Validation of a New Shortness of Breath With Daily Activities Questionnaire in Patients With Chronic Obstructive Pulmonary Disease

• ClinicalTrials.gov Identifier: NCT00984659
• Recruitment Status: Completed
• First Posted: September 25, 2009
• Results First Posted: March 15, 2012
• Last Update Posted: August 29, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The purpose of this study is to evaluate a new questionnaire to capture the patient experience of COPD. The information collected will be used to validate the Shortness of Breath with Daily Activities Questionnaire.

Condition or disease	Intervention/treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Fluticasone propionate/salmeterol combination product; Drug: Salmeterol; Drug: Placebo	Phase 4

Detailed Description:

Dyspnea, referred to by patients as "shortness of breath" or "breathlessness," is frequently associated with decreases in functional status, quality of life, and disabilities. Currently available questionnaires do not specifically address the shortness of breath component of COPD. The development of a patient reported outcome questionnaire that will specifically assess Shortness of Breath with Daily Activities (SOBDA) in patients with COPD is needed.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 366 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Validation of a New Shortness of Breath With Daily Activities Questionnaire in Patients With Chronic Obstructive Pulmonary Disease
• Study Start Date: October 29, 2009
• Actual Primary Completion Date: July 1, 2010
• Actual Study Completion Date: July 1, 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: FSC; Fluticasone propionate/salmeterol combination product 250/50mcg DISKUS twice a day	Drug: Fluticasone propionate/salmeterol combination product; Fluticasone propionate/salmeterol combination product 250/50mcg DISKUS twice a day for 8 weeks
Experimental: SAL; Salmeterol 50mcg DISKUS twice a day	Drug: Salmeterol; Salmeterol 50mcg DISKUS twice a day for 8 weeks
Placebo Comparator: Placebo; Placebo DISKUS twice a day	Drug: Placebo; Placebo DISKUS twice a day for 8 weeks

Outcome Measures

Primary Outcome Measures :

