It is frequently seen during GCP inspections that the CRF is designed to only include an overall statement
regarding a subject’s eligibility in the trial. The text in the CRF could for instance say: ‘Did the subject
satisfy all study entry criteria?’. The statement is typically intended to be answered with ‘yes’ or ‘no’.
The expectation of the GCP Inspectors’ Working Group is that adherence to all individual inclusion and
exclusion criteria are documented in the source data. Adherence to the criteria of the protocol can
originate from different sources like blood samples, physical examination, medical history, information
from the subject etc. When designing the protocol and the related CRF, the sponsor should carefully
consider where each source data originate from, with reference to a specific visit. This is important since
some data originate from screening visits, others from the randomisation visit and some data could be
historical.
It should be agreed with the investigator of a site how adherence to the individual criteria is
documented.
It is the expectation that a qualified physician who is an investigator or a sub-investigator for the trial has
assessed each individual eligibility criteria and has taken the final decision to include the subject in the
trial (ICH GCP 4.3.1). This decision should be documented prior to the subject receiving the first dose of
the IMP.
GCP inspections have revealed a substantial amount of cases where the overall eligibility statement in
the CRF confirms subject eligibility but where source data shows that the subject did not fulfil all
eligibility criteria. In addition, it has often not been documented that an investigator/sub-investigator has
reviewed all criteria prior to inclusion. It therefore seems that a system with an overall statement in the
CRF regarding a subject’s eligibility in itself does not ensure the safety of the subjects, the quality of the
data and sponsor oversight.
