Lessons Learned From FDA Establishment Inspection Reports

Posted by Paddy Wall on Jul 17, 2017 2:47:25 PM

Sponsors and CROs regularly tell us that site deviations are huge issues for their organizations. Study managers can often point to the study-specific reasons why issues occur at the study level, but is there a bigger picture we should consider in terms of common trends of typical inspection issues?

FDA Establishment Inspection Reports (EIRs) can be obtained through the Freedom of Information Act and shed a lot of light on the typical areas where clinical research sites run into trouble. For example:

  • Investigation was not conducted in accordance with the investigational plan
  • Subjects did not meet the inclusion/exclusion criteria
  • The protocol was not followed
  • Protocol-specific training was not documented

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On the surface, these issues seem inexcusable. It is the obligation of the principal investigator under ICH GCP to ensure these actions are carried out correctly. However, sites are chosen primarily for their access to target patient populations. The core competency of the principal investigator is as a caregiver in their specific therapeutic area, and not as an administrator of clinical trial protocols or as trainers to staff members on the delegation log. One EIR that we reviewed cited eight sub-investigators who were not trained on the protocol. In this case, they had received training on general tasks, but documentation on protocol-specific training was lacking, which was reflected in the observations noted at the site.

Of course, investigational site staff make every effort to comply with the protocol and site payments are in place to ensure this happens. However, common EIR observations show that, in reality, their efforts are not always successful - and to bury our heads in the sand and believe otherwise is a fallacy.

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"We must not tolerate subjecting patients to months of visits and procedures only to discard their data due to protocol deviations."

Aside from the cost, wasted resources, increase to study timelines, and potential risk to a positive study outcome that would bring better drugs to market for patients, it is the definition of anti-patient-centric.

Dedicated CRAs and site staff have been trying to combat non-compliance and protocol non-adherence for years. CRAs try to ensure that everyone is trained during monitoring visits and they have told us that they commonly generate their own protocol-specific cheat sheets to minimize deviations. The problem here is that this material is not sponsor-approved and not version controlled. If this material turns up in an audit, which has happened, the result is a finding and a “rap on the knuckles” for all involved.

It’s time to become proactive instead of flailing during inspections. How can this be achieved? By putting in place study-wide supports to reduce EIR observations and needless protocol deviations. Provide engaging and accessible on-demand training and real-time assistance for each visit in formats that fit the way site staff work today. Simply put, the most efficient and least stressful way to achieve Inspection-readiness is to empower sites do the right things, in the right way, on a daily basis.

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