02 Patient-Reported Outcome Measures

Question 1

What is a PRO Instrument?

Answer 1

A PRO is any report of the status of the patients health condition that comes directly from the patient without interpretation of the patient’s response by a clinician or anyone else. The purpose of a PRO is to measure treatment benefit or risk in medical product clinical trials

Question 2

What can PROs measure for labeling?

Answer 2

Severity of symptoms. State of disease. Concepts (Groups of symptoms. Functional capacity (things people can do). Functions that measure severity of condition

Question 3

When can PROs be used?

Answer 3

Advised when measuring a concept that is best known by the patient. May also be used to understand patients perspective on objective changes to health. Eg. HF or Asthma may affect activities of daily living

Question 4

Where does PRO data go in the label?

Answer 4

Indications and usage. Clinical studies. “Can appear in any section”

Question 5

What is an Endpoint Model?

Answer 5

Researchers must define an endpoint. How will the drug affect the patient’s reported outcome? In other works, the PRO has to make theoretical sense as an “endpoint” of treatment

Question 6

What endpoints are PRO assessments?

Answer 6

Symptoms diary, Signs diary, etc. Non-PRO assessment: Physiological effect, physical exam, etc.

Question 7

What is a Target Product Profile (TPP)?

Answer 7

Specify a priori (Prescribing information goals, Targeted labeling claims, A model for how the drug may work)

Question 8

For Concepts Measured, what is done when multiple items are used?

Answer 8

Even if multiple items are used, sponsor must demonstrate that all items are changing with treatment. If only one item is driving change, this is not sufficient for a complex PRO claim

Question 9

For measurement property: Reliability, what needs to be done?

Answer 9

Test-retest. Intra-interviewer. Internal consistency. Inter-interviewer

Question 10

For measurement property: Content Validity, what needs to be done?

Answer 10

Does the instrument measure the concepts it claims to

Question 11

For measurement property: Construct Validity, what needs to be done?

Answer 11

Are a priori hypothesis satisfied and are there logical relationships that should exist with measures of related concepts. A complex “construct” should be related to other constructs in a logical way. A construct should be correlated with like things and not related to things that do not relate to the construct

Question 12

For measurement property: Criterion Validity, what needs to be done?

Answer 12

The extent to which PRO scores are related to a known gold standard measure of the same concept (e.g. dementia evidence from brain scans vs. no evidence)

Question 13

For measurement property: what is Ability to detect change?

Answer 13

Evidence that a PRO instrument can identify differences in scores over time in individuals or groups who have changed with respect to the measurement concept. Within person change over time. Effect size statistic

Question 14

For Item Generation, what is Saturation?

Answer 14

Point where no new or relevant information emerges from collecting additional items. Want to achieve this

Question 15

For Item Generation, what is Item Tracking Matrix?

Answer 15

Used to document changes and or delations in items

Question 16

For Item Generation, what should items ask for?

Answer 16

Specific behaviors or subjective experiences rather than hypothetical’s. “Did you do X?” rather than “Can you do X?”, recall period, response options

Question 17

What is Quality of Life?

Answer 17

A general concept that implies an evaluation of the effect of all aspects of life on general well-being. Because this term implies the evaluation of nonhealth-related aspects of life, and because the term generally is accepted to mean “what the patient thinks it is”, it is too general and undefined to be considered appropriate for a medical product claim

Question 18

What is Health-Related QoL (HRQOL)?

Answer 18

HRQOL is a multidomain concept that represents the patients general perception of the effects of illness and treatment on physical, psychological, and social aspects of life

Question 19

What does claiming a statistical and meaningful improvement in HRQOL imply?

Answer 19

1) That all HRQOL domains that are important to interpreting change in how the clinical trials population feels or functions as a result of the targeted disease and its treatment were measured; 2) That a general improvement was demonstrated; and 3) That no decrement was demonstrated in any domain

Question 20

What are Proxy-Reported outcomes?

Answer 20

Based on report by someone other than the patient (i.e. spouse for an Alzheimer’s patient). Discouraged in FDA PRO document (especially for symptoms only known by patient, i.e. depression, anxiety)

Question 21

In summary, what needs to be done to use PROs for labeling?

Answer 21

Requires a priori hypothesis and evaluation of validity and reliability within target population. Proper statistical design (blinded RCT) will be required to support labeling claims