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Patient-Reported Outcome Measures: Development, Implementation and Evaluation in Clinical Trials

This FDA guidance outlines the evaluation process and requirements for using Patient-Reported Outcome (PRO) instruments to support labeling claims in medical product development. A PRO is any report coming directly from patients about their health condition without interpretation by clinicians or others. The guidance applies to PRO instruments used in clinical trials to measure treatment benefits or risks.

  1. Establish and document content validity through qualitative research with target population
  2. Develop comprehensive documentation of instrument development process including:
    • Conceptual framework
    • Item generation and reduction process
    • Cognitive interviewing results
    • Measurement properties testing
  3. Create detailed protocol specifications for:
    • Administration procedures
    • Training requirements
    • Data collection methods
    • Quality control procedures
  4. Implement appropriate electronic systems with:
    • Security controls
    • Audit trails
    • Data backup procedures
    • Access controls
  5. Develop statistical analysis plan addressing:
    • Missing data handling
    • Multiplicity adjustments
    • Interpretation methods
  6. Establish procedures for:
    • Translation/cultural adaptation
    • Missing data prevention
    • Adverse event reporting
    • Data quality control
  7. Create comprehensive user manual documenting all procedures and requirements
  8. Plan for adequate demonstration of measurement properties including reliability and ability to detect change

Key Considerations

Clinical testing

  • PRO endpoints must be stated as specific clinical trial objectives
  • Clinical trial duration must be adequate to support PRO objectives
  • Frequency and timing of PRO assessments must be appropriate
  • Plans for handling missing data must be included
  • Procedures for PRO endpoint assessment before/after patient withdrawal needed
  • Adequate blinding procedures required

Human Factors

  • Patient understanding must be confirmed through cognitive interviewing
  • Respondent burden should be evaluated and minimized
  • Training materials and procedures must be well-documented
  • Administration procedures must be standardized

Software

  • Electronic PRO systems must have appropriate security controls
  • Data integrity must be maintained during network attacks/updates
  • Audit trails required for all data changes
  • Backup systems needed to prevent data loss

Cybersecurity

  • System and security controls must be established
  • Plans needed for ensuring data integrity during network attacks
  • Secure data transmission procedures required
  • Access controls must be implemented

Labelling

  • Claims must be supported by evidence from well-defined and reliable PRO instruments
  • Labeling claims must be consistent with instrument’s documented measurement capability
  • Multiple endpoints require multiplicity adjustment in analysis

Safety

  • Adverse events detected with PRO instruments must be included in trial reports
  • Safety information must be transmitted timely to clinical investigators
  • PRO instruments can measure important safety concerns if they represent symptoms best captured from patient perspective

Other considerations

  • 21 CFR part 11: Electronic Records; Electronic Signatures
  • 21 CFR 312.50, 312.58, 312.62, and 312.68: Record keeping requirements for clinical investigators and sponsors
  • 21 CFR 812.140 and 812.145: Medical device record keeping requirements

Original guidance

  • Patient-Reported Outcome Measures: Development, Implementation and Evaluation in Clinical Trials
  • HTML / PDF
  • Issue date: 2009-12-09
  • Last changed date: 2020-05-15
  • Status: FINAL
  • Official FDA topics: Medical Devices, Good Clinical Practice (GCP), Drugs, Biologics, Clinical - Medical
  • ReguVirta summary file ID: 331a47b4e359a6ab7a2d81fccb965ed2
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