Chronic Obstructive Pulmonary 
Disease: Use of the St. Georges 
Respiratory Questionnaire as a 
PRO Assessment Tool 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
March 2018 
Clinical/Medical 
 
   
Chronic Obstructive Pulmonary 
Disease: Use of the St. Georges 
Respiratory Questionnaire as a 
PRO Assessment Tool 
Guidance for Industry 
 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD  20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: druginfo@fda.hhs.gov 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
March 2018 
Clinical/Medical 
 
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION AND BACKGROUND..................................................................... 1 
II.  CONSIDERATIONS FOR THE SGRQ ......................................................................... 2 
A.  Administration ............................................................................................................................... 2 
B.  Scoring ............................................................................................................................................ 2 
C.  Method of Analysis ........................................................................................................................ 3 
D.  Use of the SGRQ ............................................................................................................................ 3 
REFERENCES .............................................................................................................................. 5 
 
 
  Contains Nonbinding Recommendations 
Chronic Obstructive Pulmonary Disease:  
Use of the St. Georges Respiratory Questionnaire  
as a PRO Assessment Tool 
Guidance for Industry1 
 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can 
use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To 
discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title 
page.   
 
 
 
I.  INTRODUCTION AND BACKGROUND 
 
  The purpose of this guidance is to provide information to sponsors developing drugs for 
the treatment of chronic obstructive pulmonary disease (COPD).2 This guidance 
addresses the use of the St. Georges Respiratory Questionnaire (SGRQ), a patient-
reported outcome measure (PRO) assessment tool used in interventional clinical trials in 
patients with COPD.  
 
  The information on SGRQ presented in this guidance was previously provided in an 
appendix to the draft guidance for industry Chronic Obstructive Pulmonary Disease: 
Developing Drugs for Treatment, which published in May 2016 and was subsequently 
withdrawn for reasons unrelated to the subject of this guidance. 
 
  In general, FDAs guidance documents do not establish legally enforceable 
responsibilities. Instead, guidances describe the Agencys current thinking on a topic and 
should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited. The use of the word should in Agency guidances means that 
something is suggested or recommended, but not required.  
 
  COPD is a chronic progressive disease caused by chronic inflammation and destruction 
of the airways and lung parenchyma and is usually associated with tobacco smoking or 
prolonged exposure to other noxious particles and gases. The term COPD encompasses a 
                                                 
1 This guidance has been prepared by the Division of Pulmonary, Allergy, and Rheumatology Products in the Center 
for Drug Evaluation and Research at the Food and Drug Administration.  You may submit comments on this 
guidance at any time. Submit comments to Docket No. FDA-2017-D-6821 (available at 
https://www.regulations.gov/docket?D=FDA-2017-D-6821) (see the instructions for submitting comments in the 
docket).   
 
2 For the purposes of this guidance, all references to drugs include both human drugs and therapeutic biological 
products, including small and large molecule drugs, unless otherwise specified. 
1 
  Contains Nonbinding Recommendations 
spectrum of pulmonary processes, with chronic bronchitis and emphysema as two clearly 
defined entities within that spectrum. 
 
  For sponsors conducting clinical trials of drugs to treat COPD, FDA recognizes several 
categories of outcome measures that may be appropriate to assess efficacy, including 
PRO measures such as the SGRQ.  
 
  The SGRQ measures health status in patients with obstructive airway diseases such as 
COPD. 
 
 
II.  CONSIDERATIONS FOR THE SGRQ 
 
  The SGRQ is available in several versions. Up-to-date information, versions, translations, 
and manuals for each version can be found on the developers instrument website.3 This 
up-to-date information refers specifically to the version available as of 2018 at the time of 
publication of this document. The original SGRQ is a 50-item instrument (questionnaire) 
with weighted responses. There are several versions of the 50-item instrument, each with 
a different recall period: 1 year, 3 months, or 4 weeks.  
 
  As of March 2016, only the 3-month and 4-week recall versions were available from the 
developer.4   The shorter 40-item COPD-specific version, SGRQ-C, does not have a 
defined recall period. Not all versions have equivalent validation information.5  
 
A.  Administration 
 
  The SGRQ is self-administered by the patient and the investigator should score the 
SGRQ in accordance with current manuals, as appropriate.  
 
  Versions in languages other than English should undergo linguistic and cultural 
validation for all languages and cultures in which the sponsor conducts the studies.  
 
  The SGRQ can be administered using a paper or electronic platform, provided the latter 
development has followed accepted procedures (Coons et al. 2009). 
 
B.  Scoring 
 
  The SGRQ total score is made up of three components: (1) symptoms  frequency and 
severity of symptoms; (2) activity  effect of disease on common daily physical 
                                                 
3 See the St. Georges University of London Health Status Research website at http://www.healthstatus.sgul.ac.uk/. 
 
4 Ibid. 
 
5 Throughout this guidance, the term SGRQ refers to the 50-item, 3-month or 4-week recall version or the 40-item 
SGRQ-C version, unless otherwise specified. 
2 
  Contains Nonbinding Recommendations 
activities; and (3) impacts  psychosocial effects of the disease. In the context of this 
guidance, sponsors should only use the total score.  
 
  When using one or more individual domains as a measure in clinical trials, a sponsor 
should discuss this with the review division. 
 
