Preclinical Common Data Elements Discussion

A request for community feedback by the ILAE/AES Joint Translational Task Force

Deadline for comments extended to January 15, 2019

The TASK3 group of the International League Against Epilepsy (ILAE) / American Epilepsy Society (AES) Joint Translational Task Force, in collaboration with the NINDS, has created a first set of preclinical common data elements (CDEs) to be used in preclinical epilepsy research studies aiming to develop better treatments for seizures, epilepsies and comorbidities. This project aims to facilitate collaborations across labs, creation of big databases to deposit such data, as well as help comparisons of findings across different studies.

To optimize the product, the TASK3 group leaders of ILAE/AES Joint Translational Task Force is requesting community feedback from our colleagues involved in such studies. The comments received will be reviewed by the TASK3 group of the ILAE/AES Joint Translational Task Force members to implement necessary revisions to these products. The scope of the requested feedback is described in this editorial:

Special Issue on the TASK3 Preclinical epilepsy CommonData Elements (CDEs) of the ILAE/AES Joint Translational Task Force: Peer review process, acknowledgement to reviewers, and community feedback

The full set of companion papers, case report forms and common data element charts can be downloaded from the Epilepsia Open® supplement website that is dedicated to the TASK3 epilepsy preclinical CDEs: onlinelibrary.wiley.com/toc/24709239/2018/3/S1

Draft reports of this supplement:

The manuscript will be open for comments for two months, until January 15, 2019. All comments will be placed on this page as they are received and will include the name of each writer. At the end of that time, the comments will remain public, and the TASK3 group of the ILAE/AES Joint Translational Task Force will review the comments and make appropriate changes.

Please send your comments to Deb Flower, who will post them to this web page as they become available.

Thank you for your help in this important effort of the ILAE.

Aristea Galanopoulou, MD PhD, Co-chair, ILAE/AES Joint Translational Task Force

Helen Scharfman, PhD, Jacqueline French, MD, Vicky Whittemore, PhD
Co-leaders of the TASK3 of the ILAE/AES Joint Translational Task Force

Lauren Harte-Hargrove, PhD, Past project manager of the ILAE/AES Joint Translational Task Force

Comments

January 15, 2019

Please find my comments for the CRF module 1:  General Core Pharmacology.  Please let me know if you would like additional information.  

  1. Would this CRF be filled out for each animal? Consider the option to group animals on one CRF to avoid repetition of filling out the same dosing information for each animal.
  2. In addition to formulation procedure check boxes, you may also want to capture other details? For example, temperature or sonication time? CRF could provide space for those details.
  3. For single and repeated dosing, I don’t see where the investigator records the dose (except for when it is in food).   I also don’t see where the timing of the administered dose is recorded. Is this recorded on a different CRF?
  4. The CRF includes injection volume. You may also want dose volume for other ROAs. In additional formulation strength would be useful unless recorded somewhere else.
  5. In general, it might be cleaner to have a separate PK sampling CRF since there may be many samples collected from each animal which I believe is already under consideration.
  6. In the PK sampling, the “plasma” matrix might be more broadly called the “blood” matrix and then specify whether it is whole blood, plasma, serum, etc. If all sampling information is contained in this CRF, there should be room to include multiple sampling times.

Thanks,
Lisa Coles

 


January 10, 2019

Here are some comments on the CDE papers.

1. Reporting fighting - fighting may be hard to identify unless the animals are seriously injured. I'd suggest adding a box that says "suspected fighting" when there might not be overt injury but you think there may have been fighting.

2. In the interest of saving time - the CDE's might have a check box that says "Abnormal Room Temp/Humidity". Otherwise you would be filling that info out exactly the same 100% of the time.

3. There have been some shifts at NIMH about what behavioral tests are good models of depression with regard to stress-related disorders. I think some of that info may be pertinent to studies of epilepsy comorbidities as well. Please see: https://grants.nih.gov/grants/guide/notice-files/NOT-MH-18-058.html

4. For the EEG CDEs, this is a great resource which I will wholeheartedly embrace. One clarification is on the term "standing out from the background". This is very subjective. Did the group consider defining that term better? May people in the field would consider an event with an amplitude of 3X the SD of EEG background would be "something that stands out". It might be good to be specific here.

5. My final comments is that I would file a lot of what has been laid out under the "extremly onerous" category. What type of requirements and/or support did the working groups consider? If the field and funding agencies are suggesting mandating the use CDE's we should be very careful about what we define as essential elements.

Thanks,
Chris Dulla

 


January 5, 2019

Please find below my comments to the Preclinical Common Data Elements.

Core Animal Characteristics & Case Report Form for Uploaded Files (Tables 2 & 3)

  • For questions requiring two or more answers, I suggest moving the instructions from the legend to the corresponding box; this helps memorizing the request.

Terms used in the EEG preclinical CDEs (Table 1)

  • I assume that the frequency range refers to adult animals; this point should be clarified.

Best regards.
Ettore Beghi MD

 


January 1, 2019

Just a few comments regarding the preclinical EEG CDEs:

  1. Regarding grid/depth electrodes, distance between electrodes should be reported (p.93)
  2. Would not use periodicity in the definition of rhythmic, since rhythmic and periodic have distinct definitions; consider clearly stating that there is no clear interval between waveforms when 'rhythmic' per 2012 ACNS criteria (p.98)
  3. Consider changing ‘behavioral seizure’ to 'clinical seizure' to be consistent with the term 'electroclinical' seizure. This might help more precisely differentiate from stereotyped behaviors that are not believed to be epileptic in nature.

Thanks!
Atul Maheshwari, MD

 


November 29, 2018

Kevin Staley and I are initiating post-traumatic epilepsy studies in swine with a grant from CURE. The current epilepsy preclinical epilepsy CDEs appear to be exclusively geared towards rodent studies. John Wolfe at UPenn has ongoing studies in swine. We are working with Lauren on developing CDEs for PTE that includes the traumatic brain injury CDEs. Unfortunately, the pre-clinical TBI CDEs are also geared toward rodent models and missing information one would need for large animal models. The current pre-clinical epilepsy CDE's do not appear to include studies on post-traumatic epilepsy.

Regardless of species, exclusion criteria and if the animal was excluded should be included in core CDE's. Unclear exclusion criteria or excluding a subject after they do not yield the desired data points could be a contributor to the lack of reproducibility of studies. If data is to be transparent, then these central databases should include excluded animals with the exclusion criteria defined.

I am happy to be of any further assistance and serve as a resource for CDEs for large animal models.

Thank you!
Beth Bartell