Roadmap to Patient-Focused Outcome Measurement in Clinical Trials (text version)
Step One: Understanding the disease or Condition
A. Natural history of the disease or condition
- Onset/Duration/Resolution
- Diagnosis
- Pathophysiology
- Range of manifestations
B. Patient subpopulations
- By severity
- By onset
- By comorbidities
C. Healthcare environment
- Treatment alternatives
- Clinical care standards
- Healthcare system perspective
D. Patient/caregiver perspectives
- Definition of treatment benefit
- Benefit-risk tradeoffs
- Impact of disease
Step Two: Conceptualizing the Treatment Benefit
A. Identify concept(s) of interest (CoI) for meaningful treatment benefit:
- Survival
- Feelings
- Functioning
B. Define the context of use (CoU) for clinical trial:
- Disease/Condition entry criteria
- Clinical trial design
- Statistical analysis plan
C. Select clinical outcome assessment (COA) type:
- PRO
- ObsRO
- ClinRO
- Performance Outcome (motor, sensory, cognition)
Step Three: Selecting/Developing the Outcome Measure
A. Search for existing COA measuring COI in COU:
- Measure exists
- Measure exists but needs to be modified
- No measure exists
- Measure under development
B. Begin COA development
- Document content validity (qualitative or mixed methods research)
- Evaluate cross-sectional measurement properties (reliability and construct validity)
- Create a user manual
- Consider submitting to FDA for COA qualification for use in exploratory studies
C. Complete COA development:
- Document longitudinal measurement properties (construct validity, ability to detect change)
- Document guidelines for interpretation of treatment benefit and relationship to claim
- Update the user manual
- Submit to FDA for COA qualification as effectiveness endpoint to support claims