2019 China InterchangeBeijing, China | 19-20 July 2019

Rhonda FacileVp, Development Opportunities

19-20 September 2019

Agenda

• Standards Development Update

• Current Projects

• Tools to get started

• CDISC RWD Connect

Publishing Soon!

• ADaMIG v1.2

• CDASHIG 2.1

• CDASH Model v1.1

Standards Published Since the Last Year’s China Interchange

Foundational Standards

• SDTM v1.7

• SDTMIG v3.3

• SDTMIG-Medical Devices v1.1

• ADaM Conformance Rules v2.0

• Define.XML v2.1

Therapeutic Area Standards

• HIV

• PTSD

• Colorectal Cancer

• Huntington's Disease

• CDAD

• Lung Cancer

• Nutrition

Congratulations on the publication of the TAUG TCM CAD-Angina v1.0

https://www.cdisc.org/standards/therapeutic-areas/traditional-chinese-

medicine-coronary-artery-disease-angina

LOINC-CDISC Mapping

CDISC CT TEAM HAS COMPLETED THE LOINC-CDISC

LB MAPPING

CONTAINS OVER 2,000 LB

MAPPINGS

REVIEW BY THE REGENSTRIEF

INSTITUTE

SENT TO THE FDA LOINC WORKING

GROUP FOR INTERNAL REVIEW

MAPPING WILL BE RELEASED FOR

PUBLIC COMMENT

The Unified Code for Units of Measure (UCUM) Codelist Table

▪ A codelist table that allows users to toggle between UCUM and CDISC Unit codelists

▪ For each published CDISC submission value across all UNIT-based codelists in SDTM terminology, the mapping provides valid UCUM expressions associated with the unit concept

▪ Allows for a collected UCUM-compliant unit of measure to be easily matched to the appropriate CDISC submission value associated with that concept

Codetable Mapping Files

Temperature

F

C

cm

▪ Built to show explicit

relationships between

terms in different

codelists

▪ DS, CV, EG,

TU/TR/RS (Oncology)

Race/Ethnicity,

SC, TS, VS

What Are We Working on Now?

Foundational Standards in Development

Conformance Rules

SDTM v2.0SENDIG

v3.1.1ADaM

OCCDS v1.1

ADaM Data Structures for

IntegrationSDTM v3.4

SDTM Variable

Definitions

Multiple QRS and ADQRS Supplements

CDASH-SAE Supplement

v2.0

9#CDISCChina | #ClearDataClearImpact

Therapeutic Area Standards in Development

Type 1 Diabetes v1

Crohn's Disease v1

Acute Kidney

Injury v1Psoriasis v1

TCM Acupuncture

v1

Heart Failure v1

Pancreatic Cancer v1

10#CDISCChina | #ClearDataClearImpact

Publication of Known Issues

Errata

• Small errors such as typos that do not affect conformance

• Errors that affect conformance

Known Issues

• Inconsistencies within a CDISC standard

• Inconsistencies between standards

• Inconsistencies between a CDISC standard and regulatory agency advice

• Gaps in standards

Publication of Errata and Known Issues

Provide possible

solutions

Vetted and approved by

the CDISC Global

Governance Group

Will be made available in

real-time to the user

community

Curated Non-Standard Variable (NSV) Registry

Will be made available in

real-time to the

user community

Enables consistency

in the absence

of a standard variable

Will contain all non-

standard variables used in

CDISC Implementation

and User Guides

Vetted by the CDISC

Global Governance

Group

Consideration Documents for Regulatory Requirements

Race and ethnicity

Representation of SI and

conventional units

QRS logically

skipped items

PhUSE/CDISC Collaboration Primer

How to get started with CDISC

Linking of standards

Traceability

Compliance

CDISC Primer

SDTM Reorganization

Update outdated language

Move domain-specific variables

Make metadata consistent and separated

• Definitions will be added, and definition-like material will be removed from description column

Will be published in November 2020 as SDTM v2.0

Development of Principles

Guides and improves understanding of the standard

Facilitates decision making

Helps to optimize utilization of resources

Helps to manage change

Principles Hierarchy

CDISC Organization Principles

Standards Development High-Level Principles

Technical Team High-Level Principles

Cross Team and within Team Technical Implementation Principles and Rules

Accomplish the CDISC goals and mission without

promoting any individual vendor or organization

Manage scope with incremental development

Start with the end in mind

Domain variables based on the same root variable

have the same meaning in all domains

New! CDISC Knowledge Base

CDISC Knowledge

Base

An open, assessible, searchable

and user-friendly interface on

the CDISC Website to host new and

existing website content for

CDISC implementers

Knowledge Base – Components

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Coordinated with redeveloped

standards website pages

CDISC-generatedcontent - technical articles written by CDISC staff and

teams

Community-generated

content, curated by CDISC

Community questions, with curated CDISC team answers

Links to external useful content

Initial Launch end of October, new content added as it become available.

