This page and its subpages contain presentations, agendas, and documents pertinent to the PRO-CTCAE initiative to develop a patient-reported outcomes version of the NCI's Common Terminology Criteria for Adverse Events (CTCAE).
Presently, in NCI-sponsored treatment trials, adverse events are documented using items from the CTCAE. The CTCAE is a lexicon of 790 discrete items (>1000 in v3 and 790 in v4), representing laboratory tests, measurable phenomena (like temperature or blood pressure), and symptoms. Each item is graded with up to five ordinal response options, with each response option anchored to discrete clinical criteria (which may include information about severity, frequency, and/or interference with daily activities). By design, CTCAE items elicit the worst magnitude of a phenomenon being measured.
Currently, all CTCAE items are reported by research staff at clinic visits, including adverse symptoms. Patient self-reporting does not play a role. But evidence suggests that clinical staff systematically underreport symptoms compared to patients' own accounts. A further recognized limitation of the current approach is that adverse symptoms are only reported by staff at visits and not between visits, with up to several weeks elapsing between reporting instances. Since the recall period for the CTCAE represents the entire period since the prior clinic visit, symptom information may be lost due to degradation of memory about intervening events.
To address limitations of the current model, in October 2008 the NCI awarded the first of two contracts to develop a patient-reported outcomes (PRO) version of the CTCAE. The second contract was awarded in 2010. These contracts were awarded to Dr. Ethan Basch as Principal Investigator at Memorial Sloan Kettering Cancer Center (Dr. Basch subsequently moved primarily to University of North Carolina but remains Principal Investigator with the Coordinating Center remaining at Memorial Sloan Kettering Cancer Center). The Program Officer is Dr. Sandra Mitchell of the NCI Health Outcomes Branch, and was formerly Dr. Bryce Reeve. The overall Project Manager is Lauren Rogak. A consortium of subcontractors was established with site investigators at selected organizations providing content expertise applicable to the overall initiative. Subcontract cancer centers include Dana-Farber (Dr. Deborah Schrag); Mayo Clinic (Drs. Jeff Sloan and Amylou Dueck); MD Anderson (Drs. Charlie Cleeland and Tito Mendoza); Duke University (Dr. Amy Abernethy); Emory University (Dr. Deb Bruner); and Memorial Sloan Kettering (Drs. Jennifer Hay and Thomas Atkinson). Subcontracts with SemanticBits LLC as technology developer, FACITtrans to develop language translations, and Perceptive Informatics for automated telephone technology were also established. Key participants from across NCI divisions and FDA participation were also included, as well as patient advocate representatives (see below roster).
The RFP and SOW for the initial announcement, as well as sections of the response are posted as attachments to this page. Briefly, the overall scope of the initiative was divided into 9 discrete Tasks, with a site investigator designated as team leader for each. Each of these nine Tasks became a working group with independent schedules of meetings/teleconferences to provide its deliverables according to a coordinated schedule for the overall project. Each Task has its own subpage on this Wiki site to which pertinent documents are posted.
The Tasks include:
Task 1: To publish a White Paper outlining barriers and strategies for widespread implementation of the PRO-CTCAE in NCI cooperative groups (status: completed).
Task 2: To identify items in the CTCAE amenable to patient self-reporting, and create patient versions of these items. This task also includes determining the structure of PRO-CTCAE items and response options (status: completed).
Task 3: To account for issues of cultural/health literacy and respondent diversity throughout the project (status: completed).
Task 4: To conduct and publish cognitive interviews for items developed in Task 2 (status: completed).
Task 5: To create a PRO-CTCAE web-based open-source technology platform for administration of items in clinical trials, hosted at the NCI (status: completed).
Task 6: To conduct usability testing to refine the technology platform created in Task 5 (status: completed).
Task 7: To conduct a multicenter study of the measurement properties of the newly developed PRO-CTCAE items, including validity, reliability, sensitivity, and appropriate recall period (status: completed).
Task 8: To conduct multicenter feasibility studies of the PRO-CTCAE in the NCI cooperative group setting (status: completed and ongoing).
Task 9: To create print and electronic training/educational materials for the PRO-CTCAE overall system (web platform and questionnaires) (status: completed).
Task 10: To translate the PRO-CTCAE into Spanish for increased accessibility (status: completed).
Task 11: Develop an automated telephone (interactive voice response) system as a component of the PRO-CTCAE web platform (subsequently merged with Task 5 above) (status: completed).
Task 12: Conduct usability testing of the automated telephone (interactive voice response) system (subsequently merged with Task 6, above) (status: completed).
Task 13: Subsequently merged with Task 8, above.
Task 14: Evaluate shared (patient-clinician) vs. stand-alone models of symptom adverse event reporting (status: ongoing).
The overall mission of the PRO-CTCAE initiative is to "Employ rigorous scientific methods to create a system for patient self-reporting of adverse symptoms in cancer trials, which is widely accepted and used; generates useful data for investigators, regulators, clinicians and patients; and is compatible with existing adverse event reporting systems." The goal is to create a measurement system that is feasible to implement in clinical trials and which enhances understanding of the patient experience with symptomatic adverse events. For further information about PRO-CTCAE research activities, please contact the PRO-CTCAE project manager, Lauren Rogak: email@example.com.
Conference calls for all task meetings are recorded.
Please see individual Task subpages for details of meetings and teleconferences, or contact Lauren Rogak at firstname.lastname@example.org.
The PRO-CTCAE project divided into several task teams, each focused on a specific component of the overall project. Below are the tasks and the prinicples for each task team.
- Project Manager: Lauren Rogak (email@example.com)
- Finance Contacts: Yasmeen Majoka (firstname.lastname@example.org)
Brendan Phalan (email@example.com)
- Task 1: Create "white paper" report
(Basch, Bruner, Trotti, Schrag)
- Task 2: Develop PRO-CTCAE items
(Basch, Cleeland, Sloan, Mendoza, Hay)
- Task 3: Assure cultural literacy
- Task 4: Cognitive interviewing
(Basch, Hay, Atkinson, Gagne)
- Task 5: Build technology platform
(Basch, Chilukuri and SemanticBits team)
- Task 6: Usability testing
- Task 7: Assess measurement properties (validation study)
(Basch, Sloan, Cleeland, Mendoza)
- Task 8: Feasibility studies in cooperative group setting
(Basch, Schrag, Bruner, Abernathy)
- Task 9: Create training/educational materials
- Task 10: Translation of PRO-CTCAE into Spanish
(Basch, Lent, Arnold)
Non-Disclosure Agreement (NDA) and Personnel List
All investigators and their staff on the personnel list have signed a non-disclosure agreement. This is tracked and held by the project manager at MSK.
The witness listed for the NDA should be the site investigator or another PI for the contract at your site.
If necessary, please respond and update the personnel list to include all staff members at your institution that will be involved in the contract and/or will have access to the contract data/information.
Security Awareness Courses
All staff must also complete an annual refresher Security Awareness Course (http://irtsectraining.nih.gov), and return a completion certificate to MSK. Please login as "general public."
| Andy Trotti |
formerly of CBIIT, NCI
inactive, currently at PCORI
Diane St. Germain
Ann Marie Trentacosti
Kathy Fedenko, OODP