Recently, many pharmaceutical companies have implemented or evaluated metadata repositories (MDR). This article explores the drivers for an MDR, and the role it plays in clinical trials.
The clinical development lifecycle typically starts with the definition of data to be collected and analyzed for a trial in a protocol document. Data is captured in a number of systems throughout the trial during study conduct. If all goes well, the data is eventually analyzed and reported in a submission.
While the study startup and conduct stages are generally associated with one clinical trial, oftentimes analysis, reporting, and submission include aggregated data across multiple trials. Although the overall lifecycle of clinical trial is relatively standard, the processes and technologies can vary significantly across different lifecycle stages, as well as organizations. Further, data sources have grown exponentially over recent years, adding significant complexity to the lifecycle and increasing risks to the timeline and budget.
Tip 1: Simplify Complexities with Data Standards
To help with these increased complexities, standardization of data has become a priority. There are a number of data standards associated with each stage of the clinical development lifecycle that are developed and maintained by the Clinical Data Interchange Standards Consortium (CDISC). CDISC’s foundational standards are generally data models that are available in various formats supporting both human and computer consumption. However, CDISC also provides data exchange standards to facilitate system interoperability for both standardized and non-standardized data.
CDISC maintains foundational standards at a global level, which apply to all clinical trials, but also has many standards covering specific therapeutic areas (TA). These standards are extensions to the foundational standards that apply to specific disease areas. Additionally, CDISC maintains controlled terminologies that are associated with the varying data items across the CDISC standards. The terminologies and TA standards are also available in both human and computable formats.
Tip 2: Develop Internal Standards in Addition to those from CDSIC
In addition to CDISC standards, many sponsors and contract research organizations (CROs) also develop and maintain internal standards. Not only do they define internal global and TA level standards like CDISC, but many also continue down the hierarchy to a third level of compound or product.
At all levels, internal organizational standards are generally extensions to CDISC standards with additional data modeling and rules, as well as controlled terminologies. For example, a CDISC standard may indicate a variable as optional in a particular data domain, but in a specific internal TA standard the variable may be required. Additionally, many organizational standards include operational metadata to facilitate governance and automation, such as the control type for how data is collected in a data capture system (e.g., radio button versus checkbox).
Tip 3: Manage Data Standards Complexity with an MDR
Data standards development can be very complex to manage, which often drives the need for an MDR solution. While many clinical technologies have standards capabilities (e.g., Central Designer libraries for InForm trial designs), they do not generally support this level of hierarchy or cross-lifecycle traceability, from definition of the data in a protocol through tabulation and analysis datasets in a submission.
Since submission of data in standard formats is now mandated by some regulatory agencies, this has become the leading driver for pharma companies to implement an MDR. However, in addition to meeting regulatory requirements, many have a vision of automating business processes end-to-end and improving data quality with an MDR, as well. This often results in additionally managing study level metadata within the MDR. While this could result in a great return on investment, few companies, if any, have seen it completely through due to a number of challenges. These key requirements and challenges for MDR implementation will be addressed in future articles.
To end on a humorous note, in French “mdr” is a slang acronym for “mort de rire”, which means dying of laughter. It is the equivalent of using “lol” in English.
I first learned this when I led the MDR implementation at a sponsor organization that was acquired by a French company, and we were instructed to no longer use the acronym MDR. This meant finding a new name to use and updating several years of branding documents. We were not laughing!