March 9, 2010: I. Sim EHRs and Research Epi 206 — Medical Informatics Ida Sim, MD, PhD March 9, 2010 Division of General Internal Medicine, and Center.

March 9, 2010: I. Sim EHRs and ResearchEpi 206 — Medical Informatics

Ida Sim, MD, PhD

March 9, 2010

Division of General Internal Medicine, and Center for Clinical and Translational Informatics

UCSF

Informatics for Clinical Research

Copyright Ida Sim, 2010. All federal and state rights reserved for all original material presented in this course through any medium, including lecture or print.


Outline

• Clinical Research Systems Overview• Clinical Research Informatics (CRI)

– sharing research meaning• UCSF clinical research information systems

– MyResearch– Integrated Data Repository– REDCap– Epic

• Summary

Big Picture of Health Informatics

Virtual Patient

Transactions

Raw data

Medical knowledge

Clinical research

transactions

Raw research

data

Dec

isio

n su

ppor

t

Med

ical

logi

c

PATIENT CARE / WELLNES RESEARCH

Workflow modeling and support, usability, cognitive support, computer-supported cooperative work (CSCW), etc.

CRMSs


Clinic 2008

FrontDesk

Radiology

MedicalInformationBureau

Walgreens

Pharm BenefitManager

Benefits Check(RxHub)

HealthNet

B&T

UCare

Specialist

ReferralAuthorization

Internet Intranet Phone/Paper/Fax

Lab

UniLab

(HL-7)

IRB Funding Agency

Study DB

Data analysis

Results reporting

Contract R

esearch O

rganization (C

RO

)

Protocol

Trial DesignSponsorsAcademic PIs

?Site 1 Site 2 Site 3

Site Management Organization (SMO)

Clinical Research Today

• >80% on paper


IT Systems for Clinical Research

• Electronic IRB systems– electronic system for submission and review of

applications– e.g., ClickCommerce, home grown, iMedRIS (at UCSF)

• Clinical Trial Management System (CTMS)– web-based application to define variables, forms, sign-in

authentication, data entry, data cleaning, data analysis and

reporting, etc. – e.g, Velos, OnCore (at UCSF Cancer Center)


iMedRIS

• Just launched 2 weeks ago

– http://research.ucsf.edu/chr/iMedRIS/Home.asp

• Each institution can customize what information is collected– mostly administrative

data (e.g., PI name)– scientific info is all in text

(e.g., design type = RCT)


IT Systems for Clinical Research

• Electronic IRB systems– electronic system for submission and review of

applications– e.g., ClickCommerce, home grown, iMedRIS (at UCSF)

• Clinical Trial Management System (CTMS)– web-based application to define variables, forms, sign-in

authentication, data entry, data cleaning, data analysis and

reporting, etc. – e.g, Velos, OnCore (at UCSF Cancer Center)


CRMSs

• Clinical Research Management Systems are for running/managing a study– document management (protocol, case report

forms)– finances, IRB– study calendar (what to do to whom when) and

data entry– data management and analysis– reporting

• Most systems designed for supporting interventional clinical trials (CTMS)


EHR vs. CTMS Contents

• EHR• Patient demographics• Chart notes

– problem list• Visit and assessment• Lab and other orders• Lab and other results• Clinical decision-making• Discharge summary

• CTMS• Title, NCT #, IRB #• Protocol document

– interventions, design,

outcomes, etc.• Study assessment• Outcomes assessment• Case report forms• Data analysis• Trial reporting/publication


CRMS Policy at UCSF

• Currently– Cancer Center on OnCore– rest of campus on smattering of other systems

• e.g., Quesgen, Immune Tolerance Network/Stanford

• Longer term– may extend OnCore to rest of campus

• In the meantime, have a few systems providing some support – REDCap, MyResearch, IDR, etc.


Outline


– sharing research meaning • UCSF clinical research information systems

– REDCap– MyResearch– Integrated Data Repository– Epic

• Summary


Why is CRI Important?

• Clinical trials are becoming very complex– avg 460 days (2002) to 780 days (2006)– avg # of participants: 1700 to 3400 over 30 yrs– # of study procedures: 70% increase to 85 procedures, from

2000 to 2005

• Fragmented, global industry– estimated 1100 organizations involved in clinical research in

2009 in US (Sponsors, CROs, SMOs, AHCs...)

– “43% big pharma FDA trials were conducted abroad... projecting as much as 65% within 3 years” [Tufts Outlook 2008]

• Can we afford to do this all in paper??

