because that’s not trouble to be using them at the same time. They’re very different drugs than oxycodone. However, there’s also good theory to support that looking at any drug as abuse.

Are abusable is neglecting that people are abusers and a personality type makes you susceptible to. Abusing something, coffee, work, like all the, what are those called aholics, all the aholics, you know, that’s a personality issue, and it’s not necessarily a drug issue. At the same time, I don’t think that detracts in any way from the need to have appropriately designed studies looking at the potential for this.

And we may find that, for example, just to use common names, LSD has almost zero abuse potential, while MDMA Or ecstasy or 1 of the MDs has a very high abuse potential, but only above 10 milligrams, but next to 0 at 2 milligrams was still effective at 2. So we just need a lot more data on it. I’m not saying a brilliant question, so these

Kelly: are the questions that we need answers to, and in order to get them, we need to do studies.

So what are some unique challenges to designing studies using psychedelics?

Currien: A list a whole litany unique challenges. I’ve hinted at some of them. The first one is making sure that we’re using the same thing. And FDA does know in their guidance on this kind of what prompted a lot of the attention on it that these could be considered botanicals or could not be.

So if my study product is a mushroom and I say take half a mushroom a day, well, that’s not very scientific, but that may be what we’ve had in the past to use. We haven’t had manufacturing plants trying to narrow down the specific chemical involved. And there may be good reasons for that. I’ve just read a recent study on my favorite mentally active compound on caffeine, that caffeine is not the same as coffee and coffee works a lot better to do the things that I want to do than caffeine alone.

So maybe we do need to study actually the mushroom. Complicated, though, because how do you grow a mushroom? How do you test it to make sure you’re getting the same mushroominess across everyone in your 100 person, 1000 person study as opposed to another chemical that I can just make? Using other things that are issues with this is the observational data.

And if it’s going to be such a regulatory issue, can I just say, well, I just want to study people who are already using this. And the question then becomes, is that controlled again? Are they taking mushrooms? Are they taking a compound that I know it can control? And once I start to control it, then who’s making it?

Well, it’s my mushroom grower. Does that work? It’s very, very difficult to do that. The other part that’s difficult, and FDA does note this is that we’d like to think of these drugs as take home, here’s a pill, call me in a week. You know, take your X milligrams of whatever you’re taking once or twice a day.

And they probably don’t work that way, especially when we’re looking at the way that people get through mental illness. Brilliant and terrible thing about the brain is it can’t observe itself. You can’t do therapy on yourself. You can think you can, but then you’re just thinking. So trying to get a mental illness, especially powerful mental illnesses, just by here’s a pill.

Take it home. Maybe a problem. Especially we’ve seen some of the. Studies out of the psychedelic research in PTSD that it is really the therapeutic alliance. I mean, that’s really difficult for FDA who regulates drugs and not therapy and not therapeutic alliances. So to build that into the study makes it okay.

Then how do I label this drug? What is the drug doing? There’s other things such as controls that if it’s their only drug, what would you use? Like, 0 control, is that ethical at that point? And there’s a bunch of issues that go with. Well, I have really good evidence that this might work, but I’m going to complete placebo control it.

And, you know, especially if it’s a disease that has, for example, suicidality or other issues that can negate exactly what you’re going for keeping people in a study. With mental illness, when it doesn’t work, it’s really, really hard. And so your study design, placebo control, powerful study design is problematic.

There may be others.

Kelly: Okay. Are there any issues with recruiting these populations? I mean, we’re talking about pretty vulnerable groups of people here who are struggling with mental illness. Does that also add to the complexity of doing studies with these populations?

Currien: Another great question. Not only the vulnerability, but the potential for the view of it as just an easy way to get high.

Come join my study and get high for a while. Yeah. Yeah. I’m suffering real bad from what disease did you say? Doc? I don’t think that would be actually the case. I think it’s more likely we’re going to have a hard time recruiting people into the study because they’ll be vulnerable and they’ll be perhaps targeted or feel bad.

