Implementation and Operation of CDISC ODM-based EDC by UMIN Takahiro Kiuchi, M.D., Ph.D. UMIN Center, The University of Tokyo Hospital, Tokyo, Japan 1
Content 1. CDISC standards and academic research 2. What is UMIN and UMIN INDICE? 3. Implementation and operation of CDISC ODM-based EDC by UMIN 4. Practical development and operation of a real clinical trial by CDISC ODM-based EDC with Fukushima Prefectural University Hospital 2
1. CDISC standards and academic research 3
What is CDISC? CDISC: Clinical Data Interchange Standards Consortium (Non-profit organization for standardization) Mission: The CDISC mission is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare. (cited from CDISC website) Members: Pharma, CRO, IT Vendors 4
CDISC Standards 1. SDTM Study Data Tabulation Model (SAS.xpt) 2. SEND Standard Exchange for Non-clinical Data (SAS.xpt) 3. ADaM Analysis Dataset Model (SAS.xpt) NDA 4. CRT-DDS Case Report Tabulation and Data Definition Specification (PDF or XML) 5. ODM Operational Data Model (XML) 6. LAB Clinical Laboratory Model (ASCII, SAS.xpt, or XML) 7. PR Protocol Representation (UML) Data transfer 8.CDASH Clinical Data Acquisition Standards Harmonization (Standardized variables for CRF) Study design 5
CDISC Standards for regulatory clinical trials Hospital CDASH (Variable names) PR (Protocol) Lab Trial use in U.S.A. and Europe ODM (XML) Lab (XML) (XML) Clinical laboratory company Pharma SDTM SEND ADaM Practical use in U.S.A. SDTM (Clinical) SEND (Non-clinical) ADaM (Statistical analysis) SAS xpt CRT-DDS (Metadata) PDF or XML Regulatory agency SDTM SEND ADaM 6
CDISC Standards for academic research Hospital Academic data center Academic publishers CDASH (Variable names) PR (Protocol) Lab ODM (XML) Lab (XML) (XML) Clinical laboratory company SDTM ADaM Paper CDISC Standards can be used for academic clinical trials and epidemiological studies as they are. 7
CDISC Standards and ICH EMA PMDA FDA ICH CDISC Standards (Individual clinical data) A Pharma B Pharma C Pharma 8
CDISC Standards for FDA, Pharma, Hospital FDA Pharma CDISC Standards Recommendation ->Obligation Data conversion CDISC SDTM Proprietary clinical data management system CDISC SDTM CDISC Standards Recommendation ->Obligation CDISC Standards compatible clinical data management system CDISC Standards Recommendation ->Obligation CDISC SDTM CDISC Standards compatible clinical data management system CDISC ODM Hospital Vendor proprietary data interface for clinical research Vendor proprietary data interface for clinical research CDISC ODM data interface for clinical research 9
2. What is UMIN and UMIN INDICE? 10
UMIN (University hospital Medical Information Network) Important information infrastructure for academic activities in biomedicine Versatile academic information services, including research, education, and clinical practice National University Hospital Council The Univ. of Tokyo Hospital Control 320 thousands Registered users 50 million page views per month 11
UMIN Services -Overview Research AC Academic societies and meetings database ELBIS Electronic Library for Biomedical Sciences FIND Fund Information Database INDICE Internet Data and Information Center ROCOLS Recruiting System for Our Colleagues and Students CTR ICMJ-accredited clinical trial registry Clinical practice Intoxication database (Yamaguchi Univ.) HIV manual (Hokkaido Univ.) Drug information database Drug information text database for pharmacists Medical supplies and materials database Education EPOC Online evaluating system of post-graduate clinical training for physicians Debut Online evaluating system of post-graduate clinical training for dentists Web-QME Web-based Quality Management system for Educational effectiveness VHP Visible Human Project image data University hospitals Official documents database University hospitals guide Master database for patient fee calculation Standardized disease nomenclature database Mailing lists Member-only homepages Multipurpose Information and database services Collection of biomedical web sites Medical terms glossary Research institutes and hospitals database Homepage etc. hosting services Open homepage hosting service Member-only homepage hosting service Archival homepage hosting service Wiki Blog VOD hosting service Communication support services Email service, including encrypted email Mailing list service BBS service Online voting system 12
UMIN INDICE (Internet Data and Information Center for Clinical Research) Largest internet clinical research data center in Japan SaaS = Software as a Service UMIN INDICE Data collection Original software package for clinical and epidemiological research User management Internet Information Homepage hosting service Security Communication Mailing list managementsystem Hardware 13
Usage statistics of UMIN INDICE 180 155 research projects One million of registered cases 1200000 160 140 120 100 80 Accummulated Under operation 1000000 800000 600000 60 400000 40 20 200000 0 April-00 April-02 April-04 April-06 April-08 April-10 0 Apr-00 Apr-02 Apr-04 Apr-06 Apr-08 Apr-10 14
Web-based data collection by UMIN Hospital UMIN Center Web browser Manual entry of digitalized laboratory and drug prescription data (laborious and vulnerable to miss transcription) Electronic Health Record Internet Web-based UMIN INDICE Laboratory data Drug prescription 15
3. Implementation and operation of CDISC ODM-based EDC by UMIN 16
Web-based data collection by UMIN Hospital UMIN Center Web browser Manual entry of digitalized laboratory and drug prescription data (laborious and vulnerable to miss transcription) Electronic Health Record Internet Web-based UMIN INDICE Laboratory data Drug prescription 17
