High Standards

Clinical trials play a vital part in the development of life-saving medicines, and healthcare reform has placed their conduct under even more scrutiny. In times like these, the establishment of an international set of standards for data exchange has become an important goal, as CDISC’s Dave Iberson-Hurst and Tim Jaeger tell EHM.

The Clinical Data Interchange Standards Consortium (CDISC) is a global, open, multidisciplinary, nonprofit organization whose aim is to establish standards to support the acquisition, exchange, submission and archiving of clinical research data and metadata. Originally formed in 1997, CDISC was incorporated as a nonprofit in the US in 2001, and has now grown in to a global organization with over 240 members around the world.

David Iberson-Hurst, CDISC’s VP of Technical Strategy, explains that as an officially accredited standards development organization (SDO), CDISC enjoys a formal liaison status with the International Standards Organization (ISO), which enables it to establish standards within the clinical trials arena.

And as Tim M. Jaeger, Chairman of the European CDISC Coordinating Committee, and Head of Divisional Medical and Scientific Affairs at F. Hoffmann-La Roche Ltd., points out, the fact that  CDISC is vendor neutral  and technology neutral, and works on a consensus-based approach, helps  it to develop standards that are usable by and attractive for the majority of stakeholders in the organization.

“These stakeholders encompass not just the pharma industry, but also clinical research organizations, the device and diagnostics industry, electronic health record vendors and the big academic institutions. Then there are regulatory bodies like EMEA and the FDA. We cover the full range and breadth of organizations working in the standards arena, and we try to ensure through our processes and through our organization that all these partners are heard, and that standards that are robust and relevant to all of these groups are developed and adopted.”

By joining CDISC, companies have the opportunity to drive the direction of the development of standards, as well as seeing a financial benefit in terms of discounts on training. More importantly, Jaeger fully expects that one day bodies like the FDA will expect companies to submit and capture all their data in CDISC standards. “It’s critical and relevant for all of our partner organizations to have their say, and to be able to help shape standards, and it’s a true advantage if you’re sitting at the table when new standards are developed or existing standards are advanced, to be aware of the ongoing discussions with EMEA and the FDA and other important institutions. Things that are being considered and talked about at these levels today will come out as draft guidance in two to three years.

“In today’s world, no matter what area you’re working in, be it pharmaceuticals, medical devices or diagnostics,  designing a trial or protocol and gathering and working with the data, then submitting and archiving it, is a long process. During this process you will have to liaise with literally dozens of other groups, organizations and contractors. Only if you’re able to seamlessly exchange your data across time and across this multitude of partners can you ensure that in the end you have good robust data, something that EMEA or the FDA will accept.”

Mission control
CDISC’s official mission is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare.

“We need the platform, independent, vendor neutral, global data standards that help us to streamline data flow from a protocol design to submission and archival of the data,” says Jaeger. “We need this level of interoperability and compatibility not only within the clinical research environment, but also on the edges where clinical research borders with healthcare. There are synergies with the healthcare arena, where many patients are treated within clinical trials, following certain trial protocols.

“There is always the challenge when you’re identifying potential candidates for trials of whether you need to re-collect and re-document all the data points that already exist within the electronic health records, or are there ways to bridge the worlds of clinical research and healthcare? At CDISC, we believe it’s of vital importance to build that bridge.”

Iberson-Hurst adds that the growing public pressure for drugs to be developed with fewer side effects and adverse events has in turn put increased pressure on regulatory bodies to provide better safety monitoring. “They need data to perform that oversight function, and given the multitude of companies that produce drugs, they need to do it in a standardized way. They can’t monitor 4000 drug companies without standards, so that oversight function is driving standards.”

Global reach
CDISC is working to develop global standards that will work equally in countries around the world, though as Iberson-Hurst explains, different areas have different requirements. “For every drug submission, companies in the US must submit all of the data, whereas in Europe they need only submit the reports produced from the data. There is an increased need in the US for an additional data standard, but even if you’re not sending in that final block of data, your processing around how you get to that point should be the same. It’s much easier for companies operating internationally to have a common process that fulfills the needs of all regulatory authorities.

