Strategy Session on the Future of Medical Research and the Role of Standards:
“Forming Connections Towards Complementary Systems”
Strength through collaboration.
CDISC Strategy Session Summary -2August16
Page 1 of 19
Table of Contents
I.
Agenda for 2 August 2016 ……………………………………………………….………. 3
II.
Attendees ………………………………………………………….……………………………. 4
III.
Strategy Session Summary…………………………………………………………………. 9
IV.
Themes from the Meeting………………………………………………………………… 17
V.
Proposed Next Steps (post-meeting)………………………………………………… 18
VI.
Meeting Photos ………………………………………..……………………………………… 19
CDISC Strategy Session Summary -2August16
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Agenda for 2 August 2016
9:30 – 9:45 Welcome, Opening Remarks and Objectives
Opening Remarks by Dr. Robert Califf; Objectives by Dr. Rebecca Kush
9:45– 11:00 Key Topic I: The Status of Consensus-based Standards for Global Clinical Research and
their Role in Expediting Clinical Research Processes and Evidence Generation
Presenters: W. Kibbe, D. Evans, R. Dicicco, J. Rogers, L. Hudson, L. Becnel, P. Chiarelli
Panelists: B. Nelson, M. Glickman, T. Jackson, M. Ibara, C. Carr
11:00 - 12:00 Key Topic II: Regulatory Use of CDISC Standards
Presenters: R. Fitzmartin, E. Navarro, M. Shikano, M. Rocca, V. Popat, S. Khozin
Panelists: L. Rosario, G. Hussong, H. Sakaguchi, L. Amanti, C. Willoughby
12:00-12:30 Lunch Buffet
12:30 – 1:15 Key Topic III: Biopharmaceutical and Device Organizations Use of CDISC Standards
Presenters: E. Levy, R. Rudick, B. Hinkson, P. Genyn, T. Simpson, U. Palm
Panelists: J. Malone, R. Manski, C. Cooper, L. Marks
1:15 – 2:00 Key Topic IV: U.S. HHS (ONC, NIH) Use of CDISC Standards, Complementary Standards
and/or Competing Standards
Presenters: J. White, M. Braxenthaler, M. Fukushima, P. Kim, J. Galvez
Panelists: L. Curtis, M. Lauer, P. Kaufmann, M. Roche
2:00 – 2:45 Key Topic V: The Use of CDISC Standards in Academic Medical Research and PatientCentered Research
Presenters: J. Barrett, S. Volchenbaum, D. Foster, J. Speakman, B. Delaney, S. Kern
Panelists: B. Moscovitch, C. Fitzer-Attas, Y. Nakanishi, M. Haas
2:45 – 3:15 Break
3:15 – 4:30 Key Topic VI: Models for Standards Sustainability and the Future of Clinical Research
Presenters: J. Zung, M. Slack, B. Smith, B. Bierer, K. Gersing, J. Potthoff, N. Harmon
Panelists: K. Holcombe, D. Gill
4:30 – 5:00 Action Steps and Addressing Barriers to Progress in Transforming Clinical Research;
Closing Remarks (R. Califf, R. Kush)
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Attendees
Strategy Session on the Future of Medical Research and the Role of
Standards "Forming Connections Towards Complementary Systems"
Name
Title
Organization /
Representation
Key Topic
Lisa Amanti, J.D.
Director and Associate General
Counsel
Athena Health
IV-Government
Jeffrey Barrett, PhD
Vice President, Translational
Informatics
Sanofi
V-Patients and
Academia
Lauren Becnel, PhD
Senior Director, Biomedical
Informatics and Alliances
CDISC
I-Global Standards
Status
Barbara Bierer, MD
Faculty Director, Multi-Regional
Clinical Trials Center at BWH and
Harvard
Global Head Strategic Alliances,
Informatics (Roche)
Harvard MRCT
VI-Sustainability
IMI eTRIKS Project (Europe)
IV-Government
Robert Califf, MD, PhD
FDA Commissioner
U.S. Food and Drug
Administration (FDA)
Chris Carr
Director of Informatics
Radiological Society of North
America
Moderator,
Opening/Closing
Remarks
I-Global Standards
Status
Gen. Peter Chiarelli, PhD
Chief Executive Officer
One Mind
I-Global Standards
Status
Charles Cooper, MD, PhD
Worldwide Vice President,
Medical Affairs, Diagnostic
Systems
Becton Dickinson
III-Biopharmaceutical
and Device Products
Lesley Curtis, PhD
Director, Center for Pragmatic
Health Systems Research (Duke)
PCORNet, Sentinel
IV-Government
Brendan Delaney, MD, PhD
Chair in Medical Informatics and
Decision Making
Imperial College London
V-Patients and
Academia
Rob Dicicco, Pharm D
Vice President of Clinical
Pharmacology Sciences and Study
Operations
GlaxoSmithKline
I-Global Standards
Status
Dave Evans
Managing Director
Helmsley Foundation
I-Global Standards
Status
Cheryl Fitzer-Attas, PhD,
MBA
Vice President, Clinical Research
CHDI Foundation
II-Regulatory
Ron Fitzmartin, PhD
Senior Advisor, Office of Strategic
Programs
U.S. Food and Drug
Administration (FDA)
II-Regulatory
Diana Foster, PhD
Vice President, Strategy &
Development
Society for Clinical Research
Sites (SCRS)
V-Patients and
Academia
Michael Braxenthaler, PhD
CDISC Strategy Session Summary -2August16
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Masanori Fukushima, MD,
PhD
Professor of Clinical Trial Design
and Management
Translational Research
Institute, Japan; ARO Council,
Japan; Kyoto University
Hospital
IV-Government
Jose Galvez, MD, PhD
Program Director of Clinical and
Translational Informatics
Nationial Institutes of Health
(NIH)
IV-Government
Patrick Genyn
Senior Director Data Standards
Johnson & Johnson (Janssen)
III-Biopharmaceutical
and Device Products
Kenneth Gersing, MD, PhD
Director of Informatics
VI-Sustainability
Dalvir Gill, PhD
Chief Executive Officer
National Institutes of
Health/National Center for
Advancing Translational
Sciences (NCATS)
TransCelerate Biopharma Inc.
