Draft Guidance for IndustryElectronic Source Documentation in
Clinical Investigations
FDA Guidance Overview
Electronic Source Documentation in Clinical Investigations
Draft Guidance
Draft- not binding Comments invited in docket Comment period closes Apr 7 Link to the docket
– www.regulations.gov– Docket # FDA-2010-D-0643
Outline
Reasons for writing this guidance Electronic Source Documents and Source Data
– Data Entry– Data Review– Data Processing and Transmission
Regulatory Review Collaboration Conclusions
Why Did We Write This Guidance?
Difficulty with paper based studies– Burden of transcription errors– Monitoring– Archival and transporting of bulky CRF’s around the world
Advantages of electronic platform– Eliminate unnecessary duplication of data – Reduce transcription errors– Promote real time entry of data during visits– Prompts for missing data and data errors will ensure accuracy and
completeness– Potential interface with medical devices, electronic health records,
laboratory data, imaging systems, etc…– Rigorous audit trail
Three-Tiered Process
For discussion purposes we have divided the process into three tiers– Tier 1- collection and entry of data– Tier 2- data review– Tier 3- data processing and transmission
Process Overview
Tier One
Data Entry
Data Elements A data element represents a single observation associated with a subject in a clinical study e.g.
– Birth date– WBC Count– Pain severity measurement
New Data elements- for data elements created at the time of data entry, the electronic case report form is the source document
– (No other record of that data element is needed) Blood pressure Temperature resolution of a symptom or sign Laboratory measurement of hemoglobin
Data elements that are transcribed from another document e.g. progress note by physician instrument printout Blood pressure
– the source document must be maintained Corroborative data may be requested by FDA during a site inspection depending on context e.g.
evidence of blood glucose readings to corroborate a diagnosis of diabetes
Data Originators
Various parties (originators) may be authorized to enter data elements
– Investigators, study site staff– biomedical devices– Automated laboratory reporting systems– Imaging facilities– Electronic health records– Clinical study subjects (PRO)
List of Authorized Data Originators
Each study site should maintain a list of authorized data originators (persons, devices, instruments..)
– The list should include the unique user name assigned to the data originator, and the period for which authorization is given
– The site should employ controls to ensure security and integrity of user names and passwords
– Users should accept responsibility for the validity of the data they enter
Data Element Identifiers
Are pieces of electronic information that are linked to a data element
Data element identifiers should include:1. The originators of data elements, including those
entered manually (e.g., by the investigator), and automatically (e.g., from a device or instrument)
2. The date and time the data elements are entered into the eCRF
3. The study subject to whom the data elements belong.
Example of Data Elements and Data Element Identifiers
Field in CRF Data Element Data Element Identifier
Patient ID# AD0012 Randomization algorithm in central computer/June 1st, 2008/3.00 pm
AD0012
Sex Male Investigator Dr R Smith/June 1st, 2008/10.53 am AD0012
Age 25 years Investigator Dr R Smith/June 1st, 2008/10.53 am AD0012
Hemoglobin 15.3 g/l Co-op labs/June 2nd, 2008/12:06 pm AD0012
Date blood was drawn for Hemoglobindetermination June 1st, 2008 Investigator Dr R Smith/June 1st, 2008/10.53 am AD0012
Radiological report “Right upper lobe consolidation” Dr P Brown, radiological associates/ June 1st, 2008/4.12
pm AD0012
Blood pressure 124/88 AB instrument systems/ June 1st, 2008/10.53 am AD0012
Concomitant medications Lasix 40mg QD Investigator Dr R Smith/June 1st, 2008/10.53 am AD0012
Display of Data Element Identifiers
The electronic system should include a functionality that enables users to reveal the data element identifiers (e.g. by cursor placement or view mode displaying data element with its identifiers)
Modifications and Corrections
Modified data elements should carry new, write-protected data element identifiers reflecting:
– the originator of the modified element– the date and time of the change– a text field describing the reason for the change is
recommended The original data element and its identifiers should be
preserved
Example of Modification/Correction
Field in CRF Data Element Data Element IdentifierHemoglobin 12.3gm/dl Modified by: Investigator assistant
Dr B Green/July 7th, 2008/9.00 am/AD0012 Reason: Data error reported by Co- op labs July 6th 2008 due to standardization problem; sample was retested
Original data (write-protected automated carryover): Hemoglobin 15.3gm/dl
(Co-op labs/June 2nd, 2008/noon)/AD0012
Tier 2
- Data Review
Investigator Responsibilities
“Investigator is responsible for conducting the study according to the protocol and for protecting the rights safety and welfare of study subjects”
The investigator’s copy of the CRF– Contains all data elements that the investigator has reviewed– It should permanently carry proof of the investigator’s sign off– A write-protected copy should be stored– The investigator should maintain control of this copy– (In exceptional circumstances the protocol may require that certain data
elements be hidden from the investigator) Archived eSource documents should be available in read-only format to the
originators who submitted them
Tier 3
Data Processing and Transmission
Transmission and archiving of data Electronic data entry provides an opportunity for the sponsor to
transmit data real-time to designated parties– Examples: real-time transmission of critical safety data to
data safety monitoring board, real-time transmission of site performance data to CRO
Blinding should not be compromised A detailed plan for data transmission should be described by
the sponsor
Sponsor Responsibilities
Protocol should include information about the intended use of computerized systems during the conduct of a clinical study
– Description of the security measures employed to protect the data
– Detailed diagram and description of the transmission of electronic data
Describe electronic tools intended to be used to detect events in the eCRF such as, but not limited to, data inconsistencies, missing data, and entries out of range
Regulatory Review Collaboration
FDA’s review divisions are available to review sponsors’ plans for handling electronic source data
Typically discussed with FDA during:– Pre IND/IDE meetings– End of Phase II/Special Protocol Assessment– Pre NDA/BLA/PMA meetings
Conclusions
Electronic platforms for clinical investigations have enormous potential advantages
– Improvement in trial quality and safety, simpler monitoring, reduced errors, real time information flow, central data monitoring, incorporation of data from instruments, simpler archival
The success of this approach depends on dependable procedures and controls to ensure reliability of the source data
FDA is hopeful that this draft guidance will be an important step to facilitate adoption of electronic data gathering across the medical product industry
Top Related