1. Internal Consistency (IC) of the Shortness of Breath With Daily Activities (SOBDA) Questionnaire in Participants With Chronic Obstructive Pulmonary Disease (COPD) Assessed as Cronbach's Alpha Value [ Time Frame: Day 1 of the 2-week Run-in Period ]
   Cronbach's alpha (CA) is a measure of the IC of the 13-item SOBDA questionnaire (completed via electronic diary by a sample of participants). It is the ratio of the variance (var.) of the sum of the individual scores and the var. of the total score. The var. of the sum of a group of independent variables is the sum of their var.; thus, if the variables are positively correlated, the var. of the sum will be increased. If the items making up the score are identical and so perfectly correlated, CA=1. If the items are independent, CA=0. Higher scores indicate a more reliable (precise) instrument.
2. Test-retest Reliability (T-RR) of SOBDA Scores Measured as the Difference in the SOBDA Weekly Score Between Week 1 and Week 2 of the 2-week Run-in Period [ Time Frame: Week 1 and Week 2 of the 2-week Run-in Period ]
   T-RR=stability during repeat measures over time in a stable population. SOBDA score was determined by the 13-item (it.) scoring algorithm, assigning a weekly mean score of 1-4 (higher scores=more severe breathlessness with daily activities) based on the mean of 7 days of data (or >=4 days). Daily total score is computed from the mean of the participant's (par.) scores on the 13 it. (>=7 it. must have non-missing responses). Only scores of stable par. (indicating no change [score=3] on the par.-completed Patient Global Assessment of Change [PGAC]; 1 [ much worse] to 5 [much better]) were used.
3. Convergent Validity for the SOBDA Questionnaire Measured as Correlations of the Baseline SOBDA Score With Participant-completed Modified Medical Research Council (mMRC) and Physician-completed mMRC Scores at Visit 2 [ Time Frame: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period) ]
   Convergent validity is defined as the ability of the SOBDA questionnaire to measure required information and was assessed by examining the relationship between the SOBDA score and the participant/physician-completed mMRC Dyspnea Scale assessments. The physician/participant rated the degree of the participant's dyspnea (trouble breathing) on the 5-point mMRC scale (0, none; 4, very severe). Spearman's rank correlation coefficient assesses if the relationship between two variables is monotone. A correlation of +1 or -1 will occur if one variable is a perfect monotone of the other.
4. Convergent Validity for the SOBDA Questionnaire Measured as the Correlation of the Baseline SOBDA Score With the Clinician Global Assessment of Dyspnea Severity (CGI-S) Score at Visit 2 [ Time Frame: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period) ]
   Convergent validity is defined as the ability of the SOBDA questionnaire to measure the required information and was assessed by examining the relationship between the SOBDA score with the CGI-S score. Spearman's rank correlation coefficient assesses if the relationship between two variables is monotone. A correlation of +1 or -1 will occur if one variable is a perfect monotone of the other. Clinicians were asked to assess the severity of the participant's dyspnea on the CGI-S scale. This was evaluated on a 1-4 Likert scale: 1 (mild) to 4 (very severe).
5. Convergent Validity (CV) for the SOBDA Questionnaire Measured as the Correlation of the Baseline SOBDA Score With the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) Dyspnea Domain Score at Visit 2 [ Time Frame: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period) ]
   Convergent validity is defined as the ability of the SOBDA questionnaire to measure required information and was assessed by examining the relationship between the SOBDA score and the CRQ-SAS dyspnea domain score. Pearson's correlation coefficient is a measure of the linear dependence between 2 variables. A correlation of +1 or -1 will occur if the data from the 2 variables lie exactly on a line. The CRQ is a 20-item instrument measuring 4 domains (each measured on a scale of 1 [maximum impairment] to 7 [no impairment]) of functioning: mastery, fatigue, emotional function, and dyspnea.
6. Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Physician-completed (PyC) mMRC Score at Visit 2 [ Time Frame: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period) ]
   SOBDA known group validity refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the PyC mMRC. The physician rated the degree of the participant's dyspnea on the 5-point mMRC scale: 0 (none) to 4 (very severe). Known group validity was confirmed if the SOBDA score increased with increasing values of PyC mMRC, both indicating increased levels of breathlessness.
7. Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Participant-completed (ParC) mMRC Score at Visit 2 [ Time Frame: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period) ]
   SOBDA known group validity refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the ParC mMRC. The participant rated the degree of his/her dyspnea on the 5-point mMRC scale: 0 (none) to 4 (very severe). Known group validity was confirmed if the SOBDA score increased with increasing values of ParC mMRC, both indicating increased levels of breathlessness.
8. Known Group Validity (KGV) for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of CGI-S Scores at Visit 2 [ Time Frame: Baseline (last week of the 2-week Run-in Period) and pre-treatement on Visit 2 (Day 1 of the 6-week Treatment Period) ]
   SOBDA KGV refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the CGI-S score. Clinicians were asked to assess the severity of the participant's dyspnea on the CGI-S scale. This was evaluated on a 1-4 Likert scale: 1 (mild) to 4 (very severe). KGV was confirmed if the SOBDA score increased with increasing values of CGI-S, both indicating increased levels of breathlessness.
9. Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) [ Time Frame: Days 8, 15, 22, 29, 36, and 43 and Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
   The PGAC is par. completed on a 1-5 scale: 1, much worse; 2, worse; 3, no change; 4, better; 5, much better. Responders were defined as par. with a rating of "better" or "much better" (score of 4 or 5) on the PGAC at the relevant week; non-responders were defined as par. with a response of "much worse," "worse," or "no change" on the PGAC. As pre-specified in the study protocol, results are presented independent of treatment allocation . The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.
10. Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) [ Time Frame: Baseline; Days 8, 15, 22, 29, 36, and 43 and Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