Michael Glickman
President/Owner (Computer
Network Architects)
Chair, ISO Tech Committee
215
I-Global Standards
Status
Magali Haas, MD, PhD
CEO and President
Cohen Veterans Association
V-Patients and
Academia
Nicole Harmon, PhD
Chief Operating Officer
Clinical Data Interchange
Standards Consortium (CDISC)
VI-Sustainability
Brooke Hinkson
Director, Global Clinical Data
Standards
Merck
III-Biopharmaceutical
and Device Products
Kay Holcombe, MS
Senior VP for Health Policy
Biotechnology Industry
Organization (BIO)
VI-Sustainability
Lynn Hudson, PhD
Chief Science Officer
Critical Path Institute
I-Global Standards
Status
Virginia Hussong
FDA/OBI
Food and Drug
Administration/CDER
II-Regulatory
Renee Iacona
Biometrics TA Head for Oncology
& Immuno-Oncology
Astra Zeneca
III-Biopharmaceutical
and Device Products
Michael Ibara, PhD
Head of Digital Healthcare
Clinical Data Interchange
Standards Consortium (CDISC)
I-Global Standards
Status
Tammy Jackson
Director of Programming
Pharmaceutical Product
Development (PPD)
I-Global Standards
Status
Petra Kaufmann, MD, PhD
Director, Division of Clinical
Innovation
National Institutes of Health
(NIH)/National Center for
Advancing Translational
Sciences (NCATS)
IV-Government
Steven Kern, PhD
Deputy Director, Quantitative
Sciences
Gates Foundation
V-Patients and
Academia
Sean Khozin, MD, PhD
Sr Medical Officer
U.S. Food and Drug
Administration (FDA)
II-Regulatory
CDISC Strategy Session Summary -2August16
VI-Sustainability
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Waren Kibbe, MD, PhD
Director, Center for Biomedical
Informatics and IT
NIH/National Center for
Advancing Translational
Sciences (NCATS)
NIH)/National Institute of
Allergy and Infectious
Diseases (NIAID)/Division of
Acquired Immune Deficiency
Syndrome (DAIDS)
VI-Sustainability
Peter Kim, MD
Deputy Director, Therapeutics
Research Program
Rebecca Kush, PhD
President and CEO
Clinical Data Interchange
Standards Consortium (CDISC)
Opening & Closing
Remarks
Michael Lauer, MD
Deputy Director for Extramural
Research
National Institutes of Health
IV-Government
Elliott Levy, MD
Senior Vice President, Global
Development
Amgen
III-Biopharmaceutical
and Device Products
James Malone, MD
Sr. Medical Director,
Diabetes/Endocrinology, Insulins
and Devices
Eli Lilly
III-Biopharmaceutical
and Device Products
Richard Manski
Director/Global Head of
Statistical Programming
Abbvie
III-Biopharmaceutical
and Device Products
Lynn Marks, MD
SVP, Senior Clinical Advisor
GlaxoSmithKline
III-Biopharmaceutical
and Device Products
Ben Moscovitch
Officer, Medical Devices
The Pew Charitable Trusts
V-Patients and
Academia
Yoichi Nakanishi, MD, PhD
Professor, Dep of Internal
Medicine, Kyushu University;
Chair of ARO Council
Academic Research
Organization (ARO Council,
Japan)
V-Patients and
Academia
Eileen Navarro, MD
Lead Medical Officer
U.S. Food and Drug
Administration (FDA)
II-Regulatory
Barrie Nelson
VP, Foundational Standards
Clinical Data Interchange
Standards Consortium (CDISC)
I-Global Standards
Status
Ulo Palm, MD, PhD
Senior VP; Head Global Brands
Drug Development Operations
Allergan
III-Biopharmaceutical
and Device Products
Vaishali Popat, MD, MPH
Associate Director of Biomedical
Informatics and Regulatory
Review Science
U.S. Food and Drug
Administration (FDA)
II-Regulatory
John Potthoff, PhD
CEO
Elligo Health Research, Inc.
I-Global Standards
Status
Mitra Rocca
Associate Director of Medical
Informatics
U.S. Food and Drug
Administration (FDA)
II-Regulatory
Mark Roche, MD, MSMI
Chief Medical Information Officer
Avanti iHealth
IV-Government
James Rogers
President
NexTrials, Inc.