Tufts Center for the Study of Drug Development, “Growing Protocol Design Complexity Stresses Investigators, Volunteers,” Impact Report 10, no. 1 (January/February 2008).


Clinic 2008

FrontDesk

Radiology


Walgreens



HealthNet

B&T

UCare

Specialist



Lab

UniLab

(HL-7)

IRB

Trial Design

Protocol

Funding Agency

Site 1 Site 2 Site 3


Study DB

Data analysis

Results reporting

Contract R

esearch Organ

ization

(CR

O)

SponsorsAcademic PIs

?

Simplifying Clin Research Management


Need to “Interoperate”

• Can achieve through one single standard system – one end-to-end CTMS from trial inception to end– used by all PIs, industry, CROs, worldwide– like everyone using Word for word processing

• ...or through “plug and play” of multiple modular systems– define common terms, models, interchange

protocols– provide software components for assembly – provide way to “certify” compatibility of systems


Interoperation

• Ability of two or more systems or components to exchange information and to use the information that has been exchanged [IEEE Standard Computer Dictionary, 1990]

– syntactic: grammar, composition of what is said• e.g., using an exchange protocol over networks• e.g., HL7, DICOM, XML Document Type Definition (DTD)

– semantic: meaning of what is said• e.g., using a controlled vocabulary aka dictionary• e.g., SNOMED, ICD-9


Biomedical IT “Stacks”

Administrative Clinical Care Research

ClinicalBilling

Physical Networking

Communications Protocols (e.g., HL-7)

Standard Vocabulary

PracticeManagement

Systems

Medical BusinessData Model

ElectronicMedicalRecord

Clinical CareData Model

Clinical Res. Management

Systems

Clinical StudyData Models


Interoperation Over the Stack


ClinicalBilling

Physical Networking


Standard Vocabulary

PracticeManagement

Systems





Systems


Syn

tact

icS

em

ant

ic a

nd

Wo

rkflo

w


MICU

FinanceResearch

QA

Clinical / ResearchData Repository

Internet

ADT Chem EHR XRay PBM Claims

• How do the machines “talk” to each other?

Networking Basics


Internet = Network of Networks

itsa

medicine

ucsf.edu

nci.nih.gov

“the cloud”

myhome.com

Main Trunk Cables

local trunk cablethrough Berkeley

amazon.com

at homedial-in to itsa.ucsf.edu via modem

pacbell.net

aol.com

Internet Service Provider (ISP)via DSLor cable

LAN


• Protocol = grammar for machines talking to each other– e.g., hypertext transfer protocol http for web

• http://www.epibiostat.ucsf.edu/courses/schedule/med_informatics.html

– e.g., ftp file transfer protocol– all sit on top of basic networking protocol TCP/IP

• Health-specific protocols needed “on top of” http or TCP/IP– a “grammar” for how to exchange health-related data

What Happens Over the Cables

http://www.epibiostat.ucsf.edu/courses/schedule/med_informatics.html

http://www.epibiostat.ucsf.edu/courses/schedule/med_informatics.html


Health Data Interchange Protocols• HL7, “containers” for data packages, e.g., lab

• DICOM, “containers” for radiology studies– machine used, type of study, # of images, etc.

• CCD (Continuity of Care Document) for the electronic chart– e.g., problem list, allergies, family history

• “Containers” do not address the data naming issue– e.g., Na, sodium, serum sodium -- need to standardize to a SNOMED code

MSH|…message headerPID|…patient identifier<!-OBX…observation result>OBX|1|ST|84295^NA||150|mmol/l|136-148|H||A|F|19850301<CR>


Sharing Research Meaning


ClinicalBilling

Physical Networking


Standard Vocabulary

PracticeManagement

Systems





Systems


Syn

tact

icS

em

ant

ic a

nd

Wo

rkflo

w


Computable Protocol

• Study protocol is core essence of a research study– the investigational plan, including the actions to be

undertaken, the measurements, and the analysis

procedures to be followed– is not the same as the study protocol document (i.e.,

the Word or PDF file)• If this protocol is made computable, and

standardized, then all clinical studies can be described in the same way so that clinical research systems can interoperate


Components of a Study Protocol• Who

– participants: eligibility criteria, recruitment, followup– investigators: PI, sponsors, advisors, etc.

• What– interventions or exposures: experimental, control– study outcomes: primary, secondary, baseline

• When– dates of enrollment, timing of assessments

• Where– study sites

• Why– background, objective, hypothesis

• How– analytic approach, study monitoring, outcomes adjudication, etc.


