Pulmonary disease physician checking the lungs of a young patient.

EXACT

EXAcerbations of Chronic pulmonary disease Tool
Exact Program logo

The EXAcerbations of Chronic pulmonary disease Tool (EXACT®) is a patient-reported outcome (PRO) measure for standardizing the symptomatic evaluation of acute exacerbations of chronic obstructive pulmonary disease (COPD) and chronic bronchitis (AECB) in natural history studies and clinical trials.

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 Evaluating Respiratory Symptoms (E-RS):COPD scale is a derivative instrument used to measure the effect of treatment on the severity of respiratory symptoms in stable COPD.

The EXACT description

The EXACT is a 14-item PRO daily diary used to quantify and measure exacerbations of COPD.

This instrument provides a single, standardized approach for assessing the symptomatic manifestations of COPD exacerbations, with a development and validation history consistent with guidelines proposed by the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) and well-known measurement principles.

Research benefits

Exacerbations are events characterized by an acute, sustained worsening in the patient’s COPD beyond normal day-to-day variability, including an increase in respiratory symptoms such as dyspnea, cough and sputum production that may require a change in treatment.

  • The EXACT total score, computed daily over time, is designed to standardize the assessment of the patient’s condition in order to capture this dynamic process.

EXACT scores complement and extend information provided by traditional health care resource utilization (HCRU) data by:

  • Standardizing the magnitude of symptomatic change around HCRU events (those seen in the clinic, emergency room or hospital)
  • Quantifying frequency, severity and duration of reported and unreported symptom-defined events

The EXACT may be used in longitudinal, natural history studies or clinical trials, including:

  • Maintenance and prevention trials testing the efficacy of therapies to modify or prevent COPD exacerbations
  • Acute treatment trials evaluating therapies to treat exacerbations of COPD
Male sitting on a couch couging.

Content of the EXACT and E-RSa

Symptom constructItem-level construct1Item number
Breathlessness
Breathless today27
Breathless with activity38
Short of breath – personal care39
Short of breath – indoor activity310
Short of breath – outdoor activity311
Cough and sputum
Cough frequency32
Mucus quantity33
Difficulty with mucus34
Chest symptoms
Congestion21
Discomfort25
Tightness26
Additional attributes
Tired or weak212
Sleep disturbance213
Scared or worried214
This information is also provided in Leidy et al. 2014. (Note that reference to the EXACT-RS in the published paper pre-dates the name change.)

The EXACT development methods

The process involved more than 500 people, including 493 patients with COPD and 18 professionals from the U.S. and Europe with expertise in pulmonary medicine, clinical research, instrument development and drug development regulations.

Methods used to optimize content validity

Comprehensive literature review

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.

  • An iterative analytical process was used to identify themes and concepts to inform instrument content and structure.
  • A draft instrument comprising 23 items was subjected to cognitive interviewing methodology in patients with COPD.
  • During two advisory panel meetings, experts critiqued the research methods and results and assisted in the design of a prospective study to collect data for item reduction and to evaluate the performance characteristics of the final instrument in subjects with COPD.
  • Methods and results are published in Leidy et al. 2010.

Quantitative data

Quantitative data were gathered through a prospective two-group observational validation study of 410 patients with COPD.

  • Group one: 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 two: 188 stable patients completed baseline assessments and the diary over seven days.

Scoring

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.
Expert panel reviewing data on a laptop and printed charts

Tests of reliability, validity and responsiveness

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 and follow-up secondary analyses. Scores exhibited high levels of internal consistency and reproducibility.

Evidence of construct validity included:

  • Ability to discriminate acute and stable groups
  • Sensitivity to change over time in the acute group

Two expert panel meetings were held to discuss results and interpretation guidelines.

Further validation

EXACT scores were subjected to further tests of reliability and validity through secondary analyses of three clinical trial datasets, including one six-month trial in the U.S. and two three-month international trials.

Methods of administration

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. Learn more about ePRO certification.

Qualifications

The history of the EXACT and E-RS are described in Leidy and Murray 2013 and Murray and Leidy 2018.

These documents specify that the EXACT and E-RS:COPD are qualified for use as exploratory endpoints in drug development trials evaluating the effect of treatment on exacerbations (EXACT) and respiratory symptoms (E-RS:COPD) of COPD.