Lilliam Rosario, PhD
Director, Office of Computational
Science
U.S. Food and Drug
Administration (FDA)
I-Global Standards
Status
II-Regulatory
CDISC Strategy Session Summary -2August16
IV-Government
Page 6 of 19
Richard A. Rudick, MD
VP, Development Sciences
Hiroshi Sakaguchi
Biogen
III-Biopharmaceutical
and Device Products
Pharmaceuticals and Medical
Devices Agency of Japan
(PMDA)
II-Regulatory
II-Regulatory
Mayumi Shikano, PhD
Associate Center Director
Trisha Simpson
Director, Global Integrated
Standards at UCB
Pharmaceuticals and Medical
Devices Agency of Japan
(PMDA)
Union Chimique Belge (UCB
Biosciences
Mary Ann Slack
Deputy Director, Office of
Strategic Programs
U.S. Food and Drug
Administration (FDA)
VI-Sustainability
Brad Smith, PhD
Director, Policy
FasterCures
VI-Sustainability
John Speakman
Senior Director, Research
New York University Langone
Medical Center
V-Patients and
Academia
Sam Volchenboum, MD,
PhD
Director, Center for Research
Informatics
The University of Chicago
V-Patients and
Academia
Jon White, PhD
Deputy National Coordinator
Health & Human Services
(HHS)/Office of the National
Coordinator for Health IT
IV-Government
Cara Willoughby
Principal Scientific Advisor
Quintiles
I-Global Standards
Status
Jonathan Zung, PhD
Group President, Covance Drug
Development
Covance
VI-Sustainability
III-Biopharmaceutical
and Device Products
Additional Attendees:
Christina Klafehn, PharmD
Health Programs Coordinator
Staffing FDA Commissioner
Teresa Zayas Cabán, PhD
Senior Advisor to the Office of the National
Coordinator for Health IT
Deputy Chief
Health & Human Services (HHS)/Office of the
National Coordinator for Health IT
NIH Clinical Center/BRTIS
Elaine Ayers
Support Personnel:
Rhonda Facile
VP, Standards Development
CDISC
Bron Kisler
VP, Strategic Alliances
CDISC
Maura Kush
CDISC Specialist
PharmaStat
Amy Palmer
Sr. Project Manager, Standards Development
CDISC
CDISC Strategy Session Summary -2August16
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Invited – Regrets
Stan Huff, MD
Patricia Flatley Brennan, PhD
Lloyd McKenzie
Josephine Briggs, MD
Karen DeSalvo, MD
Janet Woodcock, MD
Lisa LaVange, PhD
Stephen Wilson, PhD
Andy Lee
Dave Jordan, PhD
Makoto Suematsu, MD
Kenneth Getz
Stephane Auger, PhD
Nicola Perrin, PhD
Dennis Decktor, MD
William Turner
Michael McGinnis, MD
Mike Levy
Intermountain Healthcare; HL7 Board Chair
Director of NIH/NLM
Gevity, Inc; HL7 FHIR Management Group
NIH/OD
HHS/ONC
FDA/CDER
Head of FDA/CDER/Statistics
FDA/CDER/Statistics
Head of Global Clinical Trial Operations, Merck
AbbVie, TransCelerate Data Standards Workstream Lead
Head of AMED/Japan
Tufts CSDD/CISCRP
Danone
Wellcome Trust
Medical Information, Regeneron
Programming Lead, Astra Zeneca
National Academy of Sciences
PhRMA
CDISC Strategy Session Summary -2August16
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Session Summary
Leaders in the fields of biomedical research, regulatory, informatics, patient care and related services
gathered at the National Academy of Sciences on 2 August 2016 for a Strategy Session specifically to
explore how collaboration, global CDISC standards and related enablers can catalyze more efficient and
innovative medical research processes for the benefit of all. While the adoption of electronic health
records continues to increase, there is still a need for interoperability among them and improved
alignment with research. At the same time, adoption of a global suite of consensus-based clinical
research standards continues to grow, but without a viable set of global healthcare standards with
which to “connect”. The CDISC standards will be required by regulatory authorities (U.S. FDA and Japan
PMDA) in Q4 2016 for submission of data in support of approval for new therapeutic products. The
CDISC standards are also being used to support research for global public health, nutrition and
observational research. Standards need to be maintained and to constantly reflect new science and
medical practice, thus the timing was right for a Strategy Session. This Session was designed to hear
various perspectives and to seek insights that will inform next steps for CDISC as this standards
development organization (SDO) evolves and continues to collaborate with other SDOs and a global
community to form connections towards complementary systems in healthcare and research.
Dr. Rob Califf opened the Strategy Session by bringing attention to ‘parallel universes’ between clinical
care and research and how we need to try to bring these universes together to form a learning health
system. While we need parallel universe research studies, for example, for rare diseases and pre-market
studies, we also need to capitalize more on healthcare data for post-market and late development
stages such that these do not bear the costs of today’s expensive research studies. Dr. Califf concluded
his opening: “We are seeing this tremendous explosion of targeted therapies and opportunities for
technology to take off. I think the hardest nut to crack is going to be how we embed prospective clinical
studies into integrated health systems in a way that the pace of medical practice can tolerate. The data
part we’ll talk about today can be worked out; I think it’s just a matter of time. But, right now, we’re
hearing pretty clearly from practitioners and health system CEOs that they just don’t have time, given
the pressure they are under, to do the things that would enable us to get studies done that we really
need to have done. I hope that we’ll get some insight today that will allow us to follow on about how to
bring these universes together into a comprehensive much more efficient system.”
