While most of the CDISC staff were in Europe supporting the 2013 Europe Interchange, Sheila Leaman (CDISC Director of Global Relations) and I went to Orlando for the 2013 Partnerships in Clinical Trials conference. At the conference, we met with current CDISC members, handing out “Proud to be a CDISC Member” signs for their booths and engaging with them to gain information on their experiences with CDISC. We also had the opportunity to liaise with potential members to convey the benefits of membership and answer any questions they might have. In all, this was a fantastic experience, and personally having the occasion to meet face to face with those that utilize and support CDISC standards development was tremendously rewarding.

In addition to meeting with current and potential members, we took the time to sit in on one of the discussions, “The Evolution of Clinical Trial Partnerships – Initiative to Forge Innovative Collaborations across the Entire Healthcare Chain.” Speakers during this session were Kathleen Ford of Merck Serono, Ed Pezalla of Aetna, Christine Dingivan of PPD, Kelly Davis of Express Scripts and Dalvir Gill of TransCelerate Biopharma. Sheila and I had had the opportunity to have a very successful discussion with Dr. Gill earlier in the day about the collaboration between CDISC and TransCelerate Biopharma in the area of Therapeutic Area Standards development, and were excited to hear him speak on the panel during this session.

As for previous CDISC Interchanges, the CDISC team spent the prior weekend on final preparations, making sure to keep the conference running smoothly and efficiently while providing the best possible support to our attendees.

Each year for the past 10 years, the European CDISC Coordinating Committee (E3C) has organized a CDISC Interchange. This year’s was touted as the best Interchange held in the last 5 years by many long-time attendees, and was highly regarded by those who have not had the opportunity to attend the earlier Interchanges. The success can be attributed to a program of interest to everyone, excellent keynote speakers and panel discussions that allowed the opportunity for all to participate. The venue should also be noted – many thanks to Dominik Ruisinger, who selected a comfortable hotel with a large conference area in an absolutely lovely area in Bad Nauheim, Germany, near Frankfurt. Spring was in the air and the trees and flowers were blooming in the park that surrounded this hotel. When I arrived in Frankfurt and was en route to the hotel, I was told by one of the locals that “Bad” in front of a town name in Germany means you should go there to relax. I commented that perhaps I could relax after our meetings with the E3C, the CDISC Advisory Council and the Interchange, and how I wish I had taken a day of vacation at the end of the week to do just that!

The atmosphere at the Interchange was anything but what I would call relaxing. It was stimulating, enjoyable, educational, informative and very productive. The attendees and exhibitors had great ideas for CDISC, from how to better engage the User Networks and additional projects that the E3C would like to achieve this year, to excellent suggestions from the CDISC Advisory Council members or their alternates in Europe on how they could be more effective in assisting and advising CDISC. , to the Interchange itself. This blog merely seeks to give one a flavor of the Interchange – one really had to be there to experience it appropriately! Mark your calendars for next year: 7-11 April 2014 in Paris, and don’t forget that we have one in Bethesda, MD on 4-8 November 2013, for which we are currently inviting speakers and calling for abstracts!

We had a great exhibition area in which our exhibitors, presenters and attendees met and communicated about recent accomplishments, including tools and service providers that support CDISC standards.

“With the power of our volunteers, CDISC has developed additional standards in the past 4 years including therapeutic area standards. We have been listening to your input on how we can provide additional value to CDISC stakeholders. We enhanced collaboration and education and are providing a Protocol Representation Tool and others are coming. Patients are waiting for therapies and their time is precious! We need to make sure that they understand the value of data standards”, Dr. Kush, President and CEO of CDISC stated at the opening session of the CDISC European Interchange in April in Germany. Dr. Kush also mentioned that CDISC standards are cited in the Structured Data Capture (SDC) Initiative of the U.S. Health and Human Services Office of the National Coordinator of Health IT, which offers incentives for meaningful use of electronic health records. And, CDISC has endorsed the movement of the Learning Health System (LHS) and is now leading the Essential Standards to Enable Learning (ESTEL) Initiative while participating in Europe in the IMI EHR4CR project. Communication is key, she stated at the end of her State of the CDISC Union presentation.

Recent discussions concerning the Learning Health System (LHS), and particularly Essential Standards to Enable Learning (ESTEL), have exposed varying perspectives on the relative overlap standards should have between healthcare and research. There are those who feel research and healthcare have quite different standards requirements while, on the other end of the spectrum, there are those who believe that standards for both research and healthcare should be exactly the same. Of course, there are still others who will indicate that it depends on the type of standards being referenced. Sixteen years after Bron Kisler and I developed a slide with two intersecting circles – one for healthcare and one for research – I am even more convinced that this is a Venn situation.

From Wikipedia: A Venn diagram or set diagram is a diagram that shows all possible logical relations between a finite collection of sets (aggregation of things). Venn diagrams were conceived around 1880 by John Venn. They are used to teach elementary set theory, as well as illustrate simple set relationships in probability, logic, statistics, linguistics and computer science (see logical connectives).

Below is the slide I am referencing, which was our vision in 1997 as to how to streamline research.

You have heard this before, but we are all patients; and, those of us who have been working with CDISC for the past 1.5 decades are that much older and feeling an increased urgency towards accelerating the ‘research-healthcare learning cycle’. The 17 years that it is said to take for research findings to make their way back into clinical care decisions is simply too long, and we all know that healthcare costs continue to skyrocket without the resultant improvement in speed of innovation nor quality of care.

There were many encouraging moments at CAPI, but one of the greatest highlights, to me, was the number of CDISC Board members that not only attended the bi-annual face-to-face Board of Directors meeting (held in Asia for the first time), but spent the rest of the week thoroughly engaged in the Interchange presentations and associated discussions. Eight CDISC Board members even took time out of their very hectic schedules to participate in a panel discussion and Q&A session for Interchange attendees.

