On 2016年12月18日, numerous regulatory agencies will require electronic submission of non-clinical data using CDISC’s standard format. What exactly are CDISC data standards and how will they impact drug developers? In this blog post, I will provide an overview of the CDISC SEND data standard, review some of the requirements for implementing SEND, and discuss a solution that supports SEND compliance.
What is SEND?
SEND (Standard Exchange of Non-Clinical Data) is one of the data models developed by the Clinical Data Interchange Standards Consortium (CDISC). The model supports the submission of non-clinical data to Regulatory Agencies such as the FDA and Japanese PMDA. SEND is an implementation of the CDISC Standard Data Tabulation Model (SDTM) for non-clinical studies.
Why use SEND?
Using SEND standardizes electronic data transfer thereby making it easier to transfer data between organizations. Importantly, it will improve communication between regulatory authorities and sponsors. This will also increase the efficiency and quality of scientific review by the pharmacologists and toxicologists at the FDA’s Center for Drug Evaluation (CDER).
Standardized data formats gives organizations the opportunity to:
- Warehouse the data
- Control and version it
- Use informatics tools for data mining
The ultimate goal is to phase out paper based submissions. Thus, new drug application (NDA) studies with a protocol signature date on or after 2016年12月18日 must be submitted with electronic data. The IND submission deadline is for one year later.
SEND and SDTM domains
Submission data can subdivided into 28 data sets. Each data set is termed a “domain” and groups similar types of information. Domains are defined and structured so that supersets of data can be created using pre-defined keys within individual domains. A submission will contain many domain datasets that will represent the tabulated data for a study. We will discuss generating three possible domains as part of the submission pack:
- PC domain – Pharmacokinetic (PK) Concentration
- PP domain – Pharmacokinetic Parameters
- POOLDEF domain – used for Sparse study data sets (optional)
The challenges posed by complying with the FDA mandate to use SEND
SEND is a new and evolving standard. Managing data from multiple sources to generate a standard output poses multiple challenges. Generating data that support SEND domains can be a time-consuming process requiring the manual population of data. It requires converting data from a form that is readable to humans to a machine-readable format. Thus, SEND data set generation is an informatics problem, not a scientific problem. Often, PK scientists and IT managers would rather rely on experts who understand the standard to help them create the required submission files.
Submission of SEND DATA is ultimately the sponsor’s responsibility – not that of a CRO or other external body. Thus, sponsors should have the ability to receive, review, submit and archive the SEND Data. If the submission is not fully compliant, then the FDA can “Refusal to File” (RTF) the application. While an RTF is unlikely to occur for early submissions, this seems like an imprudent risk to incur.
Compliance with CDISC SEND
Numerous manipulations must occur for a dataset to be CDISC SEND compliant. The SEND implementation guide lists controlled terminology codes which must be used for PK parameter and specimen labels. The column (field) heads are also controlled. In addition, field sizes are restricted. Dates must comply with the ISO 8601 format. Finally, additional data may be required such as the Pool ID for animals in a sparse analysis.
Why the SEND Workflow Template solution?
For Phoenix WinNonlin users who have to submit non-clinical data to the FDA, the CDISC SEND workflow template is an automated and seamless solution within Phoenix WinNonlin that generates the required outputs in the SEND format, saving time, reducing errors, and increasing compliance. By standardizing your input and output, you can systematize quality control and minimize the time spent on QC-review. This template is also reusable across different studies.
In addition to the SEND workflow template, we also offer templates for discovery PK, toxicokinetics, and clinical PK.
To learn more about how Phoenix workflow templates and plugin services can streamline your CDISC electronic data submissions, please read our white paper on the subject. Are you struggling to get your data into CDISC formats? Let me know in the comments section!