Dr. Kush summarized the pre-meeting Desired Outcomes and stated that these may morph during the
meeting, but they should give structure to the remarks from the diverse group of participants. In
summary, these Desired Outcomes related to: a) building consensus around a core dataset; b)
harmonizing protocol templates; c) conducting an EHR-enabled prospective research study; and d)
sustainability. Each presenter had five minutes to make his/her remarks after which panelists had an
opportunity to comment. There were ~ 70 speakers. No slides were used, although a few attendees
provided handouts. This Summary is excerpted from a recording of the full-day Strategy Session.
Key Topic 1: The Status of Consensus-based Standards for Global Clinical Research and their Role in
Expediting Clinical Research Processes and Evidence Generation
A number of important and varied messages came from the speakers on Key Topic 1. There was an
emphasis on the importance of following the journey of a patient and the continuum of data, from when
a patient is born until they receive a diagnosis, treatment and afterwards. Standards are important in
CDISC Strategy Session Summary -2August16
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terms of what they enable us to do with the data through the patient’s journey, for the sake of that
patient and future patients. Open science and open data are very important for unlocking the potential
of that data; we need to derive knowledge from these data by changing our focus from siloed data to
data flowing between organizations, which means we need well-annotated standards. The value of
cohesive standards from beginning to end was emphasized with a discussion on the TransCelerate
Common Protocol Template and the efforts to harmonize this with an FDA/NIH Protocol Template that
was created at around the same time; the goal is to align these templates with each other and with the
CDISC Protocol Representation Model, which was published in 2010 as a part of the BRIDG Model
(CDISC, HL7 and ISO Standard developed collaboratively with NCI and FDA to bridge research and
healthcare). There was discussion around a maturity model (based upon an Accenture survey) for
standards adoption within the industry, where the most mature organizations are those with automated
metadata-driven semantic interoperability of information across the enterprise.
Continuing the theme of using standards from beginning to end in the research process, there was an
emphasis on a) not mapping data into standards at the end of the study since this will result in loss of
integrity, not to mention wasting time and resources (leaving the clean-up for the data managers vs.
building quality in from the start); and b) that common data elements are not standards and are, in fact,
often not even ‘common’. To develop a standard requires building consensus around one way to
represent the data and harmonization across the standards from beginning to end; there is no room for
redundancy with a standard. Standards are valuable in creating process efficiencies, improving quality
and enabling the pooling of data across studies for more robust statistical analyses and truly making
effective use of the data. A contrast was made between large databases (big data, data lakes) with nonstandard data that may provide value (with caution) for identification of safety signals or possibly
genetic variations, from which hypotheses can be generated versus databases of high quality data in a
standard format from which trustworthy conclusions can be drawn.
The ‘end-to-end’ or beginning-to-end (B2E) theme was emphasized again, with a potential beginning of
using EHRs as the electronic source of the data (eSource). Concern was expressed about the resistance
to using EHRs for prospective regulated research, even though enabling technology and standards have
been available for years and the ROI in terms of these standards and methodologies improving
processes has been demonstrated and published (e.g. ASTER). Regarding the use of standards from
various Standards Development Organizations (SDOs), there is a global Joint Initiative Council (JIC)
dedicated to developing complementary and synergistic standards and to addressing gaps and overlaps,
the overlaps causing far more issues than gaps between standards. Through the JIC, leaders from HL7,
IHE, DICOM, ISO, IHTSDO, GS1 and CDISC have committed to harmonizing standards, including to
support interoperability between healthcare and research. The aforementioned BRIDG Model is an
example of a JIC project.
Another recommendation to use standards from the start was made, specifically adopting the CDISC
data collection standard, CDASH. Clinical Research Organizations (CROs) and investigative sites cannot
be efficient without standards. CDASH is the CDISC core Dataset developed through the FDA’s Critical
Path Initiative and the path to producing high quality, efficient SDTM and ADaM, which will be required
by FDA and Japan’s PMDA before the end of 2016.
Retired General Peter Chiarelli closed the presentation session for Key Topic I by stating: “I find it odd
that an organization like mine (OneMind) should have to pay to have CDISC standards implemented and
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to have NIH and FDA talk to each other. I find it odd that the NIH does not require, with the 31 billion
dollars that is given out every year, that research standards like CDISC standards be used and required
for any research that is done. I understand that we have incentives for industry in this research
ecosystem that run counter to the whole idea of open science; that, quite frankly, constitutes what we
are going to talk about in here today.”
During the discussion following this initial session, Dr. Califf commented: “Thank you, I was going to
thank you anyway, first for what you just said in the start. It brought back memories of my career of
trying to work between federal agencies. Your comment, that you are raising money to solve problems
between federal agencies, is a telling comment. I think about where we are. It just strikes me that, when
it comes to people’s health there shouldn’t be one answer that is a regulatory answer and a different
answer that is a public health answer. We ought to have the standards for truth. It doesn’t bother me so
much that truth evolves because we learn, and there are so many things that we can look at now that
we couldn’t even approach because you need such a high magnitude of data; we are not explaining that
very well. I do think we need to think seriously about whether there should be two different standards.
Also, I want to react a little bit to the comment about data collection for different purposes. Actually, I
think it’s tied to the same thing. I think what we are learning about healthcare is that the best
healthcare is delivered when information is collected in the processes of delivering healthcare that feeds
back into quality systems. If you look at a high quality-quality system, it should have exactly the same
quality as research data for regulatory purposes. The middle ground maybe prospective registries where
carefully defined data items with an inception time can be used for high quality clinical care as a primary
source and for regulated clinical trials. It just bothers me that we have these two different worlds with
the same purpose, and I don’t accept that we should continue to accept that standards should be
different for the two.”