Tools to Get Started

Conformance Rules

• CDISC authors rules that determine conformance with the standard by version of standard

• Regulatory agencies have their own rules specific to their needs, these may or may not be the same as CDISC authored conformance rules

• Historical development of rules• Standards were written before the rules which led to ambiguity

• The guides were specific to a team and standard

Future of Conformance Rules

RULES ARE NOW REQUIRED AT THE TIME OF PUBLICATION

OF ANY STANDARD

WORKING ON ESTABLISHING CROSS-TEAM RULES

DEVELOPMENT METHODS

SUPPORTED BY CDISC LIBRARY

Disclaimer: This is only a proposed draft snapshot.

Clear and transparent

conformance rules

Clear and transparent

associations (assumptions,

examples, etc.)

A catalog of cross-standard

conformance rules

Redesigned Conformance Rules

Curated Example Collection

• Examples exist across many Implementation and User Guides in PDFs

• Goal is to make examples accessible through CDISC Library

• Users will be able to select examples by biomedical concept, therapeutic area, observation class, domain etc.

• Curation to ensure examples remain consistent with one another

• Initial scope: Diabetes v1.0, Diabetic Kidney Disease v1.0, Type 1 Diabetes v1.0

Curated Examples

Disclaimer: This is only a proposed draft

snapshot.

CDISC RWD Connect

Current Landscape

For years, the pharmaceutical industry has been using CDISC data standards for new drug submissions to regulatory agencies. Currently, CDISC standards are required for electronic submission in the USA and Japan and are recommended in Europe and China.

In academic and public health settings, there are few recommended standards for health data, and many activities do not implement data standards.

Non-standardized data is collected in different formats and different terminology, which does not allow for the data to be consolidated, compared and shared.

This disconnect creates an evidence gap that slows scientific and public health advances.

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Potential Benefits of using of CDISC Standards

Bring structure and semantic clarity to collected data

Be able to make better use of the data, increase the value of their data

Encourage a culture of FAIR guiding principles1

Open the door for a myriad of opportunities for data sharing within your institution and with others

Safe and effective treatments for patients - faster

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1 Wilkinson, M, Dumontier, M, et. al. (2016). The FAIR Guiding Principles for scientific data management and

stewardship. Science Data 3, article number: 160018. Retrieved from https://www.nature.com/articles/sdata201618

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• Overarching Goals from the Blue Ribbon Commission:

• Listen to the academic community to understand the barriers to

implementing CDISC standards for RWD

• Develop a vision and strategy for the implementation of CDISC

standards in academic settings.

• Make the tools and guidance we agree are needed a reality

• Research Questions:

• What are the priorities, needs, and challenges of academics around

the use of data standards?

• How can CDISC lower the barriers to implementing CDISC

standards?

• What are the requirements for potential tools and educational

materials for implementation support?

CDISC RWD Connect

CDISC RWD Connect - Guiding Principles

Foster a better foundation for data sharing and support platform-agnostic data sharing

Standardize where possible first, focus on core cross-cutting concepts, then extend as appropriate

Encourage: free open source, or affordable, easy to use tools.

Help investigators to focus on the science, and not on standardization

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Research Activities

involving human health data (to produce generalizable knowledge)

Non-research Activitiesinvolving human health data

(not to produce generalizable knowledge)

Public health

activities

Routine

healthcare

services

Health data

self-monitoring/

self-gathering

Mobile and

wearables

Electronic

health records

Billing records

Public health

registries

Census and

vital events

Experimental

studies

Observational

studies

Household

surveys

National Health

Accounts

Regulated

studies

Non-

regulated

studies

CDISC Standards Today CDISC RWD Connect Broad Focus Area

Health claimsGenetic & other

databases

Real-World Data(non-experimental setting)

What is RWD?

