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© 2021 Clinical Data Interchange Standards Consortium, Inc. All rights reserved. 

1 Introduction

This document describes the CDISC implementation of the Exacerbations of Chronic Pulmonary Disease Tool (EXACT^®) - Patient-Reported Outcome (EXACT) instrument.The EXACT questionnaire/daily diary that is used in clinical trials to provide a measure of patient-reported symptoms of Chronic Obstructive Pulmonary Disease (COPD) exacerbations.

The Evaluating Respiratory Symptoms (E-RS^™) in COPD (E-RS^™: COPD) scale is part of the EXACT instrument. It is comprised of 11 items (of the 14-item EXACT) which provide information specific to respiratory symptoms in stable COPD. The E-RS: COPD is not administered separately from the EXACT. For this reason, a separate SDTM questionnaire supplement for the E-RS: COPD will not be developed. 

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The CDISC Intellectual Property Policy can be found on the CDISC website at: https://www.cdisc.org/about/bylaws.

1.1 Representations and Warranties, Limitations of Liability, and Disclaimers

This document is a supplement to the SDTMIG for Human Clinical Trials and is covered under Appendix F of that document, which describes representations, warranties, limitations of liability, and disclaimers. Please see Appendix F of the SDTMIG for a complete version of this material.

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Although the United States Food and Drug Administration (US FDA) has provided input with regard to this supplement, this input does not constitute US FDA endorsement of any particular instrument.

2 Copyright Status

Evidera, Inc. owns the copyright for the EXACT instrument and has granted CDISC permission to include this supplement in the CDISC library of QRS data standards supplements. Hence, CDISC developed QSTESTCD and QSTEST for each item based on the actual text on the questionnaire. There may be many versions of this instrument in the public domain or copyrighted.

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• Nancy K. Leidy, EXACT-PRO Initiative, Evidera, 7101 Wisconsin Avenue, Suite 1400, Bethesda, MD; EXACT copyright 2013, Evidera, Inc. All rights reserved). This also includes the subset EXACT-Respiratory Symptoms (E-RS) questions. http://www.exactproinitiative.com.

• The Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Patient-Reported Outcome (PRO) USER MANUAL (Version 7.0). October 2014, EXACT© 2013, Evidera, Inc. All rights reserved.

3 The QS Domain Model

3.1 Assumptions for the QS Domain Model

All assumptions and business rules described in the SDTMIG QS domain are applicable to this supplement. Additional assumptions specific to the EXACT are listed below.

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1. The scale points include a text rating (e.g., "Not at all", "Slightly", etc.). 

   1. The E-RS (EXACT-Respiratory Symptoms)* USER MANUAL (Version 4.0) May 2015 that is provided upon user's receiving copyright permission provides the numeric scoring of the responses for the questions. Based on this being copyrighted, the numeric scores cannot be provided in this supplement. Upon receiving permission, sponsors may sponsors must apply these numeric responses in their SDTM SDTMIG and ADaM datasets. For this EXACT supplement, QSORRES and QSSTRESC is populated with the text description while the numeric rating is represented as missing "xxx" in QSSTRESC and QSSTRESN.

2. The time period of evaluation for the EXACT is populated in the QSEVINTX field. The evaluation interval for the EXACT is the past 7 days (QSEVINTX = "EVERY EVENING BEFORE BEDTIME") as represented on the CRF.

3. The EXACT instrument includes 3 raw and domain respiratory symptom scores, a raw total score, and an EXACT total score that are not represented on the CRF, but described in the user manual, that are considered as captured data and is not considered as derived in the example below. These scores may be submitted in SDTM or derived in the Analysis Data Model (ADaM) per scoring instructions from the user manual. The E-RS (EXACT-Respiratory Symptoms)* USER MANUAL (Version 4.0) May 2015 that is provided upon user's receiving copyright permission provides information to calculate these items. The EXACT raw total score is computed across the 14 items and then transformed via a table lookup to obtain the EXACT total score that has a theoretical range of 0 to 100. Three raw respiratory symptom scores are also computed for: Breathlessness, Cough & Sputum, and Chest Symptoms. These raw respiratory scores are transformed via a table lookup to obtain the respiratory symptom domain scores that have a theoretical range of 0 to 100.  

   1. If operationally defined by the sponsor, it is the sponsor's responsibility to set the --DRVFL flag based on their eCRF process to derive subtotals and total scores. An investigator-derived score will be considered a captured score and not flagged. When subtotal and total scores are derived by the sponsor, the derived flag (--DRVFL) is set to "Y". However, when the subtotal and total scores are received from a central provider or vendor, the value would go into --ORRES and --DRVFL would be null (see SDTMIG Section 4.1.8.1, Origin Metadata for Variables).