Key Topic II: Regulatory Use of CDISC Standards
This session consisted of several presenters from FDA/CDER, yet with varied backgrounds and different
roles within this large Center within FDA. There were also two participants from Japan’s PMDA. The
session began with a history of the CDISC standards development from the FDA perspective. The CDISC
standards were initiated in 1997 and the Study Data Tabulation (SDTM) was initially endorsed by FDA in
2004. Steady progress has been made since then with respect to development by CDISC and adoption
by FDA. As of late 2016, any new study initiated needs to be using CDISC standards and Japan has a
similar requirement. The FDA has been testing and adopting specifications that augment SDTM for
specific therapeutic areas (TA) and the associated controlled terminology, which is a subset of the NCI
Thesaurus published by their Enterprise Vocabulary Services. There are now five of these TA
specifications cited in the FDA Standards Catalog that is referenced in binding guidance. This summit
was suggested by FDA to get input on how to make the standards better, how to sustain them and how
to encourage the use of standards from the start, including protocol and CDASH, which will enable the
production of higher quality Study Data Tabulation Model (SDTM) domains and the Analysis Dataset
Model (ADaM) much more efficiently.
The CDISC Therapeutic Area standards and user guides are being reviewed by clinicians and others in
Japan, including well over 100 medical societies, JPMA and the Japan CDISC Coordinating Committee
(J3C). These reviews are being coordinated by PMDA with a goal of ensuring that the CDISC TA standards
can be global standards and support the type of medicine that is happening beyond the U.S. borders.
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Those with substantial review expertise and experience within FDA related their interest in science and
in ensuring that they obtain information from outside of the agency and the industry to inform their
reviews. They are committed to ensuring informative and accurate product labels and instructions for
the patients who take the approved medicines. They feel that standards are enablers and that they are
very useful for efficiency in reviews. Standards also enable flexibility and traceability. Having
submissions with data in standard formats helps the reviewers find what they are looking for much
more quickly, which saves time in the review process.
FDA is now receiving data in CDISC standard format for 85% of submissions, but they wish to quickly see
100%. They feel that integrating the activities across the Agency and making the data easier for
reviewers to interpret are key goals as well, in accordance with the FDA mission that places the patient
at the center and revolves around protecting public health.
There was a recommendation to standardize INDs so that these can be submitted electronically and not
as PDFs. Standards for safety data would also be very useful. It is felt that standards are necessary to
follow a patient’s journey.
It is currently difficult to get ‘meaningful’ data from electronic health records or real world evidence.
CDISC standards enable the reviewers to be able to look across studies and to do meta-analyses. FDA is
very interested in how to use EHRs for research and have provided the eSource Guidance and the recent
draft EHR Guidance. They have issued a Federal Register Notice to encourage demonstration projects in
this space, but they encourage better alignment of the EHR data standards with those from research.
The analogy was made that there is a need to unclog some of the pipes that should allow data to flow
from EHRs to be used for research and that data standards should be able to help with this.
Non-FDA panelists in this session called for EHRs to adopt industry standards so that they can support
research better and commended the FDA for the EHR Guidance, which is forward-looking. This was
contrasted with certain public comments submitted to FDA on this draft Guidance, which were seen as
more negative and ‘antiquated’. Support was voiced for the Desired Outcomes of this Strategy Session.
Key topic III: Biopharmaceutical and Device Organization Use of CDISC Standards
The opening presentation at this session was a plea for FDA to ‘put a ring on it’ (quoting Beyonce), i.e.
for FDA to require CDASH. This plea was referenced and supported by several of the presenters during
this session. CDASH would be especially beneficial for study coordinators, nurses and site personnel who
would prefer to spend time with their patients rather than figuring out how to complete case report
forms that still differ across study sponsors. Standard case report forms (CRFs) with a core set of
common questions and response choices would not only ease the burden on site personnel, but would
also provide higher quality SDTM and preserve traceability and provenance. This benefit to the site
personnel was the basis a decade ago for the Critical Path Opportunity for standard CRFs, which
stemmed from the Critical Path Document “Innovation vs. Stagnation”, authored by Drs. Janet
Woodcock and Mark McClellan in 2004, and led to the development of CDASH (a minimum core dataset
for clinical research that is now a global standard) to be first published as v1.0 in 2008.
Emphasis was again placed during this session on the value of ‘end-to-end’ standards in terms of
avoiding misunderstandings of data that are shared and to help interpret and leverage data to get the
most from it. There is a cost to implementing new standards from the start, especially when integrating
CDISC Strategy Session Summary -2August16
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them into a major biopharmaceutical company, but the return of this investment can be huge. There is
an advantage to implement industry standards in a smaller company as this immediately makes the
company’s operations consistent with industry practice. The ‘holy grail’ was defined as being the use of
standards from beginning to end, starting with not only CDASH but a Common Protocol Template. Our
industry is far behind others (such as aerospace) in terms of implementing and appreciating the value of
standards for automation. A focus on innovation was recommended.