Other sources of

patient-reported

outcomes

Case-control

studies

Cohort studies

Cross-sectional

studies

Other types of

studies

Research

registries

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Experimental

studies

Observational

studies

Routine health

services

Public health

activities

Self-monitoring or

self-gathering

activities

Research activities

Activities involving human health data

Non-research activities

Case Report Forms

from experimental

studies

Case Report Forms

from observational

studies

Electronic health

recordsFinancial records

Registries, census,

health surveys

Mobile, wearables,

genetic self-tests, etc

Sources of data

Main data source

Other data sources

Possible data sources

Real-World Data(non-experimental setting)

Activities involving human health data and their different data sources

CDISC RWD Connect - Overall Plan and Timeline

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Phase Timeline Activities

Phase 1 Q3 2019 –

Q4 2020

• Convene an international Expert Advisory Board

• Engage the Expert Advisory Board in discussion using the Delphi method

• Develop 2-3 use cases of that demonstrate the use CDISC standards in RWD

settings

• Draft a white paper/articles documenting methods, findings and vision, strategy

and policy recommendations for the use of standards in academic settings

• Collect requirements and raise funds for building tools for academics settings.

Phase 2 2021-2022

• Develop tools and training materials.

• Test and validate tools and training materials.

• Develop a special journal supplement on data standards for RWD with

contributions from the Expert Advisory Board and partners.

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Region Academic & Research Government

Americas

Harvard Medical School

Massachussets General Hospital

University of California at San Francisco

Duke University

University of Chicago

University Arkansas Medical School

George Washington University

RedCap

SAS Institute

Pan American Health Organization / World Health Organization

National Cancer Institute (NCI)

National Institutes of Health (NIH)

Food and Drug Administration (FDA)

Patient-Centered Outcomes Research Institute (PCORI)

Europe

Oxford University

Innovative Medicines Initiative (IMI)

Liverpool Clinical Trials Research Centre

European Medicines Agency (EMA)

Asia

Daegu University Medical School, South Korea

Institute of Health Data Infrastructure for All (IDIAL)

Nagoya University Medical Center

Sapporo Medical University

Nagoya University Medical Center

Pharmaceutical and Medical Devices Agency (PMDA)

Japan Agency for Medical Research and development (AMED)

National Institute of Public Health (Japan)

The Leona M. and Harry B. Helmsley Foundation (US)

Bill and Melinda Gates Foundation (US)

Wellcome Trust (UK)

Cohen’s Veterans Network (US)

CDISC RWD Connect - Expert Advisory Board

CDISC RWD Connect - Expert Advisory BoardThe Ask

Participate in a kick-off and final project meeting.

Participate in 3 rounds of qualitative Delphi surveys (modified).

Co-author publications (articles, white paper) on vision, strategy and policy recommendations for the use of standards in academic settings.

Assist in identifying potential tool development partners and fundraising sources.

Time needed: ~ 2-4 hours to answer the first Delphi round and 1-2 hours for second and third rounds, for a total time commitment of 4-8 hours.

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CDISC RWD Connect – The Delphi Process

Use Case 1 – CDISC for Public Health Programs

PAHO HEARTS Project• Exploring implementing CDASH core variables to treat

hypertension in the HEARTS project.

• Potential strategic partner for CDISC:

• Could open the doors to all countries in Latin America and the

Caribbean

• It is part of the United Nations and WHO

• If use case is successful, it could lead to official PAHO

recommendation of CDISC standards for Ministries of Health.

• Status:

✓ Face-to-face meeting (July 25)

✓ CDISC developed CRF visualization and metadata example

table and shared with PAHO (August 9)

✓ CDISC sent proposed work plan (August 9, PAHO is

currently reviewing)

• Outcome: development of a joint manuscript on the application of

CDISC standards for HEARTS public health program.

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Use Case 2 – CDISC for Observational Research Studies

Potential - Infectious Diseases Data Observatory (IDDO)

• IDDO generates new research evidence through data re-use.

• IDDO works with researchers based in disease-endemic countries to aggregate, standardize and analyze existing health data to answer questions that can only be addressed through collaborative analysis.

• The IDDO data-sharing platform accepts clinical, laboratory, observational, and epidemiological data on poverty-related and emerging diseases.

• IDDO is using SDTM as the standard for their platform (work in progress).

• Status:

• CDISC to reach out to IDDO about jointly drafting a manuscript on the experience of using CDISC for RWD.

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Use Case 3 – CDISC for Registry Data

Evaluating potential Use Cases

• Literature review - Registries used for patient enrollment (Incl/Exclcriteria)

• TID Registry

• Others

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Research

registries

Use Case 4 - FHIR

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• Article review:

• The use of HL7 FHIR as eSource to Pre-populate CDASH Case Report Forms using a CDISC ODM API.

• Use of Fast Healthcare Interoperability Resources (FHIR) in the Generation of Real World Evidence (RWE)

• Use of FHIR in Clinical Research: From Electronic Medical Records to Analysis

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Experimental

studies

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