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DRAFT GUIDANCE
 
 
 
  This guidance attachment is being distributed for comment purposes only.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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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This draft guidance, when finalized, will represent the Food and Drug Administrations (FDAs) 
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   Contains Nonbinding Recommendations 
Draft  Not for Implementation  
1  Guidance for Industry1  
Qualification of Exacerbations of Chronic Pulmonary Disease 
2 
Tool for Measurement of Symptoms of Acute Bacterial 
3 
Exacerbation of Chronic Bronchitis in Patients With Chronic 
4 
Obstructive Pulmonary Disease 
5   
6 
  
7  DDT Type:  Clinical outcome assessment (COA) 

8 
  
9  DDT Tracking Number:  DDTCOA-000003 

10   
11  Referenced COA: Exacerbations of Chronic Pulmonary Disease Tool (EXACT)
  
12 
  
13  Type of COA: Patient-reported outcome (PRO)
  
14 
  
15  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. 
19   
20  The contact information for public access to the EXACT and its user manual also appears 
21  below.  
22   
23  Section I: Concept of Interest  
24   
25  The EXACT total score measures symptoms of ABECB-COPD. 
26   
27  Section II: Context of Use  
28   
29  The  EXACT is qualified as a well-defined and reliable measure of symptoms of ABECB-
30  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.   
33   
34  At the present time, a responder definition has not been determined to aid interpretation 
35  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 EXACTs longitudinal measurement 
40  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.  
1 

  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.   
45   
46  A.   Study population 
47   
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    
52   
53  B.   Clinical trial design  
54   
55  Superiority trial  
56   
57  C.   Endpoint positioning  
58   
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.  
61   
62  D.   Labeling or promotional claim(s) based on the COA 
63   
64  The EXACT is intended to ultimately support labeling claims related to change in 
65  ABECB-COPD symptoms.  
66   
67  Section III:  COA Interpretation  
68   
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. 
73   
74  Section IV: Contact Information for Access to the Qualified COA 
75   
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.   
2