There was concern expressed that using EHR data for regulatory submissions is “unproven and
untested”, although there is certainly interesting in addressing the ‘grey areas’. An eSource case study
was cited, MS-PATHS, which is a radical approach to gathering real world evidence using iPads for
patients with Multiple Sclerosis (MS). CDISC standards, including the MS therapeutic area standard, are
being implemented in this study. It was agreed that there remain issues with the disconnect between
healthcare and research, although this can potentially be viewed as an opportunity and should be
explored further. Once again, a mandate from FDA was recommended for requiring CDASH and also for
using EHRs in regulated research. FDA was also encouraged to have all of the centers regulating
products require standards for submissions, including CDRH (for devices).
Another opportunity mentioned during this session is CDISC SHARE (Shared Health and Research
Electronic Library). CDISC was commended as leading the way with CDISC SHARE, and hope was
expressed by Patrick Genyn of J&J that “SHARE can evolve into a technology that can be leveraged for
fully integrated foundational and therapeutic area standards covering protocol, CDASH, SDTM, ADaM,
define.xml and controlled terminology. We can repurpose and complete these industry standards,
available in eSHARE, with our company standards for measurements, assessments, statistical endpoints,
displays, CRFs etc. to achieve the long term view of automatically generated protocol-driven study
definitions. Another advantage of leveraging CDISC SHARE will be to stay in tune with the latest CDISC
standards and implementation guides.”
Key Topic IV: U.S. HHS (ONC, NIH) Use of CDISC Standards, Complementary Standards and/or Competing
Standards
This Key Topic discussion was opened by Dr. Jon White, Deputy Director of ONC, who spoke about the
dramatic increase in the adoption of EHRs in the United States in recent years; with 90-95% of clinician
now using certified health IT, healthcare is a different world. He spoke about ongoing efforts to
harmonize the standards. On the topic of regulation, he said: “You know there are sometimes where
you don’t want to use regulations in certain ways to push certain things; you want to let the industry be
able to step forward. So, I think that has got to be a part of the discussion. Where is the virtuous use of
regulation, either at the FDA or CMS or NIH-- to advance the use of these standards? And, where does
the industry step forward and say: Look we’re convening around this; we agree that we’re not going to
compete on proprietary use of standards, but instead we are going to compete on other kinds of
things.”
The example of the eTRIKS (eTranslational Research Information Knowledge System) project of the
Innovative Medicines Initiative in Europe was provided as one in which standards play a big role to
enable data sharing across IMI projects. The gap between industry and academia in terms of standards
adoption was raised, indicating that industry seems to be well ahead of academia in this regard. The
value of using standards is greater in the environment of a public private partnership such as IMI when
groups wish to come together to solve bigger problems that individual entities cannot solve.
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In Japan, there is growing interest in and adoption of global clinical research standards – specifically
CDISC standards—within academia, where there is significant work being done on new products through
INDs held by academic research organizations (AROs). Academic leaders in Japan, especially Prof.
Masanori Fukushima actually encouraged GCPs in Japan as well as data standards and terminologies,
proposing that the regulatory authorities adopt CDISC as the global standard for research. The ARO
Council in Japan is providing education on CDISC from beginning to end and also supporting adoption of
CDISC standards across AROs and by the new AMED (NIH of Japan).
One example of a U.S. NIH Center that is using CDISC standards is the Division of AIDS within NIH/NIAID.
They find that standards are necessary to enable data sharing and cross-study analyses. Thus, the CDISC
standards are being used in the largest global clinical research networks for AIDS research and also
Tuberculosis research. This has not come easily and there were substantial costs since there was also a
desire to convert all of the legacy data to CDISC standards; and, unfortunately, there is also a lack of
resources in terms of individuals who really understand CDISC standards. The value in standards is when
everyone uses them, so it is important to continue to communicate their value and the rationale for
broad adoption. That being said, there was a comment that we need stringent standards and less of
them. The incentive for adoption by the NIH Clinical Center is to make datasets more broadly available;
CDISC will play an important role in this.
A current challenge is that there are three metadata repositories that have a certain amount of
redundancy and may now essentially be competing, although their original intent and functionality may
have differed. These are the NIH/NLM CDE Repository, the NIH/NCI caDSR and CDISC SHARE. The
recommendation during this meeting was that this should be the purview of a global SDO and that all
should collaborate in the development and maintenance of such a global resource.
The comment was made that only 10% of the NIH funding goes to clinical trials, whereas the rest is
allocated to basic science and other activities. A recent GAO report provides incentive for NIH to use an
industry standard, which will give the NIH a path to require standards for NIH-funded research such that
they are not using taxpayer dollars inefficiently should they take such a path. Another recommendation
during this session was that various government-funded projects should not keep inventing new models.
For example, models from Sentinel, OMOP, and PCORNet all could potentially be harmonized and may
already be included in the ISO/CDISC/HL7 BRIDG Model, which was collaboratively developed by CDISC,
NCI, FDA and HL7 over the past decade and became an ISO standard in 2015 (after an 8-year process).
Also, SDOs should ensure that their standards are aligned within their own SDOs, and are not
redundant; the example was that HL7 has at least three different workgroups with standards that use
different requirements for Gender/Sex.
Dr. Petra Kaufmann eloquently stated: “Time is very precious for people with rare diseases who have no
treatment options available. Our resources are limited and every observation is very valuable. So, if we
have two parallel universes, where academic researchers work on studies that collect information on
disease progression biomarkers and clinical outcomes, but these are not ultimately oriented towards the
goal of serving, for example, in a regulatory context ever, then there is potentially an opportunity lost.
