Exacerbations Of Chronic Pulmonary Disease Tool Research Articles

A proof of concept for continuous, non-invasive, free-living vital signs monitoring to predict readmission following an acute exacerbation of COPD: a prospective cohort study

BackgroundThe use of vital signs monitoring in the early recognition of an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) post-hospital discharge is limited. This study investigated whether continuous vital signs monitoring could predict an AECOPD and readmission.Methods35 people were recruited at discharge following hospitalisation for an AECOPD. Participants were asked to wear an Equivital LifeMonitor during waking hours for 6 weeks and to complete the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a 14-item symptom diary, daily. The Equivital LifeMonitor recorded respiratory rate (RR), heart rate (HR), skin temperature (ST) and physical activity (PA) every 15-s. An AECOPD was classified as mild (by EXACT score), moderate (prescribed oral steroids/antibiotics) or severe (hospitalisation).ResultsOver the 6-week period, 31 participants provided vital signs and symptom data and 14 participants experienced an exacerbation, of which, 11 had sufficient data to predict an AECOPD. HR and PA were associated with EXACT score (p < 0.001). Three days prior to an exacerbation, RR increased by mean ± SD 2.0 ± 0.2 breaths/min for seven out of 11 exacerbations and HR increased by 8.1 ± 0.7 bpm for nine of these 11 exacerbations.ConclusionsIncreased heart rate and reduced physical activity were associated with worsening symptoms. Even with high-resolution data, the variation in vital signs data remains a challenge for predicting AECOPDs. Respiratory rate and heart rate should be further explored as potential predictors of an impending AECOPD.Trial registration: ISRCTN registry; ISRCTN12855961. Registered 07 November 2018—Retrospectively registered, https://www.isrctn.com/ISRCTN12855961

PNS390 EMA/FDA PARALLEL QUALIFICATION PROCEDURE FOR THE DEVELOPMENT OF NOVEL PATIENT REPORTED OUTCOME INSTRUMENTS:PROCESS AND IMPACT

The study aim is to investigate the parallel qualification procedure established between the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the development of novel patient reported outcome instruments (PROs). A comprehensive literature review was conducted in EMA and US FDA websites pertaining to the EMA/FDA parallel qualification procedure and in PubMed®. The regulatory framework for the EMA/FDA Parallel qualification procedure was identified and the published qualification decisions were extracted. The parallel qualification is a stand-alone procedure, intended to provide simultaneously advice from the EMA and FDA for the development of novel PRO instruments applicable for multiple clinical development programs. Although each Agency follows its internal rules during the qualification assessment, this procedure reduces the administrative burden, supports the regulatory bodies information scientific sharing to reach a convergence during the decision-making process to optimize the development of novel PRO instruments. Both Agencies publish independently their final qualification decisions on their websites. The use of the PRO instruments is specified in respect to the disease, trial population, type of the trials, phase of the clinical development program, endpoints positioning, target claims and can support label claims and so the direct advertising to patients in US, irrespective of the drug prescription status. So far 3 tools were submitted for parallel qualification: the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), EXACT respiratory symptoms tool (E-RS: COPD), the Modified Pediatric Ulcerative Colitis Activity Index (PUCAI) / TUMMY Scale. The EMA/FDA dialog offers the option to obtain simultaneously advice for the development of novel PRO instruments applicable for multiple clinical development programs. The procedure allows dialogue and alignment between FDA and EMA for the development of novel PRO instruments. It will likely become the preferred route for PRO development intended to inform drug development.

Patient-Reported Burden of Illness in a Prevalent COPD Population Treated with Long-Acting Muscarinic Antagonist Monotherapy: A Claims-Linked Patient Survey Study.

