The E-RS:COPD
The Evaluating Respiratory Symptoms (E-RS):COPD scale is used to measure the effect of treatment on the severity of respiratory symptoms in stable chronic obstructive pulmonary disease (COPD)
The E-RS:COPD, a derivative instrument of the EXACT (The EXAcerbations of Chronic pulmonary disease Tool), was designed to address the need for a standardized respiratory symptom diary with a development and validation history consistent with good research practices and patient-reported outcome (PRO) requirements of the U.S. Food and Drug Administration (FDA).
See the FDA PRO guidance here.
Because the EXACT includes assessment of 11 respiratory symptoms in stable and acute states, the EXACT served as the basis for development of the E-RS.
Formerly known as the EXACT-Respiratory Symptoms Scale (E-RS), it was renamed the E-RS: Evaluating Respiratory Symptoms measure at the request of the FDA, to avoid use of the term “EXACT” or “exacerbations” in cases where the E-RS is named in a product label. When referring specifically to its use in COPD, the proposed context of use for qualification, the instrument is now referred to as the “Evaluating Respiratory Symptoms in COPD (E-RS:COPD).”
The E-RS:COPD was qualified by the European Medicines Agency (EMA) in 2015 and the FDA in 2016 as a PRO instrument to assess respiratory symptoms in patients with stable COPD
In June 2023, Evidera and the COPD Foundation submitted a Type V Drug Master File (DMF) to the FDA with reference and supporting information related to responder definitions and longitudinal sensitivity to change of E-RS:COPD total and subscale scores.
The E-RS:COPD DMF is available as a reference to individual sponsors as they engage in discussions with the FDA regarding use of the instrument as a key endpoint in pivotal trials.
The E-RS:COPD development methods
Methods used to optimize content validity
Qualitative data from the EXACT development study were re-analyzed with emphasis on patient descriptions of respiratory symptoms during stable COPD (n=63). Data were also gathered from new focus groups with patients who were exacerbation-free for 12 months (n=21).
Tests of reliability, validity and responsiveness
Tests of reliability, validity and responsiveness were performed on the subset of data from stable patients (n=188) gathered as part of the prospective observational study used to develop the EXACT.
Factor analyses showed three subscales: RS-Breathlessness, RS-Cough and sputum, and RS-Chest symptoms. Second-order factor analysis supported a general factor and use of a total score to reflect respiratory symptoms overall.
Scores exhibited high levels of internal consistency and reproducibility.
Evidence of construct validity included:
- Correlations with the Saint George’s Respiratory Questionnaire (SGRQ), rescue medication use, clinician-reported Modified Medical Research Council (mMRC), forced expiratory volume (FEV1%) predicted.
- Scores differentiated groups based on chronic bronchitis diagnosis, smoking status and rescue medication use.
Further validation
E-RS scores were subjected to further tests of reliability and validity through secondary analyses of the three clinical trial datasets used to test the EXACT, including one six-month trial in the U.S. and two three-month international trials.
Methods and results, including proposed responder thresholds, are published in Leidy et al., 2014.
Methods of administration
An eDiary certification program was developed to enhance consistency across eDiary vendors and platforms. Learn more about ePRO certification.
The E-RS:IPF
The E-RS®:IPF scale is an adaptation of the E-RS:COPD for use in interstitial pulmonary fibrosis (IPF). The 11-item E-RS:COPD was evaluated for use as a measure of respiratory symptoms in studies of patients with IPF.
The E-RS:IPF utilizes the 11 respiratory symptom items contained in the 14-item EXACT. Four subscales can be used to assess breathlessness (IPF-Breathlessness), cough (IPF-Cough), sputum (IPF-Sputum) and chest-related symptoms (IPF-Chest symptoms).
Methods used to optimize content validity
Content validity was evaluated through information and data from the literature and a qualitative study of 30 patients with IPF.
Tests of reliability, validity and responsiveness
Reliability, validity and responsiveness of E-RS:IPF scores were performed using secondary analyses of data from an IPF clinical trial.
Exploratory factor analysis (EFA) showed a four-factor solution, indicating four respiratory symptom subscales to comprise the measure.
- IPF-Breathlessness (Items 7, 8, 9, 10, and 11)
- IPF-Chest symptoms (Items 1, 5, and 6)
- IPF-Cough (Item 2)
- IPF-Sputum (Items 3 and 4)
Methods of administration
Access content covered by the E-RS. Methods and results of the development and validation of the E-RS adaptation are published in Bacci et al., 2017.
The eDiary certification program also applies to the E-RS:IPF.
E-RS:COPD: The 11-items comprising the E-RS:COPD are part of the EXACT, therefore, translations of the EXACT apply.
ERS:IPF: Translations of the EXACT can be used for the ERS:IPF, however, linguistic interviews in IPF may be necessary. See more information and a full list of translations here.
The EXACT and E-RS measures are available for licensing to use in research studies.
Separate user manuals were created for the E-RS:COPD and E-RS:IPF, describing the instrument’s development, intended use, administration procedures and scoring, and are provided to all licenses users to facilitate standardized use.
Visit clinicaltrials.gov to review trials using the EXACT® or E-RS™
Source: ClinicalTrials.gov
Publications
Access a resource list of publication references.
FAQs
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