The following article was contributed by Jeff Abolafia, one of our resident CDISC experts. Jeff has more than 20 years of experience in clinical research and has successfully led multiple CTD/NDA submissions. He is the co-founder of the Research Triangle Park CDISC Users Group and a member of the CDISC ADaM and ADaM Metadata teams.

In recent years the FDA has clearly stated its preference for receiving both clinical and analysis data formatted in compliance with CDISC standards. This has been communicated through a series of guidance documents, correspondence with sponsors, and presentations at conferences. As a result, CDISC models have become the de facto standard for submitting data to the FDA.

Given the FDA’s preference for receiving CDISC data, many sponsors have begun to produce CDISC-compliant databases in order to meet FDA submission requirements. In the short term this has led to additional work and higher costs. However, when the standards are implemented properly, organizations have a tremendous opportunity for significant cost savings throughout product development.

As a CRO, Rho has had the opportunity to work with many sponsors on CDISC related projects. Most of these sponsors have noted that producing CDISC compliant deliverables have increased their costs. This has surprised many sponsors. Wasn’t producing standardized CDISC datasets supposed to reduce time and costs?

When it comes to implementing CDISC standards, perhaps sponsors are trying to solve the wrong problem. The problem that most sponsors are addressing is: how can we get the FDA what they want. Instead, we should be asking: how can implementing CDISC standards be part of a cost effective product development strategy. The problem each organization chooses to tackle will determine its implementation strategy.

When the primary goal is meeting FDA requests, the focus tends to be on producing SDTM and ADaM databases and associated documentation. At this point in time, these are the CDISC related deliverables that the FDA has requested. Under this scenario most organizations choose one of the two following implementation strategies: 1) Legacy conversions – datasets are created in a proprietary format while studies are conducted. Data is converted to CDISC format before or while the submission database is being assembled; or 2) During the course of a study convert operational data to SDTM format. Using the SDTM database as input, create an analysis data database that is ADaM compliant. Both of these approaches will get the FDA what they want. However, they also lead to lots of additional work and increased costs.

So, how can we get the FDA what they want and also save time and money? A business case study on CDISC standards by Gartner found that implementing standards from the beginning can save up to 60% of non-subject participation time and cost and that about half of the value was gained in the startup stages. The study also reported that the average study startup time can be reduced from around five months to three months. The use of CDISC standards can be extended upstream to both the protocol and to data collection.

The CDISC CDASH standard extends standards to clinical data management, with the goal of standardizing data collection. CDASH provides standard data streams and variables that are found in most clinical studies. CDASH was also designed to facilitate converting the operational database to SDTM.

CDASH provides a sponsor with a global library of data elements that are also the industry standard. The CDASH global library can be augmented by therapeutic specific libraries. CDASH Libraries can include entire forms for a given data stream, variables or data fields, controlled terminology for each variable, and pre-defined edit checks for each variable. These libraries can be utilized by the sponsor for all studies within and across product development projects.
Extending standards to data collection provides many benefits. Using a global library of standardized data elements allows for cheaper and faster Clinical Data Management System (CDMS) setup. Business case studies by Gartner and Tufts have found that CDMS setup time can be reduced by as much as 50%. Using CDASH facilitates also converting operational data to SDTM. Standardized operational data combined with standardized programs, specifications, and tools can streamline producing SDTM datasets. Producing the operational and SDTM databases can be packaged so that creating SDTM compliant clinical databases is cost effective for Phase One and Phase Two studies. This is a significant benefit for sponsors whose business goal is taking their product to market or partnering and for sponsors without a lot of resources in the earlier product development stages. Also, moving standards implementation upstream also increases communication among business units. Standards implementation is extended beyond programming and biostatistics to data management and clinical operations.

Cost effective standards implementation requires a change in philosophy. It entails re-defining what we are trying to accomplish by using CDISC standards. By integrating standards into the entire life cycle of product development and collecting standardized data instead of standardizing collected data, we can both get the FDA what they want and save time and money while doing so.

References

Rozwell et al., 2009, online at http://www.cdisc.org/business-case. A business case for standards by CDISC and Gartner.