IntroductionSymptom burden in inadequately controlled chronic obstructive pulmonary disease (COPD) considerably impacts quality of life, healthcare resource utilization (HCRU) and associated costs. This claims-linked cross-sectional survey study assessed symptom burden and HCRU among a prevalent population of COPD patients prescribed long-acting muscarinic antagonist (LAMA) monotherapy.MethodsPatients were identified using claims data from the Optum Research Database. Eligible patients were aged ≥ 40 years with 12 months’ continuous enrollment in a US health plan, ≥ 2 medical claims containing COPD diagnosis codes ≥ 30 days apart, and ≥ 2 claims for LAMA monotherapy in the latter half of the 12-month sample identification period. Patients were mailed a cross-sectional survey assessing patient-reported outcomes (PROs) [COPD assessment test (CAT) and modified medical research council dyspnea scale (mMRC)], clinical characteristics, smoking history, and demographics. Patients also completed the Exacerbations of Chronic Pulmonary Disease Tool (EXACT-PRO) daily diary for 7 days. HCRU was assessed from claims data.ResultsThe study included 433 patients with a self-reported healthcare provider COPD diagnosis, and both claims-based and self-reported LAMA monotherapy treatment (mean age 71.0 years; 59.8% female). Most patients (85.5%) reported a high symptom burden (CAT score ≥ 10), 45.5% had high levels of dyspnea (mMRC grade ≥ 2), and 64.4% reported more severe daily symptoms by the EXACT-PRO. Most patients (71.6%) reported high scores on ≥ 2 PROs. More patients with high symptom burden had COPD-related emergency department visits than those with lower disease burden (27.6% vs 12.7%, P = 0.012).ConclusionsIn conclusion, a large proportion of patients with COPD receiving LAMA monotherapy experienced a high symptom burden and may benefit from therapy escalation. Healthcare professionals can use validated PROs to help them assess symptom burden.FundingGlaxoSmithKline (GSK study number: 205862)Electronic supplementary materialThe online version of this article (10.1007/s41030-019-0091-0) contains supplementary material, which is available to authorized users.

Comparison of patient-reported outcomes during acute exacerbations of chronic obstructive pulmonary disease

IntroductionThe aim of this study was to investigate which patient-reported outcome measure was the best during the recovery phase from severe exacerbation of chronic obstructive pulmonary disease (COPD).MethodsThe Exacerbations of...

The association between daily exacerbation symptoms and physical activity in patients with chronic obstructive pulmonary disease.

BackgroundEvidence from longitudinal studies on the impact of exacerbation symptoms on physical activity in chronic obstructive pulmonary disease (COPD) is lacking. The aim of this first exploratory study was to assess the association between exacerbation symptoms and physical activity, and to quantify the relative influence of specific symptoms.MethodsWe recruited COPD patients at high risk for exacerbations from 2 pulmonary rehabilitation clinics and 1 acute care clinic in Switzerland. For 3 months after discharge, patients completed a daily symptom diary on a smartphone application, the EXAcerbations of Chronic pulmonary disease Tool (EXACT), and wore a pedometer to measure daily steps. We used mixed-effects models to determine the association of daily steps with exacerbation symptoms.ResultsA total of 21 patients (Global Initiative for Chronic Obstructive Lung Disease grades 2–4) were enrolled for a mean of 94.4 days (standard deviation 4.2). The baseline median number of daily steps was 3,264.6 (interquartile range [IQR]: 1,851.3–4,784.1) and EXACT score was 37.0 (IQR: 30.9–41.4). A 12-point increase in EXACT score (indicating the start of an exacerbation) was statistically significantly associated with a decrease in daily steps of 653.3 (95% CI 969.7–336.9). Chest symptoms (tightness, discomfort and congestion) were more strongly associated with change in steps than breathlessness, and cough and sputum (z-value −4.5 vs −2.9 and −3.0).ConclusionThis is the first study to show that, in a small cohort of COPD patients, increases in exacerbation symptoms were associated with a statistically and clinically significant reduction in daily physical activity. These results underscore the importance for symptom control and exacerbation prevention in COPD patients.

