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Patient Preference Information –

Voluntary Submission, Review in PMAs, 

HDE Applications, and De Novo 

Requests and Inclusion in Decision 

Summaries and Device Labeling: Final 

Guidance

Martin Ho

Associate Director for Quantitative Innovation

Office of the Surveillance and Biometrics

Center for Devices and Radiological Health

Anindita Saha

Director of External Expertise and Partnerships

Office of the Center Director

Center for Devices and Radiological Health

September 27, 2016 Webinar www.fda.gov
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Agenda

• Provide context and overview of Patient Preference 

Information Final Guidance

• Describe key updates to the Benefit-Risk worksheet in 

the “Factors to Consider When Making Benefit-Risk 

Determinations in Medical Device Premarket Approval 

and De Novo Classifications” Guidance 

• Q&A

www.fda.gov
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CONTEXT AND SCOPE

History of the Patient Preference Initiative and Guidance Development

www.fda.gov
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Evolution of the Role of the Patient

Traditional 

Medicine: 

Provider-led 

treatment 

decision-making

Emerging 

Diseases: 

Patient advocacy 

for availability of 

and access to 

new treatments

The Internet: 

Patient 

empowerment 

through 

information

The Future Today: 

Patient-Provider 

partnership in 

treatment decisionmaking

Patient preferences 

informing regulatory 

decisions www.fda.gov
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Benefit-Risk Guidance August 2016

Factors to Consider for Benefit – Risk Determinations 

Medical Device Premarket Approval and De Novo 

Classifications

Patient perspective on risk and perspective on benefit:

“if risks are identifiable and definable, risk tolerance will vary among 

patients, and this will affect individual patient decisions as to whether the 

risks are acceptable in exchange for a probable benefit. ... FDA recognizes 

that patient perspectives on benefits and risks may reveal reasonable 

patients who are willing to tolerate a very high level of risk to achieve a 

probable benefit, especially if that benefit results in an improvement in 

quality of life.“

www.fda.gov
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CDRH Strategic Priority 2016 – 2017

Partner with Patients

We interact with patients as partners and 

work together to advance the development 

and evaluation of innovative devices, and 

monitor the performance of marketed 

devices.

1. Promote a culture of meaningful 

patient engagement by facilitating 

CDRH interaction with patients.

2. Increase use and transparency of 

patient input as evidence in our 

decision-making.

www.fda.gov
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Patient Input

• Patient input includes a range of information and perspectives 

– Anecdotal comments in correspondence to the FDA 

– Testimony at Advisory Committee Panel meetings

– Patient opinions expressed publicly including through social media

– Patient responses to qualitative ad hoc surveys

– Quantitative measurements of patient-reported outcomes

Patient Input

Patient Perspective

Patient Preference 

Information

www.fda.gov
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Patient Perspectives

• Patient perspectives refer to a type of patient input

• Information relating to patients’ experiences with a 

disease or condition and its management

• May be useful for:

– better understanding the disease or condition and its impact 

on patients 

– identifying outcomes most important to patients

– understanding benefit-risk tradeoffs for treatment

www.fda.gov
Patient Input

Patient Perspectives

PPI PRO

www.fda.gov
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What is Patient Preference Information (PPI)?

• For the purpose of this guidance, Patient Preference Information 

(PPI) is defined as:

qualitative or quantitative assessments of the relative 

desirability or acceptability to patients of specified 

alternatives or choices among outcomes or other attributes 

that differ among alternative health interventions.

• Relevant preferences of care-partners (e.g., parents) and health 

care professionals may also be considered

www.fda.gov
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What PPI Can Provide and How It Can Be 

Used

• PPI data can provide valuable information about: 

• Which benefits and risks are most important to affected patients

• What benefit-risk tradeoffs are acceptable from the patient perspective

• How do these patients think about these tradeoffs

• Are there clinically-relevant subgroups of patients that would accept a 

particular benefit-risk profile and/or choose one treatment option over 

other alternatives

• Potential Uses of PPI:

• Inform endpoints or effect size for regulatory studies

• Inform subgroup considerations

• Labeling changes / expanded indications 

• Other potential uses outside regulatory context, such as 

shared medical decision-making.

www.fda.gov
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How is PPI different from PRO?