I have this real bad disease, but I don’t want to just get high doc. Don’t you have anything? No, this really might work. I don’t know. And once you go into a trial thinking, I don’t think this is going to work, you have like a anti effect effect. I think that’s a nocebo effect. I’m not sure. But something like that going on.

So. I think recruiting for it is going to be really difficult. Recruiting and retaining is the other part. I think retaining is going to be another really challenging issue for well controlled designs. Anytime you introduce the therapist into it, recruiting from a therapist’s clinic is really hard because there’s bias.

And if you’re trying to control for that, then you generally want to have 1 or a set group of therapists. And so to have them go to someone external to start over with the therapeutic alliance would be a problem. I think some of those are easily overcome. For example, you could have therapists all following some sort of a script or a training program or something like that, which would help normalize it.

But these are all things to think about as you were designing the trials.

Kelly: Great. And are there any particular issues with after a trial is done? I mean, these are challenging diseases. Somebody might obtain relief through participating in the study from something that was causing them a lot of distress.

Are there issues with how they might access treatment after these trials and are those different issues with these types of drugs than with other drugs?

Currien: Yeah, that is a, especially for researchers and for people like us in the IRB, looking at what is the appropriate way to review these minimizing risks, maximizing benefits, and ensuring appropriate inclusions the vulnerability of people coming in can’t be overstated from just their aspect of having a serious disease that doesn’t have good treatment.

As well The ongoing consideration of them as a vulnerable population. What happens if, for example, they’re not responding. And what’s our duty to them, just kind of punt them out. The last part that you’re just bringing up is okay. Let’s say we get through all of that. And it’s actually is working.

We’re like, trials over do we want to, for example, with some cancer drugs, just say. If you’re getting benefit, we’re just going to let you continue on it. Personally, kind of makes sense in cancer. It doesn’t make sense here. That, I think, is still a big question mark. It’s not saving someone life like it is in cancer or is it.

Hard to say, maybe yes, maybe no. Similarly, if you just say, listen, this is all the supply I have and FDA says you’re done after this, or, you know, any 1 of those kind of situation. So this is it. The person again, like I alluded to earlier says, okay, that was working real well. I’ve never felt this normal in a long, long time.

Where can I get this? And you as the researcher say, or don’t say, I know where you can get it. Cause I know people who can get it. You can’t say that, but at the same time, they know. And at the same time, you don’t want them to just go buy it from some random on the street and you’re like, this is a reputable source.

This is safe product to use. I mean, those are really tough questions for people designing studies, running studies, trying to care for their participants in the best way that they can for reviewing bodies and saying what amount of care is necessary to ensure that people are exiting the study safely.

All those sorts of things are really difficult questions. I do not have great answers.

Kelly: Well, it sounds like, I mean, that’s why we, we want to see studies in this area. And it sounds like it’s a fruitful area to study with with potential benefits and also potential risks. So, which is it is this a revolution in treatment, or is it unsupported hype over the chance to legalize getting high?

Currien: It’s all of that and more and everything in between. It entirely depends upon the people doing the work, and there will be, and I guarantee that if the IRBs or the research community as a whole have not seen attempts to hype up And say that these drugs are perfectly safe, and we should legalize them.

There will be. And if we have not seen studies that say that this is an absolute revolution in treatment, then we will see that too pretty rare to have a revolution in treatment. And at the same time, you can have bad research in any field that you want. It doesn’t matter what drug it is, doesn’t matter what device you’re studying, it can be unsupported hype over the next best thing, because people want hope.

I think there is definitely some hope here. These are powerful drugs, unarguably powerful drugs. We wouldn’t be as either scared or excited by them if we didn’t recognize the power there. I think the power though, like any other power, any other drug with power, it is about how you use it. And I think leaving these drugs untapped power in areas that are such a sore clinical need, and leaving these poor people without any treatment whatsoever, is just a wrong.

That I can say it’s just not ethical at this point. Not arguing needs to be done right. I’m a little bit worried about both sides of the coin too much oversight too much regulation too close scrutiny and not enough. Just let’s do something at the same time knowing that when you just do something, it can be random and can lead to problems like a real bad study may sour it for everything when it was just a badly designed study.

