Contains Nonbinding Recommendations 
 
 
 
Principles for Selecting, Developing, 
Modifying, and Adapting Patient-
Reported Outcome Instruments for 
Use in Medical Device Evaluation 
______________________________________________________________________________ 
Guidance for Industry and 
Food and Drug Administration Staff, 
And Other Stakeholders 
 
Document issued on January 26, 2022. 
 
The draft of this document was issued on August 31, 2020. 
 
 
For questions about this document, contact the Patient Science and Engagement Program, Office 
of Strategic Partnerships and Technology Innovation (OST) by email at CDRH-
PRO@fda.hhs.gov.  For questions about this document regarding CBER-regulated devices, 
contact the Office of Communication, Outreach, and Development (OCOD) at 1-800-835-4709 
or 240-402-8010.  
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
Center for Biologics Evaluation and Research  
  Contains Nonbinding Recommendations 
 
 
 
Preface 
 
 
Public Comment 
 
You may submit electronic comments and suggestions at any time for Agency consideration to  
https://www.regulations.gov. Submit written comments to the Dockets Management Staff, Food  
and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852.  
Identify all comments with the docket number FDA-2020-D-1564. Comments may not be acted  
upon by the Agency until the document is next revised or updated. 
 
Additional Copies 
 
CDRH 
Additional copies are available from the Internet. You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance.  Please include the document 
number 18042 and complete title of the guidance in the request. 
 
CBER 
Additional copies are available from the Center for Biologics Evaluation and Research (CBER), 
Office of Communication, Outreach, and Development (OCOD), 10903 New Hampshire Ave., 
Bldg. 71, Room 3128, Silver Spring, MD 20993-0002, or by calling 1-800-835-4709 or 240-402-
8010, by email, ocod@fda.hhs.gov or from the Internet at https://www.fda.gov/vaccines-blood-
biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances. 
 
 
 
 
  Contains Nonbinding Recommendations 
 
 
 
Table of Contents
 
I.  Introduction ............................................................................................................................. 1 
 
II.  Background ............................................................................................................................. 2 
III.  Scope .................................................................................................................................... 4 
IV.  General Considerations for PRO Instrument use in Medical Device Evaluation ................ 4 
V.  Best Practices for Least Burdensome Selection, Development, Modification and Adaptation 
of Patient-Reported Outcome Instruments...................................................................................... 5 
VI.  Summary ............................................................................................................................ 10 
VII.  Glossary ............................................................................................................................. 11 
 
 
  Contains Nonbinding Recommendations 
 
 
 
Principles for Selecting, Developing, 
Modifying and Adapting Patient-
Reported Outcome Instruments for 
Use in Medical Device Evaluation
 
______________________________________________________________________________ 
Guidance for Industry and 
Food and Drug Administration Staff, 
and Other Stakeholders 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on 
FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
or Office responsible for this guidance as listed on the title page.  
 
I.  Introduction 
The U.S. Food and Drug Administration (FDA or the Agency) encourages the collection, 
analysis, and integration of patient perspectives in the development, evaluation, and surveillance 
of medical devices. Patients perspectives on living with their health condition and its treatment 
or management are most useful in medical device evaluation when they are relevant to the 
regulatory decision and reliably measured.1 Patient-reported outcome (PRO) instruments 
facilitate the systematic collection of how patients feel, function, and survive as valid scientific 
evidence to support the regulatory and healthcare decision-making process.2  By integrating 
patients voices throughout the total product life cycle (TPLC), concepts important to patients 
can be considered in the evaluation and surveillance of medical devices. 
 
 
1  For more information, see FDAs guidance Patient Preference Information-- Voluntary Submission, Review in 
Premarket Approval Applications, Humanitarian Device Exemption Applications, and De Novo Requests, and 
Inclusion in Decision Summaries and Device Labeling, available at: https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/patient-preference-information-voluntary-submission-review-
premarket-approval-applications.  
2 For more information see FDAs guidance Patient-Reported Outcome Measures: Use in Medical Product 
Development to Support Labeling Claims, available at https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims 
1  Contains Nonbinding Recommendations 
 
 
 
The objectives of this guidance3 are to: 
 
1.  Describe principles that may be considered when using PRO instruments in the 
evaluation of medical devices (Section IV); 
2.  Provide recommendations about the importance of ensuring the PRO instruments are fit-
for-purpose (Section IV), and; 
3.  Outline best practices to help ensure relevant, reliable, and sufficiently robust PRO 
instruments are developed, modified, or adapted using the least burdensome approach 
(Section V).  
 