While the HHS ONC has mentioned that it does not want to reinvent the wheel and that the SDC Initiative will collaborate with the international standards development community, of which CDISC is a part, it is important to note the work that CDISC and others have already done in the area of adverse event reporting, and ask the necessary question: is this yet another example of redundancy?

In 2008, a pilot project was launched between CDISC, CRIX, Pfizer, Brigham and Women’s Hospital, Partners Healthcare and Harvard Medical School, entitled ASTER, or “ADE (adverse drug events) Spontaneous Triggered Event Reporting.” This project sought to enable automated ADE collection through the EHR using CDISC and IHE’s Retrieve Form for Data Capture. The application that was developed was a novel concept – it directly downloaded data held in the EHR and allowed direct submission to the FDA, all in the correct format for the electronic reporting of individual case safety reports. Follow the Link.

“The identification and harmonization of standards for the structured data capture within EHRs will […] help reduce a) the data collection burden on health care providers by enabling secure, single-point data entry that populates to multiple systems and b) the need to make site-specific modifications to EHR system capabilities in order to enable participation in important reporting and research activities.”

“Large Simple Trials (LST) and Knowledge Generation in a Learning Health System” was the topic for a meeting organized by the Institute of Medicine of the National Academy of Sciences. This meeting took place on 27-28 November, and I was invited to give a presentation with the prescribed title: “Getting to Comparable, Computable Data” in a session on infrastructure needs.

The meeting topic was very specific because there is a perceived need to run more LSTs and the planning committee wanted to explore why there are so few of this type of study actually conducted. Although difficult to find, there were a few examples cited and/or described during the meeting, mostly observational studies conducted by academic universities: Harvard University (VITaminD/OmegA3 – VITAL), Brigham and Women’s Hospital (Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MIFREE), McMaster University (Heart Outcomes Prevention Evaluation -HOPE). There were no regulated research studies recounted.

Dr. McClellan also spoke of the FDA being a ‘fire hazard’ with so many boxes of paper in storage. The FDA has now moved to their White Oak Campus with far more space and, interestingly, Dr. Janet Woodcock (Director of FDA/CDER) who gave the keynote this year in Baltimore, said that she was told by their document room that they had to ‘stop’….meaning that there is no more room to bring any more paper into the FDA. Speaking specifically about standards, she raised an analogy of the Baltimore fire of 1904, during which the city burned because fire trucks from nearby fire departments did not have hoses that would fit on the Baltimore fire hydrants – there were no fire hose standards!

Everyone is going to be a patient, and we all happen to know someone with a brain disorder, Dr. Magali Haas of One Mind Research opened her presentation. Dr. Haas spoke of the ‘moon shot’ initiative of President John F Kennedy to put a man on the moon; it is based upon this successful challenge that Patrick Kennedy has now launched the One Mind initiative to cure brain disorders in this century. Dr. Magali stated, “We will not accomplish this without common standards for data. We need to integrate solutions and new practices to improve the quality of lives. CDISC is one of the key organizations that will ensure the development of common data elements for traumatic brain injuries.”

Dr. Charles Hugh-Jones of sanofi, DataShare and the CEO Roundtable on Cancer apprised the audience on the ongoing project of implementing data sharing among biopharmaceutical companies within the environment of Oncology.

Mary Ann Slack (FDA, CDER OPI) opened the meeting reiterating the purpose to get industry input, objectively without debates. She said that they really wanted to have a discussion and that they will provide an e-mail address for thoughts that folks would like to send, even after the event. She cited some scenarios that will be placed on the FDA website to convey the ‘pressing challenges’ that FDA has with respect to receiving and reviewing data. Ms. Slack highlighted a few of the comments that were received in writing, including the need for high quality standards across the spectrum of research, recommendations including an end of Phase II data standards meeting for those developing new treatments and the need for more consistency---governance is key, she said.

The session was tailored to train instructors and presenters on global teaching and presentation skills that would motivate and stimulate the profound attention of the attendees in the material delivered. The session started at 9:00 AM and was supposed to end at 5:00 PM, but it did not end until 5:45 PM where active participation and excitement of discovery kept the attendees interested until the last minute. Attendees, who are also CDISC instructors were urged to participate continuously, analyze and discover new ideas and training methods throughout the day. Creative and positive input led to self-discovery of new teaching techniques, this atmosphere of active and analytical participation helped the attendees discover a new variety of interesting and exciting teaching methods even before they received instructions and notes from the instructor.

Please note that the applicant has a 3 month window in which to reply to this “final action” so we will continue to follow any further progress. We have consulted the formerly mentioned IP attorney about this issue and have been cautioned that patents can be saved from "final" rejections through amending the claims, filing a continuation, etc. We are hopeful, however, that based on the description above of what is meant by a “final rejection” that this application will not have a chance to move forward. We will report back on any further developments. Thanks again for your support on this issue.

This may be our best opportunity to convince FDA that an XML transport standard based on ODM for CDISC SDTM, SEND and ADaM content would be a better solution for submitting data than use of HL7 healthcare standards. We believe this forum will highlight the advantages of using the CDISC Operational Data Model (ODM), which is the basis for define.xml and a current component of the FDA study data standards. ODM has been successfully adopted by many researchers in both industry and academia, as well as technology vendors for transferring clinical data, metadata and terminologies with audit trail in a fully compliant manner.

