Nonclinical (SEND) Fit for Use Workstream
The CDISC SEND (Standard for Exchange of Nonclinical Data) team, in collaboration with the PhUSE Nonclinical Test Submissions Workgroup and the FDA CDER Office of Computational Science (OCS), conducted a workstream for piloting SEND V3.0 that was opened to the public to participate. Participants (nonclinical submitting organizations, sponsors or their delegates) have concluded submitting data, receiving pilot feedback, and determined content and deliverables to be shared broadly on this wiki site, which is open to all (ie, publicly accessible).
One of the main tenets of the Fit for Use Pilot was that feedback provided back to each participant would be shared with the public broadly, via the CDISC and PhUSE organizations working processes. Learning from this pilot is being used to inform industry CDISC and PhUSE team efforts. These teams are open to all who are interested in data standards and implementation
Learning has also been incorporated in version 3.3 of the Study Data Technical Conformance Guide.
To meet the main tenet of "shared learning", the following deliverables are available below:
Presentations (in .pdf format):
–CDISC-PhUSE Fit for Use Pilot, October 2016
–SEND Challenges, Tabular Examples from Fit for Use, October 2016
–INDUSTRY FEEDBACK, March 2017
–INDUSTRY FEEDBACK: Domain / Data File Level Learning,
Actual Feedback files (in zipped files to be extracted):
–Informational packages that include the actual (redacted) feedback from the FDA to individual sponsor participants, April 201
Pilot Charter, at initiation:
This is a public-facing wiki site for sharing lessons learned from the "Fit for Use" SEND Pilot described in the attached charter, version 1.0: The Fit for Use Pilot Work Stream Charter v1 2Sept 2016.docx.
Pilot Content, or Coverage of the pilot relative to SEND standard v3.0*:
|Row #||Study Type (Single, Repeat, Carc)||GLP / nonGLP Study?|
Was the Tumor.xpt submitted(in addition to TF domain of SEND)?
Was the SDRG & Define file submitted?
|Was the pdf of the report submitted?|
|Study Duration||Multiple Treatments and Frequency||Domains included||Housing of animals on study|
Study Design comments
|Describe any data that was not captured in SEND format||Was the protocol / ammedments/ deviations and final report included in your pilot submission?||Additional comments provided|
|1||Repeat Dose||GLP||No||Yes||Yes||monkey||4-week with recovery||subcutaneous daily dosing||BW, EX, BG, PC, PP, EG, LB, RELREC, CO, CL,DM, DS, MA, MI, OM, TE TA, TS, TX,||group||study duration changed for some animals, single supplier, main study animals also served as tk animals||ADA||final report included||no additional comments|
|2||Repeat Dose||GLP||No||Yes||Yes||dog||1-month with recovery|
|BW, CL, CO, DM, DS, EG, EX, LB, MA, MI, OM, PC, PP, RELREC, SC, SE, SUPPCL, SUPPEX, TA, TE, TS, TX, VS||single housed||Dosing remained constant; no satellite animals; single supplier.||We supplied dried blood spot analysis in SEND that was not in the study report, but nothing in the study report was missing in SEND.||Full study report with protocol amendments, deviations, etc was included|
|3||Repeat Dose||GLP||No||Yes||Yes||rat||4-week||QD||TE, TS, CO, DM, SE, TA, TX, EX, DS, BG, BW, CL, FW, LB, MA, MI, OM, PC, SUPPMA, SUPPMI||single||Study design was composed of 5 groups with 10/sex/group in the main study and 6 satellite animals/sex/group for TK. Dosing in the 600 mg/kg (high-dose) group discontinued on Days 11 and 6, respectively in males and female rats. These animals were continued on study without any further dosing.|
|4||Repeat Dose||GLP||N/A||Yes||Yes||dog||4-week with 4-week recovery||orally via gavage, once daily|
BG, BW, CL, CO, DM, DS, EG, EX, LB, MA, MI, OM, PC, PP, RELREC, SE, SUPPBG, SUPPBW, SUPPCL, SUPPDS, SUPPLB, SUPPMA, SUPPMI, SUPPTF, TA, TE, TF, TS, TX
|group||Full study report included|
We actually submitted 4 studies conducted on the same compound to the pilot. One was fully reviewed, the three others were checked for fitness.
