eSource: BIO Comments on FDA Draft Guidance on Electronic Source Data in Clinical Investigations

BIO thanks the Food and Drug Administration (FDA or Agency) for the opportunity to submit comments on the &ldquo;Draft Guidance for Industry on Electronic Source Data in Clinical Investigations.&rdquo;</p>

Re: Docket No. FDA–2010-D-0643:  Draft Guidance for Industry on Electronic Source Data in Clinical Investigations; Availability

Dear Sir/Madam:

The Biotechnology Industry Organization (BIO) thanks the Food and Drug Administration (FDA or Agency) for the opportunity to submit comments on the “Draft Guidance for Industry on Electronic Source Data in Clinical Investigations.” 

BIO represents more than 1,100 biotechnology companies, academic institutions, state biotechnology centers and related organizations across the United States and in more than 30 other nations. BIO members are involved in the research and development of innovative healthcare, agricultural, industrial and environmental biotechnology products, thereby expanding the boundaries of science to benefit humanity by providing better healthcare, enhanced agriculture, and a cleaner and safer environment. 


BIO supports FDA efforts to address the need for guidance in response to evolving technology available for electronic data capture.  BIO supports the ongoing integration of electronic health records into the healthcare delivery system and industry adoption of electronic data capture systems.  We are hopeful these systems will introduce new capabilities and efficiencies into the clinical trial enterprise. BIO commends the FDA for providing this revised and updated draft guidance in response to stakeholder concerns to the draft guidance of the same title released in January 2011.  While draft guidance addresses many issues raised by BIO’s previous comments[1] by presenting a more linear perspective to the capture and management of electronic source data in clinical investigations, BIO requests further clarification relating to the scope of the guidance and the recommendations regarding data review.

 I.        Scope of Guidance

We request that FDA clarify that the guidance applies only to source data that are initially collected electronically.  The title of the guidance, “electronic source data,” implies a limited focus – the capture and management of electronic source data that populates the pre-defined fields in an electronic case report form (eCRF) - however the guidance content addresses the role of the eCRF even when it is expressly not considered the data source (see lines 162-183).  Accordingly, BIO recommends the following revisions:

  • Lines 21-22:  “This guidance addresses source data from clinical investigations captured for the first time inused to fillthe predefined fields in an electronic case report form (eCRF), according to the protocol.”
  •  Line 162:  “Transcription ofSource Data from Paper or Electronic Sources to inthe eCRF”
  • Lines 162–183: Frame the discussion under a new heading titled “Source Data Captured Prior to eCRF”
  • Lines 343-346:  Amend the definition of eCRF to recognize that the eCRF in this guidance document represents a logical construct and in practical terms may encompass information stored in multiple distinct computer systems (i.e., that the capture, review, management, analysis, and reporting, does not occur in any single system.

In addition, and especially if the guidance is meant to be broader in scope, BIO requests greater clarity relating to how best to identify “source data”.   Since identification carries with it associated follow-on Sponsor and investigator responsibilities to maintain and make available for inspection supportive, electronic, or paper records greater clarity, including definitions of “automatic transmission”, “intervening process”, and “supportive information,” would, at the very least, help ensure investigator and Sponsor compliance and advance the goals of the guidance.

  II.        Data Review

BIO requests that the guidance reflect Agency understanding and recognition that it is not practicable or feasible to audit trail every “view” access of records by an investigator, especially because noting a “view” does not necessary indicate deliberate data review.  Systems typically capture an explicit action of the investigator attesting to their periodic review (i.e., review one or more times) of data with a signature.  This attestation is often an independent record stored in the system and is not necessarily stored in the audit trail itself as indicated in the guidance (see lines 237-238).  Moreover, that act of signing may reference a large amount of data, but each individual piece of data (data element) is generally not “tagged” with the investigator’s signature as indicated by the guidance (see lines 240-242).

Please clarify that the guidance refers to the use of individual “data elements” and “tagging” as an emerging best practice, as the current design of most electronic data capture systems do not accommodate such practices.  Please further clarify your understanding that traditional relational data base designs and audit trails are acceptable even if they do not individually tag discrete data elements.  Otherwise, Sponsors would be required to extend time and capital to make huge design changes to most of their current data capture and reporting systems, which would also likely undermine the Agency goal of encouraging the adoption of electronic source. 

[1]BIO comments on the FDA “Draft Guidance for Industry on Electronic Source Documentation in Clinical Investigations”, April 7, 2011,