1. A Regulatory Perspective on Electronic Data Capture
IMMPACT XVIII Meeting June 4, 2015, Washington, DC
Sarrit Kovacs, Ph.D.
Clinical Outcome Assessments Reviewer
COA Staff/OND/CDER/FDA

2. Disclaimer
The views expressed in this presentation are those of the speaker, and do not necessarily represent an official FDA position.

3. Clinical outcome assessments (COAs)
Overview
Clinical outcome assessments (COAs)
Types
Modes of administration
FDA Review of Electronic COAs (eCOAs)
Regulations governing electronic data capture
Guidance for Industry
Regulatory standards
Other guidelines

4. Clinical Outcome Assessments (COAs)
COAs include:
Patient-Reported Outcome (PRO)
Clinician-Reported Outcome (ClinRO)
Observer-Reported Outcome (ObsRO)
Performance Outcome (PerfO)
Electronic data capture principles and considerations discussed focus on COA data collection intended to support primary or secondary endpoints in clinical trials
But may apply to other types of data collection as well

5. Modes of Administration of COAs
Paper
Electronic
Interactive Voice Response System (IVRS)
Web- or browser-based
Tablet
Personal device (e.g., smartphone)

6. Some Advantages of Electronic Over Paper
Less risk of data error (less human error)
Direct transmission of electronic data may reduce risk to data integrity
Less risk of missing data
Potential for greater patient compliance (alarms, date/time stamps)

7. FDA Review of Electronic COAs (eCOAs)
Just as with paper COAs, documentation of development and validation of eCOAs is needed for review of evidence to support labeling claims
FDA’s PRO Guidance describes good measurement principles for developing PROs, some may be applicable to other COA types
Provides an optimal approach; both flexibility and judgment are necessary to meet practical demands of drug development
With eCOA, additional documentation may be important to review, such as:
Design features
Usability testing
Training materials for use of the device
Documentation related to reformatting from paper to electronic

8. Device-Specific Regulatory Issues
Comparability of data obtained via different collection formats
BYOD (patient’s personal device) versus site-provided device
Device should be available to entire enrolled population
Assure that replacement devices available in case of device failure or lost device (avoid missing data)
Data entry date/time stamp documentation

9. Data-Related Regulatory Issues
Sponsors and investigators must ensure that FDA regulatory requirements are met for record keeping, maintenance, and access
These responsibilities are independent of method used to record data (paper/electronic)
Sponsors should establish appropriate system and security controls
Sponsors should establish database backup
Sponsors should take steps to avoid premature or unplanned access to unblinded data

10. Who Controls the Data?
Direct control over source data should be maintained by investigator so that verification of source data can occur at the time of FDA inspection. (Avoid source document control by sponsor exclusively)
The clinical trial protocol (or another document) should specify how the eCOA source data will be maintained and how the investigator will meet the regulatory requirements.

11. Audit Trails
Direct eCOA data transmission from the eCOA data collection device to the sponsor, clinical investigator, or other 3rd party must include an electronic audit trail that documents all changes to the data after it leaves the electronic data collection device.

12. Available FDA Guidance for Industry on EDC
FDA’s PRO Guidance
Describes specific concerns when using electronic instruments; sponsor and investigator responsibilities; things to avoid
Computerized Systems Used in Clinical Investigations
“provides to sponsors, CROs, data management centers, clinical investigators, and IRBs, recommendations…applies to records in electronic form that are used to create, modify, maintain, archive, retrieve, or transmit clinical data required to be maintained or submitted to the FDA”
Electronic Source Data in Clinical Investigations
“…recommendations to sponsors, CROs, clinical investigators, and others…ensuring the reliability, quality, integrity, and traceability of data from electronic source to electronic regulatory submission”
These two latter guidance documents are to be used together.

13. FDA Regulatory Standards, and Other Guidelines Addressing EDC
21 CFR Part 11 “Electronic Records; Electronic Signatures”
Criteria under which FDA considers electronic records/signatures to be trustworthy, reliable, generally equivalent to paper records
Requires FDA-regulated sponsors to implement controls, system validations, audit trails, authority checks, electronic signatures, and device and system checks
21 CFR Parts 312 (drugs) and 812 (devices)
Regulations apply equally to both paper records and electronic records
General and specific responsibilities for sponsors and investigators
Record keeping, maintenance, monitoring, and allowing FDA access/investigation
ICH Guideline for Good Clinical Practice E6 (R1) - Section 5.5.3

14. References and Links
Coons SJ, Gwaltney CJ, Hays RD, Lundy JJ, Sloan JA, Revicki DA, Lenderking WR, Cella D, Basch E; ISPOR ePRO Task Force. Recommendations on evidence needed to support measurement equivalence between electronic and paper-based patient-reported outcome (PRO) measures: ISPOR ePRO Good Research Practices Task Force report. Value Health Jun;12(4):
Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims
Guidance for Industry: Computerized Systems Used in Clinical Investigations
Guidance for Industry: Electronic Source Data in Clinical Investigations

15. References and Links cont’d.
21 CFR Part 11 “Electronic Records; Electronic Signatures”
21 CFR Part 312 (INDs)
21 CFR Part 812 (Devices)
ICH Guideline for Good Clinical Practice E6 (R1)
ePRO Consortium

16. Backup Slides

17. FDA Review of Electronic COAs (eCOAs)
Considerations when reformatting an existing paper COA to electronic mode of administration:
These switches are evaluated as a modified instrument
Cognitive debriefing can be used to ensure the content validity of the COA is not altered when switching the mode. Some things that will likely change are:
One item per screen vs. multiple items on a page
Skip patterns
Alarms
Forced response
New respondent instructions and training materials

18. Type of Additional Testing Depends on Size of Change
Coons SJ, Gwaltney CJ, Hays RD, Lundy JJ, Sloan JA, Revicki DA, Lenderking WR, Cella D, Basch E; ISPOR ePRO Task Force. Recommendations on evidence needed to support measurement equivalence between electronic and paper-based patient-reported outcome (PRO) measures: ISPOR ePRO Good Research Practices Task Force report. Value Health Jun;12(4):
- Adapted from Shields A, Gwaltney C, Tiplady B, et al. Grasping the FDA’s PRO Guidance. Appl Clin Trials 2006;15:69–72.