Understanding and measuring symptoms and health status in asthma COPD overlap: content validity of the EXACT and SGRQ

BackgroundAsthma-chronic obstructive pulmonary disease overlap (ACO) differs from asthma and chronic obstructive pulmonary disease (COPD) in demographics, phenotypic characteristics and outcomes, yet the patient experience of ACO is poorly characterized. We aimed to understand and compare the patient experience of symptoms and domains of impact in ACO relative to COPD, and assess the content validity of existing patient-reported outcome (PRO) instruments in ACO.MethodsThis US qualitative, interview study included patients who met American Thoracic Society/European Respiratory Society spirometric criteria for COPD. Additionally, patients with ACO demonstrated reversibility (forced expiratory volume in 1 s [FEV1] increase ≥ 12% and ≥ 200 mL) to albuterol/salbutamol and an FEV1/forced vital capacity ratio < 0.7. Patients took part in concept elicitation (CE) to explore symptoms and impacts of obstructive lung disease. The Exacerbations of Chronic Pulmonary Disease Tool (EXACT), St George’s Respiratory Questionnaire (SGRQ) and a daily wheeze assessment were cognitively debriefed to assess relevance and comprehensiveness. Interviews were analyzed using Atlas.Ti. Concept saturation was evaluated at the symptom level.ResultsTwenty patients with ACO and 10 patients with COPD were recruited. Patients from both groups indicated that shortness of breath was their most frequent and bothersome symptom. The most frequently reported symptoms in both groups were shortness of breath, cough, wheezing, difficulty breathing, mucus/phlegm, chest tightness, and tiredness, weakness or fatigue. The onset, severity, frequency and duration of symptoms were consistently described across both groups, although a higher proportion of patients with ACO experienced exacerbations versus those with COPD. Impacts on daily living, physical impacts and emotional impacts were commonly described (ACO: 90–100%, COPD: 80–100%). Concept saturation was achieved in both groups. Overall, the EXACT, SGRQ and daily wheeze assessment were well understood and relevant to most patients with ACO or COPD (50–100%) and patients generally found the assessments easy to complete. The PRO instruments adequately captured symptoms described during CE, demonstrating high content validity in ACO and COPD.ConclusionsPatients with ACO and COPD experienced similar symptoms and impacts. The EXACT, SGRQ and assessment of wheeze were well understood and captured concepts relevant to patients with ACO.

The Short-term Impact of Symptom-defined COPD Exacerbation Recovery on Health Status and Lung Function.

Background: This study examined the short-term effects of symptom-defined exacerbation recovery on health status and pulmonary function in moderate to severe chronic obstructive pulmonary disease (COPD) patients. Methods: Secondary analyses of pooled data from two 12-week Phase II international, randomized controlled trials using the EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) to identify symptom-defined exacerbations were conducted. Recovery was categorized as recovered, unrecovered (persistent worsening), or censored. Multiple regression analyses were used to test the effect of recovery status on change in the St George's Respiratory Questionnaire (SGRQ) and forced expiratory volume in 1 second (FEV1) from baseline to Week 12. Evaluating Respiratory Symptom scale (E-RS) scores were used to evaluate change in stable-state respiratory symptoms from baseline to Week 12. Results: Of 1346 eligible patients, 414 (31%) experienced ≥1 symptom-defined exacerbation; 260 patients recovered from their events, 80 experienced an unrecovered event (persistent worsening), 74 patients had only censored events (excluded). Groups were similar at baseline, with the recovered group reporting significantly worse symptoms (p<0.01). Recovery group and baseline SGRQ were significant predictors of change in health status over 12 weeks (p=0.04; p<0.01); no effects were observed for lung function. Significant between-group differences in change in respiratory symptom severity from baseline to Week 12 were observed (p<0.01), with the persistent worsening group experiencing clinically meaningful deterioration in breathlessness and chest symptoms. Conclusions: Results suggest some patients have difficulty recovering from symptom-defined exacerbations, leading to a deterioration in health status, dyspnea, and chest symptoms without short-term effects on lung function. Further study of symptom-defined exacerbation recovery and health outcomes is warranted.

Fluticasone propionate/formoterol for COPD management: a randomized controlled trial.

PurposeTo evaluate fluticasone propionate/formoterol (FP/FORM) in COPD.Patients and methodsCOPD patients with forced expiratory volume in 1 s (FEV1) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations.ResultsIn total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; P≤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; P=0.084). Pre- and post-dose FEV1 and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM (P≤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; P=0.077). There were more St George’s Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; P≤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM (P≤0.066). Acute β2-agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups.ConclusionFP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 µg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments.

A longitudinal assessment of sleep variables during exacerbations of chronic obstructive pulmonary disease.