[……..] The data standards really have transformative potential here for all of us to leverage each other’s
investments better, to coordinate better so that we can bring these treatments to patients more
quickly.”
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Key Topic V: The use of CDISC Standards in Academic Medical Research and Patient-Centered
Research
This session opened with continued remarks about the value of standards, not for the sake of standards
but for the sake of patients. It is important to have a dynamically available data stream and we need
standards to readily exploit the data. The importance of having standards for pediatric patients was
raised with an emphasis on the need to augment existing global research standards from CDISC and not
to start over or create unnecessary new standards. A ‘top down’ approach was recommended, with
leadership encouraging and supporting the use of standards.
The view of investigative sites was also emphasized again with a strong statement that standardizing
anything possible will help them to conduct studies more efficiently. Facilitating clinical trials (including
more standardization) will also factor into investigator retention; there are too many cases of ‘one and
done’ where investigators do one study and no more due to excessive administrative burden.
A case study was shared from the five-year programme grant called TRANSFoRm, which was EU-funded.
EHRs were used for a Gastro-esophageal Reflux Disorder study that recruited subjects and collected data
using eSource technology. The CDISC Operational Data Model (ODM), an XML transport standard that
moves data was combined with a clinical data ontology and terminology bindings to create prepopulated CRFs within five different EHR systems. The audit trail metadata for provenance and
compliance with 21CFR11 was retained. ODM was extended by the TRANSFoRm team to enable use of
Android and iPhone devices to collect patient reported outcomes. This ODM extension is now being
offered openly through CDISC. TRANSFoRm used an ontology mapping approach rather than I~HD
(EHR4CR platform) to address the needs of small EHR vendors.
The chair of the Board of Japan’s Academic Research Organization (ARO) council requested support from
those in attendance for the IHE Retrieve Form for Data Capture (RFD) versus the HHS/ONC Structured
Data Capture. Japan will use RFD in their activities to use EHRs for research. They will leverage Japan’s
EHR data standard, SS-MIX, with RFD as a workflow enabler to produce CDASH for clinical research.
Representatives from two patient research foundations, Cohen’s Veteran (which is providing funding for
a CDISC standard for post-traumatic stress) and CHDI (which is funding a CDISC standard for
Huntington’s disease, through a project with the Critical Path Institute) emphasized the importance of
funding all of the standards development that is needed for various disease areas and that this funding
should not all come from patient foundations. In trying to use multiple datasets (not standards based)
to do sophisticated modeling efforts, CHDI has incurred significant inefficiencies. The need to address
missing metadata and other such issues has resulted in significant frustration, not to mention being a
barrier to innovation. Standards can enable innovation and should be like GCPs; everyone should accept
and follow them.
The Pew Charitable Trusts provided perspective on how federal agencies could potentially advance data
standards. FDA could enhance data standardization as part of its efforts to create an evaluation system
for devices that leverages various sources of real world data for pre-market and post-market purposes.
A coordinating center to govern this evaluation system could have data standards as one of the key
building blocks to the ‘rules of the road’ to gather better data. Additionally, CMS could examine data
standardization as part of its quality measurement programs. Finally, ONC has certification criteria that
sets standards for the functions of EHRs, including to improve the interoperable transmission of data
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among systems. Through this program, ONC could examine several policy options, including on whether
there should be a set of data elements where it makes sense to eliminate optionality, the use of APIs,
and testing criteria to ensure that EHRs can extract and receive data according to specific ways (such as
being able to receive data that conforms to all of the most prevalent options within a standard).
Key Topic VI: Models for Standards Sustainability and the Future of Clinical Research
Themes that were emphasized during this final session of the day were supportive of finding ways to
fund standards development, maintenance and sustainability. The opportunity is NOW; if we wait, we
will make a mess. A ‘trusted third party’ was proposed, which may be a standards development
organization. Data sharing requires standards and they need to be required; but, we must also find a
way to reward those who collect the data and share it. We do need to encourage the interoperability
between healthcare and research and keep the patient’s needs at the forefront. We also need to ensure
that we are helping the clinical research investigators and sites, providing infrastructure and standards
that will ease the burden of doing research and leveraging EHRs for that data.
Dr. Janssen (of Janssen Pharmaceuticals, now part of Johnson & Johnson) was quoted earlier in the day
as having said ‘The patients are waiting’. This is certainly still a current concern for patients waiting for
new cures and hoping for acceleration in bringing treatments to patients for unmet medical needs. Brad
Smith of Faster Cures pointed out that there is also evidence that ‘patients are no longer waiting’ in
terms of becoming involved directly to help with the acceleration process. Patient organizations are now
actively partnering with academia and other companies in research and development, connecting the
parallel universes that Dr. Califf referenced in his opening comments. Unfortunately, the system seems
to promote ‘silos of excellence’ where individual research activities cannot be connected into a larger
system. The CDISC Unlock Cures initiative was applauded, and there may be an opportunity to get a
better reception for data standards by leveraging the patient community’s appreciation for the
importance of data and their desire to have data returned to them so that they can share it more
broadly, connecting a number of patient communities and aligning incentives across parallel universes
by having an ‘underlying community to knit it all together’.
