The members of the Board of Trustees, of the Scientific Advisory Board as well as of the Review Committee and any other consultants of BPDRF (herein after "members of the Board") will together with all investigators and/or research centers (hereinafter "participants") that are under consideration for funding by BPDRF from January 1, 2003 on, hereby agree to the following principles and guidelines:

1. Definition of BPDRF Related Scientific Work and Primary Investigators:

This Covenant describes agreements relating to the funded investigators and the members of BPDRF and its consultants by virtue of the fact that the work was funded in part or in whole by BPDRF. The funding may have taken place via a formal grant process or via another explicit agreement.

The term "Work" will be used to include both intellectual property (e.g. findings, discoveries) and materials associated with the scientific process, including but not restricted to patents, clones, drugs, and microchips, which may have resulted from the studies funded by the BPDRF.

The term "Primary Investigator" will be used to the participants funded by BPDRF who are specifically listed as the key investigators or collaborators on the proposal submitted by BPDRF. This is in contrast to the use of Principal Investigator which, in federal grants, designates only the lead person on the proposal. Thus, on a given proposal there may be multiple Primary Investigators as well as a number of support investigators, such as postdocs, graduate students, technicians and the like.

2. Data Ownership:

In general, the rules of data ownership start with the same understanding re data ownership for individual or collaborating investigators on federally funded grants. However, there are additional considerations due to the nature of the BPDRF, as will be described below.

Phase 1 - Data Gathering: Most BPDRF projects are funded via a granting mechanism resulting from written proposals which delineate the purpose of the studies, their designs, the nature of the tools being used, and the various collaborators on the study. During the research phase, when the studies are being conducted, the data belong exclusively to the investigators designated in the proposal, using the same general rules of sharing, confidentiality and the like pertinent to federally funded grants. It is expected that the investigators designated on the grant will freely share the information among each other and with the members of the Boards. It is also expected that they will submit a written annual report of their progress to the Scientific Advisory Board; these reports can be published on BPDRF's website. In addition they are expected to give regular presentation (oral talks or posters) at the annual meetings of BPDRF to update the group of their progress. It is also expected that these presentations will be open and up-to-date. Given this expectation, it is critical that all participants and members of all Boards agree that any information learned in the context of these presentations will be held by the members in the strictest confidence, and will not be shared with others outside BPDRF without the explicit permission of the primary investigator in charge of the grant.

Phase 2 - When Study is Completed: Once the study is completed and all the data are gathered, additional sharing with the participants and the members of the Boards is expected. It is recognized here that there are many grey areas. There may be differences between basic and clinical studies, between genetic and non-genetic studies, between short-term and longer-term projects, and between small exploratory projects and larger inclusive projects, which involve a significant proportion of the project. Nevertheless, the following fundamental principles are agreed upon:

a) The funded Investigators' ability to analyze the data to the fullest should never be compromised by the fact that they are participants and members of the Boards.

b) In the case of human clinical or control data, once the funded Investigators' plans for analysis are either complete or at least very explicitly delineated, they agree to share the information with other participants and members of the Boards who may have ideas or strategies for additional uses of the data. Such sharing of data is also recommended for studies in non-human species, as well as for postmortem human studies.

c) Any such additional uses of the data are collaborative in that they involve the Primary Investigators, who will be included as authors on any resulting publications. Any participants or members of the Boards who has ideas for further analysis of data generated by other BPDRF Investigators, whether within or across studies, should formally approach the Primary Investigator(s) of the studies. A written agreement should be generated as to the nature and extent of the additional data analysis. The order of authorship should be discussed and whenever possible agreed upon in advance. A copy of the agreement should be sent to BPDRF.

d) Whereas the above is focused on clinical data sharing, and whereas the rules of sharing may different across disciplines, the sharing of data is also greatly encouraged in the basic research (primate and subprimate) arena.

Data Storage and Access: Each Investigator agrees that clinical and biological information on human subjects studied in the context of BPDRF funded projects, will be available for storage in the Data Base. The storage will proceed in two stages, in coordination with the data sharing stages described above. The first stage will be in a data base which is "private", i.e. only accessible to the designated investigators on the study. Once the study moves to the second phase where sharing is possible, then the data will be moved to a more "public" data base, accessible to all BPDRF Investigators, but not accessible to anyone outside the BPDRF. Each participant and member of the Boards pledges to maintain the full confidentiality of these data bases unless a general and explicit group decision has been reached to share with external investigators part or all of the findings. Such a decision must include the full agreement of the initial Primary Investigators (except in case of death or severe cognitive impairment).