“We are developing a continuum of standards, which are designed to support the process as a whole. These include a protocol standard, which is there to support the writing of clinical trial protocols and have them in a format such that they can be consumed not only by humans in document form but also by a machine. We will have the high level model of that available toward the end of this year, with an XML implementation probably early next year.

“There is also the Clinical Data Aquisition Standards Harmonisation (CDASH) standard. This is a standard that lays out the minimum set of content that pharmaceutical companies and biotechs  should be collecting when they collect data. This makes it easier to combine data when we bring trials together within a pharmaceutical company or within a regulatory authority, and also to start reusing data collection forms. This will make setting up trials quicker, has had a lot of support from the FDA, and is also applicable across the globe.”

Another standard CDISC is working on is the study data tabulation model (SDTM). These are the data tabulations that pharmaceutical companies submit primarily to the FDA, but which are also embedded in the way a pharma company works. These tabulations are the cleaned raw data that are collected from trials, organized in a standardized way so that the regulatory authorities can understand what has been collected. The analysis data model (ADaM) is the standard for presenting analyzes based on the raw data found in SDTM: how you took the raw, cleaned data and through your analysis show the efficacy and safety of the product that you’re submitting for approval.

There is also an operational data model (ODM) used as the basis to pass standards from machine to machine, and a laboratory model (LAB) dedicated to the passing of laboratory data from the central laboratories through to pharmaceutical companies.

Keeping in touch
One of CDISC’s mandates is to act as a kind of intermediary between companies and regulatory bodies like the FDA and EMEA. “We have a very good working relationship with both EMEA and the FDA,” says Iberson-Hurst. “We work to find the best solutions that meet the needs of both groups: the pharmaceutical companies, biotechs and academic institutions, and the regulatory bodies.

“We work with them through Health Level 7 (HL7) and ISO to move standards forward internationally. We do tend to be more heavily involved with the FDA because of its requirement to submit the underlying data. However, we are also working with regulatory bodies across the globe on projects such as the standardizing the data required for clinical trial registries.”

Working in different geographic areas and within a variety of regulatory authorities can present challenges, as Jaeger explains, “CDISC was originally very much a US-centric organization, because a lot of the critical pharmaceutical activity was taking place in the US, and the FDA tends to have the ‘highest’ authority, in that it influences much of the work in Europe. However, we increasingly see that trial activities are shifting. If you look back 10 or 15 years, a lot of trial activity went from the US to Western Europe, then Eastern Europe, and now it’s going into the India, China, and other places.

“There are good reasons for that: the availability of patients, the possibility of running large trials, and of course the fact that these are emerging markets and companies want to have a presence there. CDISC supplies global standards for global organizations, to allow them to work seamlessly across these borders.

“One important area of this is electronic data capture, which allows you to work fairly independently, because all you need is a laptop with an internet connection and you can start accessing data regardless of where you are. This is something that we want to promote and enable with the establishment of global standards that help companies use a lean front end and that allow them to collect data in a robust and compliant fashion all the way through the process. We want to eliminate the situation toward the end of the process where historically people would pull up in trucks in front of the FDA and deliver via forklift literally tons of paper.”

“The FDA always wants to be able to check source data, and if you do this via 10, 15, 20 different applications, via a number of organizations, institutions, contractors or parties, and if you do this across 10 years, how can you provide access to all that original data without having to provide mountains of paper? Doing this electronically and providing standards that allow you to reach into the data is obviously very valuable and helpful.

One of the big challenges is getting the paper out of the process,” says Iberson-Hurst. “The other challenge is that when you have a clinical program over 10 years, technology moves on and process improves, so some of the data you’re working on toward the end is quite old.”

Implementation
What, then, can companies do to implement CDISC standards? According to Jaeger, there are a number of possibilities. “CDISC offers a wide range of informational and educational activities from very broad introductory courses to extremely specialized and detailed tutorials that potentially take you into the most finely granular level of any specific standards. CDISC has very appropriate, attractive and up-to-date educational events and courses for both novices and experts, that people can use to build their understanding of this area.