Kay Holcombe of BIO stated in reference to biotechnology organizations: “I do think that what a lot of
people said today is that mandates are the way to go. You cannot leave this ambiguous. […..] Tell them
what they need to do versus leaving them in an uncertain situation in that they are not really sure
exactly what is going to be expected of them. I think they have to have confidence in the regulatory
outcome. So, there has to be a consistent message to them across the board. They have to have a
definitive goal post. They can’t have standards that are going to be phased in and then five years from
now they are going to change and there are going to be some different kinds of standards that are going
to be used. That is, to them, a moving goal post; they have to have an actual potential outcome, not a
theoretical one.”
Dr. Dalvir Gill of TransCelerate was the final panelist. He spoke of the TransCelerate support for
standards through their Data Standards workstream, Common Protocol Template workstream and
eSource workstream. He gave an excellent example for the value of standards from a new workstream
they have initiated using placebo ‘Standard of Care’ data. Due to the lack of consistency in data formats
(not only across companies but also within companies), the data are being converted to the CDISC
standard. “With less than 25 studies in the database, we already had a big win because we are
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measuring. One company provided a hemorrhagic stroke database that was converted and used by
another company. The company that used that database cancelled an entire observational study worth
millions of dollars; they reduced the number of patients in their control arm by half and they shaved 2-3
months off the time of that particular study. You can’t measure value like that--that’s real value. Not to
mention the patients, who are now not needed to be exposed to placebo. The study needed half the
number of patients. So that’s immediate and real value. That then spurs more companies to actually
start adding their data, getting it converted, and into the database. Another example is that a company
that has been implementing the Common Protocol Template is seeing ~ a 6-week reduction in time
between the time they say go and they get a protocol through to the development team. [……] So we
know these standardization efforts have benefits once they get into a company and we can show that
value. When we have these kinds of metrics and then come back from the membership to TransCelerate
and we socialize them across the membership, what that does is it brings a theoretical value to real
value and that then drives the desire for adoption.”
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Strategy Session on the Future of Medical Research and the Role of Standards:
“Forming Connections Towards Complementary Systems”
2 August Meeting – Proposed Next Steps (DRAFT 3)
I.
II.
III.
IV.
V.
Harmonize a core set of data elements and models across agencies with the ultimate goal of having a global
core (essential) standard for research data collection, ideally to support the use of analogous data from
EHRs for research.
a) Explore the feasibility of harmonization among the PCORNet Data Model, the Sentinel Model, OMOP
Model and the ISO-CDISC-HL7 BRIDG Model and related impact on existing tools.
b) Identify key elements (10-25 to start) for a core standard dataset for global clinical research; assess the
feasibility of harmonizing these elements to create a standard set of elements that will fit with new FHIR
resources, global clinical research (CDASH), NLM CDE Repository and PROMIS, NCI caDSR.
c) Explore whether NIH Centers might benefit from encouraging use of CDASH use on federally funded
studies.
d) FDA/CDER to explore the recommendation from certain meeting participants to require CDASH in the
future (e.g. in the context of traceability to SDTM).
Harmonize a Common Protocol Template for industry and government-funded clinical research
a) Complete review of mapping and opportunities with joint team (Target – End October)
b) Review proposals with TransCelerate, FDA and NIH stakeholders (Target – End of year)
c) Publish revised work product -1Q 2017
d) Simultaneously, align the protocol template libraries with global research standards for therapeutic areas
e) Test the use of SHARE to host the libraries that complement the templates
FDA has been openly encouraging the use of eSource and evidence generation from healthcare information
for clinical research and ‘re-linking’ these two universes; FDA will continue to encourage this.
a) A future meeting was proposed to explore barriers in more depth, with biopharma and EHR vendor
participation (at minimum). Determine when and how to convene this meeting.
b) The eSource Stakeholders Forum (FDA BAA grant) has convened working groups to explore various facets
related to this topic, including research data from wearables/mobile devices.
c) Work towards standards at the intersection of healthcare and research.
d) The FDA EHR Draft Guidance has received a number of comments that will be reviewed and addressed in
the near future. These can inform next steps.
e) Harmonization of common models (BRIDG, Sentinel, PCORNet) per Next Step (1) can potentially pave the
way to leverage enterprise data warehouses. See AMIA Comments on above Guidance.
CDISC standards are open and freely available to everyone. As demands increase for the maintenance,
education and implementation support and requests for more standards, so do the related costs; and, these
standards are now offered via an electronic repository (Shared Health and Research Electronic LibrarySHARE).
a) Additional collaboration can be potentially useful in this regard; a proposal was made at the 2 August
meeting to assess the redundancies among NCI caDSR, NLM CDE Repository and SHARE to evaluate
opportunities to collaborate to reduce costs and provide curated standards electronically for all.
b) Develop an appropriate business model and identify potential funders for sustaining the repository and its
standards content.
Education is needed across all parties in terms of the availability and use of standards for clinical research
and their link with healthcare.
a) The CFAST Scientific Advisory Committee is preparing a manuscript – draft due October 2017.
b) There is a course developed at the request of the ARO council in Japan (targeted to academics); this can
be offered in the U.S. in 2017.
c) A Symposium is scheduled between AMIA and the CR Forum meeting in Chicago – 2:00-5:00 on 16
November. This will be open for registration by late September.
d) Custom training, which was also requested, is available as are recorded webinars on the various TA
standards.
e) Assess other training requests and opportunities.
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Strategy Session at the National Academy of Sciences – Meeting (above) and NAS Ceiling (below)
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