Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims

Status: Final

Date: December 2009

Laws and Regulations:

Record keeping, maintenance, and access – 21 CFR Part 312 (for drugs and biologics) and 21 CFR Part 812 (for medical devices)

21 CFR Part 11 – defining the regulatory requirements for use of computerized systems. When creating and using PRO instruments, sponsors must ensure the methods of collecting data are in compliance with these regulations.


This guidance provides guidelines for the development and testing of instruments used for collecting, measuring, and assessing patient-reported outcomes (PRO) that support labeling and promotional claims. Specifically, the guideline is written to inform sponsors of how the FDA evaluates the PRO instruments developed for use in clinical trials, and it outlines the FDA’s expectations of the evidence that must be submitted to verify the validity and reliability of the PRO instrument. A PRO instrument must be shown to be a credible measure of the claim being made.

PRO instruments are designed to capture the patients’ perspective on the effectiveness of the medical product or intervention for aspects that can only be reported by the patient. Questionnaires and diaries are examples of PRO instruments used in clinical trials.


Sponsors must demonstrate that the PRO instruments used for the collection of patient-reported outcomes to support a claim of a treatment benefit have been tested and validated for both content and design and are able to effectively measure the particular concept being tested. In selecting a PRO instrument, the sponsor must evaluate whether the instrument is capable of measuring the concepts of interest in the target population. In making these evaluations, the content and design of the PRO instrument must be validated and tested to show that the results are reliable and reproducible and are able to detect change. General considerations for content and design include the type and number of questions to include, recall period (timeframe the patients are instructed to consider when answering the questions), response options (visual analog scale, Likert scale, pictorial scale, checklist), and scoring methods for items or domains.

The FDA recommends that sponsors apply the same design principles that are followed for other endpoint measures to the PRO endpoints. For example, sponsors are expected to establish procedures to ensure consistency (instructions for administration of questionnaires) and to develop methods to minimize unintentional unblinding and for handling missing data to minimize bias. The guidance also includes a section on statistical considerations for analyzing the data collected with the PRO instruments.


The guidance helps the sponsor understand the expectations of the FDA for patient-reported outcome data when the data is used for labeling claims. Following the guidelines for the development of the PRO instruments provides a sponsor with greater assurances that the data collected will be acceptable to the FDA and can be used to support labeling claims.

For more information on this issue, contact the Kulkarni Law Firm.