This guidance document from the U.S. Food and Drug Administration (FDA) outlines the evaluation process for patient-reported outcome (PRO) instruments used in clinical trials to support labeling claims for medical products. It emphasizes the importance of PRO instruments in capturing patient perspectives on treatment effectiveness, which can complement clinician observations and physiological measures. The document covers the development, validation, and use of PRO instruments, including considerations for specific populations such as children, youth, and patients with cognitive impairments. Key aspects include: 1. **Conceptual Framework and Identification**: Developers must clearly define the concepts and domains to be measured, ensuring that the instrument accurately captures the intended concepts. 2. **Development and Creation**: The document details the steps for generating items, choosing data collection methods, recall periods, response options, and format. It also highlights the importance of patient understanding and minimizing respondent burden. 3. **Assessment of Measurement Properties**: The FDA reviews reliability, validity, ability to detect change, and interpretability of PRO instruments. This includes test-retest reliability, content-related validity, and the ability to detect meaningful changes. 4. **Modification of Existing Instruments**: Additional validation is recommended when modifying an existing instrument, especially if it is used in a new population or condition, or if there are changes in item content, format, or administration mode. 5. **Study Design Considerations**: The document discusses the importance of blinding and randomization in clinical trials, quality control measures, and strategies to minimize missing data due to patient withdrawal. The guidance aims to ensure that PRO instruments are reliable, valid, and used appropriately to support claims in medical product labeling, thereby enhancing the efficiency of product development and regulatory review processes.This guidance document from the U.S. Food and Drug Administration (FDA) outlines the evaluation process for patient-reported outcome (PRO) instruments used in clinical trials to support labeling claims for medical products. It emphasizes the importance of PRO instruments in capturing patient perspectives on treatment effectiveness, which can complement clinician observations and physiological measures. The document covers the development, validation, and use of PRO instruments, including considerations for specific populations such as children, youth, and patients with cognitive impairments. Key aspects include: 1. **Conceptual Framework and Identification**: Developers must clearly define the concepts and domains to be measured, ensuring that the instrument accurately captures the intended concepts. 2. **Development and Creation**: The document details the steps for generating items, choosing data collection methods, recall periods, response options, and format. It also highlights the importance of patient understanding and minimizing respondent burden. 3. **Assessment of Measurement Properties**: The FDA reviews reliability, validity, ability to detect change, and interpretability of PRO instruments. This includes test-retest reliability, content-related validity, and the ability to detect meaningful changes. 4. **Modification of Existing Instruments**: Additional validation is recommended when modifying an existing instrument, especially if it is used in a new population or condition, or if there are changes in item content, format, or administration mode. 5. **Study Design Considerations**: The document discusses the importance of blinding and randomization in clinical trials, quality control measures, and strategies to minimize missing data due to patient withdrawal. The guidance aims to ensure that PRO instruments are reliable, valid, and used appropriately to support claims in medical product labeling, thereby enhancing the efficiency of product development and regulatory review processes.