PRO-CTCAE Face-To-Face Meeting #2Advancing the Science of Adverse Symptom
Monitoring in Cancer Treatment Trials
Ethan Basch, M.D.Memorial Sloan-Kettering Cancer Center
PROJECT OVERVIEW
May 24, 2010National Cancer Institute
Outline1. Introductions2. Project background3. Progress to date4. Goals of the day
Introductions
Background“A PRO is any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else”
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM193282.pdfz
Background• PROs are standard in multiple
settings– Symptom efficacy evaluation in clinical
trials– HRQL– Patient satisfaction– Patient preferences
• But not standard for adverse symptom reporting
Patient Experiences
Symptom
Clinician Interprets Symptom
Chart Representation
of Symptom
Data ManagerInterpretation of Symptom
ResearchDatabase
Current Model for Adverse Symptom Reporting in Cancer Trials
Patient Experiences
Symptom
ResearchDatabase
Patient direct reporting of symptoms (1)
Patient Experiences
Symptom
ResearchDatabase
Clinician
Patient direct reporting of symptoms (2)
Patient Experiences
Symptom
ResearchDatabase
Clinician
Assign attribution; initiate expedited reporting
Patient direct reporting of symptoms (4)
Patient Experiences
Symptom
ResearchDatabase
Clinician
Assign attribution; initiate expedited reporting
Enhance clinical care
Patient direct reporting of symptoms (5)
Basch: NEJM, 2010Fromme: JCO, 2004Stromgren: Acta Anesth, 2001Weingart: Arch Intern Med, 2005Pakhomov: Am J Man Care, 2008Sprangers, Acta Oncologica, 2000
Clinicians systematically downgrade symptoms compared with patients
Patient adverse symptom reports better correlate with functional status than clinician reports
Basch: JNCI, 2009
Clinician CTCAE Reporting is Unreliable
• N=393 • Seen by 1st clinician in office, then 2nd clinician ~15
minutes later
Atkinson: SBM, 2010
PROs Better Identify SAEs Early
• NCCTG 9741: Phase III trial comparing regimens for metastatic colorectal cancer
• Closed after 841/1,125 patients enrolled due to unexpected excess of early deaths in Arm 1 (“IFL”)– Associated with “GI syndrome” including severe
diarrhea
• Diarrhea reporting:– Clinicians reported CTCAE each cycle (diarrhea
required)– Patients reported diarrhea via in HRQL every other
cycleRothenberg: JCO, 2001
Clinician-Reported Diarrhea
Dueck: Unpublished Data, 2010
Patient-Reported Diarrhea
Dueck: Unpublished Data, 2010
Patient vs. Clinician Diarrheain Arm 1 (IFL)
Dueck: Unpublished Data, 2010
Development of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)
• Initiated October 2008
NCI Contract HHSN261200800043C
Mission
Develop 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 software systems
PRO-CTCAE Network
NCI
ADVISORS TECH
NETWORK
NCCCP
MSKCCCoordinatin
gCenter
Dana-Farber
MD Anderson
Mayo
Duke
Penn
FDACooperative Groups
Industry
Christiana
Hartford
OLOL
Spartanburg
St. Joseph - Orange
SemanticBits
PerceptivePatientAdvocat
es
DCPDCCPS
DCTD
CBIIT
Task-Based Project• Task 1: White paper and survey• Task 2: Item development• Task 3: Cultural literacy• Task 4: Cognitive interviews• Task 5: Technology development• Task 6: Usability testing• Task 7: Validation study• Task 8: Feasibility study• Task 9: Educational materials
Done O
ngoing
Logistics
• Multidisciplinary committee for each task– NCI representatives– FDA representatives as appropriate– Patient advocates– Methodological expertise– Clinical expertise
• Regular web-enabled teleconferences– Digitally recorded– Documentation on Wiki
PRO-CTCAE Presentations (2009-10)
• American Society of Clinical Oncology (ASCO)• International Society for Pharmacoeconomics
and Outcomes Research (ISPOR)• International Society for Quality of Life
Research (ISOQOL)• Drug Information Association (DIA)• caBIG Annual Meeting• Society of Clinical Trials (SCT)• Society of Behavioral Medicine (SBM)• Agency for Healthcare Research and Quality
(AHRQ)
Goals of the Day
• Project update – Information exchange
• Discuss future directions and challenges1. Feasibility/implementation/dissemination2. Methodological/analytic issues
• Demonstrating does not generate noise3. Technology development
• Between-visit reporting• Integration with other systems
4. Regulatory issues
Survey Highlights*729 Stakeholders in Cooperative Groups
QUESTION AGREE NEUTRAL DISAGREE
Systems to collect PROs in clinical trials should be developed
89% 5% 6%
In clinical trials, adverse events should be reported by patients
88% 8% 4%
POTENTIAL BARRIERS AGREE NEUTRAL DISAGREE
Lack of computers 69% 15% 16%
Limited personnel 57% 18% 25%
SOLUTIONS TO OVERCOME BARRIERS AGREE NEUTRAL DISAGREE
Funding (for personnel, dedicated space, training) 79% 13% 8%
Computers 72% 21% 7%
* Full survey results and White Paper available on project Wiki (https://wiki.nci.nih.gov/x/cKul)
Agenda