So again, I think it’s all of those. I’m glad we’re having the conversation of starting the conversation about this.

Kelly: I am too. So thank you very much for your time today. I’m really glad that we had the chance to have this conversation and thanks to anybody who’s listening today. I hope you come back for another one of our podcasts from WCG.

Currien: Thank you very much. Hope you all have a great day.

The post Delve into the World of Psychedelic Research and Ethical Inquiry appeared first on WCG.

How is Cannabis regulated?

Cannabis, the cannabis sativa plant, has over 80 compounds called cannabinoids. Since 1970, when the Controlled Substances Act was enacted, most uses of whole cannabis plant and cannabiniods (compounds extracted from the plant like THC) have been considered by FDA as schedule I drugs, those without accepted medical use. The use of cannabis and cannabiniods is regulated at the federal level under both the United States Food and Drug Administration (FDA) and the United States Drug Enforcement Administration (DEA).

With the passage of the 2018 Farm Bill³, hemp-derived cannabinoids with no more than 0.3% THC are no longer considered controlled substances under the Controlled substances act⁴.  Hemp and hemp-derived products with greater than 0.3% THC are still classified as schedule I drugs.

Cannabis as a drug

THC (dronabinol) is the active ingredient in the approved drug products, Marinol capsules (and generics) and Syndros oral solution. Dronabinol is used to treat nausea and vomiting caused by chemotherapy in people who have already taken other medications to treat this type of nausea and vomiting without good results. Dronabinol is also used to treat loss of appetite and weight loss in people who have acquired immunodeficiency syndrome (AIDS)⁵.

CBD is the active ingredient in the approved drug product, Epidiolex.  Epidiolex has been approved to treat two different seizure disorders, with the most recent approval in 2020.  Epidiolex does not contain tetrahydrocannabinol (THC) which is the compound in cannabis that produces a euphoric effect.  While Epidiolex has been demonstrated to be effective in controlling seizures, it is not without side effects.  The most common side effects include diarrhea, elevated liver enzymes, decreased appetite, sleepiness, fever, and vomiting⁶.

Once FDA approves a substance as a drug product, that product in any form is by FDA definition a drug, and it can no longer be considered a food product or supplement regardless of the intent of the product.  FDA has therefore concluded that it is a prohibited act to introduce or deliver for introduction into interstate commerce any food (including any animal food or feed) to which THC or CBD has been added⁷.

Cannabis as a supplement

You may have noticed the explosion of CBD wellness products for both humans and animals on store shelves in the last few years.  The consumer market for human CBD wellness products was estimated to reach $4.17 billion in 2022⁸.  It will come as no surprise that with an increase in public interest in the products, research in this area has also expanded.

FDA recently published an opinion regarding cannabidiol products as dietary supplements in response to the growing CBD products market. FDA convened a high-level internal working group to investigate the best regulatory pathway for these types of products⁹.

Between 2019 and 2022, three citizens petitions (Consumer Healthcare Products Association, Citizen Petition from The Council for Responsible Nutrition, and Natural Products Association) were received by FDA and publicly posted.  On the same day FDA published the opinion regarding CBD as dietary supplements, it also published its responses to the three pending petitions.  The petitions have been denied, with FDA recommending congress work with FDA to establish a new regulatory pathway for CBD-containing products that are not intended to be marketed as drugs¹⁰.

Research with cannabis

In December 2022, after being passed by the House and Senate, the Medical Marijuana and Cannabidiol Research Expansion Act¹¹ was signed into law by the President.  This act supports research on cannabis by creating a process for the Attorney General to approve requests to conduct research as long as the research contains provisions to prevent the diversion of cannabis for non-research use.  Additionally, the Act requires the Secretary of the National Institutes of Health and the heads of other relevant Federal agencies to submit a report on the potential therapeutic benefits of marijuana (the flowers from cannabis) and cannabidiol on serious medical conditions, the potential effects of marijuana on developing adolescent brains, cognitive abilities, such as those required to drive a vehicle or operate heavy machinery, and State-level barriers to conducting research on marijuana within one year.  These activities will be conducted via grants, contracts, and cooperative research.  This Act represents a substantial step forward in expanding research on the benefits and risks of using cannabis.

