Evidence map›Paper›PMID 25287629›Full record

Trial reportRespiratory research2014

Measuring respiratory symptoms of COPD: performance of the EXACT- Respiratory Symptoms Tool (E-RS) in three clinical trials.

Nancy K Leidy, Lindsey T Murray, Brigitta U Monz, Linda Nelsen, Mitchell Goldman, Paul W Jones, Elizabeth J Dansie, Sanjay Sethi

4 registry-linked trialsAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Respiratory research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 76 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00739648 phase2completednot on this map

Phase 2, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety, Tolerability and Efficacy of MP-376 Inhalation Solution Administered for 5 Days Every 28 Days to Prevent Acute Exacerbations in High Risk COPD Patients

TypeinterventionalSponsorAmgenRan2008 to 2010Enrolled322ConditionsChronic Obstructive Pulmonary DiseaseArmsMP-376, Placebo
NCT00949975 phase2completednot on this map

A 12-week, Randomised, Double-blind, Placebo-controlled, Parallel Group, Multinational, Phase IIb Dose Range Finding Study to Evaluate the Efficacy and Safety of AZD9668 Administered Orally at 3 Dose Levels to Patients With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Tiotropium

TypeinterventionalSponsorAstraZenecaRan2009 to 2010Enrolled838ConditionsChronic Obstructive Pulmonary DiseaseArmsAZD9668, AZD9668 Placebo
NCT01023516 phase2completednot on this map

A 12-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Multinational, Phase IIb Study to Evaluate the Efficacy and Safety of 60mg AZD9668 Administered Orally Twice Daily to Subjects With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Budesonide/Formoterol

TypeinterventionalSponsorAstraZenecaRan2009 to 2010Enrolled615ConditionsChronic Obstructive Pulmonary Disease (COPD)ArmsAZD9668, Placebo
NCT03084796 phase2completednot on this mapstarted 2017, after this paper: background citation

A 6-week, Multicenter, Randomized, Double-blind, Placebo and Active-controlled, Parallel Group, Dose-ranging Study to Evaluate the Efficacy and Safety of 4 Doses of CHF 5259 pMDI (HFA Glycopyrronium Bromide Via Pressurized Metered Dose Inhaler) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

TypeinterventionalSponsorChiesi Farmaceutici S.p.A.Ran2017 to 2018Enrolled733ConditionsCOPD, Chronic Obstructive Pulmonary DiseaseArmsCHF 5259, Placebo, Tiotropium Bromide 18 µg Inhalation Capsule
3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 4 syntheses or guidelines pooled it.

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  20. A randomized trial of symptom-based management in Japanese patients with COPD.International journal of chronic obstructive pulmonary disease · 2018
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16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Nancy K LeidyEvidera, 7101 Wisconsin Ave, Suite 1400, Bethesda, MD, 20814, USA. nancy.leidy@evidera.com.
Lindsey T MurrayEvidera, 7101 Wisconsin Ave, Suite 1400, Bethesda, MD, 20814, USA. lindsey.murray@evidera.com.
Brigitta U MonzFormerly Boehringer Ingelheim GmbH, Ingelheim, Germany. lbmonz@t-online.de.
Linda NelsenMerck, Sharp & Dohme, Corp, Whitehouse Station, NJ, USA. linda.m.nelsen@gsk.com.
Mitchell GoldmanAstraZeneca, Wilmington, DE, USA. mitchell.goldman@astrazeneca.com.
Paul W JonesSt. George's, University of London, London, UK. pjones@sgul.ac.uk.
Elizabeth J DansieEvidera, 7101 Wisconsin Ave, Suite 1400, Bethesda, MD, 20814, USA. elizabeth.dansie@evidera.com.
Sanjay SethiUniversity of Buffalo, Buffalo, NY, USA. ssethi@buffalo.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSymptomatic relief is an important treatment goal for patients with COPD. To date, no diary for evaluating respiratory symptoms in clinical trials has been developed and scientifically-validated according to FDA and EMA guidelines. The EXACT - Respiratory Symptoms (E-RS) scale is a patient-reported outcome (PRO) measure designed to address this need. The E-RS utilizes 11 respiratory symptom items from the existing and validated 14-item EXACT, which measures symptoms of exacerbation. The E-RS total score quantifies respiratory symptom severity, and 3 domains assess breathlessness, cough and sputum, and chest symptoms.

methodsThis study examined the performance of the E-RS in each of 3 controlled trials with common and unique validation variables: one 6-month (N = 235, US) and two 3-month (N = 749; N = 597; international). Subjects completed the E-RS as part of a daily eDiary. Tests of reliability, validity, and responsiveness were conducted in each dataset.

resultsIn each study, RS-Total score was internally consistent (Cronbach α) (0.88, 0.92, 0.92) and reproducible (intra-class correlation) in stable patients (2 days apart: 0.91; 7 days apart: 0.71, 0.74). RS-Total scores correlated significantly with the following criterion variables (Spearman's rho; p < 0.01, all comparisons listed here): FEV1% predicted (-0.19, -0.14, -0.15); St. George's Respiratory Questionnaire (SGRQ) (0.65, 0.52, 0.51); Breathlessness, Cough, and Sputum Scale (BCSS) (0.89, 0.89); modified Medical Research Council dyspnoea scale (mMRC) (0.40); rescue medication use (0.43, 0.42); Functional Performance Inventory Short-Form (FPI-SF) (0.43); 6-minute walk distance (6-MWT) (-0.30, -0.14) and incremental shuttle walk (ISWT) (-0.18) tests. Correlations between these variables and RS-Breathlessness, RS-Cough and Sputum, RS-Chest Symptoms scores supported subscale validity. RS-Total, RS-Breathlessness, and RS-Chest Symptoms differentiated mMRC levels of breathlessness severity (p < 0.0001). RS-Total and domain scores differentiated subjects with no rescue medication use and 3 or more puffs (p < 0.0001). Sensitivity to changes in health status (SGRQ), symptoms (BCSS), and exercise capacity (6MWT, ISWT) were also shown and responder definitions using criterion- and distribution-based methods are proposed.

conclusionsResults suggest the E-RS is a reliable, valid, and responsive measure of respiratory symptoms of COPD suitable for use in natural history studies and clinical trials.

trial registrationMPEX: NCT00739648 ; AZ1: NCT00949975 ; AZ 2: NCT01023516.

Indexed as

Surveys and QuestionnairesAgedCoughDisease ProgressionDouble-Blind MethodDyspneaExercise TestExercise ToleranceFemaleHealth StatusHumansLungMaleMiddle AgedPredictive Value of TestsPulmonary Disease, Chronic Obstructive

Identifiers

PMID25287629
PMCPMC4203869

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.