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Including the Patient Voice in Safety Reporting Ethan Basch, MD, MSc Health Outcomes Group Departments of Medicine and Epidemiology/Biostatistics Memorial Sloan-Kettering Cancer Center June 2009. Overview. Background on PROs PROs for Adverse Event Reporting Research Regulatory issues - PowerPoint PPT Presentation
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Including the Patient Voice in Safety Reporting
Ethan Basch, MD, MScHealth Outcomes Group
Departments of Medicine and Epidemiology/BiostatisticsMemorial Sloan-Kettering Cancer Center
June 2009
1. Background on PROs
2. PROs for Adverse Event Reporting
– Research
– Regulatory issues
3. CALGB 70501
Overview
What is a PRO?
FDA Definition:
“Any report that comes directly from a patient about a health condition or its treatment without interpretation of the patient’s response by a clinician or anyone else”
- Guidance (2006)
FDA Definition of PRO
• Any experience the patient knows best
– Symptoms– HRQL– Functional status– Therapy compliance– Satisfaction with care– Treatment preferences
-Guide clinical practice-Support clinical trial endpoints-Safety monitoring
-AEs in clinical trials-Postmarket surveillance
Essential activity in treatment trials• To ensure patient safety
• To provide data about drug effects
Core activity in routine cancer care• To guide therapy and supportive care
Adverse Event Monitoring
NCI-sponsored treatment trials: CTCAE ~1000 individual items, ordinal scale
Standard Approach to AE Monitoring
CATEGORY EXAMPLE DATA SOURCE
Laboratory Anemia (hemoglobin) Laboratory report
Objective Blood Pressure Clinical staff
Subjective Nausea Clinical staff or patients?
EXAMPLE: DIARRHEA
Patient Experiences
Symptom
Clinician Interprets Symptom
Clinician interviews patient at visit
Chart Representation
of SymptomClinician writes in chart
Data ManagerInterpretation of SymptomData manager
abstracts chart
ResearchDatabase
Manualdata entry
Current Model for Adverse Symptom Reporting in Oncology Trials
Patient Experiences
Symptom
ResearchDatabase
Patient direct reporting of symptoms (1)
Patient Experiences
Symptom
ResearchDatabase
Clinician
Patient direct reporting of symptoms (2)
Rationales for Using PROs for Adverse Symptom Monitoring in Oncology
• Improve efficiency, quality, completeness of data collection in clinical trials– Eliminating data collection steps, reducing errors– Providing more direct account of patient experience
• Improve delivery of clinical care– Enhancing patient-clinician communication– Providing capacity to monitor patients between visits– Enabling automated alerts to address toxicities earlier
Trotti & Basch: J Clin Oncol, 2007
Developed Initial Patient Questionnaire
• Adaptations of CTCAE symptom items – Health literacy/patient education experts– Focus groups – Cognitive debriefing
Basch: JCO, 2005
Items Loaded to Web Platform
• Online interface– Patient self-reporting– Longitudinal report– Automated alerts
• Administration– Touchscreen kiosks and wireless tablet computers
in clinic waiting areas– Home computers between visits
Basch: J Am Med Informatics Assoc, 2007
STAR (1)
STAR (2)
STAR (3)--Patient Name--
STAR (4)
STAR (5)
Feasibility Studies
• Patients receiving chemotherapy
• Most patients are willing and able to self-report CTCAE symptoms at clinic visits
– Including non-web avid, elderly, and
end-stage with high symptom burdens – No attrition in login rates up to 1.5 years
Basch, JCO, 2005
Basch, JCO, 2007
Satisfaction
• High patient satisfaction– Wish to continue using– Would recommend to others
• Clinician impressions and actions– Accurate portrayal of patient status– Altered chemotherapy doses based on patient-
reported information
Implications
• If PROs were adopted for monitoring adverse symptoms in oncology, how might this alter the frequency or severity of documented toxicities?– Do patients report toxicities differently from
clinicians?