Considerations for IRB review

When the IRB receives a protocol for review, there are two main questions the IRB will ask during its review. 

1. How is this research regulated? 
2. Is the research ethical? 

The IRB will review the protocol, advertising, and other information provided with the submission to arrive at an independent answer to the first question.  One of the most important aspects of this assessment is discriminating between research procedures and procedures that will happen regardless of the research¹². 

Sponsors should ensure that the protocol is clear and consistent via inclusion/exclusion criteria, description of procedures, and risks of the research.  Once the IRB determines which procedures are research procedures, the IRB assesses the regulations under which the research is governed.  If the research involves a test article that is regulated by FDA, the research will need to adhere to FDA regulations for research.  If the research is funded by or conducted at a federal agency, the research will need to adhere to the regulations of that agency.  Additionally, research may be subject to institutional policies and local laws as well.  Many institutions expect all research to follow Common Rule regulations because they receive federal funds. 

Case study 1:

Researchers wish to test participants’ mood and ability to perform cognitive tasks after ingesting gummies containing a cannabis extract. 

1.  Participants are habitual consumers of gummies.
2. The participants purchase and ingesting a gummy before engaging with the research staff.
3. Staff will ask questions about what was ingested, but will not direct or dispense any product.
4. Staff will assess participants’ mood using standard questionnaires and scales, and will direct them to complete a range of cognitive tasks.

Board Review:

The gummy is not a test article, it is not being studied nor directed by the research.  The research is not FDA-regulated.  The board may have safety concerns regarding participants ingesting uncontrolled gummies.  The board may have concerns about consent, privacy, and confidentiality of research data.  The product may be legally sold per local laws but may be considered a controlled substance per federal law.

Case study 2:

Researchers wish to test participants’ mood and ability to perform cognitive tasks after ingesting gummies containing a cannabis extract. 

1. Participants are habitual consumers of gummies.
2. Procedures include research staff dispensing a test article (a gummy containing a cannabis extract enriched for CBD).
3. Staff will assess participants’ mood using standard questionnaires and scales, and will direct them to complete a range of cognitive tasks.

Board Review:

The gummy is a test article and the study is FDA-regulated.  It is being given to participants as a research procedure.  The study will need an IND from FDA.  If the gummy contains over 0.3% by dry weight of THC, it is also regulated by DEA.  In order to study the gummy as a drug, the cannabis will need to be sourced from an approved source.  A list of DEA-authorized growers of Schedule I cannabis is available online¹³.

Ethical issues in research with cannabis containing THC

Because the legal landscape varies widely from state to state and THC-containing cannabis is a federally controlled substance, research participants who report being habitual users may be at legal risk if their identity is disclosed.  Researchers can consider requesting a certificate of confidentiality (CoC).  NIH provides CoC’s for unfunded or unregulated research under certain conditions, and FDA provides them for research conducted under an IND or IDE¹⁴.

Another ethical concern involves impairment.  One of the key components of ethical research is obtaining informed consent from participants.  Some research projects involving use of cannabis, such as in case study 1, could involve seeking consent from individuals who may be impaired at the time consent is sought.  Care must be taken to ensure that the consent process is effective and that participants understand the research and are freely consenting to participate.  Depending on their level of impairment, their ability to understand and make sound decisions could be compromised¹⁵. 

Final thoughts

Despite the regulatory and ethical challenges in conducting research using cannabis, the societal need for this research is compelling.  As more states permit the use of cannabis for medicinal or recreational purposes, understanding both short-term and long-term effects of its use is important for policy, health, and safety.

The post Research and Cannabis: Ethical Research in a Changing Regulatory Landscape appeared first on WCG.

The Common Rule was revised in 2018, and the FDA’s two recent NPRMs will harmonize the FDA regulations with most of those 2018 revisions. The Common Rule has been adopted by 20 federal agencies and applies to research that is conducted or supported by those agencies. One NPRM describes a potential requirement for multi-site research that is under FDA oversight to use a single IRB for the review of all study sites.² The second NPRM describes changes to FDA regulations to harmonize with the Common Rule regarding informed consent requirements, among other things.³

This article will discuss how the new proposed single IRB mandate would impact institutions which currently use their local IRB for review of this research and how to prepare for compliance with the potential new regulation.

