Development and validation procedures for the EXACT were consistent with guidelines for PRO instrument development proposed by the FDA and EMA and well-known measurement principles.
The process involved over 500 people, including 493 patients with COPD and 18 professionals from the US and Europe with expertise in pulmonary medicine, clinical research, instrument development, and drug development regulations.
A comprehensive literature review was performed to examine the clinical definition of COPD exacerbations and identify and evaluate existing PRO instruments used to evaluate exacerbation outcomes in clinical research, with specific interest in clinical trials.To ensure and document content validity through qualitative methods, 83 men and women with a diagnosis of COPD and history of exacerbations participated in elicitation focus groups or interviews.
Quantitative data were gathered through a prospective 2-group observational validation study of 410 patients with COPD.Group 1: 222 acute patients with a clinician-confirmed exacerbation completed the draft item pool and additional items via an electronic diary each evening before bedtime on Days 1-28 of their exacerbation and again on Days 60-67, with clinical assessments performed on multiple days throughout the assessment period.
Group 2: 188 stable patients completed baseline assessments and the diary over seven days.
Methods and results are published in Leidy et al. 2011.
Item analyses and Rasch item-response theory were used to derive the final 14-item EXACT and Total score algorithm.
The EXACT Total score is computed by using logit values and a simple look-up table to yield interval-level scores ranging from 0 to 100, where higher scores indicate a more severe condition.
The EXACT Total score is used to determine the patient’s stable baseline, onset of an exacerbation event (threshold of sustained worsening), and recovery from the exacerbation (threshold of sustained improvement).
Methods and results are published in Jones et al. 2011.
Content covered by the EXACT is shown here.
Tests of the reliability, validity, and responsiveness of EXACT scores were performed on data from the 410 subjects using an a priori statistical analysis plan (SAP) and follow-up secondary analyses.
Scores exhibited high levels of internal consistency and reproducibility.
Evidence of construct validity included:
Two expert panel meetings were held to discuss results and interpretation guidelines.
Methods and results are published in Leidy et al. 2011.
EXACT scores were subjected to further tests of reliability and validity through secondary analyses of three clinical trial datasets, including one 6-month trial in the United States and two 3-month international trials.
Methods and results are published in Leidy et al. 2014.
To facilitate standardized use, an EXACT-PRO User Manual was created, describing the instrument’s development, intended use, administration procedures, and scoring.
An eDiary certification program was developed to enhance consistency across eDiary vendors and platforms. See more information on ePRO certification here.
Development and validation procedures for the E-RS were consistent with guidelines for PRO instrument development proposed by the FDA and EMA and well-known measurement principles.
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.
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). (See Leidy et al. 2014).
Content covered by the E-RS:COPD is shown here
Tests of the 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 3 subscales: RS-Breathlessness, RS-Cough & 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:
Development methods and results are published in Leidy et al. 2014.
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 6-month trial in the United States and two 3-month international trials.
Methods and results, including proposed responder thresholds, are published in Leidy et al. 2014.
To facilitate standardized use, a separate E-RS:COPD User Manual was created, describing the instrument’s development, intended use, administration procedures, and scoring.
The eDiary certification program used for the EXACT applies to the E-RS:COPD. See more information on ePRO certification here.
E-RS:IPF – An adaptation of the E-RS for use in Interstitial Pulmonary Fibrosis The 11-item E-RS:COPD was evaluated for use as a measure of respiratory symptoms in studies of patients with interstitial pulmonary fibrosis (IPF).
Content validity was evaluated through information and data from:
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 comprise the measure.
See content table here for information on item content.
Methods and results of the development and validation of the E-RS adaptation are published in Bacci et al. 2017.
To facilitate standardized use, an E-RS: IPF User Manual was created, describing the instrument’s development, intended use, administration procedures, and scoring.
Translations of the parent instrument, the EXACT, can be used for the ERS:IPF. However, linguistic interviews in IPF may be necessary. See more information about translations here.
The EXACT® was developed under the EXACT-PRO Initiative®, a multi-year, multi-sponsor project involving experts in pulmonary medicine, instrument development, and drug development regulatory issues, dedicated to the development of a single, standardized instrument for evaluating the effects of treatment on acute exacerbations of COPD.
The EXACT®, E-RS®, and all related materials are owned by Evidera and are subject to Evidera’s Legal Disclaimer.