At this year’s DIA meeting in Philadelphia on 26 June, CDISC, HHS/ONC and FDA issued a ‘challenge’ to use EHRs for regulated research. Specifically, research study sponsors were challenged to use at least two different electronic health record systems at different sites to conduct a multi-site, multi-visit, standards-based regulated research study. The panelists at DIA spoke on the feasibility of this challenge, based upon technology and data standards and processes that have been developed over the past decade. In addition, a case study was presented during this session about a research study being conducted currently at Florida Hospital using the Cerner EHR system. Despite the potential and demonstrated benefits of this approach, the clinical research industry has not yet embraced these new methods and standards to conduct research studies.

This challenge will provide FDA, HHS/ONC and CDISC a means to assess the remaining barriers as well as the opportunities to streamline regulated research and increase its capacity throughout the US and the world as EHR adoption is being encouraged and increasing rapidly. Wayne Kubick, Chief Technology Officer (CDISC), spoke first at the DIA session: “CDISC has been doing demonstrations of its Healthcare Link methodology for years now, at HIMSS and at DIA. By adopting the CDISC-IHE profiles used in the CDISC Healthcare Link solution, EHRs can readily implement the standards and profiles to enable the collection of a high quality research dataset that is needed for any regulated research study.”

Dr. Kondo stated that “the purpose of Pharmaceutical Affairs is to improve the public health through regulations to secure quality, efficacy and safety of pharmaceuticals and medical devices and take necessary measures to promote R&D, where the reliability must be verified”. There are three primary roles for PMDA in their quest to improve the public health and safety of Japan: 1) to reviewing applications for marketing approval of pharmaceuticals and medical devices; 2) to conduct safety measures, and 3) to provide relief to people who have suffered from adverse drug reactions or infectious diseases.

According to a Press Release from 26 June: “AmCham China's Healthcare Cooperation Program (HCP) today signed a memorandum of understanding (MOU) with the Health Human Resources Development Center of the Chinese Ministry of Health, opening a path to increased cooperation. The MOU will help foster multi-level exchange between China and the US in the healthcare sector and provide a platform for high-level US-China dialogue on healthcare reform, medical personnel training and technology exchange.” See this link for the full press release.

According to Jun Zhou, Executive Director, AmCham is working to make it easier for companies to do business in China; his key project is the Healthcare Cooperation Program. The two workshops that AmCham and IBM planned, with CDISC as a core theme, took place in Beijing on 16 July and Guangzhou on 19 July. AmCham and IBM sponsored the workshops, along with support from CDISC, especially Sheila Leaman, CDISC Manager of Global Relations.

CDISC standards are created through a consensus-based process that includes many different people who contribute their time and expertise. Thus, the value should serve everyone and the IP be protected. Some standards in other industries were developed in a manner that included proprietary portions such that users were charged royalties. The desire to prevent royalty charges or ownership by any one organization or individual formed the basis for the CDISC IP Policy that is now posted on our website.

Questions and comments are welcome here!

The jist of the patent is this: a company, DataSci, filed a patent application in 2009 that effectively patents the use of metadata in clinical research. If this patent is granted there is a real possibility that a fee will be due to the patent holder for any use of metadata over the internet for every study done by any BioPharmaceutical company, academic research institution, government agency – basically ANY clinical research. See the original email below for more details and links that provide additional information.

Almost immediately after the email went out CDISC was contacted by Pharmaceutical, Biotech, Government, CRO and Technology company representatives company representatives asking how they could help prevent this patent from being approved. Most have forwarded the original email to their legal counsel and are looking into the process to protest this patent. Several of the large Pharma companies are also discussing how to combine efforts to fight this patent application.

CDISC appreciates all this effort and the support shown by our members. We will periodically update this blog with the status of these efforts.

Original email follows:

9-10 July 2012

Seoul, South Korea

Greetings from Seoul! Members of our CDISC team have a busy month ahead, with CDISC workshops and an interchange scattered around the Asian continent. We have begun our journey with a trip to Seoul, South Korea, where Dr. Rebecca Kush, CDISC President and CEO, Wayne Kubick, CDISC Chief Technical Officer, Dr. Pierre-Yves Lastic, CDISC E3C Past-Chair and Chair-elect of the CDISC Board of Directors, and Dr. Kiyoteru Takenouchi, CDISC J3C Past-Chair and Board Member, have all given presentations to the K3C and interested parties from the Korean Society of Clinical Development at the CDISC Korea Workshop/Symposium about the importance of using CDISC standards for clinical research. A general overview of the standards and activities was given on the first day, and in-depth training over the standards and how the work together end-to-end was offered the second day.

Questions and comments are welcome here!

The session was chaired by Dr. Chuck Cooper. Mary Ann Slack spoke first on the topic of CDER Data Standards. She opened: “We cannot improve efficiency or innovate without standards.” CDER is working, with other FDA centers, on end-to-end standards to support a standards-based review environment. They have posted a list of therapeutic area standards that they would like to have developed, to add to the existing standards (which pertain to all research studies); they have also created a ‘notional timeline’ for these. However, she stated clearly that FDA should not drive the standards development; CDISC and the Critical Path Institute, with patient advocacy groups, are working on these, with nine of the therapeutic area standards already in progress. “CDISC, C-Path and FDA collaborate constantly.” (See the CDISC-C-Path Press Release from 23 June 2012 about CFAST).

Questions and comments are welcome here!  

In March 2011, a report by the NCI’s Board of Scientific Advisors, entitled ‘Assessment of the Impact of the NCI CaBIG’, was released. Based upon these findings and recommendations, an Oversight Sub-Committee was formed to further review the caBIG projects and make additional recommendations (Members of this Sub-committee are listed at the end of this blog). Dr. Harold Varmus, the head of NCI, spoke to the Oversight Sub-committee at its initial meeting in June of 2011. His hope is that this Sub-committee serves as a model for program reviews and external advisory groups. Participants in the development of the BSA report (Drs. Stein and Califano) presented their findings to the Sub-committee after which John Czaikoski presented a response from the NCI, including actions they had taken to streamline management and to scale back certain activities that had been identified as having a less than favorable return with respect to NCI resources spent.

