Revision History

© 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 (PRO-CTCAE V1.0) instrument.

CDISC did not modify this questionnaires, ratings, and scales (QRS) instrument 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 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.

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 (NCI) at the NATIONAL INSTITUTES OF HEALTH (NIH) owns the copyright for the PRO-CTCAE V1.0 instrument and has made it exempt from copyright restrictions. Use of the PRO-CTCAE V1.0 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 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 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 in the CDISC data standards.

Reference for the PRO-CTCAE V1.0:

• These materials discuss and/or include 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) which is owned exclusively by the Division of Cancer Control and Population Sciences in the NATIONAL CANCER INSTITUTE at the NATIONAL INSTITUTES OF HEALTH (NCI). No part of the PRO-CTCAE V1.0 may be reproduced, distributed, or transmitted in any form or by any means, including photocopying recording, or other electronic or mechanical methods, without the prior written permission of NCI and payment of any applicable fees. PRO-CTCAE V1.0 copyright, NATIONAL CANCER INSTITUTE at the NATIONAL INSTITUTES OF HEALTH (NCI). All rights reserved.
• 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)).
• [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

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 are listed below.

The PRO-CTCAE V1.0 is a patient-reported outcome (PRO) instrument developed to capture symptomatic adverse events of patients in cancer clinical trials. The PRO-CTCAE V1.0 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 as described on the PRO-CTCAE website to build CRFs and instructions provided by NCI to select the items to implement in your clinical study. The PRO-CTCAE V1.0 includes multiple choice questions on the frequency, severity, interference, presence/absence and/or amount of specific adverse events.

Administration of PRO-CTCAE V1.0 may be conducted via different modes, including screen-based, interactive voice response, and paper.

1. As a CDISC QRS standard, the instrument name is PRO-CTCAE V1.0, 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 condition being studied. It is the users responsibility to identify the subset of items used from the overall PRO-CTCAE V1.0 Item Library (Version 1.0). The subsetted PRO-CTCAE V1.0 user's instrument should be titled "PRO-CTCAE sponsor-specified symptoms..." based on the sponsor's discretion when they identify the specific items being used. This will distinctly describe the subsetted instrument from the overall PRO-CTCAE V1.0.

2. For the PRO-CTCAE V1.0, QSORRES is populated with the text description while the numeric rating is represented in the standardized character and numeric result variables QSSTRESC and QSSTRESN. Please reference the PRO-CTCAE website FAQs for more details on the numeric responses. The responses for the PRO-CTCAE V1.0 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 rated from 0-1 (e.g., 0 = “No” and 1 = “Yes”);
      2. Items rated on multiple (more than two) response scale and rated from 0-1 (e.g., 0 = “No”, 1 = “Yes”, and “Not applicable” or "Not Applicable"); or
      3. Items rated on multiple (more than two) response scale and rated 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 scale and rated 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 scale and are rated from 0-4 (e.g., 0 = “Never”, 1 = “Rarely”, 2 = “Occasionally”, 3 = “Frequently”, and 4 = “Almost constantly”, "Not sexually
      active", and “Prefer not to answer”).
   4. Items assessing symptom severity are rated on a 5-point scale and are rated from 0-4 (e.g., 0 = “None”, 1 = “Mild”, 2 = “Moderate”, 3 = “Severe”, and 4 = “Very severe”, “Not applicable”, "Not sexually
      active", and “Prefer not to answer”).
   5. Items assessing symptom interference are rated on a 5-point scale and are rated from 0-4 (e.g., 0 = “Not at all”, 1 = “A little bit”, 2 = “Somewhat”, 3 = “Quite a bit”, and 4 = “Very much”).
3. The CRF represents up to 5 "other symptoms" to be recorded. In discussions with NIH, it was agreed to provide up to 10 "other symptoms" to be recorded if they existed. QSTESTCDs (QSTESTCDs "PT01082A" thru "PT0191A") and severity of the symptom at its worst (QSTESTCDs "PT01082B" thru "PT0191B").
4. Total scoring instructions have not yet been developed. Item-level scores are not combined (i.e., No total score nor symptom-specific scores are calculated.).
5. The time period of evaluation for the PRO-CTCAE V1.0 is populated in the QSEVLINT field in ISO 8601 format when the evaluation interval can be precisely described as duration. The evaluation interval for the PRO-CTCAE V1.0 is the past 7 days (QSEVLINT = "-P7D". Please reference the PRO-CTCAE website for more details on the evaluation interval.
6. Items are divided into 14 subcategories represented in the QSSCAT variable. These categorizations represent how the symptom terms are categorized 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 = "QSSYMPTM". This matches the symptom term identified in the PRO-CTCAE V1.0 Item Library (Version 1.0).

