Contains Nonbinding Recommendations
Figure 3. Development of a PRO Instrument: An Iterative Process
i. Hypothesize Conceptual Framework
• Outline hypothesized concepts and potential claims
• Determine intended population
• Determine intended application/characteristics (type of scores,
mode and frequency of administration)
• Perform literature/expert review
• Develop hypothesized conceptual framework
• Place PROs within preliminary endpoint model
• Document preliminary instrument development
PRO
↕
Claim
v. Modify Instrument
• Change wording of items,
populations, response options, recall
period, or mode/method of
administration/data collection
• Translate and culturally adapt to
other languages
• Evaluate modifications as
appropriate
• Document all changes
ii. Adjust Conceptual
Framework and Draft
Instrument
• Obtain patient input
• Generate new items
• Select recall period, response
options and format
• Select mode/method of
administration/data collection
• Conduct patient cognitive
interviewing
• Pilot test draft instrument
• Document content validity
iii. Confirm Conceptual Framework and
Assess Other Measurement Properties
• Confirm conceptual framework with scoring rule
• Assess score reliability, construct validity, and ability to
detect change
• Finalize instrument content, formats, scoring, procedures
and training materials
• Document measurement development
iv. Collect, Analyze, and
Interpret Data
• Prepare protocol and statistical analysis plan
(final endpoint model and responder
definition)
• Collect and analyze data
• Evaluate treatment response using
cumulative distribution and responder
definition
• Document interpretation of treatment benefit
in relation to claim
C. Conceptual Framework of a PRO Instrument
The adequacy of a proposed instrument to support a claim depends on the conceptual framework
of the PRO instrument. The conceptual framework explicitly defines the concepts measured by
the instrument in a diagram that presents a description of the relationships between items,
domain (subconcepts), and concepts measured and the scores produced by a PRO instrument.
1. Concepts Measured
One fundamental consideration in the review of a PRO instrument is the adequacy of the item
generation process to support the final conceptual framework of the instrument. In some cases,
the question of what to measure may be obvious given the condition being treated. For example,
to assess the effect of treatment on pain, patients from the target population are queried about
pain severity using a single-item PRO instrument. Generally, when it is not obvious, instrument
developers initially can hypothesize a conceptual framework to support the measurement of the
concept of interest drafting the domains and items to be measured based on literature reviews
and expert opinion. Subsequently, patient interviews, focus groups, and qualitative cognitive
interviewing ensures understanding and completeness of the concepts contained in the items.
(See section III.D.1., Item Generation.)
The conceptual framework of a PRO instrument will evolve and be confirmed over the course of
instrument development as a sponsor gathers empiric evidence to support item grouping and
scores. When used in a clinical trial, the PRO instrument’s conceptual framework should again
be confirmed by the observed relationships among items and domains.
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