Questions and comments are welcome here!  

The opportunity that took place last month was afforded by Mr. Joe Kanter of the Kanter Family Foundation and Kanter Health. He funded the LHS Summit; the Summit Planning Committee (including Frank Rockhold and myself) and was led by Dr. Friedman, assisted by Josh Rubin (Executive Director of Kanter Family Foundation) and students from the University of Michigan.

The Joint Initiative Council (JIC) began as a group of 3 SDOs, i.e. Standards Developing Organizations, namely ISO, CEN and HL7. They added CDISC (after a 6 month probation period) when we proved to be 'good citizens' working with the other three, particularly in areas that relate to clinical research. Two more SDOs were then included-GS 1 and IHTSDO. After leadership from HL7 and CEN, CDISC was asked to Chair the JIC, and Bron has filled this role for over a year now.

David Moner of Universitat Politecnica de Valencia was first to present during the Electronic Health Record (EHR) session on the second day of the European Interchange. Mr. Moner began his presentation by summarizing the current status of EHR use in the healthcare industry; he detailed that, while a great deal of effort and investment has been put toward the adoption of EHR systems, and although this has benefitted healthcare delivery, so far it has not been as clearly beneficial for clinical research. Specifically, the concept of EHR data reuse remains an unresolved issue.  Read More.

Kiyoteru Takenouchi, Japanese Sentinel and MIHARI Project

Kiyoteru Takenouchi of CMIC was next introduced, and began his discussion by describing how the EHR is currently in use in Japan. At this time, 90% of large hospitals in Japan have Computerized Physician’s Order Entry (CPOE). The PMDA’s (Japan’s FDA) MIHARI Project focuses on having four working groups for each information source: 1) reimbursement claims and Diagnosis Procedure Combination (DPC)/Diagnosis Related Group (DRG), 2) hospital information system, 3) spontaneous adverse events reported to PMDA, and 4) post market surveillance collected by pharmaceutical companies. Data is changed to a standard format when it is sent to storage, which allows reuse for many purposes, such as referrals to other clinics and hospitals.  Read More.

Pierre-Yves Lastic, Report from the EHR4CR Project

Pierre-Yves Lastic of Sanofi Aventis followed Mr. Takenouchi, and presented on the Innovative Medicine Initiative’s (IMI) EHR4CR Project, a four-year project (2011-14) with a budget of over 16M euros with the objective of promoting the wide-scale reuse of EHR data to accelerate regulated clinical trials across Europe (although now that the FDA is a part of the advisory committee this is anticipated to expand). The project works with 10 pharmaceutical companies, 22 public partners from academia, hospitals and SMEs (including CDISC), and five subcontractors. To date, this project is one of the largest public-private partnerships working on reuse of EHR data for clinical research. Reuse of EHR data offers opportunities to advance medical research, improve healthcare and enhance patient safety. 

“The idea of the CDASH E2B project initiated ten years ago, but just until 2010 it started taking effect” said Barry Burnstead, a member of the CDISC European Coordinating Committee (E3C) and chair of the CDASH session at the CDISC European Interchange in Stockholm.

Sonia Araujo of Medidata was the first presenter on the CDASH-E2B session

Sonia Araujo declared that the purpose of the project is to identify and describe the International Conference on Harmonization (ICH) E2B fields that are collected at investigational sites for serious adverse event reporting. Hence, a CDASH-E2B team was formed by CDISC and led by Rhonda Facile.

Members of the CDASH E2B group represent a good cross section from the healthcare industry coming from both Europe and U.S.A. The E2B group consists of representatives of biopharmaceutical companies along with software vendors, CRO representatives, sponsor companies as well as independent organizations such as the U.S. Office for Policy.

Dr. Rebecca Kush, President and CEO of CDISC, thanked the E3C, the E3C Program Committee, CDISC team members and everyone who contributes in any way to CDISC progress. Volunteers are the ‘heart and soul’ of CDISC. In particular, she thanked Joerg Dillert, who chaired the EU Interchange Program Committee this year and came up with the theme (which is the title of this blog).

Sue Dubman, BRIDGing to Improve Connection with Patients and Providers: A Case Study Ms. Dubman, who is also a director on the CDISC Board, discussed the benefits of adopting BRIDG, incorporating the example of Genzyme’s RegistryNXT! Program, a web-based disease registry platform that consolidated existing Genzyme Lysosomal Storage Disorders (LSD) registries and other rare disease registries, with BRIDG as its underlying information model.

Jozef Aerts, Multipurpose Usage of the New “Study Design Model in XML” (SDM-XML) Jozef Aerts of University of Applied Sciences FH Joanneum, Vienna, Austria presented on the multipurpose usage of the new Study Design Model in XML (SDM-XML)

The panel was formed of international experts in the healthcare/research industry: Charles Cooper of FDA, Bernard De Bono of the European Bioinformatics Institute, Bron Kisler and Wayne Kubick of CDISC and Pierre-Yves Lastic of Sanofi and the E3C answered inquiries from the attendees.

1. Does the FDA expect the community to use the latest SDTM Implementation Guide and how is this going to be approached?

Cited below is a segment from the ACRO press release on this topic:

Peddicord expressed concern about the slow progress that has been made since the release of the FDA's "Critical Path" whitepaper in 2004. He noted that while some FDA-supported efforts, such as the C-Path Institute and the Clinical Data Interchange Standards Consortium (CDISC) have had success developing tools to advance drug development, other efforts have fallen short. Notably, Peddicord singled-out the Clinical Trials Transformation Initiative (CTTI).

