Patient-Reported Outcomes (PROs) in COPD Clinical Trials: Trends and Gaps

Figures & data

Table 1 Frequency of PRO Measures Reported in the Included Trials (n=104)

Category	PRO Measures	No. of Trials (n)
Symptom-based	Baseline/Transition Dyspnea Indexes (BDI/TDI)^a	60
	Unvalidated symptom-based instruments^b	32
	Evaluating Respiratory Symptoms in COPD (E-RS™: COPD)^c	9
	Exacerbations of Chronic Pulmonary Disease Tool (EXACT)	4
	Shortness of Breath with Daily Activities (SOBDA)	4
	Chronic Respiratory Questionnaire Self-Administered Standardized (CRQ-SAS) dyspnea domain^d	4
	Early Morning and Nighttime Symptoms of COPD Instrument (EMSCI and NiSCI)	4
	Borg Dyspnea Scale	3
	Shortness of Breath Questionnaire (SOBQ)	2
	Global Chest Symptoms Questionnaire (GCSQ)	1
	Cough Symptom Score (CSS)	1
HRQoL-specific	St. George’s Respiratory Questionnaire (SGRQ)	64
	St. George’s Respiratory Questionnaire COPD-specific (SGRQ-C)	12
	COPD Assessment Test (CAT)	21
	Cough and Sputum Assessment Questionnaire (CASA-Q)	2
	Capacity of Daily Living during the Morning (CDLM)	2
	Clinical COPD Questionnaire (CCQ)	2
	Leicester Cough Questionnaire (LCQ)	1

Notes: Results presented are mutually inclusive, which means that while counting the number of PRO endpoints, there may have been cases wherein more than one PRO was used in the same trial. In such cases, results reported are based on the frequency of usage of that individual PRO from the total trials. ^aBDI/TDI are interview-based instruments (except the self-administered computerized [SAC] version); ^bUnvalidated instruments are instruments that do not have published evidence for their validation; ^cE-RSTM: COPD is subscale of EXACT; ^dCRQ-SAS is an HRQoL instrument, but in clinical trials, only the dyspnea domain was used; hence, it has been classified under symptom.

Abbreviations: COPD, chronic obstructive pulmonary disease; HRQoL, health-related quality of life; PRO, patient-reported outcome.

Table 2 Domain-Level Analysis of PRO Measures Used in Included Clinical Trials (n=104)

