The PDS team frequently presents scientific posters at industry events worldwide. Visit this page often for the latest insight into key industry topics.
FDA SEND – Process streamlining and implementation
SEND (Standard for the Exchange of Nonclinical Data) was implemented by the US FDA in December, 2016, actuating a monumental shift toward electronic submission and evaluation. Although these changes are only applicable to submissions made in the US, non-US pharmaceutical companies, CRO’s and the like are joining the rush to become SEND-compatible. Since becoming the first Japanese CRO to make a successful FDA SEND trial submission in 2015, Ina Research (INA) has been pro-active in educating the Japanese community regarding the steps toward SEND submission success. This includes process and precaution considerations for those planning to incorporate SEND into their research planning. In light of the gradual standardization of SEND Controlled Terminology (CT), INA recently conducted a simulated CT-compliant study. In order to expedite final report terminology and CT unification in a standard study, INA investigated 1) planning stage considerations, 2) system issues observed when collecting mock data, and 3) methods allowing quicker, more efficient SEND conversion. INA also considered the visualization of SEND datasets, and how it may improve study evaluation.
SEND Submissions – Pathology Best Practices
With FDA mandated electronic data submissions in SEND (Standard for Exchange of Nonclinical Data) format on studies starting after December 17, 2016, how confident are you that your company’s Pathology dataset submission is complete and accurate on all studies? Are you familiar with electronic data formats? How are you integrating study data from multiple CRO's, vendors and LIMS, including assuring that a common Controlled Terminology was applied across the dataset, especially if you outsource Pathology data? Does the nSDRG (Nonclinical Study Data Reviewer’s Guide) have the appropriate data and combine the data from all CRO's and sites involved? If incomplete or inaccurate datasets are submitted, and returned due to errors, what is your company action plan for corrections? The purpose of this poster is to share SEND experiences concerning Anatomic and Clinical Pathology dataset accuracy. SEND now in place for IND’s and NDA’s.
Utilization of Ascentos™ and Transend™ for SEND Implementation of Pivotal Studies in Support of IND Submission
The Standard for Exchange of Nonclinical Data (SEND) is an implementation of the CDISC Standard Data Tabulation Model (SDTM) for nonclinical studies, which specifies a way to present nonclinical data in a consistent format. The SEND Implementation Guide (SENDIG) is a document that provides implementers with specifications for implementing SEND, including how to model various nonclinical endpoints, rules to doing so, and examples with sample data.
Specific Toxicologist/Pathologist Responses for Standard for Exchange of Nonclinical Data (SEND)
The Standard for Exchange of Nonclinical Data (SEND), introduced by the US FDA) is a regulation for the computerization, electronic application, and screening of preclinical data. In SEND, most data, including those on pathology findings, are converted into controlled terminology (CT), but it is not a simple process to convert findings or levels of severity in the field of pathology, which is a descriptive science. We have successfully completed an U.S. FDA SEND trial submission for a toxicology test conducted at a CRO, and in doing so, acquired important knowledge.
SEND Submissions — Quality review by QA — Yes/No?
With FDA mandated electronic data submissions in SEND format for NDA, ANDA and BLA supporting Single Dose, Repeat Dose and Carcinogenicity studies, starting after December 17, 2016, how confident are you that datasets compiled into a submission package are complete and accurate for all studies? The purpose of this poster is to share SEND experiences concerning dataset accuracy, and the possible role of QA in the submission process.
Use of R Script to Create Trial Summary (ts.xpt) Domains for Nonclinical SEND Studies
The "Study Data Technical Conformance Guide" for electronic submission of study data requires a Trial Summary (ts.xpt) dataset file even for legacy studies. The Nonclinical Script Assessment Project (part of the PhUSE"Nonclinical Topics" working group) was created to explore computer scripts to help with SEND data analysis. As part of this effort, an "R" script was created and shared that generates the ts.xpt to meet this requirement. In addition, this project is also collaborating on other scripts to analyze SEND datasets.
