This is a no-brainer! You can ensure early in the enrolment phase that procedures are being done correctly. If not, a CAPA can be implemented sooner. The recently issued FDA draft guidance on Risk Based Monitoring (RBM) extols the benefit of an early monitoring visit or other early monitoring activities when determining the timing, types, frequency and extent of monitoring activities.
‘Inadequate monitoring’ remains the most common Sponsor/Monitor/CRO inspection deficiency identified in FDA Form 483 issued at close of CDER inspections. Knowing that, why wouldn’t you do that first monitoring visit soon after the first patient is enrolled to make sure everything is being done correctly? Be proactive in managing risk rather than reactive.
I recall asking one CRO PM when they expected to visit a site that enrolled many subjects in a short period of time. I was informed that ‘we are doing risk-based monitoring’ and they would not be visiting any sites until a % of the total number of subjects expected had been enrolled at each site. Granted this was in 2016 when risk- based monitoring was in its infancy and people often conflated risk management with risk-based monitoring. Enrolling a large volume of ‘complex’ subjects in a short period of time is a risk. If there has been any misunderstanding of enrolment criteria, it affects a greater number of patients. Better to visit the site and make sure the source documentation supports their eligibility and those patients have been enrolled appropriately. The last thing you need is to have to explain to FDA why you needed to exclude data collected at a particular site. That does happen.
Additional benefits of an on-site visit
Meeting people in person adds value to any relationship. You can look them in the eye, observe their body language and watch how they interact with other people. They are more likely to respond to your requests when a personal relationship has been established. Plus, you may pick up other nuances when on site. Is the work-space organized? Is the PI responsive to your request to meet with him? Is it a collaborative environment? A chaotic environment? You are not going to get all that information without visiting the site in person. Yes. You may be able to determine remotely that all is not well at a site. Delays in data entry, fewer AEs compared to other sites, higher numbers of protocol deviations and a high screen failure rate compared to other sites, may all point to an unsustainable workload and site staff who are overwhelmed and not paying attention to detail. You are more likely to get a robust CAPA if you have a good relationship with site staff and that can best be developed in person.
Financial cost
It will cost less in the long run if you conduct an early monitoring visit. Think about the savings from a big picture perspective. Fewer subjects are enrolled inappropriately so none must be replaced. Fewer queries must be generated, and the data base can be locked sooner, because the site personnel were clear on the protocol requirements. As Benjamin Franklin said: ‘An ounce of prevention is worth a pound of cure’. Make sure to build in some flexibility in the monitoring plan for an early monitoring visit to sites that are actively enrolling in order to prevent unwanted outcomes.