Domains and Sub-Domains (Number of Items)		SGRQ (50)	SGRQ-C^a (40)	CDLM (8)	LCQ (19)	CAT (8)	CCQ (10)	CASA-Q (20)	EXACT (14)	CSS (2)	SOBQ (24)	SOBDA (13)	CRQ-SAS^b (20)	GCSQ (2)	EMSCI/ NiSCI^c (6)	Borg Scale (1)
Dyspnea	General/at rest/severity	+	+	-	-	-	+	+	+	-	+	+	-	+	+	+
	During activities	+	+	-	-	+	+	-	+	-	+	+	+	-	-	+
	Impact	+	+	+	-	-	-	-	-	-	+	+	+	-	-	-
Chest symptoms	Frequency/severity	+	+	-	-	+	-	-	+	-	-	-	-	+	+	-
	Impact	+	+	+	+	-	-	-	-	-	-	-	-	-	-	-
Wheeze	Frequency/severity	+	+	-	-	-	-	-	-	-	-	-	-	-	+	-
	Impact	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Cough	Frequency/severity	+	+	-	+	+	+	+	+	+	-	-	-	-	+	-
	Impact	+	+	-	+	-	-	+	-	-	-	-	-	-	-	-
Sputum	Frequency/severity	+	+	-	-	+	+	+	+	-	-	-	-	-	+	-
	Impact	-	-	-	+	-	-	+	-	-	-	-	-	-	-	-
Other symptom related	Disease-free days	+	+	-	-	-	-	-	-	-	-	-	-	-	-	-
	Morning symptoms	+	+	+	-	-	-	-	-	-	-	-	-	-	-	-
Sleep	Sleep quality	-	-	-	-	+	-	-	-	-	-	-	-	-	-	-
	Sleep disturbance	+	+	-	+	-	-	+	+	-	-	-	-	-	-	-
	Nighttime awakening	-	-	-	-	-	-	+	-	-	-	-	-	-	-	-
Energy	Fatigue/tiredness/activeness	+	+	+	+	+	-	-	+	-	-	-	-	-	-	-
Activities of daily living	Daily activities limitations	+	+	+	+	+	+	+	+	-	+	+	-	-	+	-
	Leisure/fun activities/sports	+	+	-	+	-	-	+	-	-	-	-	-	-	-	-
	Impact on mobility	+	+	+	-	-	-	-	-	-	-	-	-	-	-	-
Psychosocial	Depression/anxiety	-	-	-	+	-	+	-	-	-	-	-	-	-	-	-
	Embarrassment	+	+	-	+	-	-	+	-	-	-	-	-	-	-	-
	Fear/panic/worry/concern	+	+	-	+	-	+	-	+	-	+	-	-	-	-	-
	Hopelessness	+	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Happiness/sadness	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Annoyance/frustration	-	-	-	+	-	-	+	-	-	-	-	-	-	-	-
	Family/personal relationship	+	+	-	+	-	-	-	-	-	-	-	-	-	-	-
	Social life	-	-	-	+	-	+	+	-	-	-	-	-	-	-	-
Treatment impact	Disease control	+	+	-	+	-	-	-	-	-	-	-	-	-	-	-
	Treatment satisfaction	+	-	-	-	-	-	-	-	-	-	-	-	-	-	-
	Medication/side effects	+	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Work	Work productivity/ job	+	-	-	+	-	-	-	-	-	-	-	-	-	-	-
Other	Environmental exposure^d	-	-	-	+	-	-	-	-	-	-	-	-	-	-	-

Notes: (+) indicates the presence and (-) indicates the absence of a domain or sub-domain. ^aAn item on overall health is included in SGRQ-C but is not included in the total score; ^bCRQ-SAS is an HRQoL instrument, but in clinical trials, only the dyspnea domain was used; hence, it has been classified under symptom; ^cEMSCI/NISCI items are included based on available literature as these instruments were not available in the public domain at the time of execution of the study; unvalidated instruments are not included in this table; ^dPrecipitation/increase in symptoms due to environmental exposure.

Abbreviations: CASA-Q, Cough and Sputum Assessment Questionnaire; CAT, COPD Assessment Test; CCQ, Clinical COPD Questionnaire; CDLM, Capacity of Daily Living during the Morning; COPD, chronic obstructive pulmonary disease; CRQ-SAS, Chronic Respiratory Questionnaire Self-Administered Standardized; CSS, Cough Symptom Score; EMSCI/NiSCI, Early Morning/Nighttime Symptoms of COPD Instrument; EXACT, Exacerbations of Chronic Pulmonary Disease Tool; GCSQ, Global Chest Symptoms Questionnaire; HRQoL, health-related quality of life; LCQ, Leicester Cough Questionnaire; PRO, patient-reported outcome; SGRQ, St. George’s Respiratory Questionnaire; SGRQ-C, St. George’s Respiratory Questionnaire COPD-specific; SOBDA, Shortness of Breath with Daily Activities; SOBQ, Shortness of Breath Questionnaire.

Figure 1 Overview of impact of COPD symptoms on HRQoL.

Notes: Data from these studies.^1–29 Clinical endpoints, symptom diaries, and EXACT were used to capture exacerbations. Cost of treatment includes both direct and indirect costs, but this aspect was not captured in this review.
Abbreviations: EXACT, Exacerbations of Chronic Pulmonary Disease ToolHRQoL, health-related quality of life.

LozanoR, NaghaviM, ForemanK, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–2128. doi:10.1016/S0140-6736(12)61728-023245604

 PubMed Web of Science ®Google Scholar

CazzolaM, MacNeeW, MartinezFJ, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J. 2008;31(2):416–469. doi:10.1183/09031936.0009930618238951

 PubMed Web of Science ®Google Scholar