Epi25 Collaborative for Large-Scale Whole Genome Sequencing in Epilepsy
Governance Structure Charter February 2015 
The Epi25 Collaborative has developed from an initiative coming out of the NIH National Human Genome Research Institute (NHGRI) in late 2014, which led the NIH-sponsored “Epi4K Center Without Walls” leadership to engage in discussions with leaders of the Broad Institute and many of the epilepsy genomics projects that presently exist throughout the world. The immediate enthusiasm in taking steps to formalize the Collaborative was based on the obvious synergy in adding epilepsy to the sequencing efforts in autism and schizophrenia planned by the Broad Institute, and a highly successful large-scale partnership that has resulted from the International League Against Epilepsy (ILAE) Consortium on Genetics of Complex Epilepsies.
The driving principle behind the Epi25 Collaborative for Large-Scale Whole Genome Sequencing in Epilepsy (Epi25 Collaborative) is that through collaboration and synergy, collectively we will make more rapid progress towards fully understanding the inherited components of epilepsy than can be achieved individually.
It follows that membership in the Epi25 Collaborative carries advantages for which some sacrifices of autonomy are considered to be a reasonable price – the collective benefits considerably outweighing the individual restrictions.
While this does not mean that all individual large-scale whole genome sequencing (WGS) efforts should be subsumed into a single collaborative effort, we do aspire to a community of ideas some of which will be best realized using a cooperative approach.
For any research that would rely wholly or in significant part on Epi25 Collaborative or resources, Members are required to discuss their ideas within the Epi25 Collaborative. This principle of “no surprises” extends to all new analyses, poster and oral presentations, manuscripts and other tools of the trade.
Members are further encouraged, but not required, to share relevant ideas that do not require use of Epi25 Collaborative data or other resources.
Amongst other advantages, benefits of this cooperative approach are expected to include the strengthening and improving of preliminary ideas via discussion with fellow experts, the possibility of attracting additional resources in support of proposed projects, access to larger sample and data sets, better analytical tools, and sharing of complementary skills.
Structure and Rules
I. Size and Shape of the Collaborative
Given the above background, and successful running of the model, the structure and rules of the Epi25 Collaborative are therefore fundamentally based on that of the ILAE Consortium.
The Collaborative is the authoritative coordinating body for the epilepsy-related WGS efforts.
The Collaborative acknowledges that even though much of the analytic work will be performed by junior investigators (PhD students, postdoctoral fellows), the junior investigators in the field are naturally disadvantaged in large collaborative projects due to the limited number of leadership roles in team science, and the ongoing emphasis by most academic institutions and funding-agencies on contributions represented by first authorship or senior authorship in manuscripts. The Collaborative will try to compensate for this imbalance by insuring that: (a) contributions of all junior investigators will be explicitly and fully stated in manuscripts; (b) senior investigators advocate strongly for junior investigators in the promotions and funding process by including detailed descriptions of the junior investigator’s creative contributions and related attributes in letters of reference; (c) junior investigators have the opportunity to take lead roles and assume first-authorship for spin-off projects; (d) junior investigators have the opportunity to present Epi25 results at high-profile symposia and related events; and (e)
junior investigators are actively involved in the key decision making processes of the Collaborative such as those related to the Strategy Committee. The Collaborative considers these junior scientists as future leaders in the field and feels responsible for their mentoring for leadership in the field.
Given these considerations, membership in Epi25 will not only extend to the individual group leaders or Principle Investigators of a group, but to other group members actively involved in the project. The Principle Investigator will propose which members of his/her group should be considered for membership in the Collaborative.
Gene identification in the epilepsies is an endeavor of a global, not national scale. Therefore, the Collaborative may serve as a bridge between a nationally funded project and the diverse requirements, limitations and capabilities of the various international partners with respect to formal support, IRB, and differences in phenotyping. The Epi25 Collaborative explicitly embraces the multicultural and international aspects of gene identification studies as it allows for the discovery of risk factors in various ethnicities.
The Collaborative consists of three parts:
1. Strategy Committee
- The group (10-20 people; TBD) within which the strategic decisions of the Collaborative will be made, as well as oversight of Epi25 operations.
