Best Practices During COVID-19: Answers to Your Trial Questions From WCG Experts
WCG Clinical hosted a widely listened-to webinar last week to discuss the impact of COVID-19 on trials. The questions and answers are edited excerpts:
Question: If a study was planned to have onsite site monitoring and is now switching to remote site monitoring, does that need to be a protocol amendment or change in research and does it need to be approved by the IRB?
Answer: In general, IRBs don’t typically review clinical monitoring plans. They’re often not part of research protocols. It really falls under sponsor obligations. Since we don’t typically review and approve those to begin with, the IRB does also not need to approve or review plans to move to remote monitoring. – David Borasky, vice president of WCG Clinical’s IRB compliance
Q: Do we have any moral obligations to continue research during this pandemic if we’re looking for new therapies for other diseases?
A: The quest to find answers to diseases is important, but I think that is probably going to have to take a back seat because that will undoubtedly divert serious amount of effort, personnel, time and energy from where we’ve got to be focused in terms of maintaining clinical care [of patients with COVID-19]. – Arthur Caplan, PhD, professor of bioethics and founding director of the division of medical ethics at NYU Langone Medical Center
Q: Written communications to participants that are going out from the sponsor or the site, letting them know the impact of clinical studies they’re participating in, do those written communications need to be approved by the IRB?
A: Yes. In general, we like the IRB to review and approve anything that’s going to be participant-facing. Obviously, if participants need to be immediately notified of something and it can’t wait because it presents an imminent threat to them, they don’t have to wait [for IRB approval]. But ideally it would get to the IRB, most of these things can be expedited. We are prioritizing and turning things around related to this very quickly. – David Borasky, vice president of WCG Clinical’s IRB compliance
Q: If a protocol is amended as such that it allows visits from home or outside lab monitoring or something like that, and the intention of this change only exists for the duration of this pandemic precautions, can the amendment of the protocol be temporary so that it returns back to the normal protocol after the precautions are lifted?
A: Yes, it can. Obviously, it’s not clear when things will “return to normal” for research studies, but protocol amendments can definitely be temporary. That’s part of the reason we’re not requiring full protocol amendments because we also presume that some of these things, should everything return normal in a relatively short period of time, will want to be unbundled from the protocol and return it to its original state. A number of sponsors will prefer the IRB be notified that amendment measures are ending after the pandemic precautions have been lifted, just to have that documentation. – David Borasky, vice president of WCG Clinical’s IRB compliance
Q: What kind of technology is available to use to help us in a time when we can’t access patients directly, and how is that technology best implemented?
A: There are eSource applications that can be used to collect not only audio information from perhaps an interview with a patient, which can be transcribed in the eSource tablet or an EDC system. There are also video applications that can be used along with those, like several of the eCOA applications commercially available. Many of the trials in neuroscience and some in oncology are using either eCOA technology or ePRO technology, they’re readily set up to be able to do this. There are also different companies that do telemedicine, which can allow for video as well as audio communication with the patient and allow recording of the source information. – Michael Cioffi, senior vice president of clinical solutions and strategic partnerships at WCG
Q: If a study is still continuing and a participant is asked to come in for a clinic visit amid the current risks and precautions, if the study participant refuses to come to the study institution because of their concerns about infection, should they stay in the study? Is it appropriate for them to stay in the study if they refuse to come in for safety monitoring and other visits, or should the investigator consider taking them out of the study if they can’t adequately assess that participant’s safety and efficacy.
A: My intuition here is to take them out. If you can’t monitor your subjects and there are risks involved in the kind of study that is being conducted, then patient safety comes first. I think those participants have to at least be suspended, if you will, if not removed. You make sure you document that happens, in terms of data integrity. It’s more likely that some people are not going to be able to travel to sites due to the shutting down of public transportation. – Arthur Caplan, PhD, professor of bioethics and founding director of the division of medical ethics at NYU Langone Medical Center
Q: Can you clarify what you mean by “virtual support staff?” Some people took this to mean that the support staff was a sponsor employee.
