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MOU for the ADSP Follow-Up Study (FUS)

Memorandum of Understanding for the ADSP Follow-Up Study (FUS)

Introduction

In response to the National Alzheimer's Project Act (NAPA) Public Law 111-375 NAPA 2012 2013, and NAPA 2016, NIA instituted a new genetics initiative (the Alzheimer’s Disease Sequencing Project [ADSP]) to understand the genetic architecture of Alzheimer’s Disease and Related Disorders (AD/ADRD). This project involves a large number of study participants from ethnically diverse populations and will capture and analyze common and rare genetic variation. The ADSP Discovery and Discovery Extension Phases have identified genomic variations associated with AD/ADRD and these findings and new discoveries are being pursued by the ADSP Follow-Up Study (FUS) for which this MOU is instituted.

Definition of the ADSP

The overarching goals of the Alzheimer's Disease Sequencing Project (ADSP) are to:

  • Identify new genes and genetic variations that contribute to increased risk for or protection against AD/ADRD
  • Provide insight as to why these genes and variations impact AD/ADRD
  • Identify potential avenues or approaches to transform genetic results into meaningful therapeutic targets for further development.

The ADSP requires a large number of study participants to capture all the relevant genetic variation. Using existing samples from numerous studies, the NIA has developed infrastructure including genotyping, sequencing, computational and functional analysis, and data processing and storage centers to produce high quality data and results, which will be made available to the scientific community through NIH-approved data repositories. Analyses of these data are expected to identify new genetic risk and protective variations. Both fundamental scientific discovery and leading-edge analytic approaches will be needed to achieve the research goals. The ADSP will conduct and facilitate analyses of these data to extend previous discoveries that may ultimately result in new directions for AD/ADRD therapeutics.

The samples for the ADSP are obtained from well-characterized, ethnically diverse cohorts and datasets of individuals characterized for AD/ADRD diagnoses with biospecimens (DNA and/or other biomarkers and tissues). Investigators in the ADSP will obtain the resulting data from NIAGADS (the NIA Genetics of Alzheimer’s Disease Data Storage Site, https://www.niagads.org/) including:

  • Quality control checked, cleaned, and harmonized sequence and phenotype data, using a set of routine checks on sample information, phenotype, GWAS, and sequencing data.  These processes are performed to ensure the data are of high quality and are ready for downstream analyses.
  • Information on the study designs of the included datasets (e.g. case-control, family-based, longitudinal, and prospective cohorts).
  • Descriptions of the study datasets including demographics.
  • Accompanying phenotypic information, minimally including age at disease onset, self-reported race/ethnicity, gender, diagnostic status, pathology, relevant biomarkers, and cognitive measures.  The ADSP will determine what additional information, if any, is needed by its members to facilitate the project.

Guiding Principles for the ADSP

The following principles of collaboration serve as a guide to the ADSP’s interactions and is based on a shared consensus about the best way to fulfill the mission of the ADSP:

Trust. The ADSP is based on a sense of mutual trust and respect among the participating members; trust cannot be imposed but is generated by transparency and fairness in all dealings. Participation in the ADSP is contingent upon each member and each group affirming this fundamental tenet and working with each other in a fair, respectful, and transparent manner.

Open communication:  It is extremely important that all decisions and activities be conducted in an open and transparent way. Each principal investigator of the individual groups that comprise the ADSP is responsible for communicating to members of his/her own group the tenants of the ADSP.

Timeliness: The ADSP members will endeavor to develop reasonable timelines for defining their activities including sample identification and transfer of biospecimens and phenotype data, genotyping array data, sequencing, quality control, data management, analytic plans, and drafting and publishing manuscripts.

Respecting priority:  The ADSP members will treat existing data contributed to the ADSP with care and adhere to NIH guidelines related to data release and embargoes.  Such data contributions can be used only with the consent of the submitters.

Mutual benefit:  The ADSP takes seriously the goal of providing mutual benefit for all those involved in the ADSP, not just those directly responsible for a particular discovery.

Supporting early stage faculty/students: The ADSP puts a high premium on the advancing the careers of trainees and early stage faculty. The ADSP encourages the next generation of scientists working in AD/ADRD and genomics to build on the results of this collaboration.

Based on the above principles, the following are also endorsed:

  • All efforts will be considered collaborative and will involve all interested parties in discussions and decisions. This includes design and selection of samples and related phenotype data, pipelines and procedures for sequence and other data processing and analysis, analysis plans and implementation, data management, data interpretation, and manuscript preparation and submission.
  • ADSP members will devise scientifically sound plans and initiate the agreed upon studies within the most expeditious timeline possible. 
  • All ADSP members will have equal access to releases of the ADSP data through NIAGADS, or under certain exceptional circumstances, from another NIH approved database.  Access to data is subject to informed consent limitations and NIH policy.  No analyses other than the quality control checks (described above) will begin until all partners have access to the data.
  • The data and results of the ADSP studies will not be communicated to study participants, relatives of participants, personal physicians, or insurance companies. Individual constituent cohorts may make their own policies on return of data to study participants outside of the auspices of the ADSP.
  • All submitters of samples and related data to the ADSP will receive any ADSP generated data specific to their own datasets.  They may use these ADSP generated data for their own analyses.  ADSP data may be used for analyses not related to AD/ADRD, subject to any informed consent limitations and NIH policies.   Members must notify the ADSP of the use of the ADSP generated data in a publication and assure appropriate ADSP authorship or acknowledgement according to current ADSP policies.
  • All submitters of samples and/or related data to the ADSP may analyze any data they themselves have collected and submitted to the ADSP.  In the interest of good faith and trust, the ADSP requests sharing the news of activities that may be relevant to the ADSP.
  • The ADSP data is considered a community resource and will be shared in accordance with existing NIH and Institute-specific protocols.  Access to the ADSP data will be made as soon as possible according to current ADSP guidelines, with the goal of making the data available as quickly as possible. Release of the DNA sequence data will be in accord with NOT-AG-16-033, which stipulates that ADSP DNA sequence data are not subject to embargo.

Membership in the ADSP

To accomplish its primary goal, the ADSP requires many different sources of participant data and biospecimens, data analyses, data interpretation, and infrastructure for genomic data generation and data management.  This requires a wide variety of expertise, which may evolve over time.  The list of members, as represented by the PIs of each participating group, is provided in Appendix A (current version available on the ADSP website).  Under the umbrella of the ADSP, support for these activities is provided competitively through a number of funding opportunity announcements (FOAs).  FOAs relevant to the ADSP are listed in Appendix B (current version available on the ADSP website).  New members may join the ADSP by funding through relevant FOAs or upon agreement of the ADSP Executive Committee.

Each ADSP group is free to add new investigators to its own group for participation in the ADSP. The PI of each of the ADSP groups is responsible for communicating the terms of participation in the ADSP to each new investigator.

Organization of the ADSP

Executive Committee:  The governing body of the ADSP will be its Executive Committee (EC). EC members will represent the interests and scientific expertise of the ADSP under the guiding principles of this MOU. The EC will be responsible for making ADSP policy decisions and resolving any conflicts that arise in the conduct of this project.  The EC is comprised of 13 members who are PIs with significant NIA funding relevant to the ADSP.  NIA representatives will attend as ex officio members, but with the ability to break ties if votes are necessary. Decisions are made by majority vote, with a quorum of eight required for a vote.   EC Membership should represent the diversity of ADSP funded activities; ethnic and gender diversity is also encouraged.  Individual EC members are reviewed every three years on a rolling basis (5, 4, 4).  Should a member resign, a new member will be appointed by majority vote of the remaining EC members.  The EC is expected to meet monthly.  Appendix C (current version available on the ADSP website) lists the current membership of the EC.

External Advisory Committee (EAC):  To assure progress and provide expert advice, the ADSP has an external advisory committee, which will meet with the ADSP at least once annually.  The constitution of the EAC is recommended by the EC with final approval by NIA staff.  The current EAC membership is provided in Appendix D (current version available on the ADSP website).

Additional Committees and Workgroups:  As a dynamic project, the ADSP requires flexibility in its organization.  Standing or ad hoc committees may be created by the EC as needed to address specific policy or process issues.  Project specific workgroups will be formed as needed to accomplish the goals of the ADSP. Workgroups may be created, expanded, contracted, or sunsetted, as needed.  Creation and sunsetting of workgroups requires EC approval.  Each workgroup will have at least two co-chairs chosen based on interest, expertise, and performance, with an attempt to balance workload across ADSP members.  Membership and attendance in the workgroups is open to all ADSP members based on interest and expertise.  Workgroups are expected to meet at least monthly, but can meet more often as necessary.  The current list of committees, workgroups, and co-chairs is provided in Appendix E (current version available on the ADSP website).

Policies and Procedures: The complex nature of the ADSP requires periodic development or modification of specific policies and procedures relating to issues such as publications, authorship, data access, analysis plans, data sharing, etc.  These are developed or modified as needed and approved by the EC.  Approved policies and procedures are available on the ADSP website (https://www.niagads.org/adsp/).

Progress Reports:  In addition to grant specific progress reports, NIA program expects regular written progress reports on the activities of the ADSP. In addition, regular scientific reports are to be provided to the Director of the NIH through a process determined by NIA staff.

Endorsement of this Memorandum of Understanding:

The Executive Committee of the ADSP has reviewed and approved this MOU, as indicated below:

[current EC membership]

Current versions of the Appendices are available on the ADSP MOU website

Appendix A:  Current list of NIA funded contact PIs who have agreed (signed) onto the MOU

Appendix B:  List of NIA FOAs for the ADSP

Appendix C:  Current members of the EC

Appendix D:  Current EAC membership

Appendix E:  Committees and workgroups with their co-chairs

 

The MOU established in 2012 is available via PDF.

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