Although sleep disturbance is common in chronic obstructive pulmonary disease (COPD), relatively little is known on the effect of the exacerbation on sleep quality. Accordingly, we longitudinally assessed sleep variables during exacerbations and clinical stability. This is a sub-study of a larger observational analysis. Inclusion criteria were clinically stable COPD and two or more clinical exacerbations in the preceding 12 months. Patients were followed for approximately 6 months and during this time the following were recorded daily: (1) COPD exacerbations, which were determined in two ways, clinically and symptom defined using the exacerbations of chronic pulmonary disease tool (EXACT); (2) daytime sleepiness, which was measured using the Stanford Sleepiness Scale; (3) subjective awakenings, which was measured from a sleep diary; and (4) sleep duration, efficiency, and objective awakenings, which was measured from actigraphy. These variables for exacerbation and non-exacerbation days were compared. Seventeen patients (9 male, age 63 ± 12 years, forced expiratory volume in 1 second 52 ± 20%) entered data over 135 ± 18 days. During this time, 15 patients had 27 symptom-defined exacerbations and 8 had 9 clinically reported exacerbations. Symptom-defined exacerbation days were 26% of the total study days. More daytime sleepiness, decreased total sleep time (TST), and decreased sleep efficiency (SE) were present during exacerbations compared with clinical stability (p < 0.001). These disturbances tended to be greater during clinically reported exacerbations than during unreported events (p < 0.05). Increased daytime sleepiness, less TST, and poorer SE are present during COPD exacerbations.

Characterisation and impact of reported and unreported exacerbations: results from ATTAIN

The frequency and impact of exacerbations identified using healthcare resource utilisation (HCRU) or the EXAcerbations of Chronic pulmonary disease Tool (EXACT) were compared prospectively in a 24-week, phase III trial (ATTAIN). Patients with moderate-to-severe chronic obstructive pulmonary disease received twice-daily aclidinium 200 μg, aclidinium 400 μg or placebo. All HCRU events were reported to physicians. "EXACT-identified" events were categorised as "EXACT-reported" (detected by EXACT and reported to the physician) and "EXACT-unreported" (detected but not reported). Health status was measured using the St George's Respiratory Questionnaire (SGRQ). Annualised EXACT-identified event rates were higher in all study arms (placebo 1.39, aclidinium 200 μg 1.00 and aclidinium 400 μg 0.98 per patient per year) versus HCRU (placebo 0.60, aclidinium 200 μg 0.43 and aclidinium 400 μg 0.40 per patient per year). Concordance between methods was low (kappa 0.16). Aclidinium reduced EXACT-identified events (rate ratio versus placebo: aclidinium 200 μg 0.72 and aclidinium 400 μg 0.71; both p<0.05); HCRU events were similarly reduced. At week 24, SGRQ scores improved (-6.6 versus baseline) in patients with no event during weeks 1-12; improvements were significantly smaller in patients with HCRU events (-3.4; p=0.036) or EXACT-unreported events (-3.0; p=0.002). Unreported events were more frequent than reported events. Both had similar negative impact on health status. Aclidinium reduced the frequency of both types of event.

Measuring respiratory symptoms in clinical trials of COPD: reliability and validity of a daily diary

BackgroundAlthough respiratory symptoms are characteristic features of COPD, there is no standardised method for quantifying their severity in stable disease.ObjectiveTo evaluate the EXACT-Respiratory Symptom (E-RS) measure, a daily diary comprising...

Performance of the EXAcerbations of Chronic Pulmonary Disease Tool Patient-reported Outcome Measure in Three Clinical Trials of Chronic Obstructive Pulmonary Disease

The EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) is a patient-reported outcome measure to standardize the symptomatic assessment of chronic obstructive pulmonary disease exacerbations, including reported and unreported events. The instrument has been validated in a short-term study of patients with acute exacerbation and stable disease; its performance in longer-term studies has not been assessed. To test the EXACT's performance in three randomized controlled trials and describe the relationship between resource-defined medically treated exacerbations (MTEs) and symptom (EXACT)-defined events. Prespecified secondary analyses of data from phase II randomized controlled trials testing new drugs for the management of chronic obstructive pulmonary disease: one 6-month trial (United States) (n = 235) and two 3-month, multinational trials (AZ 1 [n = 749], AZ 2 [n = 597]). In each case, the experimental drugs were found to be ineffective, permitting assessment of the EXACT's performance in three independent studies of moderate to severe high-risk patients on maintenance therapies. The mean age of subjects was 62 to 64 years; 48 to 76% were male. Mean FEV1 % predicted was 42 to 59%. EXACT scores exhibited internal consistency (Cronbach's α ≥ 0.90), reproducibility (intraclass correlation ≥ 0.70), correlation with St. George's Respiratory Questionnaire (Spearman rho [rs] = 0.62, 0.46, 0.46 in the three trials; P < 0.001), and Breathlessness Cough and Sputum Scale (AZ 1, rs = 0.83; AZ 2, rs = 0.83; P < 0.001). EXACT-defined events had a high correspondence with alternative indicators of worsening (94, 88, and 93%). In each trial, unreported events were similar in severity (mean EXACT score, 56, 57, 61 vs. 53, 54 [P < 0.05], 57 [P < 0.05], respectively; 100-point scale) and longer (median, 9, 8, 7 vs. 8, 7 [P < 0.01], 6 days, respectively) than moderate MTEs. Data generated through the EXACT offers insight into the symptomatic nature of MTEs and the frequency, severity, and duration of unreported symptom-defined events. Clinical trials registered with www.clinicaltrials.gov (MPEX: NCT00739648; AZ 1: NCT00949975; AZ 2: NCT01023516).

Measuring and quantifying acute exacerbations of COPD: pitfalls and practicalities

Pity the poor clinical researcher who is charged with identifying and quantifying chronic obstructive pulmonary disease (COPD) exacerbation events in clinical trials. An exacerbation of COPD is a clinical event that: 1) has no standard, consensus definition [1]; 2) often goes unreported and undetected if patients choose to stay at home instead of presenting to a healthcare provider [2]; 3) often occurs suddenly with little or no warning [3]; and 4) is subject to diagnostic uncertainty and is easily confused with pulmonary embolism, congestive heart failure or pneumonia [4–6]. Given these inherent difficulties, much-needed efforts have been made towards developing better measurement tools for quantifying COPD exacerbation events [7]. One such new measurement tool is the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a 14-item, patient-reported daily symptom diary that attempts to accurately capture the frequency, severity, and duration of exacerbations, and which is meant to be used in clinical trials and cohort studies of COPD patients [8]. A tool such as EXACT is desperately needed by COPD clinical researchers [9], assuming that it works. In this issue of the European Respiratory Journal , Mackay et al. [10] have attempted to test EXACT to see if it fulfils its expected functions. The investigators prospectively administered EXACT as well as their previously validated London COPD Cohort …

A Longitudinal Study Evaluating the Effect of Exacerbations on Physical Activity in Patients with Chronic Obstructive Pulmonary Disease

Physical inactivity is common in stable chronic obstructive pulmonary disease (COPD) and independently predicts poor outcomes. Longitudinal assessments of physical activity in outpatients with COPD, covering periods of stability and exacerbations, have not been evaluated previously. Patients with clinically stable COPD and a history of two or more clinical exacerbations in the preceding 12 months were recruited. Physical activity was measured using a triaxial accelerometer worn continuously on the nondominant wrist. Mean minutes per day of higher level physical activity was the primary outcome variable. Symptom-defined exacerbations were assessed using the 14-item Exacerbations of Chronic Pulmonary Disease Tool (EXACT) daily dairy. Clinically reported exacerbations were also captured. Minutes per day of higher level physical activity during exacerbation and nonexacerbation days were compared, using a mixed model analysis. Seventeen patients were monitored for 135 ± 18 days. Nine were male with a mean age of 63 ± 12 years and mean FEV1 of 52 ± 20%. Fifteen patients had 27 symptom (EXACT)-defined exacerbations, including 9 that were also clinically reported. Patients spent fewer minutes per day at a higher level physical activity level during exacerbation days than nonexacerbation days: 131 ± 14 versus 157 ± 14 minutes (P < 0.0001). The greatest reduction in physical activity was during the first week of the exacerbation; activity remained low for approximately 2 weeks after exacerbation resolution. Physical activity decreased significantly during exacerbations. Reduction in activity occurs early during an exacerbation and persists for about 2 weeks after symptomatic recovery.

