The Food and Drug Administration (FDA) has published a guidance document dedicated to the patient-reported outcome measures and the way they should be used in medical product development to support labeling claims. Together with the Patient Preference Information (PPI), the concept of the Patient-Reported Outcome Measures could be applied in the context of the Patient Science and Engagement Program.

It is also important to mention that due to its legal nature, the present document does not introduce any additional obligations for the parties involved, but provides additional clarifications and recommendations to be considered instead in order to achieve and sustain compliance with the applicable regulatory requirements. 

Regulatory Background 

The present document describes the way the patient-reported outcome instruments intended to be used support claims with regard to the labeling of medical devices. These instruments include questionnaires and could be used to assess the treatment benefit associated with the medical device. At the same time, the scope of the present guidance does not cover the use of such elements aside from the labeling of medical devices. The Agency also recommends considering product-specific guidelines available via the official website of the regulating authority. 

As it is stated in the guidance, by using the approach described herein, the entities interested in placing medical devices could facilitate the review process, while the data collected by using such means could be used to support claims made in the labeling.

According to the present FDA guidance, the patient-reported outcome stands for any report of the status of a patient`s health condition that comes directly from the patient, without interpretation of the patient`s response by a clinician or anyone else. The regulating authority acknowledges the importance of the information collected directly from the patients, as well as the importance of the active involvement of patients in processes and procedures related to medical devices in general. As it is stated by the Agency, the outcome could be measured either in absolute terms or as a change from a previous measure. For instance, the patient-reported outcome could be used to measure the effectiveness of the particular treatment as a part of clinical trials. Later the information collected directly from the patients could be used to support the claims made by the medical device manufacturer and reflected in labeling. The Agency recommends using the approach described herein in the context of aspects to be evaluated from the patient perspective, such as symptoms or signs. Usually, the aspects addressed in the present FDA guidance should be reflected in such sections of labeling as Indications and Usage or Clinical Studies. 

Evaluation of a Patient-Reported Outcome Instrument 

In accordance with the present FDA guidance, the evaluation of a patient-reported outcome (PRO) instrument used to support claims contained in the labeling of a medical device should cover the following aspects:

    • The population enrolled in the clinical trial,
    • The clinical trial objectives and design,
    • The PRO instrument`s conceptual framework, 


  • The PRO instrument`s measurement properties. 


Due to the nature of the instruments described herein, a party interested in placing a medical device on the market (a sponsor) shall provide duly documented evidence of patient input with the indications of the target population and conditions within the whole its development process. In the case of existing instruments, a sponsor shall justify their use in the particular case. 

One of the most important concepts related to the patient-reported outcome instruments is an endpoint model. According to the FDA guidance, an endpoint should be determined when developing the instruments and the way they should be used in the course of clinical trials. Actually, the system of endpoints should be used to evaluate the effectiveness of clinical trials, while the endpoint model describes interconnections between the concepts and endpoints.

The guidance also describes the concept of a target product profile (TPP), defined as a clinical development program summary in the context of prescribing information goals (i.e. targeted labeling claims). 

The Agency provides recommendations on the way the sponsor shall choose the particular patient-reported outcome instrument to be applied. As it is stated in the document, the planning should be commenced during the medical device development process. For this purpose, a sponsor shall evaluate the applicability of existing PRO instruments in order to determine whether some of them could be applied. Should there be no suitable PRO instrument, a new one could be developed. The Agency also mentions that such a new instrument could be based on the existing ones. According to the present guidance, when assessing the applicability of a PRO instrument, a sponsor shall consider such aspects as:

  • Characteristics, 
  • Conceptual framework,
  • Content validity,
  • Other measurement properties.

Later the regulating authority will review the information submitted in order to evaluate its admissibility. In particular, the Agency will pay attention to the following characteristics of a patient-reported outcome instrument:

  • Concepts being measured,
  • Number of items,
  • Conceptual framework of the instrument,
  • Medical condition for intended use,
  • Population for intended use,
  • Data collection method,
  • Administration mode,
  • Response options,
  • Recall period,
  • Scoring,
  • Weighting of items or domains,
  • Format,
  • Respondent burden,
  • Translation or cultural adaptation availability. 

It is advised for medical device manufacturers to ensure the accessibility of the information with regard to the patient-reported outcome instruments they are using, including the history of their development. Should such information be unavailable, a sponsor at least should provide the documents demonstrating that the PRO instrument in question works as intended and provides sufficient accuracy of the measurement. 

The development of a PRO instrument should be duly finalized before the commencement of the clinical trials. Moreover, the Agency encourages sponsors to engage the regulating authority in consultations regarding the PRO instruments starting from the development stage.

PRO Instrument Development Process

Aside from the general regulatory requirements, the present FDA guidance also describes the suggested process of development of a patient-reported outcome instrument. According to the document, such a process comprises the following steps:

  1. Formation of the initial hypothesis, including determination of the intended population, characteristics, as well as literature review and development of a hypothesized conceptual framework. 
  2. Adjustment of the conceptual framework and drafting the instrument. During this step, a sponsor shall obtain input from patients, conduct patient cognitive interviewing and conduct a pilot test by using the draft instrument. 
  3. Confirmation of the conceptual framework and assessment of other measurement properties, including the development of scoring rules, finalizing the content, format, and procedures related to the instrument, and also documenting the measurement development. 
  4. Collection, analysis, and interpretation of data. At this step, a sponsor shall prepare the appropriate protocol and statistical analysis plan, collect and analyze the data, and also evaluate the treatment response. 
  5. Modification of the instrument. A sponsor may introduce changes to the PRO instrument on the basis of the information collected when using it.

Summarizing the information provided here above, the FDA guidance on patient-reported outcome instruments describes in detail the way such instruments should be developed and applied. In particular, the document provides additional recommendations and clarifications with regards to the regulatory requirements a clinical trials sponsor shall comply with.

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