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CDISC Strategy Session Summary -2August16 Page 1 of 19

Strategy Session on the Future of Medical Research and the Role of Standards:

“Forming Connections Towards Complementary Systems”

Strength through collaboration.


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


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 Patient-Centered 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)


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

Harvard MRCT VI-Sustainability

Michael Braxenthaler, PhD Global Head Strategic Alliances, Informatics (Roche)

IMI eTRIKS Project (Europe) IV-Government

Robert Califf, MD, PhD FDA Commissioner U.S. Food and Drug Administration (FDA)

Moderator, Opening/Closing Remarks

Chris Carr Director of Informatics Radiological Society of North America

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


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 National Institutes of Health/National Center for Advancing Translational Sciences (NCATS)

VI-Sustainability

Dalvir Gill, PhD Chief Executive Officer TransCelerate Biopharma Inc. VI-Sustainability

Michael Glickman President/Owner (Computer Network Architects)

Chair, ISO Tech Committee 215


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)


Tammy Jackson Director of Programming Pharmaceutical Product Development (PPD)


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


Waren Kibbe, MD, PhD Director, Center for Biomedical Informatics and IT

NIH/National Center for Advancing Translational Sciences (NCATS)

VI-Sustainability

Peter Kim, MD Deputy Director, Therapeutics Research Program

NIH)/National Institute of Allergy and Infectious Diseases (NIAID)/Division of Acquired Immune Deficiency Syndrome (DAIDS)

IV-Government

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)


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)


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


II-Regulatory

John Potthoff, PhD CEO Elligo Health Research, Inc. I-Global Standards Status

Mitra Rocca Associate Director of Medical Informatics


II-Regulatory

Mark Roche, MD, MSMI Chief Medical Information Officer Avanti iHealth IV-Government

James Rogers President NexTrials, Inc. I-Global Standards Status

Lilliam Rosario, PhD Director, Office of Computational Science


II-Regulatory


Richard A. Rudick, MD VP, Development Sciences Biogen III-Biopharmaceutical and Device Products

Hiroshi Sakaguchi Pharmaceuticals and Medical Devices Agency of Japan (PMDA)

II-Regulatory

Mayumi Shikano, PhD Associate Center Director Pharmaceuticals and Medical Devices Agency of Japan (PMDA)

II-Regulatory

Trisha Simpson Director, Global Integrated Standards at UCB

Union Chimique Belge (UCB Biosciences

III-Biopharmaceutical and Device Products

Mary Ann Slack Deputy Director, Office of Strategic Programs


VI-Sustainability

Brad Smith, PhD Director, Policy FasterCures VI-Sustainability

John Speakman Senior Director, Research New York University Langone Medical Center


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

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

Health & Human Services (HHS)/Office of the National Coordinator for Health IT

Elaine Ayers Deputy Chief NIH Clinical Center/BRTIS

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


Invited – Regrets

Stan Huff, MD Intermountain Healthcare; HL7 Board Chair

Patricia Flatley Brennan, PhD Director of NIH/NLM

Lloyd McKenzie Gevity, Inc; HL7 FHIR Management Group

Josephine Briggs, MD NIH/OD

Karen DeSalvo, MD HHS/ONC

Janet Woodcock, MD FDA/CDER

Lisa LaVange, PhD Head of FDA/CDER/Statistics

Stephen Wilson, PhD FDA/CDER/Statistics

Andy Lee Head of Global Clinical Trial Operations, Merck

Dave Jordan, PhD AbbVie, TransCelerate Data Standards Workstream Lead

Makoto Suematsu, MD Head of AMED/Japan

Kenneth Getz Tufts CSDD/CISCRP

Stephane Auger, PhD Danone

Nicola Perrin, PhD Wellcome Trust

Dennis Decktor, MD Medical Information, Regeneron

William Turner Programming Lead, Astra Zeneca

Michael McGinnis, MD National Academy of Sciences

Mike Levy PhRMA


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


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 non-

standard 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


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.


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


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.


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.”


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 pre-

populated 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


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


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.”


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. 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).

II. 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

III. 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. IV. 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 Library- SHARE). 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.

V. 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.


Strategy Session at the National Academy of Sciences – Meeting (above) and NAS Ceiling (below)

Documents

Strategy Session on the Future of Medical Research and … · Strategy Session on the Future of Medical Research and the Role of ... 12:00-12:30 Lunch Buffet ... Strategy Session