With pandemic-related stay-at-home orders and travel restrictions piling up, researchers had to get creative to keep participants safe and allow critical research to continue. Many organizations increased utilization of “virtual” clinical service providers closer to the participant’s home. Local surgical centers, MRI scanning, and other clinical services started to be done locally, by private providers, rather than at the main academic medical center or health system. Arguably, keeping procedures local is more convenient for the participant even without the pandemic.
In this post we will explore some issues research organizations need to consider when using remote sites to perform clinical trial procedures, including whether those remote sites are considered to be engaged in research.
IRB Review Needed?
Depending on the nature of the research procedures being conducted at the remote clinic, they may be considered an additional performance site and need separate IRB review consistent with 21 CFR 50 and 56 (FDA) or 45 CFR 46 (OHRP Common Rule).
OHRP Rules – “Is the Site Engaged in the Research”
For federally funded research, the regulatory framework for determining if the remote clinic needs IRB review as a separate performance site can be found in OHRP’s 2008 guidance on “engagement.” Having the right IRB coverage in place for the remote clinic is critical for the FWA holding institution receiving federal funding for the research. Here are the key factors in making the determination:
- Are you paying the site as a sub-awardee, or as a fee-for-service like other vendors invoicing for their services? If the site is a sub-awardee, then they are engaged and need IRB review.
- Is the site administering the investigational product, or are they simply providing standard of care services (e.g., CT scan) per the study protocol that the site routinely provides as a commercial service? If the site is administering the investigational product, they are likely engaged.
- Will the staff at the remote site be obtaining consent for the research? If so, then the site is likely engaged.
There are a lot more details and nuance in the OHRP guidance. Clinical research teams should consult with their local IRB offices, or engage the Advarra HRPP consulting team, to determine if the remote site is “engaged in research” and thus needs separate IRB coverage.
FDA Rules – “Is the Clinical Investigation Being Conducted at the Site”
For non-federally funded FDA regulated research, the determination of whether the remote clinic is a separate performance site needing IRB review hinges on whether the remote clinic is conducting the clinical investigation. The recent COVID-19 guidance from FDA provides a clear indication that FDA anticipates remote clinics to be part of the solution to keep research running during the pandemic. However, it stresses the same rules apply to these sites as pre-pandemic.
Sites involved in the clinical investigation must be listed on the Form FDA 1572 or device protocol and have the appropriate IRB coverage. Remote sites which are only performing standard of care non-investigational clinical services (e.g., MRI, blood chemistry) called for in the protocol likely just need to be listed on the 1572 and be appropriately noted to the IRB as per the IRB’s procedures. Remote sites that are administering investigational product, conducting primary end-point analysis, or handling similar activities likely are considered separate clinical research sites and would need separate IRB approval as a unique performance site.
Do not bill insurance for research procedures which should be covered by the sponsor. This is easy to say, harder to implement.
In particular, the Centers for Medicare & Medicaid Services (CMS) “frown” (AKA invoke the False Claims Act [FCA], 31 USC 3729 – 3733, a federal statute) if they are inadvertently charged for research-related procedures when the change should be covered by the sponsor (42 CFR 405 Subpart B and NCD 310.1). When you engage a remote provider to perform clinical procedures as part of your clinical trial, make sure the provider has appropriate billing processes and controls in place to send the bill to you rather than to Medicare or private insurance.
Some key questions to ask the remote provider:
- Do you have the ability to flag patients the research facility sends to you as “research” versus primary care?
- Can your clinic billing systems separate out a patient’s research-related charges from standard of care charges if the person is also seeing your clinic for primary care not related to the research?
- What can we do as the primary research facility do to help you and the patient identify that they are coming to your clinic for a research-related procedure?
Bottom line: Your organization might be held responsible if research-related procedures are billed incorrectly to insurance. Have conversations with your remote providers to ensure systems are in place to get the bills going to the correct place.
Contracting, Clinical Trial Management, and Logistics
Lastly, research organizations need to consider the implications on clinical operations. Updates to the clinical trial management system procedure calendars may be necessary to accommodate new remote activities. Timelines and procedures may need to be changed to account for drug shipment and accountability tracking with remote clinic sites. Remote sites may have additional feasibility reviews and other permissions before they can perform services for your study. Clinical trial contracts between your organization and the sponsor may need to be updated to allow for utilization of additional facilities (and of course there will be a concern over the budget impact). Each of these may be a project unto itself and require attention before using remote clinic sites.
We need to move research forward as we evolve and accelerate out of the COVID-19 crisis. Adding the capability for participants to receive services closer to their homes by adding remote clinic sites can be a very effective tool to keep research running. Organizations who embrace new trial modalities, such as remote sites and virtual trial technologies, will be able to maintain enrollment and likely improve participant satisfaction. There are simply a lot of logistical and operational considerations to work through.
Need help navigating the new world of “virtual” clinical trials? Contact Advarra’s HRPP consulting team.