"While CTTI is well-intentioned, it has not taken on projects that have the potential to be 'transformative,’" said Peddicord. "Every effort at innovation that the FDA supports, directly or through the funding of public-private collaborations, should be measured against three objectives: does it make the drug development process faster, cheaper or more productive."

Gitte Frausing of Novo Nordisk presented on her CDISC SEND experience during the CDISC European Interchange in Stockholm on 18-19 April. The focus of her presentation was on lessons learned from the FDA-SEND Phase 2 Pilot, in which Novo Nordisk participated. The value of a close collaboration among the SEND team, the CDISC Terminology team and the FDA was readily apparent from this presentation.

Gitte described how different terms with varied definitions may cause inconsistencies and inaccurate results within the non-clinical analysis. She illustrated her point of view with some examples of inconsistencies within the area of microscopic findings: one of the findings showed a liver having a 3 millimeter pale area with surrounding hemorrhage, which is actually considered two findings in SEND and should not be included in the same record. Gitte also mentioned that having no place to incorporate certain data in the SEND domains caused loss of information due to the lack of standardization in the data capture phase. This was one of the ‘lessons learned’ that the FDA agency has found during their analysis of the submitted data.

Another example Ms. Frausing provided was that FDA asked Novo Nordisk to test the terminology for the severity variable in SEND standard; the outcome was to ensure the validity of the terminology already created by the SEND terminology team.

Dr. Cooper’s slides will be made available to the Interchange attendees, but here are a few highlights/quotes for those who were unable to attend:

The electronic format and standards are critical for FDA.

“We cannot improve efficiency or innovate without standards."

We want to improve regulatory decision-making through better access to structured scientific data.

Non-standard electronic data limits quality and efficiency during the review process.

PDUFA V is coming; PDUFA IV ends in late September 2012. The FDA is building a clinical trial repository (CTR), formerly called Janus, which is BRIDG-informed and is receiving input from the division data standards heads and clinical and statistical reviewers. They are using an OpenCDISC enterprise tool and will eventually share their validation checks.

The vision at FDA is a ‘standards-based end-to-end fully electronic review environment’.

By Dr. Rebecca Kush

CDISC, President and CEO

Greetings from the CDISC 2012 European Interchange in Stockholm, Sweden! Our team has been hard at work to ensure that this year’s European Interchange is our most successful yet, and we are off to a great start! On-site preparations for the Interchange began on Friday, and after preliminary meetings and a tremendous amount of unpacking and arranging, the CDISC registration booth was open for those attending CDISC Education courses to check in this morning.

On behalf of Dr. Fukushima, the director of the Translational Research Informatics Center (TRI), Kobe, Japan, Dr. Rebecca Kush was invited to be a keynote speaker at the final session of a meeting that took place on 2-3 March 2012 in Tokyo; the theme was Life Science Innovation: The Growing Role of Academia in Japan. This final session was entitled “Coordination, Support and Training Program for Translational Research” and was slated as “one of the most important national projects of the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT)”.

TRI and MEXT developed this program over the course of 5 years to increase the application of basic research to patient care, so called Translational Research, through promoting organizations, within universities to become centers of translational research. Moreover, as a part of the program, TRI has also been working on projects in relation to CDISC standards and has translated CDISC standards into Japanese.

Japan has a long established reputation for quality, based upon processes that build quality in from the beginning. The value of CDISC increases dramatically as it is implemented upstream in the medical research process---in developing case report forms or protocols. I was honored and pleased to have been invited to speak at the 3rd Global Quality Assurance Conference held in November 2011 in Kyoto (which was even more remarkable than usual, during the peak of the fall color changes). Yoshio Tsukada of GSK and the leader of the Japan CDISC Coordinating Committee (J3C) organized a pre-conference workshop entitled “CDISC Makes You Happy”. The crowd numbered ~ 250 in the splendid Kyoto Conference Center (see photos); they gathered to hear the 6 speakers of this session on Sunday afternoon, 13 November.

The main messages I took home from this session are shared here with you:

Mr. Yoshio Tsukada, as the Chair, introduced the session and speakers. He presented CDISC as one of the significant key players for efficiency for ALL stakeholders. There is a need for a simple flow in clinical research, from collection through reporting, which CDISC facilitates.

Dr. Ken Toyoda had been inviting me to speak in Kyushu for several years now, so the Kyoto QA Conference (see previous blog) offered an opportunity to do so on the prior Friday. Approximately 40 doctors, dentists and researchers, most in white coats, were in attendance for the presentation on CDISC. Dr. Toyoda leads the ISO TC215 group in Japan and I know him from ISO meetings; he also launched a Clinical Research support organization/CRO and works with the Center for Clinical and Translational Research at Kyushu University. He and Junji Kishimoto, who created an English business card especially for my visit, provided translations and comments at various points throughout the lecture. I could not resist but begin my presentation with a slide showing only 11-11-11. That was the current date and the only day of this year when metadata was not essential to interpret the date!