These clinical data bases are expected to contain information on the subjects, including data on their age, sex, psychiatric diagnosis, possibly endocrine variables, possibly genetic information, as well as the results of various functional tests, ranging from behavioral to neuroimaging. In addition, the data base should include information as to the Primary Investigator to whom the data belong and the year they are gathered, to allow appropriate procedures for any further analysis as described above.

All efforts will be made to fully preserve the confidentiality in terms of patient identity. Always, the names of the patients will not be included in the database. Rather, all patients will be entered under a code name, and the Primary Investigator, or a specified designate, will hold the key to the name code at the primary research site.

Editing of the database will be closely monitored. The database will be backed up on a regular basis, and chronological copies kept, allowing the ability to ascertain any changes in the data, which might take place after the initial entry. A special permission for editing will be required, which is easily differentiated from permission to enter new data. There will therefore exist a historical record of what information was entered initially, and who entered it and whether it was edited, the identity of the editor and the specific nature of the editing.

3. Sharing of Other Scientific Materials, Including Genes, Clones, Antibodies and Genetically Engineered Animals.

Beyond generating data (e.g. numbers, images, scores, correlations and the like), the studies funded by BPDRF will likely generate various other scientific materials, which represent valuable resources to the primary investigators, to other funded investigators and to the scientific community at large. These various resources are quite different along a number of dimensions, including whether they represent renewable resources or limited resources, whether they represent the work of a single individual or the work of a very large team, and whether they belong to a field where sharing is extremely common or to a field where it may be less so. These issues are taken into account in reaching the following principles:

Human DNA Samples, Genes, and Markers: Research on the genetics of BPD and associated traits will require access to several pedigrees, the collection of blood samples from both healthy and affected individuals, the generation of various materials to test for the existence of a genetic basis of the illness, using any number or approaches including linkage analysis, candidate gene approaches or their combination. As understanding of complex genetics increases, the need for multiple pieces of information (genetic and otherwise) related to a given individual or group of subjects accelerates. This is also a rapidly moving field with new markers emerging at rapid pace and novel technologies being constantly developed. Thus, it offers numerous challenges in terms of this Covenant.

We distinguish here between two general types of study: a) Studies which are primarily funded by BPDRF as free-standing exploration of a particular approach, gene or marker in a particular set of affected individuals or families, and b) Studies funded partially by BPDRF in the context of much larger (sometimes national or international) undertakings to explore the genetic aspects of BPDRF. We expect to see some differences in the extent of sharing of resources and data related to these two categories.

In the case of studies funded primarily by BPDRF, the general rules of data sharing described above would apply, including the two states of sharing, the first being more exclusive that the second. A parallel policy would be expected vis-à-vis the sharing of resources, including blood samples from the patients. Once the Investigator(s) have completed their planned experiments, and their logical extensions, they would open the opportunity to other participating Investigators to test these blood samples using their own unique tools such as different markers, chips, or the like. As in the case of additional data analysis described above, these second phase studies would require the agreement of the primary Investigators, and are seen as collaborative studies with appropriate co-authorship. Agreements regarding the use of samples and other tools, and the specifics of the planned tests need to be put in writing with copies forwarded to the Scientific Advisory Board. If an investigator does not plan to share his/her DNA samples in the context of such a BPDRF funded study, this should be stated explicitly at the time of the application for funding. It is understood that blood samples obtained from various pedigrees constitute a very valuable resource, which is under the control of the primary investigator, but which will be used as efficiently and productively as possible in order to advance the BPDRF and the scientific community's understanding of the genetics of mood disorders. DNA samples cannot be sent outside the BPDRF without the full and explicit agreement of the primary investigator(s) (unless dead or cognitively impaired).

Such extensive sharing beyond the primary investigators is not expected when the study is part of an already existing large consortium and the BPDRF has only funded a small component of the investigation. It is important in applying for funds to specify whether or not samples and data will be available for sharing by other participants and members of the Boards.

