Data heterogeneity is a regulatory reviewer’s nightmare. Some sponsors talk about patient “gender” whereas others list the patient’s “sex.”What about date formats? Do you use the American-style month-day-year format or the European-style day-month-year? Inconsistent data presentation makes both collaborating on drug development projects and reviewing regulatory submissions more difficult.
To address this challenge, the FDA has implemented electronic submission guidelines, for NDAs, ANDAs and certain BLAs, using standards developed by the Clinical Data Interchange Standards Consortium (CDISC)1. Later this year this requirement goes into effect for INDs. These standards support acquiring, exchanging, submitting, and archiving study data, such as Study Data Tabulation Model (SDTM) for clinical data and Standard Exchange for Nonclinical Data (SEND). SEND is an implementation of SDTM for nonclinical studies and applies to general toxicology (single- and repeat-dose), and carcinogenic studies. In this blog post, I’ll discuss how using SDTM and SEND CDISC standards provides structure for clinical and nonclinical data review between sponsors and CROs, and to facilitate regulatory submissions. I’ll also review our technology solution for preparation, analysis and regulatory submittal of CDISC pharmacokinetic (PK) study data.
How is CDISC PK data organized?
CDISC 標準準拠の PK データには、DM（Demographic）、EX（Exposure Information）、PC（PK Concentration data）、および PP（PK Parameter）ドメインが含まれます。それらのドメインデータは臨床試験データの構造を定義する SDTM に含まれ、続いてODM（Operational Data Model）を介して送信されます。このアプローチにより、審査および申請のサイクル全体を通じた申請データの一貫性が実現されます。
Why are CDISC SDTM and SEND formats for PK data important?
Standardizing data sets can reduce the risk of data loss due to personnel changes and facilitate collaboration between sponsors and CROs. Since non-clinical and clinical trials generate enormous amounts of data, the CDISC SDTM and SEND electronic formats for PK data streamline the submission and review of data.
So, why should you use SDTM and SEND electronic formats for PK study data?
Managing non-clinical and clinical trial PK data is a daunting and cumbersome task. Organizing PK study data into CDISC SDTM and SEND formats helps:
- Minimize delays in interpretation and sharing of massive data sets
- Standardize terminology for regulatory reviews
- Provide a more robust data submission protocol
- Facilitate collaboration between sponsors and CROs through better data transfer between databases
What happens if you don’t follow the CDISC study data electronic submission guidelines?
CDISC 標準に準拠しない申請の場合、承認申請における審査のプロセスに遅れが生じる可能性があります。Furthermore, retroactively standardizing data is a complex and error-prone process. The FDA recommends implementing CDISC standards as early as possible in the product development so that data standards are accounted for in the design, conduct, and analysis of studies.
What are the benefits of engaging a CDISC Registered Solutions Provider?
Organizations that demonstrate expertise and provide services or products for specific CDISC standards can become a CDISC Registered Solutions Provider. CDISC guidelines outline the requirements to become a registered provider. Along with adhering to the CDISC Code of Ethics, the provider must also “play an active role in CDISC, have a positive reputation in some aspect of clinical research, and demonstrate expertise in one or more CDISC models.”Working with a CDISC Registered Solutions Provider offers organizations expertise and resources for a service or product which may not be available in-house. Additionally, working with CDISC standards experts can streamline the process for regulatory submissions.
Certara’s CDISC solution for preparation, analysis, and submittal of CDISC PK data
In addition to complying with CDISC data standards, companies need to ensure that their processes and documentation continue to meet Good Laboratory Practice (GLP). As a CDISC Registered Solutions Provider, our up-to-date solutions help our clients streamline drug development and meeting compliance requirements.
Certara’s end-to-end solution streamlines preparing PK data for CDISC-ready submission, provides NCA-ready analysis of CDISC-formatted data in Phoenix, and eliminates the error-prone and time-consuming task of converting data to a CDISC format manually.
CDISC に準拠した PK データの作成・解析・申請に対応した Certara のソリューション
Phoenix CDISC Workflow Templates help PK scientists automate the preparation of NCA SDTM clinical and SEND non-clinical data sets into CDISC-ready formats. The Phoenix CDISC Workflow Templates transform, analyze, and prepare data to streamline routine analysis, maximize quality control, and package data for submission for clinical PK, sparse and serial TK data sets. The CDISC Export plugin enables the export of CDISC-formatted data from Phoenix to SDTM/SEND submission systems. The plugin also locks the data set so that it cannot be altered but allows the user to add free form comments.
Phoenix CDISC Navigator is an integrated solution that creates NCA analysis-ready datasets from CDISC-formatted files received from external systems, vendors, or collaborators. It can import CDISC-formatted data, prepare it for analysis, and then export results in CDISC-formatted datasets (PP and RelRec). This method is generally used when biostatistics groups are responsible for preparing and formatting the CDISC domains.
Certara Strategic Consulting’s bespoke pharmacometric deliverables are embedded in the development workflow to optimize the impact of the work. These services support your strategic drug development decisions and new drug approvals through quantitative analysis and predictive models of diseases, drugs and clinical trials.
Ready to Streamline CDISC Data Preparation for Regulatory Submission?
Understanding CDISC data standards is critical to satisfying electronic regulatory data submission requirements. Moreover, standardizing data facilitates collaboration between sponsors and CROs on projects and accelerates the review and approval process by regulatory agencies. 当社のツールおよびサービスは、CDISC 準拠の申請データ作成の定型的な作業を効率化し、CDISC の形式で作成されたデータに対するノンコンパートメント解析（NCA）の支援機能を提供し、ヒューマンエラーが発生しやすく多大な時間を要する CDISC データへの変換作業を自動化します。D360を導入することで、Sponsors and CROs obtain more effective knowledge transfer between databases and robust regulatory electronic submission protocols.
Learn more about Certara support for CDISC data standards
My colleague, Chris Lovejoy, produced a webinar where he reviewed the steps needed to prepare, transform, and format non-clinical PK data into CDISC-ready SEND format. Chris also demonstrated how the Phoenix SEND Workflow Template is used to automate CDISC SEND data preparation. I hope this blog post has helped you understand the CDISC SDTM and SEND electronic regulatory submission requirements and how implementing these standards benefits your organization. Let me know what you think in the comments section!
 Providing Regulatory Submissions in Electronic Format – Standardized Study Data. Guidance for the Industry [米国FDAガイダンス]. US Department of Health and Human Services Food and Drug Administration. December 2014.