I like to compare improving efficiency in clinical trials to eating an elephant; where do you start? With an industry that spans hundreds of companies, thousands of people all over the world, and a process that must be rigorously controlled, at some point you need to make a decision to start somewhere and build from there. This is the thought behind the FDA/PhUSE Annual Computational Science Symposium (CSS). FDA and PhUSE have worked together to define the first pieces of the elephant by defining six working groups. The topics of these working groups include: data validation, reducing risk with site selection, integrating data, converting data (CDISC SDTM), implementation of CDISC models, developing standard analyses, and non-clinical data standards implementation (CDISC SEND). Over time these working groups will evolve and the topics and issues of greatest interest will rise to the top. http://www.phuse.eu/Working-Groups.aspx

But let’s not get ahead of ourselves; these core topics are already challenging by themselves. How are we, as an industry, going to make significant advancements on this idea? Powerpoint, while good at presenting an idea, is not ideal for collaboration. The model of presenting and listening needs to evolve; we need to sit down, roll up our sleeves, dive into the details and begin putting a plan in place on how to move forward. It is understood that solutions are not going to be miraculously discovered in a two-day meeting. Working groups initialized at the CSS 2012 will continue throughout the year documenting progress on the PhUSE Wiki. CSS 2013 will start with a presentation of the work that had been completed and a kick off of next year’s goals.

29 November 2011

At the end of November, I had the opportunity to sit in on an Electronic Health Record (EHR) Roundtable discussion, which was organized by Tufts Center for Drug Development, CDISC and HL7 and took place at the GlaxoSmithKline complex in central Philadelphia, PA. There were exciting updates about the status of EHRs globally, with primary topics of discussion revolving around the expansion of EHR usage to assist in promoting safety and to enable research.

EHRs are gradually being adopted worldwide. Already, nations like Singapore have adopted nationwide EHR systems. One of the greatest hurdles to the adoption of EHRs for research has been regulatory ‘approval.’ Acceptance by regulatory entities of EHRs is critical for expanded adoption, but at the present moment there continue to be concerns voiced and misperceptions communicated, which encourages the continued practice of inefficient re-entry of data from paper.

The collaboration between CDISC, C-Path, government agencies, academia, patient groups and the AD clinical community in developing the CDISC AD standard is a valuable model of how a successful consortium can support faster and safer drug development. In much the same way that CDISC has collaborated with C-Path to develop Alzheimer’s data standards, CDISC and the Innovative Medicines Initiative (IMI) have recently signed a Memorandum of Understanding (MOU), agreeing to collaborate for the shared purpose of accelerating the development of new therapies for patients worldwide.

IMI, the largest public-private partnership in Europe, supports further innovation in healthcare through the formulation of partnerships between industrial and academic experts to aid in the creation of a more cooperative environment for R&D, encouraging the development of safer and more effective drugs for patients. IMI seeks to address certain inadequacies in R&D causing delay in the drug development pipeline through four research priorities: 1) predicting safety, 2) predicting efficacy, 3) knowledge management and 4) education and training. With knowledge management in particular, IMI seeks to more effectively utilize data to determine safety and success.

The Oncology Colloquia was one of six Colloquia sessions held during the CDISC International Interchange 2011 on 6 therapeutic areas: Oncology, Virology, Pain, Diabetes, TB and Imaging.  Bron Kisler, VP of Strategic Alliances at CDISC, initiated the session introducing himself, Bron’s background with CDISC is on Terminology.  He was one of the first people with CDISC to work on Therapeutic projects beginning with the TB and Acute Coronary Syndrome projects back in 2006.  “We have seen growing interest in disease specific standards from the CDISC community and FDA as well as communities new to CDISC including NIH institutes, foundations and professional societies”, Bron mentioned.  He also stated that one of the nice things about Oncology is that we don’t have to start from scratch due to the great work already done across the National Cancer Institute (NCI) community.  During the meeting, Dianne Reeves from NCI provided an in-depth orientation of this work, which was followed by a working session.

The attendees, who were also active CDISC team members, represented a good cross-section of organizations: Astrazeneca, Celgene Corporation, Critical Path Institute , eClinical Solutions, Eli Lilly, FDA, GlaxoSmithKline, Genentech, NCI, Otsuka Pharmaceutical and Pharmastat.  CDISC and C-Path are partnering on numerous disease projects with 9 therapeutic areas in the works and at various stages of development.  CDISC is so pleased to be partnering with the C-Path team out of Tucson, AZ on this new work as they bring incredible value including their project management expertise.  It was also exciting to hear that FDA was very pleased with the growing CDISC C-Path relationship.

7-8 November 2011

A fascinating panel at Partnering for Cures in New York City was that of the ending plenary session, where leaders from academia, non-profit and for-profit companies, and government came together to discuss best practices in successful collaborations. Those on the panel were:

• Gordon R. Bernard, M.D., Professor of Medicine, Associate Vice Chancellor for Research, and Senior Associate Dean for Clinical Science, Vanderbilt University
• Kathy Giusti, MBA, Founder and Chief Executive Officer, Multiple Myeloma Research Foundation
• Brian Harvey, M.D., Ph.D., Vice President, U.S. Regulatory Policy, Sanofi
• Thomas R. Insel, M.D., Director, National Institute of Mental Health (NIMH), National Institutes of Health
• Jeffrey M. Trent, Ph.D., FACMG, President and Research Director, Van Andel Research Institute; President and Research Director, The Translational Genomics Research Institute (TGen)

The plenary began with each panelist introducing their background and key components of successful collaborations that each of their organizations had been able to forge. Highlights during this discussion were of successfully merging the business and science at the beginning of the process of collaborating, thereby gaining information from a wider-varied number of backgrounds, but at the same time making certain the partnerships that are being formed are strategically created for the work that needs to be done.

If there is something that clearly caught my attention during Dr. Buckman’s keynote speech is that FDA needs to have a standards-based environment, from end-to-end, to support a fully electronic receipt, review, and dissemination environment.

Dr. Buckman started her presentation talking about the current challenges for the 21st Century Drug Development.

Patients want the most up to date information on products and quickly, and this is only one part of an extremely complicated healthcare system. “The amount of time spent in the preclinical and clinical trials as well as the amount of time it takes for one FDA drug approval, involves tremendous effort, time and money!” Dr. Buckman stated.