This guidance is not meant to replace the Patient-Focused Drug Development (PFDD) guidance 
series, led by FDAs Center for Drug Evaluation and Research (CDER) and CBER.4 
 
The contents of this document do not have the force and effect of law and are not meant to bind 
the public in any way, unless specifically incorporated into a contract. This document is intended 
only to provide clarity to the public regarding existing requirements under the law. FDA 
guidance documents, including this guidance, should be viewed only as recommendations, unless 
specific regulatory or statutory requirements are cited. The use of the word should in Agency 
guidance means that something is suggested or recommended, but not required. 
 
II.  Background 
PRO instruments allow for the collection of certain data as valid scientific evidence of safety 
and/or effectiveness which is complementary to other evidence of clinical outcomes and/or 
biomarkers. Use of PRO instruments is generally voluntary but may be specifically 
recommended in certain standards and guidances. PRO instruments can include patient diaries, 
visual analog and numeric rating scales (e.g., measures of pain severity), symptom measures, as 
well as multi-item, multidomain questionnaires measuring aspects of health-related quality of life 
(HRQOL).5 A PRO can be measured by self-report or by an interview, provided that the 
interviewer records only the patients response.6 Symptoms and unobservable concepts known 
only to the patient (e.g., pain intensity and anxiety level) can be measured using PRO 
instruments. A PRO instrument can be used in clinical studies to measure the effects of a medical 
intervention or changes in the health status of a patient.  
 
 
3 This guidance is intended to improve the regulatory predictability and impact of PROs, as noted in the Patient 
Engagement and the Science of Patient Input section of the Medical Device User Fee Amendments (MDUFA IV). 
For more information, see the MDUFA IV Commitment Letter, pg. 16 Section 3a-c: 
https://www.fda.gov/media/100848/download.  The term bridging studies listed in Section 3c refers to 
modification and adaptation of PRO instruments. 
4 For more information, please see the FDA Patient-Focused Drug Development Guidance Series website:  
https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-guidance-
series-enhancing-incorporation-patients-voice-medical  
5 It is important to note that HRQOL is a multidimensional measure of the health and treatment experience of the 
patient, generally involving physical, social, and emotional domains and should not be used interchangeably with 
the term PRO, which is broader. 
6 See Footnote 2. 
2  Contains Nonbinding Recommendations 
 
 
 
FDA has produced several resources to assist the sponsor in selecting, modifying or developing a 
PRO instrument. These include the guidance entitled, Patient-Reported Outcome Measures: Use 
in Medical Product Development to Support Labeling Claims;7 the series of guidance 
documents and other resources related to Patient-Focused Drug Development;8 and the following 
resources that were posted to FDAs website as part of CDRHs 2016-2017 Strategic Priorities: 
Value and Use of Patient-Reported Outcomes (PROs) in Assessing Effects of Medical 
Devices,9 COA Case Studies,10 and PRO Compendium.11 The COA Case Studies include 
examples of PRO instruments used to support medical device regulatory submissions and the 
PRO Compendium lists some, but not all, of the PRO instruments that have been used and 
publicly reported in medical device premarket clinical investigations across a wide variety of 
devices and indications.  
 
In addition, PRO instruments have been qualified under the Medical Device Development Tools 
(MDDT) program as tools that medical device sponsors can use in the development and 
evaluation of medical devices. Qualification under the MDDT program means CDRH has 
evaluated the tool and concurs with available supporting evidence that the tool produces 
scientifically-plausible measurements and works as intended within the specified context of 
use.12  
 
With the development of novel technologies and novel uses for existing technologies, it is 
important that outcomes important to patients are measured and included in medical device 
submissions, when appropriate. As part of providing valid scientific evidence to assess the safety 
and/or effectiveness of medical devices, PRO instruments can measure the impact of medical 
devices on patient well-being and other concepts that may influence healthcare providers and 
patients when making decisions about potential treatments or management options.     
 
