CTEP, NCI Adverse Event ReportingProgrammatic & Workflow Processes

Prepared by:Ann Setser

May 24, 2010

Agenda

• Conceptual overview of NCI AE reporting • CTEP Adverse Event Reporting Systems

– Multiple mechanisms for AE data submission• Routine via CTMS; CDUS; CDS • Expedited via AdEERS

• AE Reporting Workflow– Variable practices

• Issues to consider for integration of PRO-CTCAE

NCI AE Reporting Overview• Methodology varies widely among sites, modalities,

specialties, practices • There are no guidelines or uniform methods for how to

capture, present and interpret AE data • Within NCI, requirements differ

– Paper CRF – Multiple data systems (Groups, Centers, CTEP, contractors, others)

• At the patient encounter, most clinician- documented AE / symptom data are not CTCAE terms and often include notes that do not promote straightforward translation to CTCAE Grade (severity indicator)

NCI AE Reporting Overview…

• From patient encounter to sponsor analysis and publication, many layers of ‘interpretation and translation’ of AE terms and severity indicators occur.

• CTCAE data is a collection of secondary endpoints used to generate an overall picture or general safety profile of a given treatment, to identify gross trends and differences between studies, arms, groups, etc.

CTEP Adverse Event Reporting Systems1. Clinical Data Update System

CDUS• Primary resource of clinical trial data for NCI DCTD and

DCP• Types of Data Sets

– Abbreviated CDUS (Phase 3 - no AE data)– Complete CDUS (Phase 1, 2 AE data)

• Methods of Data Submission– ftp data transfer– web

• Contents of data set– Cumulative data per protocol

CTEP Adverse Event Reporting Systems…

CDUS Data Submission• Early Phase 1

– via CTMS (Clinical Trials Monitoring System) • File Transfer Protocol (FTP)• Monthly

• Other Phase trials: – via CDUS

• Lead Group or Lead Institution submits data set• FTP or web • Quarterly

Adverse Events Screen

Steps

CTEP Adverse Event Reporting Systems…AdEERS

Adverse Event Expedited Reporting System• Expedited AE reporting tool for CTEP sponsored trials

• Expedited reporting (AdEERS) is always in addition to Routine Reporting• All AEs (meeting the CDUS reporting requirements) must

be submitted as part of routine reporting

• AdEERS does not replace Routine Reporting

CTEP Expedited AE ReportingAdEERS

• CTEP-specific rules as a sponsor reporting to FDA

• The foundation of AdEERS is CTCAE– Unlike industry (verbatim coded to MedDRA)

• AdEERS ‘rules’ based on CTCAE depend on Phase of Trial

Example: CTEP AdEERS ‘Rules’

CTEP Expedited AE ReportingAdEERS

• Because of timeline requirements, AdEERS data is usually closer to patient encounter

• Requires extensive patient level data entry each time a report is generated

• Data reviewed by CTEP almost real-time– 24 hours– 5 days– 10 days

• Next slide: Screensnap of AdEERS with Sections of Report

Screensnap of AdEERS with Sections of Report

CDUS-reported and AdEERS-reported AEs

1. Design and expectations of two systems are very different• CDUS = summary cumulative AE data by quarter• AdEERS = detailed AE data in real-time

2. Initially there was no expectation for comparison of data from the two systems

• Programmatic data element requirements differ• Different staff with different AE expertise submit to the different

systems 3. AdEERS-CDUS Reconciliation implemented April 1, 2006

• Comparison of the data reported to the 2 systems• All Grade 5 discrepancies must be resolved• All other discrepancies result in a CDUS caution

Workflow Processes for reporting Routine AEs - Paper

1. At the patient encounter clinician documents AEs / symptoms

– On paper• Patient chart / Progress Note• Trial-specific ‘cheat sheet’ / AE CRF

– Electronic• Electronic Health Record• Remote Data Capture System

2. Nurse, CRA, or Data Manager retrospectively reviews source data

– Translates symptoms into CTCAE terms and grades and transcribes onto trial-specific AE CRF

Workflow Processes for reporting Routine AEs - Paper…

3. Site personnel submit paper CRF to Cooperative Group or Lead Organization

4. Cooperative Group or Lead Organization personnel enter AE data into data system

5. Technical staff prepare and submit electronic data to CTEP via CDUS ftp

Workflow Processes for reporting Routine AEs - Electronic…

1. Site access to RDC, CDMS, etc.2. Site technical staff program local data file

transfer to Group data system3. Group technical staff prepare CTEP- required

subset of all Group data and reprograms for submission to CTEP CDUS

Going Forward with PRO-CTCAE

1. Understand strengths and limitations of current AE data systems and processes—from patient encounter to sponsor to regulators to publication

2. With awareness of the varied processes (paper, electronic), how best might PROs be integrated and help achieve more real-time AE reporting?

3. How will PRO data be analyzed / utilized relative to clinician-reported AE data?

4. How can we achieve a common method to summarize and communicate overall AE burden?

AcronymsAdEERS Adverse Event Expedited Reporting SystemCDUS Clinical Data Update System (FTP submission)CDS Clinical Data System (Web submission)CDMS Clinical Data Management SystemCTCAE Common Terminology Criteria for Adverse EventsCTEP Cancer Therapy Evaluation ProgramCRA Clinical Research AssociateCRF Case Report FormCTMS Clinical Trials Monitoring SystemDCP Division of Cancer PreventionDCTD Division of Cancer Treatment and DiagnosisFTP File Transfer ProtocolRDC Remote data capture

Discussion