The SEND [Standard for Exchange of Nonclinical Data] Implementation Guide v3.1, “SEND 3.1,” changes the model for the reporting of cardiovascular and respiratory endpoints.
SEND 3.1 became effective 15 March 2019 for NDA/BLA submissions; and it will become effective 15 March 2020 for IND submissions, overlapping with the effective period of the previous version, SEND 3.0. (See chart below.)
Chart 1. SEND 3.0 and 3.1 roll-outs.
Some additional regulatory considerations during this transition period include:
- The SEND version required for your submission is determined by the study start date (aka protocol finalization date).
- If you are including non-GLP studies in a regulatory submission, a SEND dataset is also required.
- If you have legacy studies in your submission, an abbreviated TS file (Trial Summary file) is required for each one.
Domains and Domain Placement: Findings General Observation Class (Section 6.3)
Reporting electrocardiographic test results (EG) remain the same in SEND 3.1; however, the Vital Signs (VS) domain has been condensed due to the inclusion of new domains for Cardiovascular (CV) and Respiratory test results (RE). The Cardiovascular and Respiratory test results will be placed in the Safety Pharmacology section of the electronic submission.
Table 1 below shows in which domain the endpoints are now placed. Despite the updated domains in SEND 3.1, the Controlled Terminology for these endpoints remains the same.
Table 1. New domains for SEND 3.1 safety pharmacology endpoints.
Latin Square Study Design: Trial Design Domains (Section 7).
The Latin Square study design is a new design for SEND reporting coming with the safety pharmacology study type in SEND 3.1. The Latin Square design is often used for standalone cardiovascular studies: it is designed to ensure that all dose levels are represented on each dosing day with each subject receiving every dose once and all subjects receiving different dose sequences. This design provides a unique perspective to the more traditional study set ups and reduces the amount of subjects that are required on a particular study. Since Latin Square studies are more complicated to standardize, special consideration must be made for the trial design.
Figure 2 shows a sample cardiovascular Latin Square design and how the trial element (TE), trial arms (TA) and trial sets (TX) would be encoded.
Sample Latin Square trial design overview
Sample Trial Elements (TE)
Sample Trial Arm (TA)
Sample Trial Sets (TX)
Figure 2. Sample Latin Square trial design and the SEND datasets encoding study information.
Are you ready for SEND 3.1?
The expansion of reporting requirements under SEND 3.1 should harmonize your company’s preclinical data collection and facilitate the regulatory submission process.
Our team of experts have many years’ experience with SEND data set service, and been involved with federal SEND consortia. We aim to make your company’s transition from SEND 3.0 to SEND 3.1 as seamless as possible.