FDA believes that information from well-defined and reliable PRO instruments13 can provide 
valuable evidence for benefit-risk assessments, and can be used in medical device labeling to 
communicate the effect of a treatment on patient symptoms, functioning or HRQOL, when the 
use is consistent with the PRO instruments documented and supported measurement properties. 
The Agency recognizes there are many ways PRO instruments can be used across the TPLC, 
 
7 See Footnote 2. 
8 For more information see FDAs Patient Focused Drug Development website on the guidance and discussion guide 
series https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-development-
guidance-series-enhancing-incorporation-patients-voice-medical. 
9 https://www.fda.gov/media/109626/download  
10 https://www.fda.gov/about-fda/cdrh-patient-science-and-engagement-program/clinical-outcome-assessments-
coas-medical-device-decision-making 
11 https://www.fda.gov/media/109629/download  
12 See FDAs guidance Qualification of Medical Device Development Tools, available at  
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/qualification-medical-device-
development-tools.  See also FDAs website for a listing of qualified MDDT: https://www.fda.gov/medical-
devices/science-and-research-medical-devices/medical-device-development-tools-mddt. 
13 For brevity, the text of this guidance does not distinguish between the PRO instrument and the score(s) that result 
from the administration and scoring of the PRO instrument. Instead, references to instructions, administration 
materials, content, formatting, and scoring rules should be interpreted as based on the instrument. References to the 
psychometric properties, such as reliability, should be interpreted as a properties of the score(s) they are based on.  
3  Contains Nonbinding Recommendations 
 
 
 
including early feasibility, feasibilty, pivotal, and postmarket clinical studies. For example, PRO 
instruments may be used to help determine a patients eligibility for inclusion within a study, to 
measure primary or secondary safety and/or effectiveness endpoints, either as a stand-alone or as 
a component of a composite endpoint. PRO instruments also may be valuable early in the design 
and development of a device and in postmarket surveillance efforts such as registries. When data 
from a PRO instrument is used in the evaluation of a medical device, FDA determines the 
validity evidence needed to support the PRO instruments specified use for a regulatory purpose.  
FDA uses the term fit-for-purpose to describe this flexible approach.14   
   
III.  Scope 
FDA intends the principles outlined in this guidance to apply to PRO instruments used in 
medical device evaluation across the TPLC. This guidance is intended to supplement the 
aforementioned resources by outlining recommended best practices for developing relevant, 
reliable, and sufficiently robust PRO instruments using the least burdensome approach. This 
guidance document does not detail the methods and steps of developing, modifying, or adapting 
a PRO instrument. Instead, it communicates what FDA believes are some of the best practices 
for selecting, developing, and modifying PRO instruments for use in medical device evaluation. 
A glossary is also included as an Appendix to clarify terminology.   
 
IV.  General Considerations for PRO Instrument use in 
Medical Device Evaluation 
  Key Principles  
FDA believes the following principles are important to consider when incorporating PRO 
instruments into the evaluation of the TPLC of medical devices:  
 
1.  Establish and define the concept of interest (COI) the PRO instrument is intended 
to capture;  
2.  Clearly identify the role of the PRO (e.g., primary, secondary, ancillary, 
effectiveness, safety) in the clinical study protocol and statistical analysis plan;  
3.  Provide evidence showing that the PRO instrument reliably assesses the COI; and  
4.  Effectively and appropriately communicate the PRO-related results in the labeling 
to inform healthcare provider and patient decision making.   
 
  Importance of ensuring PRO Instruments are fit-for-
purpose  
 
14 See Section VII for glossary. BEST Glossary, FDA-NIH Biomarker Working Group. BEST (Biomarkers, 
Endpoints, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. 
Glossary. 2016 Jan 28 [Updated 2018 May 2]. Co-published by National Institutes of Health (US), Bethesda (MD). 
https://www.ncbi.nlm.nih.gov/books/NBK338448/. 
4  Contains Nonbinding Recommendations 
 
 
 
PRO instruments that are fit-for-purpose should be used for a specific context of use 
(COU). FDA believes three factors should be considered when selecting a PRO 
instrument that is fit for purpose: 
 
1.  Is the concept being measured by the PRO instrument meaningful to patients and 
would a change in the concept of interest be meaningful to patients? 
2.  What role (e.g., primary, secondary, ancillary, effectiveness, safety) will the PRO 
instrument serve in the clinical study protocol and statistical analysis plan? 
3.  Does the evidence support the PRO instruments use in measuring the COI as 
specified in the clinical study protocol and statistical analysis plan?  
 