This does not preclude their use as secondary, co-primary or primary endpoints. Sponsors should discuss their proposed use of the EXACT and/or E-RS with regulatory authorities prior to positioning in pivotal trials. Decisions related to positioning and potential for labeling claims are made on a case-by-case basis.

Arabic female doctor referring to a laptop while writing notes

EXACT and E-RS translations

The EXACT has been translated into more than 55 languages.

Methods used to translate the EXACT followed the Principles of Good Translation and Cultural Adaptation Practice as suggested by ISPOR in 2005.

These methods include:

  • Development of a definition document to guide all translations
  • Dual forward translation; reconciliation; dual back translation; back translation review; and harmonization
  • Cognitive testing with COPD patients in each target country
  • Clinician review as needed to verify terminology
  • Final proofing, including diacritics

This approach is designed to yield translated versions of the EXACT that are conceptually equivalent to the English source version and easily understood by the target population of patients with COPD.

Items comprising the E-RS:COPD are included in the EXACT and were therefore included in this translation process.

All EXACT translations are completed in partnership with FACIT Translation Services (FACITtrans). To ensure standardized translations, users are not permitted to translate the EXACT without prior, written consent.

How to acquire translations

We hold copyrights to the EXACT, E-RS and all derivative measures in English and all translations. Translations can be obtained through the EXACT licensing procedure.

Each translated version includes certification of the procedures used to assure conceptual equivalence. To ensure standardized translations, users are not permitted to translate the EXACT without prior, written consent.

Please contact CRGexactpro@thermofisher.com if you have questions related to developing a new EXACT translation.

Available EXACT/E-RS certified translations

Scroll the table to view the full list of translations of December 2024.

LanguagesCountries tested1
Afrikaans South Africa
Albanian Albania 
Arabic (Universal)Egypt, Israel, Oman, Saudi Arabia, Tunisia, United Arab Emirates
BengaliIndia
BosnianBosnia
BulgarianBulgaria 
CatalanSpain
CebuanoPhilippines
Chinese (Simplified)China, Malaysia, Singapore
Chinese (Traditional)Taiwan, Hong Kong
CroatianCroatia
CzechCzech Republic
DanishDenmark
DholuoKenya
Dutch (Universal)Belgium, the Netherlands
English (Universal)USa, Australia, Canada, Hong Kong, India, Ireland, Israel, New Zealand, Philippines, Singapore, South Africa, UK
EstonianEstonia
FinnishFinland
French (Universal)Francea, Canada, Belgium, Switzerland, Tunisia
GeorgianGeorgia
GermanGermany, Austria, Belgium, Switzerland
GreekGreece
GujaratiIndia
Haitian CreoleHaiti
HausaNigeria
Hiligaynon/IlonggoPhilippines
HindiIndia
HungarianHungary
IgboNigeria
IlocanoPhilippines
ItalianItaly
JapaneseJapan
KannadaIndia
KoreanKorea
HebrewIsrael
LatvianLatvia
LithuanianLithuania
MacedonianMacedonia
MalayMalaysia, Singapore
MalayalamIndia
MarathiIndia
North SesothoSouth Africa
NorwegianNorway
OdiaIndia
PolishPoland
Portuguese (Universal)Brazil, Portugal
PunjabiIndia
RomanianRomania
RussianRussiaa, Ukraine, Latvia, Lithuania, Israel, Estonia
Serbian (Cyrillic)Serbia
Serbian (Latin)Serbia
SesothoSouth Africa
SetswanaSouth Africa
SlovakSlovakia
SloveneSlovenia
Spanish (Universal)USa,b,, Spaina,b, Mexicob, Chilea,b, Argentinab, Peru, Colombia, Guatemala
SwahiliKenya
SwedishSweden, Finland
TagalogPhilippines
TamilIndia, Malaysia, Singapore
TeluguIndia
ThaiThailand
TurkishTurkey
UkrainianUkraine
UrduIndia
VietnameseVietnam
XhosaSouth Africa
YorubaNigeria
ZuluSouth Africa

Licensing

The EXACT and E-RS measures are available for licensing to use in research studies.

Resources

Visit clinicaltrials.gov to obtain a list of trials using these measures.
Source: ClinicalTrials.gov

Access a resource list of publication references.

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