In this series on Implementing E6 R3, we're taking a deep dive into complex or new GCP requirements. Last week, we featured posts on configuring and implementing IRT systems. Today, we look at the issue of clinical site support, in which we tie ourselves in knots contemplating the philosophical differences between different types of clinical site support vendors. Let's go!
Resourcing at investigational sites has always been a concern, but the COVID pandemic exacerbated the gaps. Some sponsors have addressed shortages by hiring independent resources, such as study coordinators and research nurses from a staffing agency, to support clinical sites. This isn't a new idea - back in the early days of EDC, sponsors sometimes hired data entry coordinators to travel to sites to enter CRF data into EDC systems and upload the data (connected by telephone modem, naturally!).
Another industry trend amplified by the pandemic, decentralization, has also led to situations that blur the lines between sponsor and site. For example, sponsors may hire home health nurses or mobile vision clinics to visit study participants at home to capture key assessments.
The prospect of the sponsor compensating resources at the clinical site can raise concerns about conflict of interest; however, sponsors have long retained centralized suppliers like central labs, reading centers, and even EDC vendors to provide clinical trial services that sites cannot perform, or that a central vendor can perform more consistently. It's an interesting philosophical question: What is the difference between a sponsor-paid home health nurse and a central lab in terms of their role on a clinical trial? Most of us would assume a home health nurse should be listed on a site's delegation log, whereas technicians at a central lab would not, but why? It feels like interaction with study participants should be a differentiating factor, but delegated site staff like radiologists or local lab technicians may work at a remove from participants, just like a central lab technician.
Without getting into the philosophical differences, E6 R3 has added several new points to govern the situations where the sponsor hires resources to support the site. From the investigator's side we have the following requirements:
- Section III. 2.3.1, regarding investigator responsibilities, now states, "The investigator may delegate trial-related activities to other persons or parties. The investigator may be supported by the sponsor in the identification of a suitable service provider(s); however, the investigator retains the final decision on whether the service provider intended to support the investigator is appropriate based on information provided by the sponsor." Based on this point, sponsors and investigators should be prepared to provide evidence that they provided the investigator with information about staff qualifications as well as evidence that the investigator approved each staff member.
- Per Section III. 2.3.1, the investigator should "maintain appropriate oversight of the persons or parties undertaking the activities delegated...The level of investigator oversight of the delegated activities should depend on the nature of the...activities and be proportionate to the importance of the data being collected and the risks to trial participant safety and reliability." Here we see the "risk-based approach" concept in action. Presumably, investigators would maintain direct oversight over a contract study coordinator; some oversight over home-health nurses; and less direct oversight over a vendor like a mobile vision assessor, due to the "nature of the activities."
- Per Section III. 2.3.2, the investigator should ensure that a "record is maintained" of the persons and parties to whom the investigator has delegated activities. Note that the requirement for a "list" in E6 R2 has been changed to a "record" in R3, suggesting that the Delegation of Authority log is not the only means of delegation. This point goes on to state that "Documentation of delegation should be proportionate to the significance of the trial-related activities. In situations where the activities are performed as part of clinical practice, delegation documentation may not be required." This change suggests some welcome flexibility in the approach to delegation.
- Principle 10.2 notes that where activities are delegated to service providers, the investigator remains accountable for the quality and integrity of trial data.
The Sponsor Responsibilities section only calls out this situation once - in III.3.6.5, which reiterates the point above about the sponsor's requirement to provide the site with information about any resources the sponsor is hiring on the site's behalf. This section, however, includes a number of statements about sponsor service providers that align sort of awkwardly with situations in which the sponsor is hiring resources for the site. For example,
- Section III. 3.6 notes that any trial-related activities that the sponsor transfers to a service provider must be documented in an agreement prior to performance of activities, but it does not explicitly call out trial-related activities that the sponsor contracts with the vendor to perform on the investigator's behalf.
- Section III. 3.6.6 states that "any service provider used to perform clinical trial activities should implement appropriate quality management and report to the sponsor incidents that might have an impact on the safety of trial participants and/or trial results." We would expect a vendor such as an agency that provides home health nurses to have a quality management system, but what about individual staffers like study coordinators? Does their agency need its own quality management system, or can they simply work under the sites' SOPs? Does a sponsor-hired study coordinator "report to the sponsor," or to the investigator? Common sense can be our guide here, but we can see the thorny situations that might arise if we accept that this step applies to all sponsor-contracted site support services.
