Can a Sponsor’s TMF be Used to Manage the Investigator Site File?

April 24, 2013

  • eTMF Best Practices

Recently, I have been involved in, or heard about, several discussions where people voiced the suggestion that a sponsor’s Trial Master File (generally in the form of an eTMF) could be used to manage the Investigator Site File – the records that regulatory authorities require to be located in the files of the investigator or institution responsible for the conduct of a trial at a trial site. The suggestion was that by enhancing the TMF to account for additional document types, a single system could be used to collect all of the essential documents for a trial.

I found this discussion rather surprising as the regulatory authorities have been rather clear that this approach is not acceptable. Recently, in the European Medicines Agency (EMA)’s draft “Reflection paper on GCP compliance in relation to trial master files (paper and/or electronic) for management, audit and inspection of clinical trials”, this position was stated:

“The investigator should retain control of the documentation contained in the investigator
site file. The investigator site file should never be sent to the sponsor organisation except in
sponsor-investigator situations.”

EMA does go on to clarify that an external sponsor can arrange the archiving on behalf of the investigator as long as certain key conditions are met regarding the archiving arrangements.

The MHRA provides detailed justification in the “Good Clinical Practice Guide”:

“In organising the TMF, it is essential to segregate those documents that are generated or held
by the sponsor of the trial from those of the investigator, as some documentation held by the
investigator should not be provided to the sponsor. This requirement is firstly due to subject
confidentiality issues (for example, the sponsor must not have documents such as consent
forms and subject identification lists… Secondly, where the investigator site file contains source
documents, the case report forms (CRFs) contain source data or the CRFs are the investigator’s
independent copy of the transcribed data, providing this to the sponsor would remove the
investigator’s control. This could lead to the sponsor making uncontrolled and unauthorised
edits to the investigator’s documentation.”

MHRA also states that sending site records to a sponsor for upload to an eTMF breaches the requirement that the investigator site remain in control of the records.

There is no regulation that prohibits a sponsor from providing a separate eTMF for the site that is under the control of the site. However, a number of non-regulatory obstacles remain – here are a few examples:

  • Contracts would have to be re-negotiated with the sites. Some sites would drop out altogether as they don’t have the bandwidth; others would want more money. Sponsors are loath to take on anything that would make it harder to recruit sites.
  • Sites often have very little technology and may have no scanner, or at least no adequate scanner. Site personnel would need training and SOPs if they were assigned scanning responsibilities.
  • Sponsors would have to be able to prove ROI on the total cost of the eTMF plus additional costs payable to the sites for using the eTMF. Ultimately, the need for remote, risk-based monitoring may provide this ROI.
  • A mechanism for electronic access over many years would need to be in place, long after the investigator has left the institution, retired, or passed away. Who would then have access and control? As access is by named user, the paradigm is somewhat different that access to archived paper.
  • Unless valid electronic identities and electronic signature are provided for all site personnel needing to sign documents, hard copies would still have to be retained for wet ink signed documents.

Due to these challenges, it would seem that industry is still a few years away from providing investigator-controlled eTMF that provides a solid return on investment.