Overview

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 (basche@mskcc.org)

• Laura Sit (sitl@mskcc.org)