An enduring constant in clinical research is change, brought on by advancements in technology, revisions to healthcare legislation and government regulations. 

One specific change to the investigational site model is the utilization of mid-level practitioners, Nurse Practitioners (NPs) and Physician’s Assistants (PA) as Sub Investigators (Sub Is). The number of sites adopting this practice, and the accompanying sponsors approving this practice, has increased exponentially.

A more common practice for research-driven physician investigators who share the burden of patient treatment with their Sub Is (PA or NP), is the formal documentation of Principal Investigator (PI) oversight of the delegation process. Some institutions/sites require the PI to co-sign diagnostic assessments and patient eligibility criteria for study patients treated by these Sub Is. Other sites require the PI to review and sign all central lab results, and complete all Adverse Event documentation on all study patients, regardless of the treating clinician. These measures may be reflected in written SOPs that confirm due diligence and serve as a key indicator of investigator involvement.

The PI is responsible for a successful study outcome. Delegation practices have a large influence on site performance. I have seen examples of both questionable and credible delegation practices as well as their impact on study participation.

I once conducted a pre-study assessment meeting at an academic institution where the PI was a renowned therapeutic expert. The PI had designated a physician and NP as his Sub Is, and all were in attendance for the study design discussion. The PI was engaging and the resulting discussions were a success. After the investigator portion concluded, I started the ancillary staff experience and facilities discussion with the NP Sub I, and was subsequently provided insight into patient treatment practices that made me uncomfortable. The questions were as standard as I expected the responses to be (e.g., what percentage of patients do the PI and Sub Is treat, what days of the week is the PI available for study conduct, etc.). The assessment of workload is critical to overall site consideration because an investigational site spread across many protocols may not have the staff or resources to successfully conduct another trial.

The nurse practitioner gave an unfettered response regarding patient distribution that I knew she instantly regretted: “The workload isn’t an issue because I treat all of the study patients anyway.”  The ensuing silence was uncomfortable as I processed what I had heard. The responsibilities of a Key Opinion Leader included lecturing and public appearances; investigator absence was understandable to some degree. But fulfilling an investigator commitment required more involvement that what was preliminarily demonstrated here. I asked the NP if the PI would be willing to treat more study patients to ensure adequate oversight. The NP nodded uncomfortably and then suggested we start the facilities tour. I was not satisfied with her response and resolved to speak to the project manager after the visit. I needed more assurance of investigator involvement before I could fully recommend the site.

While that pre-study assessment meeting was not the hoped-for setup, the opposite rang true when I conducted a similar meeting at a large, physician-owned practice with a research department that had a much stronger division of labor. The PI had two Sub Is; a PA who treated study patients and a physician who was available to respond to an SAE or in the event the PI was not able to treat study patients. The PI treated approximately 70% of the study patients and the Sub I PA treated approximately 30% of the study patients. The site had a documented oversight process that detailed investigator communication and assessment of Sub I treatment practices. During the pre-study assessment meeting, the site was very transparent about patient treatment practices and went so far as to share their institutional guidelines with me.

• The Sub I PA completed medical history and physical exams on some study patients. The PI cosigned each assessment note.
• The PI completed all study patient adverse event documentation and reviewed/signed all study patient lab results.
• The PI completed and documented the final verification of patient eligibility for the study in the source documents.
• The PI completed and signed all serious adverse event paperwork.
• The site had a documented communication plan that detailed weekly meetings between the PI, Sub I and research department to discuss study status, enrollment and patients.
• The PI was responsible for performing study update and amendment training and all attendees had to sign a training log.  

Elizabeth Blair Weeks-Rowe, LVN, CCRA, currently works in relationship development/study startup in the CRO industry. Email ebwcra@yahoo.com

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