- The composition of the Strategy Committee and other working groups will reflect the international nature of the Epi25 initiative and will aim to include representatives from Europe, Asia, Oceania, Africa and the Americas.
- Each member of the Strategy Committee must either bring a substantial number of epilepsy DNA samples or a key skill set or technical capacity of value to the Collaborative. (See below for details.)
- Meets ~ monthly or bi-monthly by telephone and occasionally in person.
- Reaches decisions by informal consensus of those participating in calls, not by formal vote.
- Term limit of three years, renewable.
- Disputes or impasses are settled through consensus. None of the members of the Strategy Committee have a formal "veto", but in case of disagreement are expected to respect and represent the consensus opinion.
- Led by a Chair who is responsible for effective administration of the organizational activities of the Collaborative, including communication internally and externally, scheduling of meetings, documentation of Collaborative deliberations, decisions, and other related activities. The Chair will be a member of the Executive Committee and will have a term of three years, renewable.
- Subcommittees of the Strategy Committee may include: Phenotype Subcommittee, Analysis Subcommittee, Publication Subcommittee
2. Executive Committee
- A small group (3-4 members) that is responsible for day-to-day, operational matters of Epi25 and serves as the point of contact and primary source for Epi25-related communications.
- The composition of the Executive Committee will aim to maximize the opportunity for effective interactions with NIH and other funding agencies, the ILAE, and other relevant entities.
- Each member of the Executive Committee must be a senior investigator with substantial experience in large-scale epilepsy genetics projects, and the group must have a demonstrated track record of working together effectively.
- Meets monthly by telephone and occasionally in person.
- Reaches decisions by informal consensus of those participating in calls, not by formal vote.
- Term limit of three years, renewable.
- A member of the Executive Committee will serve as the Chair of the Strategy Committee
3. Working Groups
- Temporary ad hoc groups established by the Strategy Committee to pursue specific and time limited projects that are better handled by smaller, specialist groups.
- A chair is appointed for each Working Group.
- Working Groups report progress and findings to the Strategy Committee.
- Working Groups meet by teleconference according to a timetable established by each Working Group chair.
- An initial Working Group will be the “Broad Liaison Working Group”, which is charged with handling all direct interactions with the Broad Institute for the completion of the application and fulfilling the scientific aims of the grant.
4. Regular Members
- A large group with no strictly defined membership criteria, not only limited to principle investigators, but all individuals providing intellectual contribution to Epi25 activities.
- Regular Members can be added upon request and need to be confirmed by the Strategy Committee, who will evaluate whether the intended contribution of a new member will add to the aims of the Collaborative.
- Regular Members are added to the email listserv.
- Regular Members can listen in and participate in teleconference calls, and can join Working Groups, if approved by their Strategy Committee representative.
II. Strategy Committee in More Detail
- To be appointed after application.
- 80% of the Members must be independent investigators who are able to submit a substantial number (generally more than 200) of patients (or controls) with DNA samples and requisite phenotypic data.
- Ethical approval will allow use of analysis (although not necessarily primary data) by the Collaborative.
- Taken from sufficiently characterized patients (details of this to be determined).
- Sequencing-grade DNA.
- 20% of the Members will be junior investigators who have a strong track record in epilepsy genetics and a clear commitment to the collaborative spirit of Epi25.
- he Strategy Committee will also include 1-2 members who are patient representatives.
New Collaborative members will sign this Charter document indicating that they agree with the policies listed here and that they have obtained the required ethical clearances to participate or send data.
All Strategy Committee investigators are equal contributors and are encouraged to participate in the regular teleconference meetings. Failing to actively participate in the majority of meeting and teleconferences may result in expulsion from the Strategy Committee.
All Strategy Committee members agree that they will be held to a high degree of credibility and reliability within the Collaborative and acknowledge that they will be proactive in declaring conflicts of interests, entanglement in competing projects, or commercial interests. The Strategy Committee members acknowledge that their responsibility for the Collaborative extends beyond the sphere of their own group, institution, or national funding framework and they will be actively working towards transparent communication within the Collaborative.
