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© 2022 Clinical Data Interchange Standards Consortium, Inc. All rights reserved. 

1 Introduction

This document describes the CDISC implementation of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events Item Library Version 1.0 Version Date 4/26/2020 (PRO-CTCAE V1.0 VERSION DATE 4/26/2020) instrument.

CDISC does not modify QRS instruments to meet Clinical Data Acquisition Standards Harmonization (CDASH) case report form (CRF) standards.

The representation of data collected for this instrument is based on the Study Data Tabulation Model Implementation Guide (SDTMIG) Questionnaires (QS) domain model, which can be found at the CDISC website at: https://www.cdisc.org/standards/foundational/sdtmig.

These specific implementation details for this instrument are meant to be used in conjunction with the SDTMIG. All instrument documentation can be found on the CDISC web site at: https://www.cdisc.org/standards/foundational/qrs.

The CDISC Intellectual Property Policy can be found on the CDISC web site 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.

CDISC specifies how to structure the data that has been collected in a database, not what should be collected or how to conduct clinical assessments or protocols. CDISC disclaims any liability for your use of this material.

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

The NATIONAL CANCER INSTITUTE at the NATIONAL INSTITUTES OF HEALTH (NCI) owns the copyright for the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 instrument and has made it exempt from copyright restrictions. Use of the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 is subject to NCI terms of use (See https://healthcaredelivery.cancer.gov/pro-ctcae/terms_of_use.html). CDISC has included this supplement in the CDISC inventory of QRS data standards supplements. Hence, CDISC developed QSTESTCD and QSTEST for each item based on the actual text on the instrument. 

The CDISC documentation of this instrument consists of: (1) controlled terminology, (2) standard database structure with examples, and (3) CRF(s) annotated with the CDISC SDTMIG variables with submission values.

Note: CDISC Controlled Terminology is maintained by National Cancer Institute (NCI) Enterprise Vocabulary Services (EVS). The most recent version should be accessed through the CDISC website at: https://www.cdisc.org/standards/terminology/controlled-terminology.

CDISC has developed this documentation at no cost to copyright holder or any additional cost to users of the instrument beyond the normal licenses fees charged by the copyright holder.

CDISC acknowledges the Sandra Mitchell, PhD, CRNP, Research Scientist and Program Director Scientific Lead, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Outcomes Research Branch; Healthcare Delivery Research Program Division of Cancer Control and Population Sciences, National Cancer Institute, for the approval to include the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 in the CDISC data standards.

Reference for the PRO-CTCAE V1.0 VERSION DATE 4/26/2020:

• The PRO-CTCAE trademark items and information herein were developed by the Division of Cancer Control and Population Sciences in the NATIONAL CANCER INSTITUTE at the NATIONAL INSTITUTES OF HEALTH, in Bethesda, Maryland, U.S.A. Use of the PRO-CTCAE is subject to NCI's "Terms of Use". PRO-CTCAE Measurement System content should be downloaded using the "Instrument & Form Builder". https://healthcaredelivery.cancer.gov/prot-ctcae/. (Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, Mendoza TR, Hay J, Atkinson TM, Abernethy AP, Bruner DW, Cleeland CS, Sloan JA, Chilukuri R, Baumgartner P, Denicoff A, St Germain D, O'Mara AM, Chen A, Kelaghan J, Bennett AV, Sit L, Rogak L, Barz A, Paul DB, Schrag D. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst 2014 Sept 29;106(9)).

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 PRO-CTCAE V1.0 VERSION DATE 4/26/2020 are listed below.

The PRO-CTCAE V1.0 VERSION DATE 4/26/2020 a patient-reported outcome (PRO) instrument developed to capture symptomatic adverse events in patients on cancer clinical trials. The PRO-CTCAE V1.0 VERSION DATE 4/26/2020 was designed to be used in conjunction with the Common Terminology Criteria for Adverse Events (CTCAE).[1] It consists of an item library rather than a static/fixed question type of instrument. You should use the form builder at: https://healthcaredelivery.cancer.gov/pro-ctcae/instrument.html and instructions provided by NCI to select the items to implement in your clinical study. The PRO-CTCAE V1.0 VERSION DATE 4/26/2020 includes multiple choice questions on the frequency. severity, interference, presence/absence and amount of adverse events.The items are rated on a 5-point scale ("0-4"). Total scoring instructions have not yet been developed.

Administration of PRO-CTCAE V1.0 VERSION DATE 4/26/2020 may be conducted via different modes, including screen-based, interactive voice response, and paper, offers flexibility for patients and for study operations personnel.

[1] National Institutes of Health – National Cancer Institute, Division of Cancer Control & Population Sciences. (2017, July 2) https://healthcaredelivery.cancer.gov/pro-ctcae/overview.html

1. As a CDISC QRS standard, the instrument name is PRO-CTCAE V1.0 VERSION DATE 4/26/2020, as provided in this supplement. As an item library, sponsors may select items from the overall library as a subset of items with the same CDISC controlled terminology as appropriate for the condiction being studied. It is the users responsibility to identify the subset of items used from the ovearll PRO-CTCAE V1.0 Item Library (Version 1.0) for this use case. The subsetted PRO-CTCAE V1.0 VERSION DATE 4/26/2020 user's instrument can be named based on the user's descretion when they identify the specifc items being used.

