The US FDA has finalized guidance on electronic case report forms (eCRFs), which offers advice for sponsors and CROs on how and in what cases to capture electronic source data.
The final guidance encourages CROs and sponsors to view source data early to detect any study-related problems, such as safety concerns or protocol deviations, as well as problems with conducting the study in terms of missing data or data discrepancies.
Electronic source data, according to the FDA, includes information recorded in an electronic format in all original records and certified copies of clinical findings, observations, or other activities in a clinical investigation to ensure adequate protection of the rights, welfare, and safety of human subjects and the quality and integrity of the trial data.
In addition to laying out the responsibilities for reviewing and retaining electronic data, the agency evaluates cases when the eCRF is a source, such as when a device like a blood pressure monitoring device or glucometer, is the source and data are automatically transmitted directly to the eCRF.
“The eCRF should include the capability to record who entered or generated the data and when it was entered or generated,” the FDA says. “Changes to the data must not obscure the original entry, and must record who made the change, when, and why.”
ACRO, Quintiles Comments
But the final guidance does not seem to address some of the sticking points raised by ACRO (Association of Contract Research Organizations) and CRO Quintiles from the draft guidance.
For instance, ACRO questions what CROs and sponsors should do if documentation is not available for review at a particular site, or how specific the description should be when modifying or correcting an electronic data element.
ACRO also calls on the FDA to provide some “perspective as to whether it is necessary for CROs to consider supplying some type of validation summary with the systems we provide, to answer the basic questions surrounding validation, security controls, backups, etc.” to help sites respond to FDA questions.
Likewise, Quintiles says that the draft does not discuss the “required characteristics of the data or systems used to generate data” in electronic source documents.
And in some cases, Quintiles claims, investigators would not have control or the knowledge of whether or not an EHR (electronic health record) or software program transfers accurate and complete data to an eCRF.
The FDA does not offer specific answers, but says it “does not intend to assess the compliance of EHRs, though sponsors should include -- in the protocol, data management plan, or investigational plan -- information about the use of computerized systems for a clinical investigation, a description of the security measures to protect the data, and a description or diagram of the electronic data flow.”