This post is Part 3 of a 6 part series. Visit weekly or enter your email to subscribe.
eSource solutions must allow PI access to electronic data. Developing and planning eSource solutions should also address data transfer to the sponsor in an effort to protect the rights, safety, and welfare of subjects. Sean Kassim of the FDA recently pointed out that in the world of eDiary and DCDC, direct transfer of ePRO to the sponsor is NOT appropriate. As part of their oversight, the Principal Investigator (PI) needs to have access to this data typically via site access to an online portal (See Figure).
In addition, “To comply with the requirement to maintain accurate case histories (21 CFR 312.62(b)) and 812.140(a) (3)), investigators should review and electronically sign the eCRF for each subject before the data are archived” and released to the parties (IRB, Data Management Center, SMO/CRO, Regulatory authority).1 Data that goes directly to the sponsor may contain information wholly relevant to patient care and human subject protection (HSP). For example, PROs with multiple entries of shortness of breath should be reviewed by the PI to determine whether or not clinical intervention is indicated. Compliance with this requirement for PI oversight can be in the form of a formal process for review of the data or the electronic instrument can alert the PI to review certain criteria specified at the onset of the study – either way, the PI needs to have access to the data.
In the process of data management, data entered into the diary by the subject should be available primarily for subject safety, but also to review and query for accuracy. In the figure above, the electronic model indicates PRO questionnaires are accessible as view only data and not editable by the site staff while the PI/designee with a specific user role is able to modify concomitant meds (CM), infusion data, and untoward events in response to a query. Some have suggested only the originator, in this case the subject via the eDiary, should be allowed to change or modify the “original source”. The most recent FDA draft guidance however, suggests someone other than the “originator” can modify original electronic source so long as the modifications meet the standards in the guidance:
- Modified or corrected data carry a new data element identifier
- Identifier includes date, time and originator of the change
- Both the modified data element and the identifier is write-protected (read only)
- The original data element with its original data element identifiers is preserved and available for FDA investigators1
Additionally, when it makes sense to wipe out data to recycle the device, the local information including the audit trail of data modifications needs to be saved, and a data file (CD or pdf) serves as the certified copy representative of data collected in compliance with the standards in the guidance as well as 21 CFR§11.1.2
1 Guidance for Industry Electronic Source Documentation in Clinical Investigations Draft Guidance. U. S. Department of Health and Human Services, Food and Drug Administration, Office of the Commissioner. November 2012. Retrieved December 18, 2012 at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM328691.pdf
2 Helfgott, J., Kassim, S. 2012. Drug Information Association Clinical Management Teleconference “FDA on FDA Perspective on ePRO”. October 19, 2012.
to be continued…………..