2. The PRO-CTCAE V1.0 VERSION DATE 4/26/2020, QSORRES is populated with the text description and the numeric rating is represented in the standardized character and numeric result variables QSSTRESC and QSSTRESN. Please reference the PRO-CTCAE website for more details on the scoring criteria at: https://healthcaredelivery.cancer.gov/pro-ctcae/faqs.html. The responses for the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 are as follows:

   1. Depending on the symptomatic AE being measured, items assessing symptom presence/absence are rated as follows:
      1. Items rated on a binary response scale and scored from "0-1" (e.g., "0 = “No” and "1" = “Yes”);
      2. Items rated on a polytomous response scale and scored from "0-1" (e.g., "0" = “No”, "1 " =“Yes”, and “Not applicable”); or
      3. Items rated on a polytomous response scale and scored from "0-1" (e.g., "0" = “No”, "1" = “Yes”, “Not sexually active”, and “Prefer not to answer”).
   2. Items assessing symptom amount are rated on a 5-point Likert scale and scored from "0-4" (e.g., "0" = “Not at all”, "1" = “A little bit”, "2" = “Somewhat”, "3" = “Quite a bit”, and '4 ' = “Very much”).
   3. Items assessing symptom frequency are rated on a 5-point Likert scale and are scored from "0-4" (e.g., "0" = “Never”, "1" = “Rarely”, "2" =“Occasionally”, "3" = “Frequently”, and "4" = “Almost constantly”).
   4. Items assessing symptom severity are rated on a 5-point Likert scale and are scored from "0-4" (e.g., "0" = “None”, "1" = “Mild”, "2" = “Moderate”, "3" = “Severe”, and "4" = “Very severe”).
   5. Items assessing symptom interference are rated on a 5-point Likert scale and are scored from "0-4" (e.g., "0" = “Not at all”, "1" = “A little bit”, "2" = “Somewhat”, "3 ' = “Quite a bit”, and "4" = “Very much”). 
   6. Item-level scores are not combined (e.g., no total score nor symptom-specific scores are calculated).
3. The time period of evaluation for the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 is populated in the QSEVLINT field in ISO 8601 format when the evaluation interval can be precisely described as duration. The recommended evaluation interval for the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 is the past 7 days (QSEVLINT = "-P7D". Please reference the PRO-CTCAE website for more details on the evaluation interval at: https://healthcaredelivery.cancer.gov/pro-ctcae/faqs.html.
4. Items are divided into 14 subcategories represented in the QSSCAT variable. These categorizations represent how the symptom terms are catgroized in the PRO-CTCAE V1.0 Item Library (Version 1.0). See Section 4, SDTM Mapping Strategy, for a list of these subcategory values. 
   1. The symptomatic AE being measured by a given item (e.g., the Symptom Term represented on the CRF corresponding to a given item) is stored in the SUPPQS dataset with the QNAM = "QSSYMTRM". This matches the symptom term identified in the PRO-CTCAE V1.0 Item Library (Version 1.0).

5. Conditional branching is used in the conduct of the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 for symptom terms that have two or more items. The logic branches from frequency, then to severity, then to interference. For example, if frequency is > (greater than) never, you next pose the severity question, and if severity>none, you pose the interference question. Please reference the PRO-CTCAE website for more details on the conditional branching approach at: https://healthcaredelivery.cancer.gov/pro-ctcae/faqs.html.

   1. These branching items on the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 may be logically skipped per the instrument instructions. For example, If the item "In the last 7 days, how OFTEN did you have PAIN IN THE ABDOMEN (BELLY AREA)? (QSTESTCD = "PT01017A") is answered as "Never". The related symptom items for severity and interference are logically skipped (QSTESTCD = "PT01017B" and "PT01017C"), since the symptom did not occur. A record is created in qs.xpt for all items. When an item is considered a logically skipped item, it is represented as follows:

      1. RSSTAT = "NOT DONE".

      2. RSREASND = "LOGICALLY SKIPPED ITEM".
         

      3. RSORRES, is set to null (missing).

      4. RSSTRESC and RSSTRESN are represented with the numeric value 0 as specified in the scoring criteria. Please reference the FAQ "How is the PRO-CTCAE scored" on the website at: https://healthcaredelivery.cancer.gov/pro-ctcae/faqs.html.
6. The language in which the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 was administered (e.g., English, Spanish, Japanese) is collected with the Form Builder application and may be represented as a supplemental qualifier with QNAM = "QSLANG". Reference the PRO-CTCAE V1.0 website for a list of available translations at: https://healthcaredelivery.cancer.gov/pro-ctcae/.
7. Terminology

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

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

3.2 Example for the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 QS Domain Model

The PRO-CTCAE V1.0 VERSION DATE 4/26/2020 example below shows the terminology used to implement the instrument in the QS domain. This example shows the data for 1 subject collected at the baseline visit for a PRO-CTCAE V1.0 VERSION DATE 4/26/2020 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 then transformed into thestandard numeric score in QSSTRESN and a character representation of the standard numeric score in QSSTRESC.

The table represents the items from the PRO-CTCAE V1.0 VERSION DATE 4/26/2020 instrument.

The suppqs dataset relates the symptom term from the PRO-CTCAE ITEM LIBRARY (Version 1.0) to each symptom item represented in the qs dataset.