Detection and severity grading of COPD exacerbations using the exacerbations of chronic pulmonary disease tool (EXACT).

Uncertainty exists over the ability of the exacerbations of chronic pulmonary disease tool (EXACT) patient-reported outcome diary to quantify exacerbation severity and frequency. To clarify this, we investigated the ability of the EXACT to assess severity of exacerbations and examined the relationship between exacerbations diagnosed using London chronic obstructive pulmonary disease (COPD) cohort diary cards, physician review and symptom-defined events using the EXACT. 58 patients enrolled in the London Chronic Obstructive Pulmonary Disease (COPD) cohort prospectively completed the EXACT during 128 cohort diary card-defined exacerbations between January 2010 and April 2012. Mean ± sd EXACT scores increased from 42.6 ± 8.6 at baseline to 48.0 ± 8.6 at exacerbation onset (p<0.001), and rose further to a maximum score of 54.1 ± 8.9. Maximum EXACT scores were significantly higher in treated than untreated events. Time taken for EXACT scores to return to baseline was significantly related to symptom recovery time as judged by London COPD cohort diary cards, and to peak expiratory flow rate recovery. ∼50% of both diary card-defined and healthcare utilisation exacerbations crossed the EXACT event threshold. However, only 27.9% of diary card-defined and 34.6% of healthcare utilisation exacerbations fully met the criteria for an EXACT event. Patients exhibited smaller rises in the EXACT score at exacerbation as baseline disease severity increased. The EXACT is an effective method of evaluating chronic obstructive pulmonary disease exacerbation severity. However, concerns remain about the ability of the EXACT to accurately detect exacerbations.

Patient-reported Outcome (PRO) Measures for Clinical Trials of COPD: The EXACT and E-RS

The precise assessment of treatment efficacy in clinical trials requires scientific instruments that are not only relevant to the target population and treatment, but have been shown to be reliable, valid, and sensitive to change within the intended context of use. This paper describes the background, procedures, and current status of 2 patient-reported outcome (PRO) instruments developed for use in clinical trials of chronic obstructive pulmonary disease (COPD). The first measure, the EXAcerbations of Chronic pulmonary disease Tool (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 second measure, the EXACT-Respiratory Symptoms (E-RS) scale, is a derivative instrument comprising a subset of EXACT items to test the effect of treatment on the severity of respiratory symptoms in stable COPD. The EXACT-PRO Initiative was the first PRO instrument development consortia, and the EXACT and E-RS are the first PRO measures to undergo qualification review by the United States Food and Drug Administration (FDA).

A trial of beclomethasone/formoterol in COPD using EXACT-PRO to measure exacerbations

Combination inhalers containing corticosteroids and long-acting β-agonists are used to reduce exacerbation rates in patients with severe chronic obstructive pulmonary disease (COPD). The FORWARD (Foster 48-week Trial to Reduce Exacerbations in COPD) clinical trial in severe COPD patients is a comparison of extrafine beclomethasone dipropionate and formoterol in a combination inhaler with extrafine formoterol; the co-primary end-points are exacerbation rates over 48 weeks and improvement in forced expiratory volume in 1 s over 12 weeks. The traditional physician diagnosis of exacerbations is a co-primary outcome, and the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) means of collecting patient-reported outcome data are also being used to enhance the detection of exacerbation events. EXACT data are being collected using a novel application of a digital platform technology. FORWARD is therefore expected to provide information on the ability of EXACT to detect and measure exacerbations in a large clinical trial setting. The study design of FORWARD is described in this article.