Patient vs. Clinician Reporting (1)
• Paper survey
• 400 patient-clinician pairs– Cancer outpatient clinics
• Patients and clinicians answered the same CTCAE items
Basch, Lancet Oncol, 2006
Basch, Lancet Oncol, 2006
Patient vs. Clinician Reporting (2)
Longitudinal Reporting
Patient-reporting
Clinician-reporting
CTCAE Grade-2 (Moderate) CTCAE Grade-3 (Severe)
Patient-reporting
Clinician-reporting
Basch, JNCI, 2009
• Clinician-reported CTCAE symptoms – More predictive of death and hospitalization
• Patient-reported CTCAE symptoms– More correlated with daily health status
• Complementary information– Both have value in characterizing patient experience
with disease and treatment
Basch, JNCI, 2009
Prediction Model
Drug Labels
• Should both be included in clinical trial results and labels?• Would this cause confusion?• Instructive to consider examples outside of healthcare
Metacritic.com
CNET Reviews
Tripadvisor
Docetaxel Drug Label
NCI HHSN261200800043C
NCI Contract Awarded 9/08
NCI Survey
• 729 stakeholders– Administered at cooperative groups / NCI listservs 11/08-2/09
TOTAL N = 729 N*
NCI Representative 41
FDA Representative 26
Cooperative Group Leadership 52
Cooperative Group Member 130
Lead PI 84
Investigator 103
CRA 161
Research Nurse 185
Patient Advocate 121
Industry 30*Not mutually exclusive
Survey Results
QUESTION AGREE NEUTRAL DISAGREE
Systems to collect PROs in clinical trials should be developed 89% 5% 6%
In clinical trials, AEs should be reported by clinicians and patients
88% 8% 4%
Both patient and clinician reported AEs should be reported in clinical trial results and in drug labels
76% 15% 9%
77 CTCAE Items Identified for PRO
NCI Contract
• Patient interviews
• Building technology
• Validation study
CALGB 70501
• Stand-alone companion trial
• Linked to selected treatment trials
70501 Aims
1. Assess feasibility of patient CTCAE reporting in cooperative group trials
2. Compare patient vs. clinician reportingAccrual goal: 175
Eligibility
• Any patient enrolling in a linked treatment trial can also enroll in 70501, anytime prior to cycle/visit #2
• To participate, a site must be listed with CALGB (contact us or CALGB)
• Additional accrual / cancer control credit assigned for 70501 enrollment
Currently Linked Treatment TrialsCALGB 30607: Randomized, phase III, double-blind placebo-controlled trial of sunitinib as
maintenance therapy in non-progressing patients following an initial four cycles of platinum-based combination chemotherapy in advanced, stage IIIB/IV non-small cell lung cancer
CALGB 30704: A randomized phase II study to assess the efficacy of pemetrexed or sunitinib or pemetrexed plus sunitinib in the second-line treatment of advanced non-small cell lung cancer
CALGB 40502: A randomized phase III trial of weekly paclitaxel compared to weekly nanoparticule albumin bound nab-paclitaxel or ixabepilone combined with bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer
CALGB 40503: Endocrine therapy in combination with anti-VEGF therapy: a randomized, double-blind, placebo-controlled phase III trial of endocrine therapy alone or endocrine therapy plus bevacizumab for women with hormone receptor-positive advanced breast cancer
CALGB 40601: Randomized phase III trial of paclitaxel combined with trastuzumab, lapatinib, or both as neoadjuvant treatment of HER2-positive primary breast cancer
CALGB 40603: Randomized phase II 2 x 2 factorial trial of the addition of carboplatin +/- bevacizumab to neoadjuvant weekly paclitaxel followed by dose-dense AC in hormone receptor-poor/HER2-negative resectable breast cancer
CALGB 70604: A randomized, phase III study of standard dosing versus longer dosing interval of zoledronic acid in metastatic cancer
CALGB 80405: A phase II trial of irinotecan/5-FU/leucovorin or oxaliplatin/5-FU/leucovorin with bevacizumab, or cetuximab (C225), or with the combination of bevacizumab and cetuximab for patients with untreated metastatic adenocarcinoma of the colon or rectum
Schema
Interested Sites for 70501
Contact:
• Ethan Basch ([email protected])
• Laura Sit ([email protected])