7. Electronic Conditional branching is used in the conduct of the PRO-CTCAE V1.0 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. In the conduct of the PRO-CTCAE V1.0 it expects responses for each item and there should be no missing responses.

8. The language in which the PRO-CTCAE V1.0 was administered (e.g., English, Spanish, Japanese) is collected with the Form Builder application and may be represented as a supplemental qualifier with QNAM = "QSLANGDC". Reference the PRO-CTCAE V1.0 website for a list of available language translations.
9. Terminology

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

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

3.2 Example for the PRO-CTCAE V1.0 QS Domain Model

The PRO-CTCAE V1.0 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 instrument. The example uses CDISC Controlled Terminology for QSTESTCD, QSTEST, and QSCAT. All original results, matching the CRF item response text, are represented in QSORRES. This result is then represented as a standard numeric score in QSSTRESN and as a standard character representation in QSSTRESC.

The table represents the items from the PRO-CTCAE V1.0 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.

4 SDTM Mapping Strategy

This section is used for reference regarding the CRF data capture and to understand the alignment of the instrument to the SDTM QS domain. It also provides guidance on how the result variables (QSORRES, QSSTRESC, and QSSTRESN) should be populated.

QSSCAT alignment with QSTESTCD

As stated in Section 3.1 assumptions, the PRO-CTCAE V1.0 symptom terms are grouped into subcategories as represented in the PRO-CTCAE ITEM LIBRARY (Version 1.0). The table below includes the subcategory names along with the applicable question numbers for each category. The values of the subcategories are used to populate QSSCAT and are annotated on the CRF.

All PRO-CTCAE V1.0 Severity Questions

All PRO-CTCAE V1.0 Interference Questions

All PRO-CTCAE V1.0 Frequency Questions

All PRO-CTCAE V1.0 Presence Questions

All PRO-CTCAE V1.0 Amount Questions

QSTESTCD = "PT01066A" QSTEST = "PT01-Achieve/Maintain Erection Severity"

QSTESTCD = "PT01068A" QSTEST = "PT01-Decreased Libido Severity"

QSTESTCD = "PT01071A" QSTEST = "PT01-Pain w/Sexual Intercourse Severity"

QSTESTCD = "PT01067A" QSTEST = "PT01-Ejaculation Frequency"

QSTESTCD = "PT01069A" QSTEST = "PT01-Delayed Orgasm Presence"

QSTESTCD = "PT01070A" QSTEST = "PT01-Unable to Have Orgasm Presence"

QSTESTCD = "PT01036A" QSTEST = "PT01-Radiation Skin Reaction Severity"

QSTESTCD = "PT01057A" QSTEST = "PT01-Irregular Menstrual Period Presence"

QSTESTCD = "PT01058A" QSTEST = "PT01-Missed Menstrual Period Presence"

QSTESTCD = "PT01079A" QSTEST = "PT01-Pain&Swelling at Inj Site Presence"

5 Supplemental Qualifier Name Codes

The following table contains additional standard name codes for use in the Supplement Qualifiers for Questionnaires (SUPPQS) special purpose dataset.

PRO-CTCAE V1.0 supported languages

PRO-CTCAE ITEM LIBRARY (Version 1.0) symptom terms

End of Document