A key consideration when assessing whether a PRO instrument is fit-for-purpose for a 
particular COU is the population in which the validity evidence was generated.15  The  
population in which the validation work was performed should be consistent with the 
intended use population in the clinical study protocol. By assessing the similarities and 
differences between the population in the clinical study and in the development of the 
PRO instrument, FDA can determine whether the PRO instrument is fit-for-purpose.16 
For example, patients with late-stage disease may have different symptoms or 
perspectives than patients in the early stage. Hence, the items on the PRO instrument 
developed in early stage patients may not be applicable to patients experiencing later 
stages of the disease. Additionally, PRO instruments should not include items that could 
be misinterpreted or that are not applicable to the intended use population.   
 
V.  Best Practices for Least Burdensome Selection, 
Development, Modification and Adaptation of Patient-
Reported Outcome Instruments 
  Measure Concepts Important to Patients 
One purpose of using PRO instruments should be to assess outcomes that matter to 
patients; however, not all PRO instruments used in clinical studies accomplish this goal.  
Incorporating outcomes that reflect patient priorities in the clinical study protocol can 
help to seamlessly integrate factors included in a patients decision-making process into 
FDAs benefit-risk determinations.17 Assessing outcomes that patients find meaningful 
 
15 See Footnote 2. 
16 For more information on methods used to gather comprehensive input from patients, please see  Patient-Focused 
Drug Development: Collecting Comprehensive and Representative Input. Guidance for Industry, Food and Drug 
Administration Staff, and Other Stakeholders available at https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/patient-focused-drug-development-collecting-comprehensive-and-representative-input. While 
the scope of this guidance is currently limited to drugs, we believe the recommendations are also applicable to 
medical device development and evaluation.  
17FDA has several guidances on benefit-risk determinations. Please see Factors to Consider When Making Benefit-
Risk Determinations for Medical Device Investigational Device Exemptions, available at: 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/factors-consider-when-making-benefit-
 
5  Contains Nonbinding Recommendations 
 
 
 
may reduce the collection of less important PROs, thereby limiting the unnecessary 
burden on patients. Ultimately, including outcomes of importance to patients 
appropriately in the medical device labeling may help inform patient and healthcare 
provider conversations about treatment or management options.   
 
During PRO instrument development or selection, effective engagement,18 concept 
elicitation interviews, and cognitive interviews with patients can help ensure that the 
COIs intended to be measured by a PRO instrument are important to the daily lived 
experience of patients and could be useful to inform their future decisions regarding the 
use of the medical device. Concept elicitation interviews identify or confirm the 
concept(s) measured by the PRO instrument as well as what aspects of the concept are 
most important to the patients, such as the frequency, severity, and/or interference with 
daily life. For example, pain is a concept and the aspects that may be most important to 
patients are its severity and how it interferes with daily life. 
  Ensure Patient-Reported Outcome Instruments are 
Understandable to Patients 
The elements of a PRO instrument include the instructions, items, recall period, and 
response options. FDA recommends that these elements be composed using plain 
language to help ensure that patients with varying levels of overall literacy and health 
literacy understand and are able to provide informed responses. In addition, using 
appropriate benchmarks (e.g., a point of reference against which things may be compared 
or assessed), activities, or symptom wording may facilitate patients being able to 
accurately report their health status. For example, a sponsor may be interested in 
assessing visual function. The concept may be measured with items assessing difficulties 
patients have with activities they may do in everyday life such as reading books, menus, 
and labels on medicine bottles. FDA recommends conducting cognitive interviews to 
generate evidence supporting the wording of these elements.    
The response options to the items should be consistent with the wording of the item. For 
example, if the frequency of itching was identified through the concept elicitation 
interviews as important, then the response options should be measures of frequency (e.g., 
 
risk-determinations-medical-device-investigational-device. Please see Factors to Consider When Making Benefit-
Risk Determinations in Medical Device Premarket Approval and De Novo Classifications, available at:  
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/factors-consider-when-making-benefit-
risk-determinations-medical-device-premarket-approval-and-de. Please see Factors to Consider Regarding 
Benenfit-Risk in Medical Device Product Availability, Compliance, and Enforcement Decisions, available at: 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/factors-consider-regarding-benefit-
risk-medical-device-product-availability-compliance-and. Please see Benefit-Risk Factors to Consider When 
Determining Substantial Equivalence in Premarket Notifications (510(k)) with Different Technological 
Characteristics, available at:  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/benefit-
risk-factors-consider-when-determining-substantial-equivalence-premarket-notifications-510k.  
18 See FDAs guidance Patient Engagement in the Design and Conduct of Medical Device Clinical Studies, 
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-engagement-
design-and-conduct-medical-device-clinical-studies. 
6  Contains Nonbinding Recommendations 
 