|5||Repeat Dose||GLP||No||Yes||Yes||rat||3-Month||QD, oral||BG, BW, CL, CO, DM, DS, EX, FW, LB, MA, MI, OM, PC, PM, POOLDEF, PP, RELREC, SUPPBG, SUPPBW, SUPPCL, SUPPDS, SUPPFW, SUPPLB, SUPPMA, SUPPMI, SUPPPM, SUPPTF, TA, TE, TF, TS, TX||group||Satellite groups used for TK, pooled samples.||Full study report included||Two studies submitted, rodent reviewed in full, 90-day dog was checked for fitness only.|
|6||Repeat Dose||No||Yes||No||monkey||28-day with 28-day recovery period||IV slow bolus|
MI,OM,PC,PP,VS,EG,RELREC, SUPPMA, SUPPMI, SUPPCL, SUPPPC, SUPPLB
|7||Repeat Dose||NonGLP||No||Yes||Yes||male rat||7 day||Oral|
BG,BW, CL, DM, DS, EX, LB, MA, MI, PC, PP,SE SUPPBG, SUPPBW, SUPPCL, SUPPDS, SUPPLB, SUPPMI, TA, TE, TS, TX
|Socially-housed||Standard, male only||MICRONUCLEUS Assay, PBMC (Peripheral blood mononuclear cell analysis) data assessment, PP domain included individual data values while the study report only has the means calculated from these individual values.|
Protocol, Amendments, Deviations and final report included: Protocol included. There were no deviations or amendments.
|no additional comments|
|8||Repeat Dose||GLP||NA||Yes||Yes||dog||4-week no recovery||Oral (gavage) daily dosing|
BG, BW,CL, CO,DM, DS, EG, EX,FW, LB,MA, MI,OM, PC, POOLDEF,PP, RELREC, SE, SUPPMA, SUPPMI, TA TE, TS, TX,
Dog/Beagle, Single supplier, main study animals also funded TK
24 on study (3/sex/group)
No - Final Report only (which states the final methodology)
|9||Repeat Dose||No||No SDRG provided||Yes||dog||28-Day with 28-Day recovery period||Oral Gavage daily dosing||BG, BW, CL, CO, DM, DS, EX, FW, LB, MA, MI, OM, PC, PP, RELREC, SE, SUPPCL, SUPPMA, SUPPMI, TA, TE, TS, TX, and VS||Group except during feeding||Standard, males only||ECG|
Protocol included: Protocol and amendments are part of the PDF report submitted
SDRG not submitted due to oversight
|10||Repeat Dose||No||Yes||Yes||dog||14-Day||Oral gavage daily dosing|
|11||Carcinogenicity||No||Yes||Yes||transgenic mouse||26-Week||Oral gavage daily dosing|
|12||Repeat Dose||non-GLP||No||Yes||Yes||Cynomolgus Monkeys||4 weeks||2 doses, three weeks apart||TA, TE, TS, TX, CO, DM, SE, EX, DS, BW, BG, CL, LB, MA, MI, OM, PC, PP, SUPPBG,SUPPBW, SUPPCL, SUPPDS, SUPPLB, SUPPMA SUPPMI||Group||females only||Full study report with protocol amendments, deviations, etc. was included||When sanitizing the datasets an error was introduced in the PC domain. In the PC domain, PCTPTNUM=0.17 in the original dataset and replaced with PCTPTNUM=0 in the sanatized dataset.|
|13||Repeat Dose||non-GLP||No||Yes||Yes||Rat||3 weeks||2 test articles dosed once weekly for 3 weeks||BG, BW, CL, CO, DM, DS, EX, LB, MA, MI, OM, PC, PP, RELREC, SE, SUPPLCL, SUPPMA, SUPPMI, TA, TE, TS, TX|
3 rats per cage
The animal rooms were maintained at a temperature between 68 and 72 degrees Fahrenheit, and relative humidity between 20 and 80%. The temperature and humidity were recorded throughout the study by an automatic monitoring system. The light/dark cycle in the rooms was 14 hours of light, starting at 5:30 am, followed by 10 hours of darkness. The ventilation system ensured a minimum of 15 air changes per hour.
Tox arm: Group 1 (control), 2, 3, 6TK arm: Group 4, 5, 7
|Urinalysis data were not captured due to internal data system limitations, which are being addressed in 2017.|
*The contents of this table were provided very early in the pilot effort to demonstrate the amount and coverage of data provided in the pilot; an individual row(s) does not necessarily align with any other feedback posted at this site.