Computable Protocol


ClinicalBilling

Physical Networking


Standard Vocabulary

PracticeManagement

Systems





Systems

Computable Protocol

Syn

tact

icS

em

ant

ic a

nd

Wo

rkflo

w


Need Standardization To...

• Common computable study protocol– the study plan: e.g., eligibility criteria, treatment, outcomes

• CTOM, SDTM, BRIDG, OCRe, etc. etc.

• Common variables– clinicallly-agreed upon data items for research

• e.g., “menopause” defined a certain way

• Terminologies/vocabularies– base terms used to describe biomedical concepts

• e.g., SNOMED, NCI Thesaurus

• Common interchange standards– e.g., CDISC (“HL7 for clinical research”)


Scientific Case for Standardization

• Interventional studies fundamentally done to demonstrate differences between interventions, by types of patients [Clarke M, Trials 2007]

– common eligibility criteria would facilitate cross-study comparisons and synthesis

• e.g., post-menopause, congestive heart failure– common study outcomes (phenotypes) necessary for

pooling/meta-analysis• e.g., 5-year cancer free survival, common asthma measures

• Similar argument for observational studies– e.g., comparative effectiveness research


NCI Approach in Cancer

• NCI caDSR (Data Standards Repository)– library of Common Data Elements (CDEs) that

others have defined– you can define new CDEs using terms from NCI

Thesaurus

• Let’s go search...– https://cdebrowser.nci.nih.gov/CDEBrowser/

https://cdebrowser.nci.nih.gov/CDEBrowser/


Case Report Forms (CRF)

• Why reinvent the wheel for common forms?• NCI has a Forms Builder

– “shop” for CDEs, put them into your cart– insert CDEs into your case report form

• can download as HTML, XML, Excel, Word, PDF

• NCI now building library of forms – e.g., Demographics Case Report Form built from

CDEs• PDF, Word, etc. or directly to CTMS for direct data

entry

• Grant proposals to NCI are beginning to be reviewed on use of CDEs


Summary: Interoperation of Research Data

• Interoperation = meaningful exchange of data among computers– syntactic: how things are said, the grammar– semantic: what is said, the meaning

• Semantic standardization a greater challenge in research than clinical care– need a common computable protocol model– need to be very precise, research needs change as

knowledge grows, researchers very individualistic• Moving towards standardized, coded variables


Outline


– sharing research meaning • UCSF clinical research information systems

– REDCap– MyResearch– Integrated Data Repository– Epic

• Summary


Clinic 2008

FrontDesk

Radiology


Walgreens



HealthNet

B&T

UCare

Specialist



Lab

UniLab

(HL-7) IRB Funding Agency

MyResearch

Data analysis

Results reporting

On

cor C

RM

S?

Protocol




UCSF Research Info Systems

Integrated Data Repository

REDCap

Epic


REDCap

• Web-based tool for building study databases and defining data entry forms– https://redcap.ucsfopenresearch.org/– https://redcap.ucsfopenresearch.org/index.php?ac

tion=training– is HIPAA-compliant (unlike Survey Monkey)

• Example web-based survey– https://redcap.ucsfopenresearch.org/surveys/index

.php?hash=c9f0f895fb98ab9159f51fd0297e236d• Now available to you for free

https://redcap.ucsfopenresearch.org/

https://redcap.ucsfopenresearch.org/index.php?action=training

https://redcap.ucsfopenresearch.org/index.php?action=training

https://redcap.ucsfopenresearch.org/surveys/index.php?hash=c9f0f895fb98ab9159f51fd0297e236d

https://redcap.ucsfopenresearch.org/surveys/index.php?hash=c9f0f895fb98ab9159f51fd0297e236d


Clinic 2008

FrontDesk

Radiology


Walgreens



HealthNet

B&T

UCare

Specialist



Lab

UniLab


MyResearch

Data analysis

Results reporting

On

cor C

RM

S?

Protocol




Where Should REDCap Data Go?


REDCap

Epic


Risks of Data Security Breach

• PIs storing Protected Health Information (PHI) data on laptops, unsecured desktops

– thefts, losses– VA, cancer registry

• New CA law: you can be fined up to $250,000 for PHI breach

• MyResearch is ultra-secure storage for your PHI data

IRB Funding Agency

MyResearch

Data analysis

Results reporting

On

cor C

RM

S?