• Patient-reported outcome (PRO) is 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

• PRO instruments are designed to measure a patient’s 

perceptions of health status before, during, and after therapy

• In contrast, patient preference 

studies measure what specified 

type of therapy or attributes of a 

given therapeutic or diagnostic 

strategy a patient might prefer

www.fda.gov
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GUIDANCE OVERVIEW

Highlights Objectives, Scope, and Guidance Sections

www.fda.gov
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Objectives

1. To encourage submission of PPI, if available, by sponsors or other 

stakeholders to FDA and to aid in FDA decision-making; 

2. To outline recommended qualities of patient preference studies, 

which may result in valid scientific evidence; 

3. To provide recommendations for collecting and submitting PPI to 

FDA; and, 

4. To discuss FDA’s inclusion of PPI in its decision summaries and 

provide recommendations for the inclusion of such information in 

device labeling. 

www.fda.gov
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Scope

• Explains concepts that sponsors and other stakeholders should 

consider when choosing to collect PPI, which may inform FDA’s 

benefit-risk determinations in the premarket review of PMAs, HDE 

applications, and de novo requests.

• Discusses FDA’s inclusion of PPI in its decision summaries and provides 

recommendations for the inclusion of such information in device 

labeling for certain devices.

www.fda.gov
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PPI Submission to FDA is Voluntary

• PPI may not be relevant or appropriate for all device types. 

• May be useful for sponsors to collect and submit such information 

where usage decisions by patients and health care professionals are 

preference-sensitive.

• Devices that could benefit from PPI include those with the following 

characteristics:

– A direct patient interface,

– Intended to yield significant health and appearance benefits, 

– Intended to directly affect health-related quality of life,

– Certain life-saving but high-risk devices,

– Developed to fill an unmet medical need or treat a rare disease or 

condition,

– Offer alternative benefits to those already marketed; and,

– A novel technology.

www.fda.gov
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PPI as Valid Scientific Evidence

• FDA may consider submitted PPI along with other evidence from 

clinical and nonclinical testing when making benefit-risk 

determinations.

• This guidance does not change any review standards for safety 

or effectiveness.

• It provides recommendations relating to the voluntary collection 

of PPI that may be submitted for consideration as valid scientific 

evidence as part of FDA’s benefit-risk assessment.

www.fda.gov
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Recommended Qualities of Patient 

Preference Studies

Well-designed and conducted patient preference studies can provide 

valid scientific evidence regarding patients’ risk tolerance and 

perspective on benefit. This may inform FDA’s evaluation of a device’s 

benefit-risk profile during the PMA, HDE application, and de novo

request review processes.

A. All about Patients

• Patient Centeredness

• Sample Representativeness 

• Capturing Heterogeneous Patient Preferences

• Comprehension by Study Participants

B. Good Study Design

• Established Good Research Practices

• Effective Benefit-Risk Communication

• Minimal Cognitive Bias

• Relevance

C. Good Study Conduct and Analysis 

• Study Conduct

• Logical Soundness

• Robustness of Analysis of Results

www.fda.gov
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Recommended Study Qualities: 

All about Patients

Patient Centeredness

• Patients are the focus of the study

• Studies should measure the preferences and perspectives of well-informed patients

Representativeness of the Sample and Generalizability of Results

• Studies should measure the preferences of a representative sample of adequate size 

so that the study results can be reasonably generalized to the population of interest

Capturing Heterogeneity of Patients’ Preferences

• Patients’ benefit-risk tradeoff preferences may be heterogeneous even among those 

with the same disease or condition

• Studies should reflect the preferences of patients from the full spectrum of disease 

for which the device is intended to be used

Comprehension by Study Participants

• Ensure that study participants fully understand the harm, risk, benefit, uncertainty, 

and other medical information being communicated to them

www.fda.gov
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Established Good Research Practices by Recognized Professional Organizations

• Quality of a study may be established if it follows guidelines for good research practices 

established by a recognized professional organization

Effective Communication of Benefit, Harm, Risk, and Uncertainty

• Reduce uncertainty caused by health numeracy

• Example 1: Avoid solely verbal descriptions of uncertainty; Use multiple formats simultaneously

• Example 2: Pretest the communication format

Minimal Cognitive Bias

• Minimize cognitive biases such as framing, anchoring, simplifying heuristics, or ordering effect

Relevance

• Inclusion and omission of harm, risk, benefit, and uncertainty should be well justified

• Useful to ensure some consistency among the benefits, harms, risks and other attributes

• Relevance of specific endpoints to potential clinical outcomes should be clearly communicated 

to patients to properly elicit preference

Recommended Study Qualities: 

Good Study Design

www.fda.gov
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Study Conduct

• Compliance of research staff and study participants with the study protocol

Logical Soundness

• Data should include internal-validity tests of logic and consistency

• Verified for conformity with logic and consistency

Robustness of Analysis of Results

• Sources of uncertainty 

• Sensitivity analysis

Recommended Study Qualities 

Study Conduct and Analysis

www.fda.gov
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Regulatory Considerations

• For studies submitted with other premarket review data, 

applicable regulations including IDE regulations in 21 CFR 

Part 812 must be followed.

