Clinical Data Interchange Standards Consortium Overview  HCLSIG BioRDF Sub-group 10 Mar 2008 Clinical Data Interchange Standards Consortium Overview Stephen J Ruberg, PhD Senior Research Fellow Eli Lilly & Company

Background Who is Steve Ruberg? How does pharma generate and utilize clinical data? What is CDISC? What has CDISC done, what are they doing, and what are they considering? Where does CDISC need help?

Steve Ruberg Statistician Not IT, though much learning over last decade Creator, recipient, analyzer, archiver, submitter of clinical data Helped launch CDISC as not-for-profit in 2000 First Chairman; just finished my term on the Board in Dec, 2007

 Pharma Clinical Data Company executed trial Getting data from investigators Paper and electronic Getting data from labs Central vs local Getting data from other sources Growing variety of electronic data capture

Electronic Data Capture at an Investigator Site

 Pharma Clinical Data Other considerations Working with a CRO Defining data specs Receiving datasets Submissions to the FDA Observed/raw data and derived/analysis data Analysis programs, reports

 Pharma Clinical Data Value of Standards Operational efficiency Reduce programming and re-mapping of data Increase automation; better tools Scientific effectiveness INTEGRATION OF DATA Better analysis, interpretation, understanding FDA remit: Promote and protect health

What is CDISC CDISC is a global, open, multidisciplinary, non-profit organization that has established standards to support the acquisition, exchange, submission and archive of clinical research data and metadata. 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.  CDISC standards are vendor-neutral, platform-independent and freely available via the CDISC website. Established as a non-profit in 200 Most members from pharma or companies (CROs, software vendors) that support pharma clinical research

What is CDISC Doing CDISC models SDTM – Submission Data Tabulation Model (used for FDA submissions; can also be used for CRO submissions to pharma sponsor) Defines structure (vertical) and some categorization/data domains and minimal terminology ODM – Operational Data Model XML messaging standard LAB – Clinical laboratory data model

What is CDISC Doing CDISC models SEND – Standard for Exchange of Non-clinical Data Non-clinical version of SDTM Used for FDA submissions; can also be used for CRO submissions to pharma sponsor Defines structure (vertical) and some categorization/data domains and minimal terminology ADaM – Analysis Data Model Suggested structures for FDA submission of analysis data Protocol Representation Group Terminology/data definitions to describe a protocol/study

What is CDISC Doing CDISC models CDASH – Clinical Data Acquisition Standards Harmonization Non-clinical version of SDTM Used for FDA submissions; can also be used for CRO submissions to pharma sponsor Defines structure (vertical) and some categorization/data domains and minimal terminology ADaM – Analysis Data Model Suggested formats for FDA submission of analysis datasets Terminology Creating more detailed data element specifications for use in SDTM

 What is CDISC Doing CDISC works in virtual teams Conference calls, meetings Tends to focus on pieces (data domains like adverse events, demography, vitals signs, etc.) of the clinical business Progress, but slow and limited

What is CDISC Considering  What is CDISC Considering CDISC models have some utility but cannot meet data integration needs Not enough unambiguous data element definitions (i.e. terminology) Caution: terminology means different things to different people Concept Valid value set

 Proposal WHAT Build a comprehensive, industry-wide electronically accessible and consumable data element dictionary that contains the “clinical words” used in clinical research studies

What Is a Data Element Definition?  What Is a Data Element Definition? All the pieces of information (i.e. attributes) needed to unambiguously describe a concept English dictionary analogy Word – desk Phonetic spelling – dĕsk Part of speech – noun Definition – a piece of furniture with a flat top for writing [could also be thought of as the concept] Source – Latin, discus etc.

The English Dictionary as Attributes  The English Dictionary as Attributes Word Phonetic spelling Part of Speech Definition Source Year Other Forms Synonym / Example desk dĕsk Noun 1. A table, frame or case with horizontal or slightly sloping surface for writing or reading Latin, discus Old English None counter 2. A division of an organization specializing in a particular activity e.g. the Russian desk at the State Department run rən Verb 1. To go faster than a walk by springing the feet so that only one is touching the ground at a time Old English, iernan run across run a fever Sprint, jog, scuttle, dart, scamper, dash Something that flows in the course of an operation Operate, conduct

Clinical Data Element for Pharma  Clinical Data Element for Pharma DRAFT DRAFT Variable name Label / concept Valid values of the variable itself Data type (num, char, date, …) Units Key words (e.g. biomarker, osteoporosis, …) – facilitate searches Source / reference (as needed) SDTM data domain Regulatory requirement [A team needs to define what are the essential attributes that are parsimonious – enough to eliminate ambiguity, but few enough to be useful, consumable, understandable, burdenless.]

The Clinical Data Element Dictionary  The Clinical Data Element Dictionary Variable Name Concept / Label Data Type Format Valid Values Units SDTM Domain Source Keywords URL HAMD_Q1 Response to question #1 on the Ham-D 21 Depression Scale Num I1 0,1,2,3,4 NA NS “A rating scale for depression” 1960 Max Hamilton Journal of Neurology, Neurosurgery and Psychiatry. vol 23 pp 56-62 Depression, rating scale, questionnaire, mood http:// HAMD_Q16 Response to question #16 on the Ham-D 21 Depression Scale 0,1,2,3 As above Depression, rating scale, questionnaire, weight loss AE_verb Verbatim adverse event reported by the investigator Char 200 English text AE See GCP Safety, risk, drug reaction, side effect, treatment-emergent AE_LLT Coded adverse event using the MedDRA lowest level term 50 Lowest level terms from MedDRA See MedDRA reference

 Proposal HOW - Business model An open, electronic, peer production environment with appropriate governance (e.g. a wiki) Like MedDRA, but open and free Like Wikipedia, but more governance Like LINUX, but more granular and dynamic We must adopt a more flexible and rapid development process to get this in place

Clinical Data Element Standards Electronic submission Governance Template Submission Review Final Anyone Anywhere Based on 8-10 attributes Downloadable (define.xml) Searchable – text, key words search shows status (submit, review, final)

Governance for the CDED Governing Board Full-Time CDISC Employees Lead 1 Lead 2 Lead 3 ... Lead k Team 1 Team 2 Team 3 Team k Lead 1 Lead 2 Lead 3 Lead k . . . ~ 6-8 SME’s ~ 6-8 SME’s ~ 6-8 SME’s ~ 6-8 SME’s

 Next Steps CDISC is considering this need (data element dictionary) and seems to be moving in this direction Make your voice heard to CDISC if you see the value Create a sense of urgency as you see fit CDISC is considering the wiki approach Let me and/or CDISC know of your willingness to contribute to a wiki We could build this together much faster Requires a new business model / approach Can W3C give advice, input or help?