Actions for FDA SEND: What Pathologists/Toxicologists Need To Know
The Study Data Tabulation Model (SDTM) serves as the model for clinical study data. SEND is the implementation of SDTM for nonclinical studies and specifies the rules for standardizing nonclinical study data. Both SEND and SDTM require the mapping of controlled terminology (CT), and dealing with pathological terms will be a huge challenge. To create the SEND data set for a study, input (source) electronic pathological data is transferred directly to the SEND conversion tool, TranSEND®, using Ascentos® PathData version 11 (made by PDS) for immediate automatic conversions.
PP26 FDA SEND Submissions: Does the Pinnacle 21 Open Source Community Validator Predict Findings from FDA’s SEND Validators?
The Pinnacle 21 Community SEND validator is an open source tool used by many sponsors to evaluate SEND datasets for compliance to CDISC's SEND standard. An appreciation of how well it predicts results from the different SEND validators used by FDA SEND at this point in time is important. Our poster presentation summarizes and compares FDA SEND validator findings to Pinnacle 21 SEND validator findings (current version, 2.1.0) for several recent FDA SEND repeat-dose toxicology submissions.
Strategic Approaches to the Use of SEND Controlled Terminology
Starting in December 2016, SEND (Standard for Exchange of Nonclinical Data) will become mandatory for nonclinical FDA submissions. One requirement of SEND is the mapping of specified study terms to CDISC SEND controlled terms (CT). However, the SEND model itself also requires inclusion of original terms recorded by pathologists and other scientists, in addition to the mapping of these terms to SEND CT. This dual representation provides sponsors with strategic options.
Template, User Guide, and Examples for Nonclinical Study Data Reviewer’s Guide for SEND Submissions
According to FDA’s Study Data Technical Conformance Guide v2.2 (June 2015), preparation of a Study Data Reviewer’s Guide (SDRG) is recommended as an integral part of a CDISC standards-compliant study data submission. An SDRG template, completion guidelines, and examples for clinical studies have been available since May 2013.
Challenges and Solutions for Mapping Pathology Data to SEND
Based on our experience creating SEND datasets for FDA submission, we can group SEND mapping challenges for pathology into several patterns.
FDA SEND in Non-US Countries Responses to the Standard for Exchange of Nonclinical Data (SEND) in Non-US Countries
The Standard for the Exchange of Nonclinical Data (SEND), adopted by the US FDA, is part of a set of regulations and guidances requiring the submission of standardized electronic study data for nonclinical and clinical data submissions.
Comparison of FDA and OpenCDISC SEND Validator v1.4.1 Rules
A rule-by-rule comparison was made between FDA and OpenCDISC v1.4.1 SEND validation rules to determine which were present in the FDA set but not in OpenCDISC, which only in OpenCDISC and which in both. This analysis was a first step in a process to extend the OpenCDISC validator to also include FDA validation rules.
SEND Architecture Facilitates Harmonization and Aggregation of Data From Different Organizations/LIMS
Toxicology studies in today’s business environment involve multiple testing sites, LIMS and/or departments. PDS offers a software architecture for SEND that accomplishes the aggregation, harmonization and translation of data from different sources into one complete dataset including all XPTs, define files and validation report(s).
Selecting a CRO for Creating and Integrating SEND Datasets From Multiple Organizations
Creating and integrating SEND datasets from multiple CROs and LIMS can be a complex process requiring good partnerships and upfront understandings between sponsors and CROs. The Interorganizational SEND (I-SEND) Project Team within the FDA/PhUSE Nonclinical Working Group has developed a guide to help establish CRO capabilities, logistics and sponsor expectations.
The Occurrence of Microscopic Vacuoles in Toxicology Studies With Marketed Pegylated Proteins Is Associated with High Doses, High Clinical Multiples and Accumulation
The Food and Drug Administration (FDA) Biologics License Applications (BLA) provided reviews for nine of 11 pegylated proteins marketed in the United States. These proteins were analyzed to obtain a more complete understanding of microscopic vacuoles in nonclinical toxicology studies,