She portrayed the current situation by providing an example of having “one New Molecular Entity” and explained that it will entail having over 9 gb of data and over 8.8 gb of documentation. She went on to mentioned that if the FDA receives a copy of a submission, that will require ~1.7 million pages, while if they have five copies then printed at FDA, they will need 8.5 million pages! The FDA spends a lot of money on paper, and solving this issue requires having some sort of electronic submission interface which will also certainly allow for greater efficiencies. We will have efficiencies if we have new ways to get eSubmissions; we can then improve regulatory decision-making through advanced analytics.

Shannon Labout, Senior Director of Education for CDISC, opened the session and introduced the speakers:

• Rebecca Kush, CDISC President and CEO, speaking on behalf of Dr. Sukil Kim, Korea CDISC Coordinating Committee (K3C)

• Sheila Leaman, CDISC Manager of Global Relations, speaking on behalf of Simon Wang, China CDISC Coordinating Committee (C3C)

• Dr. Yoshio Tsukada and Hiroshi Azuma, Japan CDISC Coordinating Committee (J3C)

• Peter Van Reusel, speaking on behalf of Dr. Pierre-Yves Lastic, Europe CDISC Coordinating Committee (E3C)

Dr. Friedman cited the definition of a Learning Health System from the Institute of Medicine (IOM). A Learning Health System (LHS): …one in which progress in science, informatics, and care culture align to generate new knowledge as an ongoing, natural by-product of the care experience, and seamlessly refine and deliver best practices for continuous improvement in health and health care.

“In other words, it’s what your group does,” he stated. The vision would be nationwide safety surveillance with personalized medicine based upon research results upon which clinical decisions can be made--- not in the 17 years it currently takes, but in 17 months or 17 days(…or someday 17 seconds?)

The first colloquia session that I attended was on Tuesday, 11 October. It focused on the Virology domains and datasets. There was an FDA presenter, Helena Sviglin, who had drafted the initial Virology domains for comment. There were also 3 FDA reviewers attending this session, along with CDISC team members and experts from other organizations. Ms. Sviglin was happy to share the updates with us and was asking for comments from the attendees. She started off the session by telling us that they work with Dr. Chuck Cooper on validating data efforts of any of the review divisions; Dr. Cooper is an FDA reviewer, MD, in the Office of Translational Sciences, CDER, FDA.

Starting with the last presentation first: Jan Kratky talked about CDISC’s brand new SDM-XML standard, which is posted on the CDISC website under Standards and Innovations. Jan mentioned that the SDM-XML addresses data about a study in the BRIDG “Planned” mode (which, of course, is much different from study data in the “execution” or “performed” mode). The standard addresses Study Design in 4 components: Study Summary/Inclusion Exclusion Criteria, Study Structure, Study Workflow, and Study Timing. The package also includes an example stylesheet for rendering the contents of an SDM-XML file. CDISC would like people to “kick the tires” of this standard and let us know about any improvements they would like to see.

Rich Gleeson gave the second talk, which was about using BRIDG as a foundation for e-clinical software integration. Starting with BRIDG as their conceptual model, they then created a logical model and then a physical model to support all applications. Yay! Model-driven architecture in practice! Based on BRIDG!

The first speaker, Gabriel Backianathan, talked about the PRM [CDISC’s Protocol Representation Model], and hopes that the Statistical Analysis Plan (SAP) will soon be added to that model. In fact, his wish will soon come true since we (the SCC) will begin harmonizing the Statistics Domain Analysis Model with BRIDG next week!

There will be more blogs coming about the Interchange, and we will keep you informed of the harmonization of the statistical aspects into BRIDG so that we can augment the Protocol Representation Model to include the SAP.

Julie Evans Sr. Director, Technical Services, CDISC

Monday's keynote address introduced the concept of a distributed patient and research data sharing environment (similar to the internet) which could be used to significantly decrease the time it takes to get important safety, dosing or disease outbreak information back into the hands of clinicians at the point of patient care, thereby allowing clinicians to make well-informed patient care decisions.

I had mixed feelings, having been too new to serve on the committees that had been formed prior to my appointment. I felt guilty to have been in the midst of those who truly deserved the praise. On the other hand, I felt pleasure that at least a couple of us from CDISC (Bron Kisler and myself) had given prior testimony to Task Forces of the HIT Standards Committee. I also felt fear and concern, hoping that the ‘train that has left the station’ has not already gone too far ahead for us to cleanly bring in the clinical research standards work that we have been doing for the past 14 years. Most of all, I felt opportunity…. that there is now an acknowledgement of the importance of global clinical research in this critical effort to encourage the adoption of EHRs across the U.S. and beyond. Many of the members of the HIT Standards Committee are well aware of the efforts of CDISC and of our willingness to collaborate, including two key players who have served on the CDISC Board of Directors.

Here are a few notes and quotes from the meeting that preceded the reception --- the culmination of “Summer Camp”--- during which friendship bracelets and whistles were distributed!

You will see more pictures from the showcase upon reading the full article.