What Is the Single IRB Mandate?

If the proposed regulation is implemented, it would require any institution located in the United States (US) to rely on review and approval of a single IRB for FDA-regulated cooperative research. “Cooperative research” is defined as multi-institutional studies, multi-site studies, or multi-center studies. “Institution,” as used here, means university, community hospital, health system, or independent research site. Sponsors of FDA-regulated cooperative research will be responsible for choosing the IRB of record. Universities, hospitals, and health systems with their own IRBs will be required to cede review to the IRB of record if they wish to participate in the cooperative research.

Using a single IRB for cooperative research is not a new concept for most universities. The National Institutes of Health (NIH) led the way in announcing they would require a single IRB for multi-center research proposals in 2016, with the policy becoming effective in 2018. When the revised Common rule was finalized in 2018, it expanded this concept to research funded by the additional Common Rule Departments and Agencies. The rule became effective in January 2020.⁴ The FDA’s proposed rule would further expand this requirement but should not require any completely new policies or procedures for universities and other institutions already familiar with using a single IRB for federally-funded research.

Some exceptions to the proposed rule include research that requires review by more than one IRB by law (including tribal law), research involving an FDA-regulated product requiring specialized or local expertise, research on drugs exempt from the investigational new drug (IND) regulations, and research involving devices that are not subject to investigational drug exemption (IDE) regulations or are subject to abbreviated IDE requirements (non-significant risk devices). The FDA is proposing specific exceptions to the single IRB requirement rather than proposing a case-by-case assessment of each protocol due to the administrative burden such a policy would cause. The FDA requested input from stakeholders during the comment period regarding whether the exceptions proposed are sufficient or whether additional exceptions should be considered. These exceptions would be made for the entire protocol, not at a site-by-site level.

How Does External IRB Review Fit into Institutional Oversight of Research?

Research oversight at institutions often involves several offices or functions, one of which is IRB administration. The figure below provides a visual representation of how IRB review may fit into a larger constellation of research oversight at an academic institution. Even if an institution cedes IRB review to another institution or independent IRB, the institution will retain control of research oversight and will need to ensure it has procedures in place for appropriate communication between the IRB and the larger research oversight enterprise. Institutions have been working through the complexities of overseeing federally-funded research requiring review by a single IRB for several years now.

IRB Review Under the Single IRB Mandate

IRB Review Without the Single IRB Requirement

Implementation of the proposed rule might alter the balance of internally and externally reviewed research, but investigator-led, single-site research will still require support from an internal IRB unless an institution chooses to use an independent IRB. Institutional leadership may need to re-evaluate workflows and functions, including shifting staff to new purposes. For example, staff who currently support the IRB review functions might transition to a reliance team responsible for ensuring strong communication between the researchers, the internal research compliance office, and the external IRB.

How Will Investigators and Departments Be Expected to Submit to External IRBs?

Consider the requirements investigators and departments are required to meet prior to the review of your local IRB and whether the same requirements should be in place before submission to an external IRB. If you have a system in place for single IRB review for NIH-funded research, you may be able to adapt those systems to include FDA-regulated research. To make final decisions about how to manage this process, you may want to reach out to external IRBs to ask questions about their practices and policies.

Qualities to Look for in an External IRB

Accreditation: Association for the Accreditation of Human Research Protection Programs (AAHRPP) is an independent nonprofit accrediting body. AAHRPP accreditation confirms that the IRB meets industry standards for its operations and ethical reviews. You can search a list of accredited IRBs on the AAHRPP website.⁵

Institutional Requirements: You should ask how an external IRB collects information regarding local requirements at research sites. These requirements could include specific consent form language around conflict-of-interest management, compensation for injury, or data sharing policies. This information may be included in submission forms or instructional documents as well.