    Responsiveness reflects the ability of the SOBDA questionnaire to detect change under conditions of known change. Responders (Rs)=participants (par.) with a rating of "better"/"much better" (score of 4/5) on the PGAC (range; 1 [much worse] to 5 [much better]) at the relevant week; NRs=par. with a response of "much worse," "worse," or "no change" (score of 3). Mean difference between Rs and NRs in the change from the previous week to the current week's SOBDA score was calculated. For Visit 3/PD, the change from Baseline to the last treatment week's SOBDA score for Rs and NRs was calculated.
11. Number of Participants Classified as Responders and Non-responders by Clinician Global Impression of Change Question (CGI-C) Response at Visit 3/PD [ Time Frame: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
    Clinicians were asked to provide their clinical impression regarding change in the participant's shortness of breath by CGI-C. This was evaluated on a 1-5 Likert scale: 1 (much worse) to 5 (much better), with 3 being no change. A CGI-C responder was defined as a participant who had a response of "better" (4) or "much better" (5), and a non-responder was defined as a participant who had a response of "much worse" (1), "worse" (2), or "no change" (3).
12. Number of Participants Classified as Responders and Non-responders by CRQ-SAS Dyspnea Domain Response at Visit 3/PD [ Time Frame: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
    A CRQ-SAS dyspnea domain responder was defined as a participant who had a score increase of 0.5 units or more for the dyspnea domain of the CRQ-SAS between Visit 2 and Visit 3/Premature Discontinuation. A non-responder was defined as a participant who had a decrease in the score, or an increase of less than 0.5 units.
13. Number of Participants Classified as Responders and Non-responders by Physician-completed and Participant-completed mMRC Response at Visit 3/PD [ Time Frame: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
    A Physician-completed and Participant-completed mMRC responder was defined as a participant who had a score decrease of one unit or more between Visit 2 and Visit 3/Premature Discontinuation. A non-responder was defined as a participant who had the same score or an increase in score.
14. Change From Baseline to Last Treatment Week in the SOBDA Score by CGI-C Responses at Visit 3/PD [ Time Frame: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
    The responsiveness of the SOBDA questionnaire was assessed by comparing score changes between responders and non-responders. The CGI-C is clinician completed on a 1 to 5 scale: 1, much worse; 2, worse; 3, no change; 4, better; 5, much better. Changes in mean SOBDA scores during the last week of treatment in responders and non-responders using definitions based on the CGI-C conducted at Visit 3/Premature Discontinuation were assessed.
15. Change From Baseline to Last Treatment Week in the SOBDA Score by CRQ-SAS Dyspnea Domain (DD) Responses at Visit 3/PD [ Time Frame: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
    The responsiveness of the SOBDA questionnaire was assessed by comparing score changes of responders (Rs) versus non-responders (NRs). The CRQ-SAS DD includes 5 questions (q.) scored 1 (maximum impairment) to 7 (no impairment). Individual q. were equally weighted, and domain scores (DSs) (range=1-7) were calculated as the mean across the non-missing items within each domain (DSs were calculated although an individual item score was missing). Changes in mean SOBDA scores during the last treatment week in Rs and NRs using definitions based on the CRQ-SAS DD conducted at Visit 3/PD were assessed.
16. Change From Baseline to Last Treatment Week in the SOBDA Score by Physician-completed mMRC and Participant-completed mMRC Responses at Visit 3/PD [ Time Frame: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
    The responsiveness of the SOBDA questionnaire was assessed by comparing score changes between responders and non-responders. The mMRC ranges from 0 (no breathlessness except with strenous exercise) to 4 (too breathless to leave the house; breathless when dressing/undressing) and is completed by the clinician or the participant as indicated. Changes in mean SOBDA scores during the last week of treatment in responders and non-responders using definitions based on the Physician-completed (Ph-C) and Participant-completed (Pa-C) mMRC conducted at Visit 3/Premature Discontinuation were assessed.
17. SOBDA Threshold for Response Assessed as Mean Change From the Previous Week's SOBDA Score Based on a Participant-completed PGAC Score Rated of "Better" [ Time Frame: Baseline (last week of the 2-week Run-in Period) and Weeks 1, 2, 3, 4, 5, and 6 (6-week Treatment Period) ]
    Changes from Baseline in the SOBDA score for responders (Rs) and non-responders (NRs) (using the PGAC assessment; 1 [much worse] to 5 [much better]), together with the cumulative proportions of Rs and NRs, was used to establish the threshold for defining SOBDA questionnaire Rs. The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on PGAC scores pre-specified as "better" or demonstrating meaningful improvement.
18. SOBDA Threshold for Response as Assessed by Mean Change From Baseline to the Last Treatment Week in the SOBDA Score Based on a CGI-C Response Rated as "Better" [ Time Frame: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
    The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on CGI-C scores pre-specified as "better" or demonstrating meaningful improvement. The CGI-C is clinician completed on a 1 to 5 scale: 1, much worse, 2, worse; 3, no change; 4, better; 5, much better.
19. SOBDA Threshold for Response as Assessed by Mean Change From Baseline to the Last Treatment Week in the SOBDA Score Based on a CRQ-SAS Dyspnea Domain (DD) Response Rated as "Better" [ Time Frame: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
    The threshold of response (TOR) is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit. The TOR was evaluated as the change from Baseline in the SOBDA score based on CRQ-SAS scores pre-specified as "better" or demonstrating meaningful improvement. The CRQ-SAS DD includes 5 questions (q.) scored 1 (maximum impairment) to 7 (no impairment). Individual q. were equally weighted, and domain scores (DSs) (range=1-7) were calculated as the mean across the non-missing items within each domain (DSs were calculated although an individual item score was missing).
20. SOBDA Threshold for Response Assessed as Mean Change From Baseline to Last Treatment Week in the SOBDA Score Based on Forced Expiratory Volume in One Second (FEV1) Change From Baseline of 50 Milliliters (mL) to <100 mL [ Time Frame: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8) ]
    FEV1 response was rated as 1=No change or worse (i.e., change of <50 mL); 2=Better (i.e., change of 50 to <100 mL); 3=Much better (i.e., change of >=100 mL). The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on study assessment (FEV1) scores pre-specified as "better" or demonstrating meaningful improvement.

