June 22, 2019

Flatiron EHR-enabled Evidence
Generation
A new paradigm in oncology
Ken Carson, MD, PhD
Senior Medical Director, Flatiron Health
Assistant Professor of Medicine,
Washington University School of Medicine© Flatiron Health 2018

1

The Flatiron Network
2.2M
Active Patients

2,500
Clinicians

280
Cancer Clinics

HIPR

800
Patient Count

Unique Sites of Care
© Flatiron Health 20182

Standardize EHR data to a common data model
Diagnosis

Visits
Structured
Data Processing

Demographics
Labs

Therapies

EHR
Pathology

Discharge Notes

Physician Notes

Unstructured
Data Processing

RWE
Database

Radiology ReportHospital

Reports© Flatiron Health 20183Standardize EHR data to a common data model
2220
QD25001600
QD25001400
QD50058600
QD50055700
CL3215104
LC001081
LC003718
LC001488
LC133751
CL3215162
CL3215160
3234
LC133686
QD50060710

Blood Serum Albumin
ALBUMIN/GLOBULIN RATIO QD
ALBUMIN QD
ALBUMIN
ALBUMIN
Albumin % (EPR)
ALBUMIN, SERUM (001081)
Albumin, U
AlbuminAlbumin, U
Albumin%, Urine
Albumin, Urine
ALBUMIN SSAlbumin, U
MICROALBUMIN

g/dL(calc)
g/dL%
g/dL
%
g/dL%
g/dL
%%
mg/24hr
g/dL%
mg/dLQD50061100

MICROALBUMIN/CREATININE RATIO,RANDOM URINE

mcg/mg creat

QD85991610
50058600
CL3210074
QD86008211
LC149520
QD45069600
QD900415245
QD900429745
CL3215124
LC016931
QD50060800
QD50060900
QD85994821
CL3213320

ALBUMIN
ALBUMIN UPEP RANDALBUMIN LEVELALBUMIN/GLOBULIN RATIOAlbumin
PREALBUMIN
ALBUMIN, SERUM
ALBUMIN
Albumin Electrophoresis
Prealbumin
MICROALBUMIN, 24 HOUR UR
MICROALBUMIN, 24 HOUR UR
ALBUMIN,SERUM
PREALBUMIN

relative %%g/dL(calc)
g/dL
mg/dL
mg/dl
g/dL
g/dLmg/dL
mg/24 hmcg/min
g/dL
mg/dL

QD85995225

PROTEIN ELECTROPHORESIS ALBUMIN

g/dL

Harmonization and normalization ofstructured data
● Certain structured data elements may be
coded and collected in multiple ways in the
EHR across practices (example: albumin)● Combine and map datasets across sites to asingle dataset● Map all data elements to a single set ofdefinitions (data model)

1751-7

Albumin [Mass/volume]in Serum or Plasmag/dL© Flatiron Health 20184

Key data elements in oncology are unstructured
Section of PD-L1 ReportFor every PD-1/PD-L1 test a patient
receives, Flatiron biomarker Data Modelcaptures:Tissue Collection SiteResultResult

●
●
●
●
●
●
●
●
●
●

Test result
Date biopsy collected
Date biopsy received by laboratory
Date result received by provider
Lab nameSample typeTissue collection site
Type of test (e.g., IHC)
Assay / kit (e.g., Ventana 142)
Percent staining & staining intensity

Lab Name© Flatiron Health 20185

Source

Process

Validation

Technology Enabled Abstraction

Expert Abstractors
A network of abstractors comprised ofoncology nurses, certiﬁed tumor registrars,
and oncology clinical researchprofessionals.

Flatiron Technology
Software helps trained human abstractors
eﬃciently organize and review unstructured
documents to capture key data elements inpredetermined forms.