Management of Financial Conflicts of Interest: External IRB review can provide a neutral review of institutional conflicts of interest that may arise related to ownership of patent rights or equity in companies based on institutional intellectual property. You should ask about how financial conflict of interest information is obtained and reviewed by the external IRB. Ask about how any institutional determinations regarding conflict management plans should be communicated to the reviewing IRB. Once you have this information, you can begin a conversation with leadership at your institution to plan for incorporating any institutional instructions/requirements, such as consent language, into the workflow. There should also be discussion to ensure that institutional decisions, such as those related to financial conflict of interest management, are included within the panel documentation for IRB assessment.

Institutional Training: Training should be provided for Principal Investigators (PIs) and department staff who handle research administration on how to interact with the Human Research Protection Program (HRPP) office, other research reviews, and the IRB. Training on the IRB submission process for staff and PIs should also be provided so they are familiar with your new process. Training should include support for both the mechanics of how to submit a project for review and any institutional requirements you put in place.

Conclusion

The federal government has been moving in the direction of requiring a single IRB to oversee multi-site research for several years. The goal of this transition is to reduce the burden on institutions and sponsors so that important research developments can reach the public more quickly without sacrificing ethical oversight.

Institutions may have concerns about the risk of ceding control over such an important aspect of research oversight. We encourage you to think about how the impending single IRB mandate fits into your current research oversight program and to reach out to ask questions early on so that you can plan carefully for this transition.

References

1. 21st Century Cures Act, Section 1002, Public Law 114-255. https://www.govinfo.gov/app/details/PLAW-114publ255.
2. Notice of Proposed Rulemaking: Institutional Review Boards; Cooperative Research (87 FR 58752) https://www.federalregister.gov/documents/2022/09/28/2022-21089/institutional-review-boards-cooperative-research.
3. Notice of Proposed Rulemaking: Protection of Human Subjects and Institutional Review Boards (87 FR 58733). https://www.federalregister.gov/documents/2022/11/14/2022-24689/protection-of-human-subjects-and-institutional-review-boards-and-institutional-review-boards.
4. Code of Federal regulations Title 45 46.114 https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-A/part-46/subpart-A/section-46.114.
5. AAHRPP. https://www.aahrpp.org/find-an-accredited-organization.

The post What Can Institutions with Local IRBs Do to Prepare for the Proposed FDA Single IRB Mandate? appeared first on WCG.

“My company is developing a medical device, and the device includes software that is intended to be used by a clinician to program the therapy for each patient. Before we conduct a clinical trial with patients, we plan to conduct human factors testing with clinicians to ensure that the software is usable. Does this testing require IRB review and approval?”
– CEO, medical device company

Response:

Human factors or usability testing plays an important role in the development of medical devices. The application of human factors testing to new medical devices helps the developer minimize the risks and improve the usability of the device by testing its use in a real-world setting.

Most human factors testing for medical devices requires IRB review because the testing is considered by FDA to be a clinical investigation involving human research subjects. In this case, the clinicians participating in the testing are human subjects as defined by the FDA regulations.

Additionally, these investigations require IRB review for FDA to consider the data as part of a marketing permit:

The post What are the IRB review requirements for human factors/usability testing? appeared first on WCG.

“Can a physician submit a single humanitarian use device (HUD) submission to the IRB; or does a site need to submit an IRB application for each physician at the site authorized to use the device? If a single IRB application can be used, would changes to the list of authorized physicians at the site require review by the convened IRB?”
—Independent Research Center

Response:

WCG IRB approves HUDs for clinical use for the facility not the individual. A single application may be submitted to the IRB. You will need to designate a principal investigator (PI) who is responsible for use of the HUD at that facility. The PI must be a licensed medical doctor. The submission does not need to include a list of all the investigators authorized by the site to use the HUD.

A change in the PI responsible for use at that facility requires review and approval by the IRB. That change would likely be eligible for expedited review. However, some changes in research may require review by the convened IRB, for example, if the PI had a conflict of interest with the device manufacturer or an administrative action related to medical licensure.

The post Can a physician submit a single humanitarian use device (HUD) submission to the IRB? appeared first on WCG.