 
 
never, rarely, sometimes, often, always) and the wording for the response options and 
items confirmed using cognitive interviews.19 These interviews should be conducted 
prior to using a PRO instrument to collect outcomes in a clinical study. Technologies 
such as tele- or videoconferencing may facilitate conducting cognitive interviews, 
allowing diverse patient feedback on the interpretation of the PRO instrument elements. 
FDA encourages sponsor interactions through the voluntary Q-submission program20 
with the relevant review offices and the Patient Science and Engagement Program21 to 
help determine the appropriateness of the cognitive interview approach.  
FDA recommends that sponsors consider offering PRO instruments in different 
languages, where appropriate, in order to measure the patient experience in patients with 
limited English language proficiency. FDA believes that collecting PRO data from all 
patients, including those with limited English language proficiency and health literacy, 
can help ensure that the clinical study findings are generalizable to the intended use 
population. Moreover, adequate patient interpretation of the questionnaire items may help 
minimize missing data, improve the consistency of item interpretation, and potentially 
improve the data collected in the clinical study. 
 
FDA recommends that sponsors also consider the impact on patients in responding to 
PRO instruments with the goal of reducing unnecessary burden. For example, sponsors 
may choose to use a well-developed short form version of a PRO instrument when 
available.   
  Be Clear About the Role of PRO Instrument in the 
Clinical Study Protocol and Statistical Analysis Plan 
FDA determines the strength of evidence needed to support the measurement properties 
of a PRO instrument based on the role of the instrument specified in the clinical study 
protocol and statistical analysis plan. For example, a PRO instrument used to measure a 
secondary effectiveness endpoint may need different validity evidence22 than a PRO 
instrument used to descriptively assess a safety endpoint.    
 
 
19 See FDAs PFDD Guidance Public Workshop Discussion Guide 2 Methods to Identify What is Important to 
Patients  & Select, Develop or Modify Fit-for-Purpose Clinical Outcomes Assessments available at  
https://www.fda.gov/media/116276/download  
20 The Q-Submission Program is used by sponsors and FDA to discuss certain questions relating to a submission 
(current or future) with review offices and/or broader device programs. For more information on the process for 
requesting feedback or meetings with FDA for medical device submissions, see FDAs guidance Requests for 
Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, available at: 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-
medical-device-submissions-q-submission-program. 
21 For more information, please see the CDRH Patient Science and Engagement Program website: 
https://www.fda.gov/about-fda/center-devices-and-radiological-health/cdrh-patient-science-and-engagement-
program. 
22 Different validity evidence may refer to different types of evidence, different quality of evidence, and/or different 
amounts of evidence. 
7  Contains Nonbinding Recommendations 
 
 
 
FDA believes the COI and COU in which a PRO instrument is used should be clearly 
conveyed in the clinical study protocol and the statistical analysis plan. As such, FDA 
recommends that the COI be clearly defined by a statement of what is being measured, 
how it is being measured and interpreted, and how the results will be communicated in 
the labeling. Similarly, FDA recommends that the COU describe the specific role of the 
PRO instrument in the medical device development and evaluation process, which 
includes defining what endpoint the PRO instrument is being used to capture in the 
clinical study (e.g., safety versus effectiveness, primary versus secondary versus 
ancillary) and an estimate of the amount of change measured by the PRO instrument that 
is clinically meaningful.23 The sponsor should plainly state and clearly identify the PRO 
instruments COU in the clinical study protocol and statistical analysis plan. For example, 
pain intensity as the concept, reduction in pain intensity as the primary effectiveness 
outcome with the endpoint being a specified reduction in the pain intensity scale score at 
three months compared to baseline.  
 