© Flatiron Health 20176

Source

Process

Validation

Undergoes surgery forearly-stage disease

Progresses on 1L, tested for
PD-L1 andre-tested for EGFR

Tested for EGFR
and ALK

Diagnosed with
Stage II NSCLCStarts 1L therapy

Develops metastatic
diseaseDeath

Starts 2L therapy, deteriorates
and is hospitalized

Documentation of source, quality and provenance.
© Flatiron Health 20177Source

Process

Validation

Undergoes surgery forearly-stage disease
Tested for EGFR
and ALK

Progresses on 1L, tested for
PD-L1 andre-tested for EGFR

Abstraction Details> Abstracted by Sue Smith on 4/30/17 at 10:10am> Physician notes and scan interpretation reviewed> Starts
Medical1L1L
recordfrom West Florida Cancer Clinic
therapy
Startstherapy

Diagnosed withStage II NSCLC
Develops metastaticdisease

Patient
Jane Doe

Quality of Progression abstraction
Starts 2L therapy, deteriorates===================================and is hospitalized> Completeness: 99%> Sue Smith is 96% accurate at last testing> Inter-abstractor agreement: 97%> Kappa: 0.93

> Audit trail for any changes> Datasetfreeze and storage
Stage at Dx
Biomarkers
2L Treatment
IIDeathEGFR-, ALK-, PD-L1-

nivolumab

Progression

Date of Death2017-03-08

2017-04-12© Flatiron Health 20178

Source

Process

Validation

Flatiron abstraction quality assurance & quality control
Centralized Controlled Environment
Upfront

Ongoing

Dataset QA

Feasibility

Auditing &Monitoring

Cohort QA

Policies &Procedures

Performance
Management

Data AlignmentTraining & Testing

Review Panel

Clinical Assertions© Flatiron Health 20179ResearchCollaborations
to Accelerate“RegulatoryGrade RWE”

Oncology Center ofExcellence (OCE)

Cancer Therapy
Evaluation Program

Dr. Sean Khozin,
Associate Director

Dr. Elad Sharon,
Medical Officer

Objectives
1.

Deﬁne speciﬁc types of regulatory decisions thatcan be informed by high quality real-world
data/evidence

2.

Deﬁne the quality (relevance and reliability)
standards for each of these types of regulatory
decisions3.

Develop and validate an approach to criticalvariables (endpoints) that meet the quality standard
for each use case4.

Demonstrate the ability to use high quality RWE for
speciﬁc, prioritized retrospective and prospective
use cases through proof-of-concept projects© Flatiron Health 201910

Our ongoing partnership with the FDA has resulted
in peer-reviewed publications

Oncology Center of Excellence

CDER Office of Biostatistics© Flatiron Health | 201911

FDA has legislative mandate to explore IF and WHEN RWE may
support new indications (approved drugs)/post marketing requirements

Frameworkhttps://www.fda.gov/downloads/ScienceResearch/SpecialTopics/RealWorldEvidence/UCM627769.pdf© Flatiron Health 2019
Source: Dr. Jacqueline Corrigan-Curay (Director Oﬃce of Medical Policy), FDA, “Framework for FDA’s Real-World Evidence Program”, webinar on March 15, 2019

We will continue to evolve our regulatory support
as the FDA evolves its guidance for RWD/RWE
Draft guidance from May 2019:

FDA will start to track INDs, NDAs,
and BLAs that contain RWD/RWE
To aid in this the FDA encourages
sponsors to self identify if theirsubmission contains RWD/RWE© Flatiron Health 201713April 2019:
Using RWE,
FDA approved
IBRANCE(palbociclib) for alabel expansion© Flatiron Health 201914

April 2019:
Using RWE,
FDA approved
IBRANCE(palbociclib) for alabel expansion●FDA approved this sNDA for label expansion●Data sources: Flatiron’s Breast Cancer Enhanced
Datamart, IQVIA’s insurance database, Pﬁzer’s
global safety database© Flatiron Health 2019

Thank you© Flatiron Health 201816