Lost your password? (close)

Instrument Development

EXACT®

  • 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.
  • Methods used to optimize content validity:
    • 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 assure 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 2 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 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.
    • 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.
  • First 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 (SAP) 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.
    • Methods and results are published in Leidy et al. 2011.
  • Further validation
    • EXACT scores were subjected to further tests of reliability and validity through secondary analyses of 3 clinical trial datasets, including one 6-month trial in the United States and 2 3-month international trials.
    • Methods and results are published in Leidy et al. 2014.
  • 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. See more information on ePRO certification here.
  • Translations
    • The EXACT has been translated into over 50 languages. See more information about translations here.
  • The history of the EXACT and E-RS are described in Leidy & Murray 2013.

E-RS

  • The 11 respiratory symptom items comprising the E-RS were selected from the 14-item EXACT diary.
  • Content validity was optimized and documented through information and data from
    • The literature;
    • Secondary analyses of qualitative data gathered during the development of the EXACT;
    • Results of an additional prospective qualitative study of patients with stable COPD and no history of exacerbation for at least 12 months.
  • Tests of the reliability, validity, and responsiveness of E-RS scores were performed with validation data from the parent instrument (EXACT) using an E-RS specific a priori SAP and follow-up post hoc analyses.
    • Exploratory factor analysis of the 11 E-RS respiratory items in patients with stable COPD showed the presence of 3 factors that can serve as symptom subscales:
      • RS-Breathlessness (5 items), RS-Cough and Sputum (3 items), and RS-Chest Symptoms (3 items).
  • Methods and results of the qualitative and initial quantitative work are published in Leidy et al. 2014.
  • Further validation
    • E-RS scores were subjected to further tests of reliability and validity through secondary analyses of 3 clinical trial datasets, including one 6-month trial in the United States and 2 3-month international trials.
    • Methods and results are published in Leidy et al. 2014.
  • Methods of administration
    • To facilitate standardized use, an E-RS User Manual was created, describing the instrument’s development, intended use, administration procedures, and scoring.
    • The eDiary certification program applies to the E-RS.
  • Translation
    • The EXACT, and therefore the E-RS, has been translated into over 50 languages. See more information about translations here.
  • The history of the EXACT and E-RS are described in Leidy & Murray 2013.
© 2017 Evidera     +1 301 654 9729 (US)     +44 (0) 208 576 5000 (EU)