• For studies done independent from a device clinical study, 

FDA generally considers the studies to be nonsignificant

risk.

• Conditions of Approval

– FDA may impose conditions of approval in certain PMA approvals, 

including where the Agency takes PPI into account to mitigate risk 

and facilitate use in patients for whom benefits are expected to 

outweigh risks. 

– FDA may require collection of postmarket evidence through a 

postmarket approval surveillance study for PMAs. 

www.fda.gov
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Submission of PPI to FDA

FDA encourages sponsors and other stakeholders to have early 

interactions with the relevant FDA review division if considering 

collecting and submitting PPI.

• Request an informational pre-submission meeting to discuss plans for 

designing or submitting a patient preference study

• Request participation from Martin.Ho@fda.hhs.gov and 

Anindita.Saha@fda.hhs.gov

www.fda.gov
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Inclusion of PPI in Decision Summaries 

and Device Labeling

• When FDA considers patient preference studies in its 

consideration of a premarket submission, such studies generally 

are included in the decision summary

• Inclusion of PPI in FDA’s public decision summaries can be 

helpful to health care professionals and patients in making 

health care decisions involving difficult benefit-risk tradeoffs or 

novel treatments

• PPI that is reviewed by FDA and supports FDA’s approval or 

marketing authorization should also be described in the device 

labeling

– It is important for the device product labeling to contain sufficient information 

about the benefits and risks of the treatment and diagnostic options under 

consideration (Please see FDA Guidance: Labeling – Regulatory Requirements for 

Medical Devices (FDA 89-4203).

www.fda.gov
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Examples and Resources

• CDRH Patient Preference Obesity Study

– M. Ho, M. Gonzalez, H. Lerner, C. Neuland, J. Whang, M. McMurry-Heath, A. 

Hauber, and T. Irony. "Incorporating patient-preference evidence into regulatory 

decision making." Surgical endoscopy.29(10): 2984-2993 

• Guidance for Industry and Food and Drug Administration Staff : Factors to 

Consider for Benefit – Risk Determinations in Medical Device Premarket 

Approval and De Novo Classifications

• Guidance on Medical Device Patient Labeling

www.fda.gov

• MDIC Patient-Centered Benefit Risk Project: A 

Framework for Incorporating Information on 

Patient Preferences Regarding Benefit and Risk 

into Regulatory Assessments of New Medical 

Technology (http://mdic.org/pcbr)
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UPDATING THE BENEFIT-RISK 

WORKSHEET

Summary of changes to the Benefit-Risk Guidance 

www.fda.gov
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Changes to the Benefit-Risk Worksheet

• Updated the PMA and de novo Benefit-Risk Guidance for 

consistency with the terminology and concepts in the PPI 

Guidance

– Section 4: Factors FDA Considers in Making Benefit-Risk 

Determinations

• 4.3: Additional Factors in the Assessment of the Probable Benefits and 

Risks of Devices

• Addition of PPI in the worksheet that FDA staff uses to 

guide benefit-risk determinations of PMA and de novo 

requests

– Patient perspective on risk and perspective on benefit

• PPI guidance and the Benefit-Risk guidance have a 60 day 

implementation period from the date of publication

www.fda.gov
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Final Considerations

• Voluntary submission of PPI may be informative during benefit-risk 

determination.

• PPI may also be informative earlier in device development (e.g., to 

inform clinical study parameters such as endpoint selection and effect 

size).

• FDA encourages early interactions with FDA review staff if planning to 

design a PPI study or to submit PPI.

• Contact Martin.Ho@fda.hhs.gov and Anindita.Saha@fda.hhs.gov 

www.fda.gov
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Thank You

www.fda.gov
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Questions?

Division of Industry and Consumer Education: 

DICE@fda.hhs.gov

Slide Presentation, Transcript and Webinar Recording 

will be available at:

http://www.fda.gov/training/cdrhlearn

Under Heading: How to Study and Market Your 

Device; Sub-heading: Cross-Cutting Premarket Policy 

www.fda.gov