“There’s also the opportunity to attend the meetings that CDISC organizes, including the international interchange – a two-day meeting plus three days of courses, tutorials, and other educational events held every autumn in the US – and the similar European CDISC interchange in April. We’ve also recently started interchanges in China and other countries.”

Jaeger explains that companies with a presence in Europe can also get involved with user groups organized by language, along with a large number of groups that are independent of CDISC but whose members are heavily involved with establishing standards in their organizations and using them as part of their daily work.

The main way, of course, to benefit from CDISC’s activities is to become a member. Members have privileged access to all materials and events at attractive rates, and CDISC will even design programs especially for you, come to your company and educate your people and set up specific courses to meet your needs.

Looking ahead
CDISC’s future plan is to move toward ensuring the continuum of standards is well implemented, works together and is easily adopted by pharmaceutical companies and everyone else within the industry. This will make it easier for companies to work with their partners to, for example, exchange protocols and the collected data, because the data will be exchanged in a form that everyone can use and understand.

“It’s all about making the move into the data much more smooth within companies and across company boundaries,” Iberson-Hurst explains. “This is one of the reasons we work with bodies like the National Cancer Institute, because they have a lot of academic institutions who all want to share and pool data so they can see things that maybe they’re not seeing in their own data.

“Our aim is to ensure that they can use the data quickly without having to worry about how do I get the data and how do I merge it with my data and how do I combine it, and can I even combine it? Our task over the next 10 years or so is to look at how people can get the data they need to make better safety decisions. The right data needs to be visible to the right people and supported by the standards we’re developing.”

Jaeger names three key themes for CDISC: simplification, globalization, and a broader approach. “First, we need to simplify a very complex process, with all the different parties involved, all the different data types over a long period of time with different applications. We aim to simplify that through the use of commonly accepted and globally adopted standards.

“We’re also working on simplifying our own standards. We started with a range of standards that became a continuum, and those now are being integrated into something that is increasingly simple.

“The second theme is globalization. CDISC was originally US-centric, but we have made strong, bold moves over the past few years to venture out into other parts of the world, beginning with Europe, where there’s a lot of activity and a strong foundation for CDISC. Some of our European activities are now at the same level as the US ones, and we’re moving into India, China and other areas.

“The third theme is to carefully broaden some of the activities CDISC carries out. We’re working to better define the convergence between healthcare and clinical research and to provide to this area the standards, the insights, the expertise and the experience that CDISC undoubtedly has. We also want to move from the traditional pharmaceutical research model into models for the diagnostics of the medical device world, and other areas where there is a different type of research going on compared to the traditional big pharma model of running big trials in multi-national environments. These are the three big themes that CDISC is driven by over the next few years.”

Dave Iberson-Hurst is founder of Assero Limited, with 25 years experience of computer system development within a number of industry sectors. Iberson-Hurst is active within CDISC and was appointed as VP for Technical Strategy in September 2007 to oversee all technical work within CDISC. He is Vice Chair of the European CDISC Coordinating Committee (E3C), co-leads the CDISC Technical Advisory Committee (TAC) and is co-lead of the CDISC electronic Source Data Interchange (eSDI) group that is working with the Food and Drug Administration (FDA), examining the difficult topic of electronic source documents and data.

Tim Jaeger is Chairman of CDISC’s European Coordination Committee, a member of the CDISC Board of Directors and a member of its global strategy committee. He joined the Diagnostics Division of F.Hoffmann-La Roche Ltd in November 2005, and is currently he is Head of Divisional Medical and Scientific Affairs and develops and coordinates Divisional medical strategies. Jaeger establishes and maintains relationships with key thought leaders, investigators and institutions strategic to Roche Diagnostics. He also is the business owner for the global Diagnostics Clinical Information Management System, where currently more than 500 trials are registered and conducted electronically.