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Source Data/Documentation
"Since ICH E6 does not specify explicitly the approach to signing/dating of CRFs, [there appears to be] no basis
for suggesting that [signing] needs to be done on each/every page of the CRF-but rather somewhere (generally
the front page) of the CRF."
6.46 Q. Assume that an investigational site (Site 1) is being closed and that subjects in the ongoing study will
be shifted to a new site and investigator (Site 2) different from the current site/investigator. In this case,
what documents must be transferred from Site 1 to Site 2 for the active subjects? For subjects no longer
participating in the trial, where should the CRFs, source documents, etc., be maintained?
A. In an informal response to this question, an official in the FDA's Good Clinical Practice Program stated that, "I
believe FDA would expect to find the records for the subjects who have already completed the trial to be available
at the site of the investigator who enrolled those subjects so that the FDA employee could also question the relevant
personnel about the conduct of the study. Therefore, I'd recommend that they be maintained by Site 1. I would
also recommend that Site 1 maintain copies of the records they pass on to Site 2 because any activities performed
up to that point, again, were done by the staff at Site 1 and any questions about how those 'pre-transfer' activities
were carried out would need to be answered by the staff/investigator at Site 1. This would also cut down on the
possibility of records being irretrievably lost during the transfer (because copies are maintained at Site 1)."
6.47 Q. Assume that patient data for a study are recorded directly on the case report form (CRF), making the
CRF the source document. In the FDA's view, is it appropriate for a sponsor to collect the original CRFs
and leave the clinical investigator/site with only a copy of the CRF to serve as the source document?
A. In an informal response to this question, the FDA stated that, "the clinical investigator must be able to produce
required records for FDA inspection. ICH GCP (while guidance and not FDA regulation) indicates in Section 8
that source documents should be located in the files of the clinical investigators along with a copy of the CRF, and
the original CRF should be located in the files of the sponsor. When the CRF serves as a source document, the
sponsor may develop an SOP to retain the original CRF at the sponsor site and a certified copy at the investigator
site. The investigator still retains regulatory responsibility for ensuring the accuracy of the CRF (and, by extension,
any certified copies); this should be clear in the SOP and in instructions to the clinical investigators. On inspection,
FDA would expect to be able to access both the certified copy of the CRF (if this is what is retained at the [clinical
investigator] site) and the original CRF at the sponsor site as needed and/or requested."
6.48 Q. FDA officials have expressed strong and numerous concerns about the maintenance of source
documentation when electronic patient reported outcome (ePRO) tools, such as electronic patient diaries,
are used in collecting the data directly from clinical study subjects. What should a principal investigator
do about the retention of source documentation at his or her site if electronic patient diaries are used?
A. This has been a controversial issue, particularly with FDA compliance officials. While long-standing FDA
regulations require that source documents for clinical study data be maintained by the clinical investigator at the
investigational site and that the sites allow the FDA to inspect, review, and copy records at any time (including
while the study is in progress), many e-diary implementations have involved either an immediate original recording
in the sponsor's database (if entry by the study subject is web-based or into an interactive voice response system)
or short-term capture on some type of device (such as a PDA), with upload to the sponsor's database. Alternatively,
the software vendor may have hosted the database.
In its December 2009 final guidance entitled, "Patient-Reported Outcome Measures: Use in Medical Product
Development to Support Labeling Claims," however, the FDA makes clear that ePRO systems "may be a problem"
if a sponsor or CRO, rather than a clinical investigator, has "direct control" over the source data.
"The investigator's responsibility to control, access, and maintain source documentation can be satisfied easily
when paper PRO instruments are used, because the subject usually returns the diary to the investigator who either
retains the original or a certified copy as part of the case history," the agency states in the guidance. "The use of
electronic PRO instruments, however, may pose a problem if direct control over source data is maintained by the
sponsor or the contract research organization and not by the clinical investigator. We consider the investigator to
have met his or her responsibility when the investigator retains the ability to control and provide access to the
records that serve as the electronic source documentation for the purpose of an FDA inspection. The clinical trial

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