   2. If scores are received by the sponsor, it is recommended that they are submitted to SDTM and verified in ADaM.
4. VISITNUM is null at the time of publication of this document until CDISC develops guidance on how to consistently model timing information for daily diary instruments.
   1. The QSDTC variable contains the date/time the EXACT was completed by the subject and is used for the timing of this measure.
5. As described in the user manual, where no diary entry exists for a given day, create a record in the data file for that day. Each day a patient is followed in the study must have a record for the day. For these missing diary days, a records is created for each question with QSORRES, QSSTRESC and QSSTRESN are represented with missing values and QSSTAT = "NOT DONE". If a reason for not collecting an item is collected, it is represneted in the QSREASND variable. Collecting this reason would be a good practice, but is not specfically described in the manual.

   1. “Presence of Data” items missing data rule:

      1. A record is created in qs.xpt for all items.
      2. If the reason for the not done record is known, then QSSTAT=“NOT DONE” and QSREASND=reason provided (e.g., “PREFER NOT TO ANSWER”). If a reason for the not done record is not provided, the QSREASND variable is not populated,
6. The EXACT instrument is conducted as a diary with planned assessments between visits in which the subject reports the diary data to the investigator. To align the timing of the diary data to visits in a study, the foloowing timing varibles are used.
   1. VISITNUM (Visit Number) variable represents the visit number in which the subject's diary data was reported to the investigator. 
   2. QSDTC (Date/Time of Assessment Collection) variable represents the date the diary day information was recorded by the subject.
   3. QSTPT (Planned Time Point) variable represents timing of the planned diary day.
   4. QSTPTREF (Planned Timepoint Reference) variable represents the visit name the subject attends to return the diary data.
   5. QSRFTDTC (Date/Time of the Reference Timepoint) variable represents the visit date the subject returned diary data.
   6. QSEVLINT (Evaluation Interval) variable represents the evaluation interval timing for the diary information.
7. As described in the user manual, where no diary entry exists for a given day, create a record in the data file for that day. Each day a patient is followed in the study must have a record for the day. For these missing diary days, a records is created for each question with QSORRES, QSSTRESC and QSSTRESN are represented with missing values and QSSTAT = "NOT DONE". If a reason for not collecting an item is collected, it is represneted in the QSREASND variable. Collecting this reason would be a good practice, but is not specfically described in the manual.

   1. “Presence of Data” items missing data rule:

      1. A record is created in qs.xpt for all items.
      2. If the reason for the not done record is known, then QSSTAT=“NOT DONE” and QSREASND=reason provided (e.g., “PREFER NOT TO ANSWER”). If a reason for the not done record is not provided, the QSREASND variable is not populated,

8. Terminology

   1. QSCAT,

   Terminology

   1. QSCAT, QSTESTCD, and QSTEST values are included in CDISC Controlled Terminology.

   2. A full list of value sets for the result fields is provided in Section 4, SDTM Mapping Strategy.

3.2 Example for the EXACT QS Domain Model

The EXACT example below shows the terminology used to implement the instrument in the QS domain. This example shows the data for 1 subject collected at 1 eveningat 7 evenings of diary data capture and an additional evening in which no responses were captured on capture on the EXACT instrument. The example uses CDISC Controlled Terminology for QSTESTCD, QSTEST, and QSCAT. All original results are represented with preferred terminology in QSORRES. This result is also represented as the standard character representation in QSSTRESC. Based on assumption 1. above, the numeric values from the user manual is represented as "xxx" in QSSTRESC and QSSTRESN. There is no baseline observation flags flag represented, since the user manual describes how to drive and potentially re-derive the baseline EXACT domain and total scores as an analysis variable based on the subject disease status.

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The table represents the items from the EXACT instrument. Rows 18 15 - 25 reprsent the 22 represent the bedtime day -7 raw, domain, and EXACT total scores at the first diary day as described in assumption 3 above. These are also represented for each additonal diary day. The subject did not fill out the EXACT at the second dairy day and the observations on this day are represented as described in assumption 3 above.

Example without numeric scores as described in the manual in accordance with assumption 1.a. and V1.0 published supplement with "xxx" indicating the derived score values

bedtime day -6 dairy day and the observations on this day are represented as described in assumption 3 above. The remaining diary day information follows the same pattern of information thru the completion of the dairy.