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adults ≥ 40 years of age
• Established clinical history of COPD by ATS/ERS definition
• Former or current smoker > 10 pack years
• Evidence of dyspnea

Exclusion Criteria:

• Has a respiratory disorder other than COPD
• Cancer not in complete clinical remission
• Clinically significant cardiovascular, neurological, psychiatric, renal, gastro-intestinal, immunological, endocrine, or hematological abnormalities that are uncontrolled

Contacts and Locations

Locations

United States, Alabama

GSK Investigational Site

Jasper, Alabama, United States, 35501

GSK Investigational Site

Mobile, Alabama, United States, 36608

United States, California

GSK Investigational Site

Los Angeles, California, United States, 90095-1690

GSK Investigational Site

Riverside, California, United States, 92506

United States, Colorado

GSK Investigational Site

Wheat Ridge, Colorado, United States, 80033

United States, Connecticut

GSK Investigational Site

Stamford, Connecticut, United States, 06902

United States, Florida

GSK Investigational Site

Tamarac, Florida, United States, 33321

United States, Georgia

GSK Investigational Site

Decatur, Georgia, United States, 30033

GSK Investigational Site

Lawrenceville, Georgia, United States, 30046

United States, Indiana

GSK Investigational Site

Evansville, Indiana, United States, 47710

GSK Investigational Site

Evansville, Indiana, United States, 47714

GSK Investigational Site

South Bend, Indiana, United States, 46617

United States, Kentucky

GSK Investigational Site

Madisonville, Kentucky, United States, 42431

United States, Louisiana

GSK Investigational Site

New Orleans, Louisiana, United States, 70115

GSK Investigational Site

Sunset, Louisiana, United States, 70584

United States, Missouri

GSK Investigational Site

Saint Louis, Missouri, United States, 63141

United States, New Jersey

GSK Investigational Site

Summit, New Jersey, United States, 07091

United States, North Carolina

GSK Investigational Site

Charlotte, North Carolina, United States, 28207

GSK Investigational Site

Elizabeth City, North Carolina, United States, 27909

United States, Ohio

GSK Investigational Site

Canton, Ohio, United States, 44718

GSK Investigational Site

Cincinnati, Ohio, United States, 45231

United States, Oregon

GSK Investigational Site

Lake Oswego, Oregon, United States, 97035

GSK Investigational Site

Portland, Oregon, United States, 97213

United States, Pennsylvania

GSK Investigational Site

Erie, Pennsylvania, United States, 16508

GSK Investigational Site

Philadelphia, Pennsylvania, United States, 19140

United States, South Carolina

GSK Investigational Site

Charleston, South Carolina, United States, 29406-7108

GSK Investigational Site

Chester, South Carolina, United States, 29706

GSK Investigational Site

Clinton, South Carolina, United States, 29325

GSK Investigational Site

Easley, South Carolina, United States, 29640

GSK Investigational Site

Gaffney, South Carolina, United States, 29340

GSK Investigational Site

Greenwood, South Carolina, United States, 29646

GSK Investigational Site

Seneca, South Carolina, United States, 29678

GSK Investigational Site

Spartanburg, South Carolina, United States, 29303

United States, Tennessee

GSK Investigational Site

Johnson City, Tennessee, United States, 37601

United States, Texas

GSK Investigational Site

Houston, Texas, United States, 77054

GSK Investigational Site

New Braunfels, Texas, United States, 78130

United States, Virginia

GSK Investigational Site

Abingdon, Virginia, United States, 24210

GSK Investigational Site

Richmond, Virginia, United States, 23229

United States, Washington

GSK Investigational Site

Spokane, Washington, United States, 99204

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. 

Study Data/Documents: Dataset Specification 

Identifier: 112989
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 112989
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 112989
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: 112989
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 112989
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 112989
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 112989
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Watkins ML, Wilcox TK, Tabberer M, Brooks JM, Donohue JF, Anzueto A, Chen WH, Crim C. Shortness of Breath with Daily Activities questionnaire: validation and responder thresholds in patients with chronic obstructive pulmonary disease. BMJ Open. 2013 Oct 22;3(10):e003048. doi: 10.1136/bmjopen-2013-003048.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00984659
• Other Study ID Numbers: 112989
• First Posted: September 25, 2009
• Results First Posted: March 15, 2012
• Last Update Posted: August 29, 2018
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:

Pulmonary Disease, Chronic Obstructive; Dyspnea

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Dyspnea; Chronic Disease; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Respiration Disorders; Signs and Symptoms, Respiratory; Fluticasone; Xhance; Salmeterol Xinafoate; Anti-Inflammatory Agents; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Dermatologic Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action