FDA encourages sponsors to engage FDA throughout the TPLC of the device.  During 
the study design stage, prior to the Investigational Device Exemption (IDE) submission 
or conducting of the pivotal study,24 sponsors are encouraged to engage FDA regarding 
the relevance and suitability of a proposed PRO instrument to the benefit-risk assessment. 
The Q-Submission process should be used to obtain feedback per the FDA guidance 
Requests for Feedback and Meetings for Medical Device Submissions: The Q-
Submission Program.25  
When presenting results from a clinical study which includes a PRO instrument in a 
medical device submission, the sponsor should confirm that the concept measured by the 
PRO instrument matches the COI stated in the COU, and that the specified change in the 
PRO instrument is clinically meaningful. Sponsors should consider clearly identifying the 
location of this information within the application. Examples of the way PRO instruments 
have been used in FDA submissions can be found in the COA Case Studies resource on 
the FDA website.26 
  Leverage Existing PRO Instruments and Validity 
Evidence 
Sponsors often choose to select from existing PRO instruments rather than develop a new 
PRO instrument. Existing PRO instruments can be used as-is, modified, or adapted, 
which is often less resource intensive than creating a new PRO instrument due to the 
 
23 See FDAs PFDD Guidance 3 Public Workshop Discussion Guide Methods to Identify What is Important to 
Patients  & Select, Develop or Modify Fit-for-Purpose Clinical Outcomes Assessments, available at 
https://www.fda.gov/media/116277/download.  
24 See FDAs guidance Design Considerations for Pivotal Clinical Investigations for Medical Devices, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/design-considerations-pivotal-clinical-
investigations-medical-devices. 
25 See https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-
meetings-medical-device-submissions-q-submission-program. 
26 See Footnote 10. 
8  Contains Nonbinding Recommendations 
 
 
 
ability to leverage existing validity evidence. Modifying27 or adapting an existing PRO 
instrument may be a least burdensome approach for a new COU. FDA encourages the 
modification or adaptation of existing PRO instruments where it is feasible and such an 
approach would still result in a relevant and reliable PRO instrument for the COU. When 
modifications are made to an existing PRO instrument for use in a clinical study, we 
recommend that the modifications be clearly described in the documentation 
accompanying the submission (e.g., PRO dossier or appendix). It would also be helpful to 
note existing publications or data demonstrating the use and/or supporting the validity of 
the modified PRO instrument. New evidence may be needed to support the validity, 
depending on the extent of modification made. 
 
FDA recommends reviewing peer-reviewed literature as a starting point for identifying 
the validity evidence associated with the development, use, or evaluation of the PRO 
instrument of interest while keeping in mind that PRO instruments should reflect 
contemporary activities of daily life. Accordingly, PRO instruments historically used to 
assess patient functioning may not adequately reflect functioning in the present due to 
technological advances that may facilitate the performance of certain tasks. Modification 
of the items may be needed to ensure a given COI is still adequately being measured. To 
modify the PRO instrument, the sponsor may conduct supplementary cognitive 
interviews and construct new items as needed to adequately capture the COI. Sponsors 
are encouraged to engage in discussion with FDA through the Q-submission process 
regarding the approach to modifying or adapting an existing PRO instrument.     
  Consider Alternative Platforms and Parallel Development 
for Generating Validity Evidence for PRO Instruments 
Real-world evidence derived from multiple sources outside of the clinical research setting 
(such as electronic health records, claims and billing activities, product and disease 
registries, or health-monitoring devices) may be used to generate validity evidence for 
PRO instruments. With the proliferation of real-world data (RWD), it is possible that 
PRO instrument development could be nested in a RWD source.28 Professional 
organization and patient-driven registries may also help identify patients and facilitate 
generation of validity evidence. FDA encourages sponsors to consider these alternative 
approaches to generate validity evidence for PRO instruments as potentially less 
burdensome approaches.   
 
Sponsors proactively developing or modifying PRO instruments for use in future product 
development may want to also consider using early feasibility, phased clinical studies, 
pivotal clinical studies, postmarket clinical studies, and/or real-world data platforms to 
collect and generate quantitative validity evidence. Such an approach of using the parallel 
 
27 Modification may change the properties of the PRO instrument such that new evidence would be needed to 
evaluate the properties of the modified PRO instrument. 
28 See FDAs guidance Use of Real-World Evidence to Support Regulatory Decision-Making for Medical 
Devices,  available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-real-world-
evidence-support-regulatory-decision-making-medical-devices    
9  Contains Nonbinding Recommendations 
 
 
 
development work may be more efficient and cost effective than conducting a sequential, 
separate PRO instrument validation study. In addition, a separate study done in tandem 
with a pivotal clinical study may be needed to confirm particular measurement properties 
of a PRO instruments score. It is possible that a tandem study may not support the 
intended use of the instrument. When choosing any of these options, sponsors should 
prospectively specify in the clinical study protocol and statistical analysis plan the intent 
to generate quantitative validity evidence for the PRO instrument.   
 
