Attachement - Qualification Process for Drug Development Tools: Qualification of Exacerbations of Chronic Pulmonary Disease Tool for Measurement of Symptoms of Acute Bacterial Exacerbation of Chronic Bronchitis in Patients With Chronic Obstructive Pulmonary Disease

Administrative draft guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Attachment to
Guidance on Qualification Process for Drug
Development Tools
Qualification of Exacerbations of Chronic Pulmonary
Disease Tool for Measurement of Symptoms of Acute
Bacterial Exacerbation of Chronic Bronchitis in Patients
With Chronic Obstructive Pulmonary Disease
DRAFT GUIDANCE
This guidance attachment is being distributed for comment purposes only.
Comments and suggestions regarding this draft document should be submitted within 90 days of
publication in the Federal Register of the notice announcing the availability of the draft
guidance. Submit electronic comments to http://www.regulations.gov. Submit written
comments to the Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with
the docket number listed in the notice of availability that publishes in the Federal Register.
For questions regarding this draft document contact Dr. Elektra Papadopoulos at 301-796-0900.
This draft guidance, when finalized, will represent the Food and Drug Administration’s (FDA’s)
current thinking on this topic. It does not create or confer any rights for or on any person and
does not operate to bind FDA or the public. You can use an alternative approach if the approach
satisfies the requirements of the applicable statutes and regulations. If you want to discuss an
alternative approach, contact the FDA staff responsible for implementing this guidance. If you
cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of
this guidance.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
January 2014
Clinical/Medical
16306dft.doc
01/08/14

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Contains Nonbinding Recommendations
Draft — Not for Implementation
1 	Guidance for Industry1
2 	Qualification of Exacerbations of Chronic Pulmonary Disease
3 	Tool for Measurement of Symptoms of Acute Bacterial
4 	Exacerbation of Chronic Bronchitis in Patients With Chronic
Obstructive Pulmonary Disease
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7 	DDT Type: Clinical outcome assessment (COA)
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9 	DDT Tracking Number: DDTCOA-000003
11 	Referenced COA: Exacerbations of Chronic Pulmonary Disease Tool (EXACT)
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13 	Type of COA: Patient-reported outcome (PRO)
14
The Center for Drug Evaluation and Research (CDER) has determined that the EXACT,
16 	an electronically administered PRO measure, is qualified as a measure of symptoms of
17 	acute bacterial exacerbation of chronic bronchitis in patients with chronic obstructive
18 	pulmonary disease (ABECB-COPD) in the context of use described below.
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The contact information for public access to the EXACT and its user manual also appears
21 	below.
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23 	Section I: Concept of Interest
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The EXACT total score measures symptoms of ABECB-COPD.
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27 	Section II: Context of Use
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29 	The EXACT is qualified as a well-defined and reliable measure of symptoms of ABECB-
COPD, for use in phase 2 studies. Additional development work is needed to further
31 	assess measurement properties over the course of an exacerbation, including ability to
32 	detect meaningful change in response to an acute intervention.
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34 	At the present time, a responder definition has not been determined to aid interpretation
of the clinical meaningfulness of changes observed in clinical study results. When
36 	designing confirmatory clinical trials, sponsors should discuss the interpretation of
37 	clinically meaningful change with the appropriate CDER review division.
38
39 	We encourage exploratory analyses to evaluate the EXACT’s longitudinal measurement
properties and the amount of change in an individual patient that can be considered
41 	meaningful for use in the interpretation of effectiveness. We expect that as further
42 	experience with the instrument is gained, the qualification statement will be expanded to
1 This guidance has been prepared by the Office of New Drugs in the Center for Drug Evaluation and
Research (CDER) at the Food and Drug Administration.
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Contains Nonbinding Recommendations
Draft — Not for Implementation
43 	include recommendations for a responder definition or other additional information to aid
44 	in interpretation of clinically meaningful change.
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46 	A. Study population
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48 	Outpatients with acute bacterial exacerbations of chronic bronchitis in patients with
49 	COPD who meet the clinical trial entry criteria as described in the guidance for industry
50 	Acute Bacterial Exacerbations of Chronic Bronchitis in Patients With Chronic
51 	Obstructive Pulmonary Disease: Developing Antimicrobial Drugs for Treatment2
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53 	B. Clinical trial design
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55 	Superiority trial
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57 	C. Endpoint positioning
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59 	The EXACT is currently qualified as an endpoint in phase 2 studies. It is intended for
60 	ultimate use as a primary or secondary endpoint in confirmatory clinical trials.
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62 	D. Labeling or promotional claim(s) based on the COA
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64 	The EXACT is intended to ultimately support labeling claims related to change in
65 	ABECB-COPD symptoms.
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67 	Section III: COA Interpretation
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69 	A responder definition for the targeted patient population is not yet available. FDA
70 	recommends that a responder definition be evaluated and identified. When designing
71 	confirmatory clinical trials, sponsors should discuss with the appropriate CDER review
72 	division how EXACT may be used.
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74 	Section IV: Contact Information for Access to the Qualified COA
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76 	Evidera
77 	7101 Wisconsin Avenue, Suite 600
78 	Bethesda, MD 20814
79 	exactpro@evidera.com
80 	Phone: (301) 664-7272
81 	Fax: (301) 654-9864
82
83 	Instructions for Use in a Regulatory Submission: Please reference DDT # [DDTCOA-
84 	000003] and this guidance in your application.
2 We update guidances periodically. To make sure you have the most recent version of a guidance, check
the FDA Drugs guidance Web page at
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
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