A: We, at WCG, are supporting engagements just like this. Virtual support staff does not mean a sponsor employee. It’s a third party like us [WCG] that is coming in and supporting these institutions. I cannot express to you the administrative burden that can be lifted off nurses by just setting up phone calls, just following up with patients that they know aren’t going to be able to come in. If there’s something that nurses are going to be stressed about, they don’t want to leave their patients in the dark while they’re treating and triaging the COVID-19 patients. To have an independent party that’s part of the study, that knows what’s going on in the study and knows that they’re reaching out to the participants of that study has really been helpful. Sponsors have been reaching out to us [WCG] for this virtual support. – Suzanne Caruso, vice president of clinical solutions at WCG
Q: The stress of the pandemic likely has an effect on a patient, but when it comes to measuring quality of life outcomes remotely, how will sponsors be able to separate that stress from the impact of the intervention in studies where quality of life is an endpoint?
A: This is part of the challenge in what can affect measurement. Given if a patient is infected by COVID-19 or just the stress and pressures of quarantine because of government orders, this could absolutely affect the measurement. I think what we’re partly seeing from the FDA’s guidance is that if we feel we’re going to miss assessments or if an assessment may be altered by the pandemic crisis, we should note and document that the assessments were taken under conditions such as this. – Michael Cioffi, senior vice president of clinical solutions and strategic partnerships at WCG
Q: If a site puts in a general screening procedure for COVID-19 that applies to every person that comes into the institution, does that require a protocol amendment if it also applies to study participants?
A: The FDA guidance actually discusses this. If screening procedures are mandated by the healthcare system, you do not need to report the amendment to the protocol, even if it’s done for the mere purpose of that person coming in for a study visit. You would only need to do that if you are going to incorporate the data that are collected as part of your research objective. If it’s just being done as general screening where someone comes to that hospital and every single person is getting that screening regardless of whether they’re coming for that clinical trial or not, it doesn’t have to be submitted. If you are collecting that screening data as part of your study objective, it will have to be submitted. – Suzanne Caruso, vice president of clinical solutions at WCG
Q: We’re making a lot of changes to protocols now to move things toward a more remote setting. Now that more sponsors and sites are using telemedicine and remote measures and are getting comfortable with this during this time, do you think more trials will continue to move toward using more virtual aspects well after this pandemic has ended?
A: I’m going to say 100% yes. I think one of the legacies of all this will be much more remote and telemedicine activity [in trials]. I think people are going to like not having to go in and having the option to being consented and monitored remotely. This won’t be true for everything, and there still will be onsite visits, but I think it’s going to be a major shift. But even if we self-quarantine and practice social isolation as we should, it doesn’t mean the virus is going away. I think we’re going to managing this with more remote and telemedicine things for the next year until we hear about a vaccine or some therapy. – Arthur Caplan, PhD, professor of bioethics and founding director of the division of medical ethics at NYU Langone Medical Center
Q: You mentioned stopping all “non-beneficial studies” whereas other people are simply wanting to modify trials to allow for more virtual and remote visits. You didn’t mean stop all trials that aren’t related to the virus, did you?
A: I think non-beneficial research — exploratory research and phase 1 — I would say suspend that now. Secondly, you don’t want people who are supposed to be socially isolating coming in and conducting research. Think about your own workforce too. Beneficial research I think will be proceeding, but I think you’re going to see a lot of interruptions of ongoing and certainly novel experiments and research. – Arthur Caplan, PhD, professor of bioethics and founding director of the division of medical ethics at NYU Langone Medical Center
Q: And when you use the term “beneficial research,” can you clarify what you mean by that?
A: If someone was really in a phase 3 study and we knew they were really getting efficacy for their cancer or being helped by whatever the research product/intervention was, then I think there should be a negotiation with the sponsor and the institution to try and maintain access to the agent. It might even require a study design change and pulling out a placebo arm and so forth. That might require not talking to the IRB but the DSMB. But I don’t want people who are getting something that has demonstrated efficacy beyond minimal to be left adrift or not be able to have access. That said, every company that I’m talking to is saying that they’re reorienting not only their staff and scientists, but also their manufacturing capability to get ready to make COVID-19 medicines or vaccines. – Arthur Caplan, PhD, professor of bioethics and founding director of the division of medical ethics at NYU Langone Medical Center