caBIG Population Sciences SIG

Ethan Basch, MD, MScMemorial Sloan-Kettering Cancer Center

PRO-CTCAEA system for patient self-reporting of adverse symptoms in oncology trials

May 7, 2009

Overview

1. Background– Adverse Event reporting in oncology

2. PRO-CTCAE contract overview3. System/functionality requirements4. Demonstration

Essential activity in clinical trials• To ensure patient safety • To provide data about drug effects

– Trialists, regulators, clinicians, patients

Core activity in routine cancer care• To guide therapy and supportive care

Adverse Event Monitoring

NCI-sponsored treatment trials: CTCAE v3 ~1000 individual items

Standard Approach to AE Monitoring

CATEGORY EXAMPLE DATA SOURCE

Laboratory Anemia (hemoglobin) Laboratory report

“Objective” Blood Pressure Clinical staff

“Subjective” Nausea Clinical staff and patients

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)

• FDA DEFNITION OF PATIENT-REPORTED OUTCOME (PRO):

“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”

Increasing Regulatory Interest in PROs

Rationales for Patient-Reported Outcomes Approach to Adverse Symptom Reporting

• Improve efficiency of data collection– Eliminating data collection steps, reducing errors

• Provide more direct account of patient experience– Eliminating filtering of patient reports by others

• Engage patients as active participants in trials • Enable real-time data capture (ePROs)

– Automated alerts, between-visit reporting

• Provide subsequent patients with AE information reported by their peers, not clinical staff

• Harmonize CTCAE with current standards for symptom measurement using PROs– Eg, FDA guidance

Trotti, Colevas, Setser, Basch: JCO, 2007

• Patients willing and able to report CTCAE symptoms via computer at clinic visits

• Patient reporting is discrepant from clinician reporting – Patients generally self-report worse severity– Patient reports better reflect day-to-day experience

• Clinicians will accept patient-reported AEs for treatment decisions and documentation

Prior Research Findings

Currently no standard approach or technology platform for collecting patent-reported adverse symptoms in oncology trials

• 2-Year Contract– Started on 10/1/08

NCI Contract HHSN261200800043C

Overall Mission of Project

• Employ rigorous scientific methods to create a system for patient self-reporting of adverse symptoms in cancer trials (called the PRO-CTCAE), which is widely accepted and used; generates useful data for investigators, regulators, clinicians and patients; and is compatible with existing adverse event reporting systems

SOWMultiple Interrelated Tasks

• Generate White Paper identifying barriers, ideal conditions, and solutions to implement PRO-CTCAE

• Create PRO-CTCAE items• Build/evaluate electronic PRO-CTCAE platform• Evaluate measurement properties of items• Develop training materials• Design cooperative group study

YEAR 1

YEAR 2

Task-Based Framework for Project

Expert Investigative Team and Subcontracts

Overview of Project

• Brief review of relevant non-technology tasks of project

Progress to Date (1)Task 1: Create White Paper

• Survey of 729 stakeholdersRole 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

Progress to Date (2)Task 1: Create White Paper

• Survey resultsQUESTION AGREE NEUTRAL DISAGREESystems 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%

Progress to Date (3)Task 1: Create White Paper

• Potential barriers to CTCAE PROsQUESTION AGREE NEUTRAL DISAGREESevere illness/debilitation of patients 88% 6% 6%

Caregiver/proxy reporting should be permitted 70% 12% 18%

Lack of computers 69% 15% 16%

Limited time 58% 19% 23%

Limited personnel 57% 18% 25%

Limited clinic space 48% 21% 29%

Progress to Date (4)Task 1: Create White Paper

• Solutions: funds and new computersQUESTION AGREE NEUTRAL DISAGREEThese barriers could be overcome with adequate funding 79% 13% 8%

My site has clinic staff who could assist patients to self-report 66% 18% 16%

My site has clinic areas that could be used for patient reporting 47% 28% 25%

My site has computers that could be used for patient reporting 24% 25% 51%

My site would need new computers 72% 21% 7%

Wireless computers are feasible at my site 58% 12% 19%

Paper-based reporting is feasible at my site 86% 14% 4%

Progress to Date (5)Task 2: Develop Items

• 77 CTCAE symptoms identified amendable to patient self-reporting

• PRO-CTCAE items created– Different in format from CTCAE– Can be viewed on Wiki

PRO-CTCAE Item ListAbdominal pain Depression Edema – Limb Hot flashes Myalgia Rash Urticaria

Acne Dermatitis (Radiation)

Ejaculatory dysfunction

Hyper-pigmentation

Nail changes Rash: Hand-Foot

Vaginal discharge

Alopecia/hair loss Diarrhea Epistaxis (Nosebleeds)

Hypohidrosis Nausea Rigors/chills Vaginal dryness

Amenorrhea Distension/bloating, abdominal

Erectile dysfunction

Incontinence, anal Neuropathy-sensory

Skin Breakdown

Vision – blurred

Anorexia Dizziness Fatigue Incontinence, urinary

Odor Striae Voice changes

Anxiety Dry mouth/ xerostomia Flashing lights Injection site reaction/

extravasation

Orgasmic dysfunction

Sweating (diaphoresis)

Vomiting

Arthralgia (joint pain)

Dry skin Flatulence Insomnia Pain Taste alteration

Watery eye

Bronchospasm, wheezing Dyspareunia Floaters Irregular menses Painful urination

Tinnitus Decreased concentration

Chelilitis Dysphagia Gynecomastia Libido Palpitations Tremor Depression 2Constipation Dyspnea Heartburn/

dyspepsiaMemory

impairmentPhoto-

sensitivityUrinary

frequencyNail changes 2

(color)

Cough Easy bruising Hiccoughs Mucositis/stomatitis

Pruritus/ Itching Urine color change

Nail changes 3(shape)

Progress to DateTask 2: Develop Items

• For each symptom, evaluate multiple dimensions– Frequency, severity, interference with activities

• Developed structure of questionnaire items

Generic Structure of Items

FREQUENCY:How OFTEN did you have XXXX:• Never, Rarely, Occasionally, Frequently, Almost Constantly

SEVERITY:At its worst, what was SEVERITY of your XXXX:• None / Mild / Moderate / Severe / Very severe

INTERFERENCE:How much did XXXX INTERFERE with your (daily activities):• Not at all / A little bit / Somewhat / Quite a bit / Very much

Task 5: Platform Development

• Envisioned a system to allow PIs to create forms for electronic administration of PRO-CTCAE items to patients at clinic visits

Platform Components/Functionality• Components

– Form builder– Study calendar– Patient interface– Study-level reports– Patient-level reports– Automated alerts/notifications

• Skip pattern rules• User-level access/permissions• Interoperability with caAERS

Publishing Tool and FormBuilder

Task 5: Approach

• Subcontract to SemanticBits LLC• Weekly teleconferences since 10/08

– Committee: investigators, research study personnel, oncologists, patient representatives, psychometricians, FDA representatives, NCI representatives

• DEMONSTRATION:– Ram Chilukuri, SemanticBits LLC