By most accounts, the Showcase was a success, with good traffic, enlightening demos, a central concept. At one point an attendee asked me a question which will provide the focus for this post: “what does it take to put something like this on?” To which I answered “oh, about 5 years”. No, I don’t mean that it took five years to organize this one event. But it is true that this Showcase was the culmination of five years (or more?) of effort under the heading of CDISC’s Healthcare Link initiative. During this initiative, CDISC reached across the divide between research and healthcare to engage with EHR vendors in the sister organization IHE. The Showcase demonstrated the results of this effort. Here’s what made it a success:

After the Town Hall opening remarks, attendees from the audience asked questions of the panelists. I must admit that the questions surprised me---I had not anticipated the dichotomy. They fell primarily into two categories – 1) skepticism about using EHRs for research and the related regulatory constraints and data quality concerns; 2) requests from the audience participants to more broadly communicate the positive comments from the panelists to help move the use of EHRs for research forward. Clearly, there is more here than some may think….and by that I mean several things, which I will try to delineate further in this blog. [It did not help that some asked questions without having seen the Interoperability Showcase demonstrations. After being informed that they were missing at least half of the conversation if they had not seen the demo, it was reported that several went to see it the following day!]

The Town Hall opened with each panelist providing brief remarks. I found these to be incredibly valuable, so I will do my best to recount the essence of at least some of what they said as accurately as possible (and will welcome their additional comments):

Dr. Leslie Ball, Director of the Office of Scientific Investigation (OSI), opened by asking the audience how many of them had navigated the DIA 2011 with the paper program? And, how many used the new DIA ‘Ap’ to navigate? And, how many had used both? She stated that this is an example of many of us who are caught struggling now between the two worlds – our paper past and the technology of the future. She commented that she now believes in EHRs, particularly since the site of her medical fellowship had converted to EHRs while she was there; this dramatically improved the availability of medical charts and x-ray images---suddenly they were all there, in the EHR system. No such seamless interface currently exists to get EHRs to communicate to the research world and Dr. Ball believes that we can get there. She stated that she would like to say we/FDA OSI support this effort, and she thanked CDISC folks for moving it forward. She feels it is a technical problem to be solved and closed by saying that it is only through the collective efforts of all in the room that we will solve it. Dr. Ball responded to questions from the audience about concerns on data quality in an EHR by asking back: “How do you assure the quality of the data in a paper medical record today?” She also commented that it would have been essentially impossible to falsify patient data in her experience with EHRs.

The Joint Initiative Council (JIC) and ISO TC-215 for Health Informatics met the week of 22 May in Kuopio, Finland. JIC is a collaborative initiative between 6 SDO organizations (CEN, CDISC, GS-1, HL7, IHTSDO and ISO), and is focused on Health Informatics Standardization. These organizations and their communities are bound together by a common purpose...Standardization across the healthcare spectrum that leads to interoperability between independent systems, enabling compatibility and consistency for health information and data while reducing redundancies and duplication of effort. Leading up to the meeting in Finland, there were 6 JIC projects approved for joint work and balloting:

Progress continues within CDISC on the development of standards to support research in a number of therapeutic areas:   Pain/Analgesics (with the University of Rochester), Polycystic Kidney Disease (with Tufts University), Alzheimer’s Disease (with the Critical Path Institute), Oncology (with FDA and NCI), Cardiovascular Diseases (with ACC and Duke), Parkinson’s Disease (with C-Path and NINDS) and Tuberculosis (with the Gates Foundation and TB Alliance).   CDISC also responded to an FDA RFP for funds to continue Therapeutic Area Standards development. [Watch for the first TA “Package” on Alzheimer’s Disease coming soon.]   A presentation was made on the C-Path and Gates Foundation collaborations with CDISC (including progress on PKD, TB and Alzheimer’s standards and therapy development) at the Annual ACRP meeting in Seattle on 30 April.

Ann Martin of the Innovative Medicines Initiative (IMI) presented “The Role of Standards in Knowledge Management”, beginning with an overview of what IMI is and how they are involved:

• to promote knowledge creation, together with its disclosure and exploitation;

• to achieve fair allocation of rights;

• to reward innovation;

• to provide flexibility for participants to establish the most appropriate agreements serving the project objectives.

Shannon Labout and Rhonda Facile finished the presentations for the session with an update on CDASH. The new version is posted and new CDISC Education courses available.

To bring a great ending to the CDISC European Interchange, Dr. Pierre-Yves Lastic presented awards for the best poster and for a random drawing among CDISC Value surveys that were handed in by attendees.

Dr. Pierre-Yves Lastic, Chair of the European CDISC Coordinating Committee (E3C), opened the Interchange with a presentation on 10 years of CDISC in Europe. It was great to see the progress CDISC has made in Europe during this past decade. Many thanks for the hard work of the E3C and CDISC Operations.

Stay tuned to the next European Interchange blogs! These will be posted over the next two weeks. And get ready for the upcoming CDISC North America Interchange in Baltimore, MD on October 10 - 14.

Please consider a sponsorship or a booth and send in your abstracts; the deadline for submission is Friday, 6 May, 2011.

Both of these quotes, which I used to open my presentation at this year’s North American Interchange, were from John Perry Barlow--- the first as the lyricist for The Grateful Dead in the ‘70s and the second for Wired Magazine in 1994.

Over the next 3 days, you can read about CDISC's presence on the global stage, as Dr. Kush reports from Korea, China and Japan.

There are some very clear messages coming from FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER).  As of a meeting with CDER and CBER Representatives and the CDISC Executive Committee on 1 February ....

Those of us who started working toward a structured protocol representation in 2003 were motivated by the feeling that there had to be a better way to communicate information about a study than a text document.  The protocol is at the heart of clinical research, so it's just not effective or efficient for all the parties involved to extract data from text ...

Rather than write about it ... take a look at the wonderful photos taken by Pierre-Yves Lastic.

The International Standards Organization (ISO) recently held one of its twice-yearly meetings in Durham, North Carolina. Past meetings CDISC attended were in Istanbul, Turkey; Goteborg, Sweden; Edinburgh, Scotland. Here you can see one of the banners at the Durham meetings, thanks to Bron Kisler for the photo...

The other day, I looked at one of my computer screens. My twitter feed started reporting...