The following was provided by the audience question and answer session that was part of the Complion webinar, “Best Practices for Participant Safety: Assessment, Documentation & Reporting of Adverse Events,” featuring Elizabeth Ness, MS, BSN, RN at the Center for Cancer Research, NCI, Ilana Logvinov, RN, MSN, CCRP at Mayo Clinic College of Medicine, and Yolanda McKinney, RN, BSN, CCRC at the Center for Cancer Research, NCI.
Q. What are the key points in adverse event reporting requirements in Phase 2 studies with an FDA-approved drug?
A. IND regulations don’t necessarily apply, unless the study uses a marketed product. But the study still may be conducted under an IND, in which case the IND regulations apply. If so, all SAEs need to be reported. If not -- if the study is IND-exempt, and it’s a marketed product and of scientific interest -- then the FDA reporting is what is required of 314. It’s under the marketing drug approval and the voluntary MedWatch program. - Elizabeth Ness
Q. I’m an old-school nurse CRC who spoke to her patients. I see a lot of dependency on EMR only, with little assessment, not the final involved investigator formal assessment. This occurs with researchers as in CRCs. I use data collection forms that incorporate EDC ECRFs, plus additional information to address safety. This takes a lot of time upfront, but it’s time well spent. Do you have any recommendations?
A. I know that for FDA-regulated research and INDs in particular, the FDA wants to see the PI involvement in decision-making about adverse events -- the assessment, the attribution. Is it an important medical event? That can occur in a couple of different ways. One is within the medical record. The other is keeping some type of minutes related to the team meeting. So, even though how we interact and collect adverse events from our research participants really shouldn’t change because of EHRs, EMRs, they may be more limited in how we can document in terms of narratives. I always recommend that somebody from clinical research is at the table when deciding on what EMR or EHR is going to be used within an organization. - Elizabeth Ness
Q. Can you suggest any best practices for notifying other members of the team, short of the IRB reporting acknowledgement?
A. Yes! Education and sharing documentation with the clinical staff is important to the success of the study. When you’re starting a new study, it’s important to meet with the team members and the clinical units and let them know what would be important for them to contribute to the research. - Yolanda McKinney
Q. When training new CRCs or research nurses, I ask them to read the safety section of the investigator brochures, so they’re aware of what should be on their radar. If we don’t use targeted questions about AEs, the participants typically have variable memory of various concerns. This leads to inconsistent reports and recollections of AE at a much later date when the details are even less clear. How can this be addressed?
A. I tell my patients to keep a pad of paper and a pen at their bedsides. Every night, before they go to bed, they should write down anything that happened. Write down adverse events or any other experiences. Some protocols will require a patient diary, which, as we all know, does not really get completed in real time. E-diaries that can be used, but again, it’s only as good as the patient.
It’s important to understand how to use open-ended questioning with our research participants. So, if you know that fatigue is a possible adverse event, then we can ask, “have you noticed any change in your energy level? Do you take naps when you didn’t used to?” So, there are other ways to get at that.
If a drug causes constipation or diarrhea, you can ask the general question, “have you noticed a change in your bowel habits?” It’s really about knowing what the expected events are and how to phrase the question. Depending upon the frequency of the visits, you may need to do phone follow up if there’s going to be a long period of time that you’re not going to be seeing the patient. - Elizabeth Ness
Q. Is there a specific timeframe for following up on SAE reporting?
A. I haven’t found anything. It depends upon sponsor SOPs and your IRB SOPs, if they have specific windows of time that they want that information. - Elizabeth Ness
Q. For IND safety reports received from the sponsor, is the sponsor not required to analyze and the let the site know if it’s considered a SUSAR, instead of the investigator, per the FDA guidelines, in order to report only when it meets the criteria? The investigator might not have all the information or analysis aggregated to make the SUSAR determination on a single report. Can you please clarify this?
A. In the 2009 guidance document, the FDA said that they are getting IND safety reports that don’t meet the definition of an IND safety report. Some IND sponsors are better at providing their own assessment and will indicate that they don’t think that it is related, but they still wanted to share the information with all of the participating investigators.
With international, global research that is being conducted, sometimes things need to be, from a regulatory perspective, shared in other countries. So, it just comes part and parcel with just sending it on to all participants under that IND here in the States. I think the FDA recognizes they probably get more IND safety reports that are not true SUSARs. I’m not sure what else to say beyond that, but that doesn’t necessarily mean they meet the definition to be reported to your IRB or even to make any changes or amendments to your protocol. - Elizabeth Ness
Q. Does anyone have a good system to record AEs in Epic that makes it simple for all clinicians involved in care to contribute to the details?
A. I did, I’d be wealthy. One of the more challenging things is to really look in the aggregate at the documentation. I don’t have any great suggestions for that, per se. It depends upon a lot of things, including your medical record documentation practices within your institution. - Elizabeth Ness