All Principal Investigators within the Collaborative are encouraged to include their colleagues, including junior MDs, PhD students and postdoctoral fellows, within the Epi25 Collaborative. The amount of members per site should be fair and balanced and the contribution of each partner should be evident to the Collaborative and indicated upon request. For additional members added after the initial conception of Epi25, the Strategy Committee will decide whether an applicant is admitted to Epi25 and will communicate this decision in a transparent manner.
III. Project Decisions
Assuming successful funding of the NHGRI application, the initial, primary work of the Collaborative will be defined by the specific aims and experiments described in the application, and any subsequent work that develops as a consequence of these planned studies and relies on all or a substantial part of the samples and data associated with the Epi25 Collaborative.
Any project (large or small) using the combined DNA samples or phenotype data gathered together by the Collaborative, or other unpublished Collaborative data must be formally proposed to the Strategy Committee Group. Each proposal will include:
- A description of what data is required.
- A description of the analysis to be performed.
- A timetable.
- The name of the Collaborative member who will be responsible for the project and a list of others who will be involved.
- A publishing/authorship plan (see section 5.)
All proposals will be distributed to all Strategy Committee members.
Each proposal will be discussed during Strategy Committee meetings and either approved or declined by consensus.
If a project is approved, no data will be used without the express permission of the investigators who contributed that data.
All project proposals must include a specific publishing/authorship plan.
Typically the plan will be one of the following three options taken from the MS model:
- A full Epi25 Collaborative paper: The Epi25 Collaborative is listed as the author (along with other Collaboratives/Consortia, as appropriate), with a list of individual contributors made according to the journal’s style preference. No individual Member will be designated as a corresponding author – the corresponding author will be listed as the Epi25 Collaborative with a mailing and email address.
- A partial Epi25 Collaborative paper: Individual authors listed. The Collaborative name is included in the author list, along with other Collaboratives/Consortia, as appropriate. (This option must include a list of authors.)
- A local paper: Simply acknowledges the Epi25 Collaborative.
All publications by the Collaborative will be open-access.
Junior scientists (PhD students, postdoctoral fellows) will be given preference in presenting data of the Collaborative at conferences.
Collaborative members will be reasonable and self-critical in their claims for authorship
All members of the Collaborative are bound by a "no surprise" policy with respect to Epi25 data and possibly interfering data from individual groups. The members acknowledge that "conflict of interest" can have a wide range of interpretations within the international framework of the Collaborative. Therefore, members are encouraged to proactively indicate conflicts if they feel that they might arise.
1. To consider participation in primary analyses and secondary analyses proposed by the Epi25 Collaborative, subject to constraints or limitations that I can impose in each case.
2. To abide by the guidelines for authorship and publication, and other guidelines described in this document.
3. To openly declare conflicts of interests that will arise during the participation of Epi25, such as the participation in related projects, awareness of information that significantly alters the interpretation of Epi25 data, or commercial interests regarding to results of the Epi25 data.
4. To try and solve conflicts relating to data arising from Epi25 jointly and peacefully. Such a situation may arise if data from the Collaborative would add to pre-existing projects of two or more collaborators, resulting in conflicts regarding the use of the data. If a joint decision cannot be reached, the decision of the Strategy committee is binding.
5. Not to distribute or communicate any privileged information to individuals who are not members without consent of the entire Collaborative. This includes any other existing collaborators who are not members of the Epi25 Collaborative. Privileged information includes results of any unpublished analyses completed by members of the Collaborative.
6. Not to distribute or copy any data collected by the Collaborative without prior written consent of all Strategy Committee members.
7. That the Epi25 Collaborative Strategy Committee will review and evaluate future scientific opportunities, and will make recommendations regarding the needed expertise and research program to maximize those opportunities in the best possible way.
8. That failure to uphold this agreement may result in my expulsion from the Epi25 Collaborative (but I will still be bound by publication moratorium on Epi25 Collaborative work, as described above).
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Modeled with permission on the Charter of the International Multiple Sclerosis Genetics Consortium (https://www.imsgc.org) and the ENIGMA Consortium Memorandum of Understanding.