Characterizing and Quantifying the Symptomatic Features of COPD Exacerbations

There is a need for a standardized, valid, and reliable instrument for quantifying exacerbations of COPD. The objective of this study was to identify symptom items that characterize COPD exacerbations to form a new patient diary for evaluating exacerbation frequency, severity, and duration. Twenty-three symptom items identified from patient interviews were administered to 410 patients with COPD aged (mean ± SD) 65 ± 10 years with stable FEV(1) of 51% predicted ± 20% predicted and 1.8 ± 1.8 exacerbations in the preceding 12 months. A total of 222 patients had a physician-diagnosed exacerbation; 188 were stable. Item-level analyses (floor and ceiling effects, criterion keying, item-total correlation) were used in the first stage of item reduction. Further reduction was conducted using Rasch model and descriptive item analyses. Exploratory factor analysis was performed on the items that survived the exclusion process. No item behaved differently between stable and exacerbation conditions. One item was removed after item-level analysis, and eight were removed following Rasch analysis. Together, the surviving 14 items met the criteria for a unidimensional measure of exacerbation severity. Internal consistency (person separation index) was excellent at 0.92. Post hoc exploratory factor analysis revealed one dominant factor, with three domains (breathlessness, cough and sputum, and chest symptoms) that accounted for 68% of the variance. An exacerbation appears to be a quantitative rather than qualitative change from the stable state. This analysis identified a range of symptoms that form a unidimensional construct of overall exacerbation severity. The 14 items identified form the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a daily diary for detecting and quantifying exacerbation severity in COPD.

Standardizing Measurement of Chronic Obstructive Pulmonary Disease Exacerbations

Although exacerbations are an important problem in chronic obstructive pulmonary disease (COPD) and a target of intervention, there is no valid, standardized tool for assessing their frequency, severity, and duration. This study tested the properties of the Exacerbations of Chronic Pulmonary Disease Tool (EXACT), a new patient-reported outcome diary. A prospective, two-group, observational study was conducted in patients with COPD. The acute group (n = 222) was enrolled during a clinic visit for exacerbation with follow-up visits on Days 10, 29, and 60. The stable group (n = 188), recruited by telephone or during routine visits, was exacerbation free for at least 60 days. Acute patients completed the diary on Days 1-29 and 60-67; stable patients for 7 days. All patients provided stable-state spirometry and completed the St. George Respiratory Questionnaire-COPD (SGRQ-C). Acute patient assessments included clinician and patient global ratings of exacerbation severity and recovery. Mean age of the sample (n = 410) was 65 (± 10) years; 48% were male; stable FEV₁ was 51% predicted (± 20). Internal consistency (Pearson separation index) for the EXACT was 0.92, 1-week reproducibility (stable patients; intraclass correlation) was 0.77. EXACT scores correlated with SGRQ-C (r = 0.64; P < 0.0001) and differentiated acute and stable patients (P < 0.0001). In acute patients, scores improved over time (P < 0.0001) and differentiated between degrees of clinician-rated exacerbation severity (P < 0.05). EXACT change scores differentiated responders and nonresponders on Day 10, as judged by clinicians or patients (P < 0.0001). Results suggest the EXACT is reliable, valid, and sensitive to change with exacerbation recovery.

PRS29 CAN OLDER, CHRONICALLY ILL ADULTS USE ELECTRONIC DIARIES? COMPLIANCE RATES IN A PROSPECTIVE STUDY OF PATIENTS WITH COPD

ABSTRACTBACKGROUNDPURPOSEDISCUSSIONRESULTS Can Older, Chronically Ill Adults Use Electronic Diaries? Compliance Rates in a Prospective Study of Patients with COPD Charlotte Cates, MA 1 ; Laurie Roberts, MPH 1 ; Sonya Eremenco, MA 1 ; Teresa Wilcox, PhD 1 ; Nancy Kline Leidy, PhD 1 1 United BioSource, Bethesda, MD, USA Presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 14th Annual International Meeting. May 16–20, 2009; Orlando, FL EXACT-PRO i n i t i a t i v e UNRESTRICTED SPONSORSHIP – PHARMACEUTICAL COMPANIES Background: Electronic data capture for daily diary and survey-style patient-reported outcomes (e-PRO) is becoming widespread. Concern has been expressed that older adults may have difficulty with this methodology, particularly e-Diaries requiring independent completion and data transmission at home. Objective: To evaluate e-diary compliance rates in adults with stable and acute chronic obstructive pulmonary disease (COPD) using data from the EXACT (Exacerbations of Chronic Pulmonary Disease Tool) prospective item-reduction and validation study.