Sponsors should note that generating validity evidence as part of the pivotal clinical study 
does not mean the PRO instruments can be used to support specific statements regarding 
safety and/or effectiveness in that pivotal study, in the labeling, or in public summaries. 
Instead, the validity evidence may support the PRO instruments use in future clinical 
studies, including postmarket studies.      
  Collaborate with Others in the Pre-Competitive Space 
Where possible and appropriate, FDA encourages sponsors and other stakeholders to 
work together in the pre-competitive space to develop, modify, or adapt a PRO 
instrument for use in regulatory submissions. Sponsors are encouraged to consider 
relevant stakeholders for potential collaborations, including but not limited to, patient 
organizations, health professional organizations, and research institutions with expertise 
in PRO instrument development. Collaborative development of a PRO instrument may 
also engender broader acceptance of results due to fewer concerns about bias in assessing 
the relevant aspects of the condition or its treatment or management of patients 
(compared to customized questionnaires developed by a single sponsor). Sponsors should 
consider submitting PRO instruments for qualification under the Medical Device 
Development Tools (MDDT) Program.29  
VI.  Summary 
To further integrate patient voices throughout the TPLC of medical devices, it is important to 
consider concepts important to patients in the regulatory evaluation and surveillance of medical 
devices. Well-designed PRO instruments facilitate incorporating patient perspectives as scientific 
evidence to support regulatory and healthcare decision-making. 
  
FDA believes that the recommendations outlined in this guidance will help ensure that PRO 
instruments are developed, modified, adapted, and used in the evaluation of medical devices in 
ways that generates relevant, reliable and sufficiently robust data to assess outcomes of 
importance to patients, regulators, and healthcare providers.   
 
 
29See FDAs guidance Qualification of Medical Device Development Tools, available at  
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/qualification-medical-device-
development-tools.  See also FDAs website for a listing of qualified MDDT: https://www.fda.gov/medical-
devices/science-and-research-medical-devices/medical-device-development-tools-mddt.  For more information, see 
Medical Device Development Tools available at https://www.fda.gov/medical-devices/science-and-research-
medical-devices/medical-device-development-tools-mddt. 
10  Contains Nonbinding Recommendations 
 
 
 
This guidance outlines flexible approaches to developing, modifying, or adapting a PRO 
instrument. FDA encourages sponsors and other stakeholders to explore other least burdensome 
approaches and discuss those approaches with FDA to help determine whether or how they can 
be applied to support regulatory submissions.  
VII. Glossary   
The following glossary is provided to clarify the meaning of terms used in this guidance 
document relating to patient-reported outcome instruments for medical device submissions. The 
terms used in this glossary have been defined in the BEST glossary, which was a joint FDA-
National Institutes of Health (NIH) effort and the guidance entitled Patient-Reported Outcome 
Measures: Use in Medical Product Development to Support Labeling Claims, unless otherwise 
noted. These terms are not intended to be applied in any context beyond this guidance. 
Understanding that terminology in this field may change over time, we intend to publish this 
glossary on our website and update it periodically. 
Adaptation  Any change made to the test that has been translated into the language of a target 
group and that takes into account the nuances of the language and the culture of the group.30 
Adaptation does not change the items comprising the PRO instrument but involves the transfer of 
a PRO instruments content to another mode31, language32 or population.33 Adaption studies are 
undertaken to confirm the properties of the PRO instrument in the new situation or language. 
Cognitive Interview  A cognitive interview is a type of qualitative research method used to 
determine whether the concepts and items of a PRO instrument are understood by patients as 
intended by the instrument developers.34, 35 
 