Protocol




REDCap


No More Lax Storage

PI #2

PI #1

MyResearch

Secure location with backup

SAS, R

Firewall

Pixels only

Secure Global Desktop


• PHI stored in FISMA level secure database system

• Data never physically leaves MyResearch

• Your browser is a “dumb” window onto the MyResearch computer– SAS, etc. runs on data

on MyResearch– you see pixels only, no

local caching on your

computer

MyResearch

MyResearch

Secure location with backup

SAS, R

Firewall

Pixels only

Secure Global Desktop


Using MyResearch

• Satisfies soon-to-be required CHR criteria for secure data storage– if you don’t use MyResearch, must show you are

as secure (i.e., FISMA level, very difficult)• Works on PC, Mac with Leopard, Unix• Is brand new, still has bugs • Will cost ~$400/yr/PI starting ~July• http://oaais.ucsf.edu/OAAIS/networking/

research_data/1034-DSY.html


Clinic 2008

FrontDesk

Radiology


Walgreens



HealthNet

B&T

UCare

Specialist



Lab

UniLab


MyResearch

Data analysis

Results reporting

On

cor C

RM

S?

Protocol




UCSF Research Info Systems


REDCap

Epic


• Retrospective cohort study of outpatients• Compare 5 year rate for congestive heart failure for

diabetics treated with a glitazone vs. not– find diabetics– find whether treated with a glitazone– for these patients, find all subsequent cases of congestive

heart failure – analyze at 5 years

• adjust for age, sex, severity of diabetes, previous CHF,

other meds, etc., etc.

Outcomes Research Project


• Diabetes diagnosis– chart, HgbA1C, meds taken, problem list...

• Glitazone usage– orders, pharmacy

• Potential confounders– age, sex, severity, other meds, etc.

Health System Minnesota: 50 paper, 50 computer

200,000 lives, 460 physicians

Health System Minnesota: 50 paper, 50 computer

200,000 lives, 460 physicians

Types of Data Needed


MICU

FinanceResearch

QA

IntegratedData Repository

Internet

ADT Chem EHR XRay PBM Claims

• autofeed nightly, data stored securely with backup

Data from UCare to IDR

The IDR Is Live!

• Complete UCare Data Set– 2.7 Million patient records– 5 Million encounter records– Currently inpatient data – Beginning to get billing data– Importing Dentistry (Axium system)

• Pilot Release to Select Investigators– Slow ramp up of customers will continue– Building full support for all users– Self Service interface

43

Typical Research Query

• A typical query:

To do retrospective patient analyses using ICD-9 code searches/discharge diagnoses, e.g. a UCSF clinician is interested in looking at a patient population composed of children <21yo with heparin induced thrombocytopenia (ICD=289.84) in the last 5 years.


i2b2 Demo

• UCSF IDR built using the i2b2 software suite from Harvard Partners

• Demo of i2b2 query interface to over 5000 anonymized real records from Partners

– http://services.i2b2.org/webclient/#

IDR User Interface


Changing UCSF Research Culture

• Must keep all data/analyses in MyResearch environment

• Can search IDR for non-PHI and PHI-sensitive data• Policies established on who owns what data when

and when to share under what circumstances– e.g., what if you put data in then leave UCSF?

• In 2 years, UCSF will revisit policy on IDR use– may well require all PIs to deposit final research data

into IDR for sharing• Slow uptake, many reasons


Clinic 2008

FrontDesk

Radiology


Walgreens



HealthNet

B&T

UCare

Specialist



Lab

UniLab


MyResearch

Data analysis

Results reporting

On

cor C

RM

S?

Protocol




Epic Research Functionality?


REDCap

Epic


Summary• Clinical research fragmented, global, essentially

separate from clinical care• Clinical research informatics ongoing in two worlds

– most still paper, commercial CTMSs mostly document centered (PDFs) rather than data or concept-centered

– moving towards modular component approach with • standard data elements (CDEs) and case report forms (CRFs)• common computable protocol models and interchange exchange

standards (CDISC)

• UCSF offering web-based data entry and databases, secure data storage and access to UCare data via IDR

• Still very very early in design and use of clinical research information systems



Market Facts

• In early 90s, 80% trials done in academia, now 20% – about 10% of UCSF studies are pharma-related

• Huge business– Big Pharma: $15.9 b on clinical trials [2006], out of $50.3 b total

R&D [2009 PhRMA Industry Profile]

– NIH budget $29.5 billion 2009

• Fragmented, global industry– estimated 1100 organizations involved in clinical research in

2009 in US (Sponsors, CROs, SMOs, AHCs...)– CROs $15b market in 2007– “43% big pharma FDA trials were conducted abroad...

projecting as much as 65% within 3 years” [Tufts Outlook 2008]

March 9, 2010: I. Sim EHRs and Research Epi 206 — Medical Informatics Ida Sim, MD, PhD March 9, 2010 Division of General Internal Medicine, and Center.

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