Procedure for developing CDISC ODM-based EDC in UMIN 1. Analysis of a protocol and CRFs 2. Development of web-based EDC server system 3. Development of routine which processes CDISC ODMbased data and accommodate them to web-based EDC server system 4. Development of routine which extract trial data from web-based EDC server system and create CDISC ODMbased data. 5. Development of templates of CDISC ODM which are sent from hospitals to UMIN. 18
Hospital Web browser CDISC ODM and Web-based data collection by UMIN (2009/11/6) UMIN Center Manual entry of digitalized laboratory and drug prescription data (laborious and vulnerable to miss transcription) Electronic Health Record Internet Web-based CDISC ODMbased UMIN INDICE Laboratory data Drug prescription Full or semi-automated fulfillment of digitalized laboratory and drug prescription data Entry of other data from electronic health record 19
UMIN needs partner hospitals for CDISC ODM-based EDC UMIN could receive CDISC ODM data in early 2009. But were there any hospitals which develop CDISC ODM-based research data submission system linked to EHR, using their own funds? => There were two university hospitals! 20
Implemention strategy for development of CDISC ODM-based research data submission system linked to EHR Data automatically or semi-automatically collected from EHR are limited to demographic, laboratory, and drug prescription data, which usually covers more than half of trial data. RFD (Retrieve Form for Data), which is based on XForm technology, is not used because the technology is immature and the implementation cost is expensive. 21
Implementation procedure for development of CDISC ODM-based research data submission system linked to EHR 1. Development of CRF entry system CRF entry system TP 4.5mg/dl Manual entry 2. Development of a routine for automated or semi-automated fulfillment of demographic, laboratory, and drug prescription data TP 4.5mg/dl Cr 1.1mg/dl Automated entry 3. Development of a routine for checking CRF data TP 4.5mg/dl Cr 1.1mg/dl TC mg/dl Deficit check 4. Development of a routine for creating CDISC ODM from CRF data 5. Submission of CDISC ODM-based data CDISC CDISC ODM ODM-based data submission Conversion to CDISC ODM TP 4.5mg/dl Cr 1.1mg/dl TC110mg/dl 22
Packaging Future perspective of the development of CDISC ODM-based research data submission system linked to EHR 1. Proprietary implementation of each hospital for each trial 2. Vendor packaging 1)Vendor-specific module installed by a vendor for each trial 2)Vendor-specific module installed by a hospital for each trial 3)Vendor-specific module automated installed online for each trial 4)CDISC standardized module automated installed online for each trial Development in most EHR vendors Interoperability of CDISC ODM 23
4. Practical development and operation of a real clinical trial by CDISC ODM-based EDC with Fukushima Prefectural University Hospital 24
Overview of the clinical trial Title Effect of topping up of Toremifene to preoperative chemotherapy of breast cancer Principal investigators Seiichi Takenouchi and Tohru Ohtake The number of cases planned 20 cases The number of participant institutions 7 hospitals, including Fukushima Prefectural Univ. Hospital The study start date Nov. 9 th, 2009 25
EHR and CRF data entry form EHR CRF data entry form Automated fulfillment 26 10
Using Yahgee for the implementation(1) What is Yahgee 1)Software tool Data entry forms can be developed and corrected by users themselves (hospitals). 2)Interface for most EHRs sold in Japan Data can be entered and extracted from most EHRs sold in Japan through Yahgee. Yahgee Yahgee interface Yahgee Yahgee interface Yahgee Yahgee interface A company s EHR B company s EHR C company s EHR 27
Using Yahgee for the implementation(2) UMIN INDICE Web interface CDISC ODM interface CDISC ODM interface CDISC ODM interface CDISC ODM interface CDISC ODM interface Yahgee Yaghee intereface Yahgee Yaghee interface A company s EHR P hospital B company s EHR Q hospital A company s EHR Fukushima Prefectural Univ. hospital B company s EHR R hospital 28
Why the real clinical trial, based on CDISC ODM, realized in Japan first. Realized as an academic (non-profit) clinical trial It is difficult to realize a real EDC in regulatory data collection, using new and immature technology like CDISC Standards. CDISC Standards are misunderstood as those for only new drug application. In fact, their scope are much wider now. Pharma companies concern obligatory CDISC-based new drug application over CDISC-based EDC. Web-based academic EDC system - UMIN INDICE Practical approach for the development of CDISC ODM-based research data submission system linked to EHR 1) Data collected from EHR are limited to demographic, laboratory, and drug prescription data. 2) RFD (Retrieve Form for Data) is not used because the technology is immature and the implementation cost is expensive. 29
Thank you for your attention. The presenter s doctor thesis Research on the Use of World Wide Web for a Data Management System for Use in Multi-institutional Clinical Trials Published papers related to the doctor thesis 1) Kiuchi T, Ohashi Y, Konishi M, Bandai Y, Kosuge T, Kakizoe T: A World Wide Web-based user interface for a data management system for use in multiinstitutional clinical trials - Development and experimental operation of an automated patient registration and random allocation system. Controlled Clinical Trials 17:476-493, 1996 2) Kiuchi T, Kaihara S: C-HTTP - The development of a secure, closed HTTPbased network on the Internet. Proceedings of the 1996 Symposium on Network and Distributed System Security, IEEE Computer Society Press, 64-75, 1996 3) Kiuchi T, Kaihara S: Automated generation of a World Wide Web-based data entry and check program for medical applications. Computer Methods and Programs in Biomedicine 52:129-138, 1997 30