30 American Educational Research Association, American Psychological Association, National Council on 
Measurement in Education. Standards for educational and psychological testing. Washington, DC: American 
Educational Research Association; 2014. 
31 Coons SJ, Gwaltney CJ, Hays RD, et al. Recommendations on evidence needed to support measurement 
equivalence between electronic and paperbased patientreported outcome (PRO) measures: ISPOR ePRO good 
research practices task force report. Value in Health. 2009;12(4):419-429. 
32 Wild D, Grove A, Martin M, et al. Principles of good practice for the translation and cultural adaptation process 
for patientreported outcomes (PRO) measures: report of the ISPOR Task Force for Translation and Cultural 
Adaptation. Value in Health. 2005;8(2):94-104. 
33 Wild D, Eremenco S, Mear I, et al. Multinational TrialsRecommendations on the Translations Required, 
Approaches to Using the Same Language in Different Countries, and the Approaches to Support Pooling the Data: 
The ISPOR Patient-Reported Outcomes Translation and Linguistic Validation Good Research Practices Task Force 
Report. Value in Health. 2009;12(4):430-440. 
34 See FDAs Patient Focused Drug Development Guidance 2 Public Workshop Discussion documents Methods to 
Identify What is Important to Patients & Select, Develop or Modify Fit-for-Purpose Clinical Outcomes 
Assessments, available at https://www.fda.gov/media/116276/download and the Public Workshop Legislation 
Background and Glossary available at https://www.fda.gov/media/116280/download.  
35 Forsyth, B. H., & Lessler, J. T. (2011). Cognitive Laboratory Methods: A Taxonomy. In P. P. Biemer, R. M. 
Groves, L. E. Lyberg, N. A. Mathiowetz, & S. Sudman (Eds.), Measurement Errors in Surveys (Vol. 173): John 
Wiley & Sons. 
11  Contains Nonbinding Recommendations 
 
 
 
Concept Elicitation Interviews  Concept elicitation is a process to collect a holistic set of 
relevant concepts that are important to patients. Concepts can be elicited using qualitative, 
quantitative, or mixed methods.36 
Concept (also referred to as Concept of Interest [COI])  In a regulatory context, the concept 
is the aspect of an individuals clinical, biological, physical or functional state, or experience that 
the assessment (PRO instrument) is intended to capture (or reflect).37 For a PRO, the concept 
represents aspects of how patients function or feel related to a health condition or its treatment.38 
Context of Use (COU)  The context of use is a statement that fully and clearly describes the 
way the PRO instrument is used and the medical product-related purpose of its use. 
Fit-for-Purpose  A conclusion that the level of validation associated with a medical product 
development tool is sufficient to support its context of use. 
Item  An individual question, statement, or task (and its standardized response options) that is 
evaluated by the patient to address a particular concept.39 
Modification  A change in instrument content, format (including response formats), and/or 
administration conditions.40   
Patient-reported outcome (PRO)  A type of clinical outcome assessment that is based on a 
report that comes directly from the patient about the status of a patients health condition without 
interpretation of the patients response by a clinician or anyone else.41  
 
Patient-reported outcome instrument  The measure or tool used to collect the PRO. 
Questionnaire  A type of patient-reported outcome instrument that is a set of questions or 
items shown to a respondent to get answers for research purposes. Types of questionnaires 
include diaries and event logs.42 
Recall period  The period of time patients are asked to consider in responding to a PRO item or 
question. Recall can be momentary (real time) or retrospective of varying lengths.43 
Score  Any specific number resulting from the assessment of an individual, such as a raw score, 
a scale score, or a rating.44 
 
36 See Footnote 34.   
37 For additional information see Patient-Focused Drug Development Glossary, available at  
https://www.fda.gov/drugs/development-approval-process-drugs/patient-focused-drug-development-glossary.  
38 See Footnote 2. 
39 See Footnote 2. 
40 American Educational Research Association, American Psychological Association, National Council on 
Measurement in Education. Standards for educational and psychological testing. Washington, DC: American 
Educational Research Association; 2014. 
41 See Footnote 2.  
42 See Footnote 2.  
43 See Footnote 2. 
44 Adapted from American Educational Research Association, American Psychological Association, National 
Council on Measurement in Education. Standards for educational and psychological testing. Washington, DC: 
American Educational Research Association; 2014. 
12  Contains Nonbinding Recommendations 
 
 
 
Validation  The process to establish that the performance of a PRO instrument is acceptable for 
its intended purpose.   
Validity  Validity is the degree to which evidence supports the performance of a PRO 
instrument result for its intended purpose.45 
Validity Evidence  Data that supports the validity of a PRO instrument for its proposed uses.46  
 
45 American Educational Research Association, American Psychological Association, National Council on 
Measurement in Education. Standards for educational and psychological testing. Washington, DC: American 
Educational Research Association; 2014. 
46 Adapted from Kane, MT Validation. In R. L. Brennan (Ed.), Educational Measurement (4th edition).  Westport:  
American Council on Education and Praeger, 2006. 
13