Transgenic/Knockout and other Special Animals: Production of specially engineered animals, including mice, rats, rabbits (or other species which may become possible in the future) represents a major investment in time and resources. These include transgenic animals, knockout animals and animals specifically bred to favor certain genetic patterns (e.g. recombinant inbreds). If this production is partly or wholly funded via BPDRF funds, the primary investigators undertake to eventually make these animals available to other participants and members of the Boards. Here again, during the early phases of research, when the studies are being carried out to fulfill the primary purpose of the proposed studies, the animals may remain as the exclusive property of the primary investigator. During later phases, these investigators agree to share these animals. The decisions to carry out these studies collaboratively, and the explicit nature of the studies and the rules of authorship should all be clearly documented, and this documentation copied to the Scientific Advisory Board.

4. Ownership of Discoveries, Patents and other Materials

If any discoveries or patents should result from work funded by BPDRF the general rules of patenting applied in the individual institution will be used. If the work is the result of collaboration among the participating investigators, the patent will be held jointly by the multiple institutions involved in the collaboration. This process should follow the same rules and regulations used for any other scientific collaborations across institutions. The main proviso in this particular case is that any proceeds resulting from the patents should be returned by the universities to benefit research on BPD, either by directing these proceeds to the people holding the patent, or, in their absence, to BPDRF or barring this, to departments and units with active research in the area of mood disorders.

If BPDRF has sponsored the purchase of equipment in connection with a grant, the equipment stays with the respective investigator(s) as long as he continues to be funded by BPDRF and uses the equipment for this sponsored project. If the investigator is no longer funded, the equipment can be purchased by him/her or the research center the investigator belongs to at the same price the foundation paid for depreciated over 10 years. If the investigator continues to be funded but no longer uses the equipment for the project, BPDRF is to be refunded for the equipment at the rate of depreciation.

5. Authorship

The general rules of assigning authorship, which are practiced in the context of research, in general are applicable in the context of BPDRF. Each author should have made some explicit contributions to the paper, be they intellectual, technical, clinical or based on the provision of critical tools and resources. When projects are being carried out across different research centers, some discussion may be in order regarding the local culture in terms of including research nursing staff or technical staff as co-authors. When statistical advice is used, the nature of the interaction with the statistician -e.g. consultation or collaboration should be spelled out. Participants and members of the Boards are not automatically authors on publication unless they actively contribute to a given study, by providing resources or intellectual input. As noted above, discussion of authorship is critical when a colleague provides essential materials such as clones, antisera, cell lines, or special animals. Collaboration is expected when the papers are based directly on data or samples gathered by another investigator. The overarching and critical principle is that issue of authorship should be discussed clearly to begin with. Should the project shift focus, or should additional aspects and elements be added to it, renewed discussions of authorship should take place. In case of dispute, the issue should be placed in front of the Scientific Advisory Board for resolution.

6. Future Grant Funds

It is expected that many of the projects seeded by BPDRF will generate results which will form the foundation for further grant proposals, either to the federal government or to private sources of funds. The following are the principles which should guide the sue of such data for further grant funding:

• It is fully the right of a primary investigator to use his/her data generated from BPDRF projects as the basis for subsequent grant funding. In general, the data belong first to the primary investigators listed on the grant, and only secondarily to the BPDRF.
  
  
• It is possible for collaborators to use the same body of data as the basis of separate and distinct proposals (e.g. aimed in different scientific directions), but it is critical that the collaborators apprise each other of their planned use of those data.
  
  
• No data found in the common database should ever be used in a grant proposal by someone other than the primary investigators with the explicit knowledge and agreement of these investigators.
  
  
• When BPDRF Investigators plan to apply for outside grant funding based in whole or in part on data generated from a BPDRF project, they should advise the Chairman of the Scientific Advisory Board of their intent at a very early stage (i.e. before the proposal is written, when it is still in the planning phase) and should inform them of the Specific Aims of the proposal.

7. Collaborations Outside the BPDRF

Participants and members of the Boards are expected and even encouraged to collaborate with other scientists outside BPDRF. Primary investigators who have generated the data and resources can follow the same rules they use insetting up independent collaborations in areas beyond those specifically covered by the proposal. However, the common data base cannot, in whole or in part, be made available to members outside BPDRF without the explicit and written approval of both the primary investigators who generated the data and the Scientific Advisory Board. In addition, if more than one primary investigator is involved in a BPDRF funded proposal, then all these investigators have to be made aware of the planned collaboration and their consent is needed as well.

Any disputes arising under this covenant shall be determined in New York under the rules of the American Arbitration Association and each party agrees to the application of New York law.

These rules form an integral part of the applications and eventual research agreements of each investigator and also apply to the mandates of members of the Boards as well as consultants retained by BPDRF and/or investigators.

6/28/02