  The minimum clinically important difference for the total score between patients and 
within-patient has been determined to be at least 4 units on the SGRQ scale (Jones 2002; 
Jones 2005). For the FDA, no evidence exists to support the use of other values. 
 
C.  Method of Analysis 
 
  Responder analysis is the FDAs preferred primary method for reporting results from 
SGRQ data. This analysis compares patients who improve with patients who deteriorate 
or do not change. A sponsor can present responder analyses as the responder rate for each 
arm and the difference in the responder rates, or the odds ratio. Other analyses may be 
appropriate, and the sponsor should discuss these with the review division. 
 
  Because the time course of SGRQ responses can provide useful information, frequent 
measurements (e.g., once a month)6 during a clinical trial are appropriate. Because 
treatment effect may be slow in onset, in shorter trials (such as those of 6 months or less), 
an average estimate over the trial period may underestimate the benefit with chronic 
therapy; end-of-treatment measurements may provide a more accurate estimate of the 
benefit from chronic therapies. In longer trials, taking an average over the latter part of 
the trial period, such as over the last 3 months, may be appropriate. 
 
  At the study design phase, a sponsor should consider missing data and their plan to 
adequately address the missing data in the analysis.  A sponsor should consider that an 
absent SGRQ score caused by patient withdrawal may not be missing at random. During 
the protocol development phase, a sponsor should discuss with the review division 
methods of addressing missing data. 
 
D.  Use of the SGRQ 
 
  A sponsor can obtain scores from the SGRQ either using the SGRQ or the shorter SGRQ-
C. For the FDA, both versions are acceptable in COPD trials. However, within the same 
drug development program, or at least within the same trial, the sponsor should use only 
one version (i.e., the SGRQ or the SGRQ-C).  
 
  A sponsor can use the SGRQ as a PRO assessment of efficacy in submissions to 
investigational new drug applications, new drug applications, and biologics license 
applications. A sponsor should discuss with the review division the use of the SGRQ for 
stratification or enrichment purposes early in the protocol development phase.   
                                                 
6 This is applicable to SGRQ-C, which does not have a specific recall period, and the version of the SGRQ with a 4-
week recall period, but this is not applicable to the version of the SGRQ that has a 3-month recall period. 
3 
  Contains Nonbinding Recommendations 
 
  A sponsor can use the SGRQ as a coprimary endpoint7 or as a secondary endpoint 
providing supporting evidence of efficacy in a clinical trial. For example, a sponsor can 
consider the use of SGRQ as a coprimary endpoint, along with another measure of 
efficacy (such as measure of lung function), in a trial with a drug that has a relatively 
small effect on a single outcome measure (such as lung function), which may become 
more clinically convincing through corroboration by SGRQ data.   
 
  In general, FDA considers SGRQ information to be clinically important, and a sponsor 
should report the data obtained in clinical trials irrespective of the direction of the results. 
 
                                                 
7 Multiple primary endpoints become coprimary endpoints when it is necessary to demonstrate an effect on each of 
the endpoints to conclude that a drug is effective.  
4 
  Contains Nonbinding Recommendations 
REFERENCES 
 
Cazzola, M, NA Hanania, W MacNee, K Rudell, C Hackford, and N Tamimi, 2015, A Review of 
the Most Common Patient-Reported Outcomes in COPD  Revisiting Current Knowledge and 
Estimating Future Challenges, Int J Chron Obstruct Pulmon Dis, 10:725738. 
 
Coons, SJ, CJ Gwaltney, RD Hays, JJ Lundy, JA Sloan, DA Revidki, WR Lenderking, D Cella, 
E Basch, and ISPOR ePRO Task Force, 2009, Recommendations on Evidence Needed to 
Support Measurement Equivalence Between Electronic and Paper-Based Patient-Reported 
Outcome (PRO) Measures: ISPOR ePRO Good Research Practice Task Force Report, Value 
Health, 12(4):419429. 
 
Glaab, T, C Vogelmeier, and R Buhl, 2010, Outcome Measures in Chronic Obstructive 
Pulmonary Disease (COPD):  Strengths and Limitations, Respir Res, 11:79. 
 
Jones, PW, 2002, Interpreting Thresholds for a Clinically Significant Change in Health Status in 
Asthma and COPD, EUR Respir J, 19(3):398404. 
 
Jones, PW, 2005, St Georges Respiratory Questionnaire: MCID, COPD, 2(1):7579.  
 
Jones, PW, FH Quirk, CM Baveystock, and P Littlejohns, 1992, A Self-Complete Measure of 
Health Status for Chronic Airflow Limitation, Am Rev Respir Dis, 145(6):13211327. 
 
Martinez, FJ, JF Donohue, and SI Rennard, 2011, The Future of Chronic Obstructive Pulmonary 
Disease Treatment  Difficulties of and Barriers to Drug Development, Lancet, 378:10271037. 
 
Meguro, M, EA Barley, S Spencer, and PW Jones, 2007, Development and Validation of an 
Improved, COPD-Specific Version of the St. George Respiratory Questionnaire, Chest, 
132(2):456463. 
 
Schunemann, HJ, L Griffith, R Jaeschke, R Goldstein, D Stubbing, and GH Guyatt, 2003, 
Evaluation of the Minimal Important Difference for the Feeling Thermometer and the St. 
Georges Respiratory Questionnaire in Patients With Chronic Airflow Obstruction, J Clin 
Epidemiol, 56(12):11701176. 
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