The 2019 Clinical Data Interchange Standards Consortium (CDISC) Interchange took place on October 14 – 18th in sunny San Diego at the Marriott Waterfront – quite an inspiring place to discuss standards and innovation. The President and CEO of CDISC, David R. Bobbitt, reminded us that CDISC continues a journey of change that will require clinical data standards to evolve. This change is being shaped by new sources of data and technology. “A future where data standardization facilitates good science to help reduce human suffering,” said Mr. Bobbitt.
The conference kicked off with a keynote from Paul Slater, co-founder of the Clinical Research Innovation Hub (CRIH) at Microsoft. While happy to know that folks are cutting and pasting in MS Word to create protocols, he emphasized the need for an electronic protocol (eProtocol) that would allow for emerging technologies to consume protocol metadata. In addition, industry should be employing natural language processing to surface research data from existing journals. There is the need for big ideas to shift technology companies, as risk aversion limits innovation and baby steps will not work. It was inspiring to hear his call out suggesting research should be using all available data and all patients that would benefit from research projects should be included. In the future, we may not be talking about electronic data capture (EDC) and clinical trial management systems (CTMS), with research data coming from electronic health records (EHRs) and electronic clinical outcome assessments (eCOA). Lastly, the use of data lakes and graph database are needed to better connect new data sources.
The CDISC organization continued to emphasize the two overarching projects, the CDISC Library and CDISC 360. Both projects are linking the various clinical data standards in a more useable fashion. Gone is the need to use PDF and Excel documents to implement clinical data standards. From an application programming interface (API) and available now, CDISC member organizations have a link to the standards metadata repository for a “single truth” through the CDISC Library.
The ambitious project, CDISC 360, is metadata enabling end-to-end automation which is adding a conceptual layer to CDISC standards through biomedical concepts. Biomedical concepts are being developed that are machine readable and machine executable algorithms. CDISC 360, when available, will produce the forms and associated metadata that can be consumed via ODM.xml by EDC or eCOA systems. The project began April 8th, 2019 with a projected duration of 18 months. The overall CDISC membership seems excited about the project, however there was some skepticism that the first subset of standards was from the CDISC Type 1 Diabetes therapeutic area user guide (TAUG). This was selected because it provides a ready set of end-to-end standards, but some in the community of standards professionals I spoke with wished a different therapeutic area was selected that better reflects current research and development activities.
What’s Important and What’s not
Regulatory agencies continue to expand their requirements for CDISC data submission with China’s NMPA issuing eCTD guidance that they would allow for CDISC data, SDTM and ADaM. Japanese and US regulators continue to not only emphasize the need to submit data in SDTM and ADaM, but the need to submit good documentation including well written reviewers’ guides and well commented, easy to understand analysis programs that follow good programming practices. FDA seemed to caution sponsors that they would likely get information requests if analysis programs are not submitted.
PMDA is updating the version of Pinnacle 21 Enterprise they use to review standardized data and have published a schedule as it relates to submissions as announced on September 27th. The new rules take affect on April 1, 2020. SDTM v1.7 and SDTMIG v3.3 are currently under review at the PMDA. The newest version of the ADaMIG v1.2 will be considered after the review of ADaMIG v1.1 with ADaM conformance rules v2.0 has been completed. Impact of define.xml v2.1 is also under review. PMDA made a point that when sponsor work with the agency, advance review of electronic data has been successful.
FDA speaker, Dr. Kenneth Quinto, supports the agency’s evaluation of real world evidence (RWE) projects as mandated by 21st century cures act. He discussed the varied sources of real world data (RWD) and gaps in data collection activities. When sponsors are considering RWE for a submission, they should discuss with FDA the RWD fitness for use, RWE study design, and other regulatory considerations. Combined with RWD, sponsors should explore use of digital health technologies, ePROs, and wearables to fill gaps in the data.
At the start of the conference, there was a slide on the great work CDISC and its volunteers have completed regarding updates to foundational standards. The standards like SDTM v1.7 & v1.8, SDTMIG v3.3, define.xml v2.1, and ADaMIG v1.2 are now available. It was not clear from the conference when these standards would actually be allowed to be submitted to regulatory bodies. As stated earlier, PMDA was currently evaluating. It seemed to me that it is fair to continue to assume there will be a longer stabilization for industry on SDTM v1.4, SDTMIG v3.2, define.xml v2.0, and ADaMIG v1.1.
For clinical data collection standards including COA and patient-reported outcomes (PROs), we can look forward to CDASHIG v2.1, CDASH model v1.1, and more QRS supplements. CDISC has committed to some other data collection projects like a consideration document on how to handle questionnaires, ratings and scales (QRS) logically skipped fields and data quality review. In addition, a build out of a CDASH CRF library based on ODM is coming with an initial release of Q3 2020. The controlled terminology team has also released helpful codetable mapping files that help with codelists that may have relationships to other terms within other codelists. Check these out at www.cdisc.org under controlled terminology.
All in all, there was completion this year of several updates to many of the foundational clinical data standards we use every day. CDISC standards are here to stay and provide regulatory bodies the submission data in a form that improves and accelerates their review. CDISC sees the need for end to start computer readable process metadata that influences the data collection modules and metadata. Using a common protocol template and collection standards are the next steps to achieving the vision.