Abstracts

Rationale: Rigor and reproducibility are of critical importance in the design, completion, and reporting of preclinical data in order to better facilitate translation of novel therapies to clinical development. Recent efforts have included the use of common terms, harmonized methods, and standardized reporting (Barker-Haliski, Harte-Hargrove et al. 2018, Gorter, van Vliet et al. 2018, Harte-Hargrove, Galanopoulou et al. 2018, Mazarati, Jones et al. 2018, Ono, Wagenaar et al. 2018, Scharfman, Galanopoulou et al. 2018). The National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program’s (ETSP) contract site at the University of Utah has modified and implemented Case Report Forms (CRFs) that utilize Common Data Elements (CDEs) for tests aimed at identifying novel therapies for drug-resistant epilepsy. An improved study reporting framework was also developed, as well as a quality control (QC) review system for comparison of raw data and study reporting.

Methods: We developed and optimized CRFs for tests in preclinical animal models including 6 Hz (mouse and rat), maximal electroshock (mouse and rat), corneal kindling (mouse), lamotrigine-resistant amygdala kindling (rat), tolerability testing (mouse and rat), and spontaneously seizing rats (intraperitoneal kainate model). This approach was also taken for hyperthermia-induced seizures in a model of Dravet Syndrome (Pernici, Mensah et al. 2021). Draft CRFs were developed, optimized, and implemented for several tests. Standardized study reports were also drafted for all tests that include harmonized formatting, organization, and reporting elements. A two-factor QC process was implemented that included raw data study report review by two separate reviewers. Data collection using CRFs was implemented over the course of several months and included training and guidance from senior laboratory staff members. Key CDEs including species, strain, drug formulation, route of administration, pre-treatment time, and other parameters were included. Feedback from laboratory staff was solicited and aided in refining the CRFs for each assay.

Results: QC review was successfully implemented using standardized data review forms and was integrated into the NINDS information technology infrastructure for reporting ETSP data. Implementation of this material has aided in compiling and reporting of data, comparing between individual studies, and identifying and preventing errors. CRFs of individual assays are available to participants in the ETSP.

Conclusions: While the use of standardized reporting forms, study reports, and QC review may be more common in industrial settings, these methodologies are less commonly used in academic lab settings. The Contract Site for the ETSP is optimally positioned to implement such a data collection and reporting structure that may be informative to other academic laboratories and the epilepsy research community.

Funding: Please list any funding that was received in support of this abstract.: This project has been funded by Federal funds from the National Institute of Neurological Disorders and Stroke, Epilepsy Therapy Screening Program, National Institutes of Health and Department of Health and Human Services, under Contract No. HHSN271201600048C.