PROMETRIKA invites you to read and enjoy a two-part blog series on risk-based monitoring (RBM) and the different clinical trial monitoring approaches based on our clinical operations team’s experience and research objectives. We will explore the differences between the traditional 100% source document verification (SDV) approach and RBM through the lens of two hypothetical clinical research associates (CRAs) as told in the style of an afternoon soap opera. You are currently reading part 1 of the 2-part series.
Narrator: Thank you for tuning in to the first of our 2-part series, “As the Trial Churns,” where we follow the fates of two CRAs working toward the same goals, but destined to walk different paths.
As newly minted CRAs, Patty and Emma met at the same company and looked forward to ensuring that the rights of the patients on their studies were protected, that the study data was accurate and complete and their studies were conducted in compliance with the protocol and applicable laws and regulations. (1)
To accomplish these goals, they have been responsible for many activities driven by federal regs (2):
- Verify the investigator, site staff and facilities are qualified and adequate at the start of the study and throughout the duration of the site’s involvement in a trial
- Verify the delegation of authority is documented and delegations are made only to trained and qualified professionals
- Verify the control, handling and accountability of investigational product maintained by the site
- Identify, report and document all deviations to the protocol, SOPs, GCP and applicable regulatory requirements and ensure appropriate preventive and corrective actions are taken to prevent recurrence
- Verify all subjects are consented appropriately and prior to participation in any part of the trial
- Ensure data is complete when compared to source documents when entered in the database, and inform the investigator of any errors
- Verify only eligible subjects per the protocol are enrolled into the trial
- Verify source documents follow ALCOA+
- Verify investigators receive timely notification of safety alerts and they take appropriate action as per regulations and local requirements
- Review and confirm all adverse events are reported according to the protocol, GCP, IRB/IEC, sponsor and regulatory requirements to protect human subject safety
- Verify the investigator maintains all E6(R2) required essential documents throughout the life of the study according to the contract and regulatory requirements
In time, Patty and Emma moved on to different companies where we catch up with them now.
Scene 1: As Patty hits the alarm and sits up in the hotel bed, she looks out the window at a familiar skyline. After all, she’s here every six weeks or so to monitor one of her assigned sites. Things were unusual, to say the least, during the height of COVID with sites going fully remote. Some of her sites were able to rapidly adapt to remote monitoring, but her company was another matter. They are very much entrenched in the mindset of 100% SDV, on-site whenever possible, so conducting remote visits was a bit like hammering a square peg into a round hole with only minimal changes to the company’s monitoring processes.
Getting back to routine on-site monitoring has been something of a relief, and being on-the-go again feels familiar. She enjoys the road-warrior life after all, but at times, it gets tiring being in 2-3 different states every week. No time for those thoughts now, though; it’s time for some tea and to get ready for the investigator site visit!
Scene 2: Emma stretches as she reaches to shut off her phone’s alarm. It hasn’t been the most restful night of sleep; she doesn’t spend as much time at hotels as she used to. Over her all-important first cup of coffee, she takes a few minutes to review the priority action items the company’s centralized monitor has put together based on review of the site data against the study overall. It was an adjustment, but Emma is glad to have the centralized monitor’s support and that her company took the time and effort to adapt in the face of the pandemic. Considering the FDA guidance on RBM, she thinks it was the right choice to move to a model of monitoring that emphasizes a more statistical analysis of data and processes critical to a study’s success rather than sticking with the 100% SDV model (3).
While the traveling lifestyle works for now, Emma thinks she will have a chat with her boss about moving into a centralized monitor role once she’s back at home base after this visit. She realizes it will take training and mentoring to learn a new skill set but looks forward to the challenge (4). That can wait though; it’s time to get going to the investigator site visit!
Narrator: Join us next time to see what adventures await our CRAs at their investigator site visits. Will there be intrigue? Will there be mystery? Will there be time to stop for lunch? Only time will tell… As the Trial Churns.
- FDA. (2018). E6(R2) Good clinical practice: Integrated addendum to ICH E6(R1): Guidance for industry. 5.18.4 Monitor’s Responsibilities. https://www.fda.gov/media/93884/download
- FDA. (2018). E6(R2) Good clinical practice: Integrated addendum to ICH E6(R1): Guidance for industry. 5.18.1 Purpose. https://www.fda.gov/media/93884/download
- FDA. (2013). Guidance for industry: Oversight of clinical investigations – A risk-based approach to monitoring. Guidance for Industry (fda.gov)
- Transcelerate. (2013). Position paper: Risk-based monitoring methodology. TransCelerate-RBM-Position-Paper-FINAL-30MAY2013.pdf.pdf (transceleratebiopharmainc.com)