Accelerating the Recovery – Design and IRB Review of Safety Monitoring Plans During COVID-19
COVID-19 is rapidly changing the way research is conducted. One of the biggest changes is the move from traditional face-to-face study interactions toward remote visits and data collection. This general approach holds clear benefits. In addition to mitigating public health risks and permitting research to continue, it may promote participant autonomy by yielding more flexibility over the research experience. However, it also holds challenges. One such challenge is how to conduct effective participant safety monitoring at a distance.
Both FDA and HHS regulations enjoin IRBs to make sure “the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.” Such monitoring may range from simple physical and verbal assessments, like the collection of vital signs and information about adverse events, to more invasive and complex measures, such as blood draws, imaging, and monitoring of organ function.
Given that such interactions typically take place during face-to-face visits with participants, how does the move toward remote visits and data collection impact participant monitoring? What techniques will satisfy the regulatory obligation to conduct safety and data monitoring in this new remote research world? How should IRBs reviewing these plans assess their adequacy?
Regulatory Provisions During COVID-19
Regulatory bodies in the US have made provisions that facilitate remote monitoring strategies. FDA has published guidance indicating that, during the COVID-19 pandemic, they do not intend to object to “limited modifications to the indications, claims, functionality, or hardware or software of certain non-invasive remote monitoring devices that are used to support patient monitoring”; HHS has chosen to exercise enforcement discretion over HIPAA-compliance for telehealth platforms. This should encourage sponsors and sites to leverage a variety of technologies to meet remote monitoring obligations and IRBs to look favorably on remote monitoring generally.
When establishing a remote monitoring schedule, the underlying principle should be to apply the same considerations that determine an appropriate in-person monitoring schedule. Typically, the appropriate number, frequency, and timing of monitoring assessments is similar for in-person and remote monitoring plans. What differs is not the schedule of assessments, but rather the mode or medium over which they take place. Several modalities should be considered when designing remote monitoring plans. In what follows we summarize each, emphasizing that they are not mutually exclusive: an adequate monitoring plan may contain a mix of them.
Home health visits by a research team member or associated clinician permit monitoring assessments to be made in-person. For this reason, they are likely to use traditional monitoring modalities and provide accurate safety data. At the same time, precisely because they involve face-to-face interaction, they involve the risk of virus transmission for both participants and the visiting clinician. While home visits may be less burdensome for participants, they still pose public health risks; this may prompt deeper consideration of alternative approaches.
Electronic Records Review
To the extent possible, use existing information in the medical records rather than gathering new information. This is especially important during COVID-19 to reduce in-person visits. Key to using the medical records is verifying that the data collected for healthcare purposes was gathered in a manner consistent with the protocol. Protocols may need to be expanded to include flexibility in how and when data is collected so medical record information can be utilized. This avoids double collection and by extension reduces direct interaction with the participant.
Telehealth platforms like Doxy.me have gained prominence since the start of COVID-19 and may provide a viable alternative to in-person visits. While HIPAA compliance is desirable, it is not always necessary given the regulatory provisions alluded to earlier. Consult HHS and Advarra guidance for examples of platforms that may and may not be used to provide telehealth services during the pandemic.
Telehealth may be combined with the coding of patient reported outcome instruments into online platforms, so that study team members can provide them to participants virtually and review them during telehealth visits. While telehealth permits collection of adverse events, an obvious drawback is that it does not permit forms of monitoring that require physical contact, such as vital sign collection. For this reason, telehealth monitoring alone may not suffice for trials that require more intensive approaches.
Mobile Applications and Wearable Sensors
Mobile health (mHealth) technologies—wearable sensors, smart devices, and mobile applications—may be important components of remote monitoring plans. Such technologies permit the collection of vital signs, like body temperature and blood pressure, as well as the measurement of more complicated parameters, such as oxygen saturation, electrocardiogram, or blood glucose. This data may be transferred from participant-facing mHealth platforms to cloud-based storage systems accessible by study staff.
Monitoring plans that include the use of mHealth technologies should specify at what points research staff will access incoming data. In general, such data should be accessed during the study, at intervals that ensure the timely detection of safety concerns. mHealth monitoring strategies also demand increased privacy and confidentiality protections, which IRBs should take care to ensure.
IRBs face a challenge: How should they assess if the data monitoring plan outlined in the protocol is adequate to ensure the safety of participants, in line with the IRB’s regulatory obligations, given that the data is collected by these new remote modalities? In addition to the typical evaluation of the plan’s adequacy, IRBs should consider where and how the data is collected in the first place. For instance, does the protocol make additional provisions to verify data collected by telehealth contractors is consistent with direct collection by in-clinic site personnel? Consistent data collection ensures the data monitoring plan can be executed as outlined in the protocol.
While the strategies reviewed here may not completely remove the need for in-person assessments and interaction, they may minimize the number of in-person visits, thereby also minimizing the public health risks of research, while satisfying regulatory obligations.
Adopting virtual and remote research modalities can be challenging. Ensure your documentation and workflows are appropriate and compliant with support from Advarra.