Ancillary Studies Policies and Procedures

Ancillary Studies Policies and Procedures

Contents: MESA Ancillary Studies Policy

MESA Ancillary Studies Review Procedures

Appendix 1: Committee Members Lists

1. 
   Do not interfere with the main MESA objectives
   
2. 
   Have the highest scientific merit
   
3. 
   Produce the smallest burden on MESA participants and the least demand on MESA resources, such as blood samples
   
4. 
   Require the unique characteristics of the MESA cohort
   

In addition, priority for studies requesting biological samples will be highest if they:

1. 
   Do not make use of samples from those participants with the fewest samples;
   
2. 
   Use thawed samples whenever possible;
   
3. 
   Involve assays that may be done on more than one sample type to allow selection of the most abundant type available (e.g. serum or EDTA plasma);
   
4. 
   Use the smallest sample volume possible; evidence of attempts to minimize volumes will be examined by the Blood Laboratory Subcommittee.
   
5. 
   Can be integrated with other studies to conserve sample or limit freeze-thaw cycles.
   

Responsibilities of Ancillary Study Investigators

1. 
   Costs. The investigator applying for an ancillary study must supply all additional funds required to conduct the study. The Steering Committee will be concerned with both the obvious and the hidden costs to MESA entailed by an ancillary study (such as costs to the Coordinating Center for coordinating the additional data collection, costs to Field Centers for notification of alert values, costs to laboratory for retrieving samples, etc).
   

It is important to note that the MESA Coordinating Center (CC) at the University of Washington nearly always incurs expenses on behalf of ancillary studies by providing support in data collection, data management, quality control, data analysis, study coordination and communications, events ascertainment, and other functions. These services can be of critical value to an ancillary study. PIs who plan to propose an ancillary study with the intention of seeking grant funding should first consult with the MESA CC Project Director to determine what level of involvement will be required of the CC and the associated costs. In general, this will result in a subcontract proposal from the CC to be included in the PI’s grant application.

2. 
   Confidentiality and identification of MESA participants. Confidentiality of individually identifiable data about MESA participants must be assured. As a general rule, no personal identification of participants will be provided to ancillary studies staff. There are no assurances that participants will be able to be identified and contacted in the future for the purposes of an ancillary study, particularly after MESA ends.
   

3. 
   Clinical implications of findings. The proposing investigator must clearly delineate any findings of clinical significance that may result from the study, including genetic findings, and propose how these will be handled, including reporting to participants and their physicians and providing recommendations for follow up. This includes incidental findings, such as pathology identified from an imaging study that is not the focus of the study.
   

4. 
   Genetic studies. Genetics studies may include only participants who provided appropriate informed consent. Investigators should consult the Coordinating Center to determine the number of participant samples eligible for analysis based on responses from the appropriate informed consent. Medical and other (ethical, legal and social) implications of the findings and reporting of results must be addressed in the proposal.
   

5. 
   Ancillary studies to existing MESA ancillary studies. A new ancillary study that involves participants, staff, or biological samples of an existing MESA ancillary study but not those of the main MESA study is considered an ancillary study only to the parent (existing) ancillary study. (An example would be a proposal that involves air pollution monitoring only in new recruits in the MESA Air Study, but does not involve main MESA study participants.) Such proposals are to be submitted to the parent ancillary study for review and approval, and will also be circulated to the main MESA Ancillary Study and Steering Committees for informational purposes. If a new ancillary study involves participants, staff, or biological samples of an existing MESA ancillary study as well as those of the main MESA study, review and approval process by both the parent ancillary study and main MESA study will be required. Please contact the PI of the parent ancillary study for information regarding the appropriate administrative contact.
   

6. 
   Inclusion of Sponsoring MESA investigator(s). A MESA-affiliated investigator must be included as a co-investigator on an ancillary study. This individual is responsible for presenting the study to the Ancillary Studies Committee, monitoring the study to assure continuing compatibility with MESA and serving as a liaison to the MESA Steering Committee. In addition, each manuscript and abstract is generally expected to include a MESA investigator.
   

7. 
   Early communication with MESA Centers. The proposing investigator and/or his/her liaison should consult with PIs of pertinent Field Centers, Reading Centers, Laboratories, and/or the Coordinating Center, depending on the anticipated involvement of Field Center staff and oversight, blood or urine analysis, and data management and analysis. Such discussions should focus on feasibility and provision of necessary resources and do not constitute formal approval of the study.
   

8. 
   Timeline. All proposed ancillary studies must be submitted to the MESA Coordinating Center for subsequent circulation and review. Studies must be submitted 6 weeks prior to a funding application; 8 weeks if biospecimens are requested. Studies submitted after these deadlines may not receive timely approval. In addition, studies that involve a subcontract to the Coordinating Center must have their final budget negotiated and approved for internal University of Washington review no later than 5 weeks prior to a funding application.
   

9. 
   Final application or proposal. A copy of the final proposal as submitted for funding should be submitted to the Coordinating Center and to the NHLBI Project Officer.
   

10. 
    Industry participation. Proposals for industry sponsorship or collaboration will be evaluated in accordance with the procedures described above. In addition, it will be the responsibility of the PI to obtain agreement through an appropriate contractual mechanism that all data relevant to the MESA ancillary study will be shared with the Coordinating Center. As an initial step in study planning, the PI should contact the MESA Project Officer to determine if an agreement between NHLBI and industry should be developed and implemented or to approve the agreement between industry and the investigator’s institution. Industry-sponsored ancillary studies shall include only participants who provided appropriate informed consent and must comply with current NHLBI guidelines, which are available from the Coordinating Center or Project Office upon request.
    

11. 
    Status reports. The ancillary study PI should keep the MESA Coordinating Center apprised of major developments in the life of the application or proposal, including success of funding, start date, changes in protocol, and any resulting publications or presentations. The MESA Coordinating Center will query PIs twice per year, or as needed, for a status update of their ancillary studies, the results of which will be included in the Steering Committee and Monitoring Board reports.
    

12. 
    Revising or resubmitting proposals. Ancillary Studies that are not approved or not funded become inactive. If the PI wishes to resubmit the proposal for funding, s/he must communicate this to the Coordinating Center.
    

Substantial changes to the science or scope of an approved ancillary study require review by the MESA Ancillary Studies and Steering Committees and, if relevant, Lab or Genetics Subcommittee. The PI must submit to the MESA Ancillary Studies coordinator:

1. 
   A revised study proposal with changes tracked, highlighted, or bolded;
   
2. 
   A brief modification request memo summarizing the changes and stating the rationale for the changes. The memo may be addressed to the MESA Ancillary Studies Committee.
   

            Substantial changes include:

• 
  requests for additional biospecimens
  
• 
  significant additional data
  
• 
  requests to add new outcomes or change the main analytical exposure
  
• 
  any additional participant burden
  

Formal modification requests are NOT needed for the following:

• 
  notification of a reduction in needed biospecimens
  
• 
  requests to add co-investigators
  
• 
  requests to slightly modify the analytic approach
  

However, all such minor changes must still be communicated to the Ancillary Studies Coordinator via a memo addressed to the MESA Ancillary Studies Committee.

13. 
    Review of publications and presentations. Manuscript proposals based on ancillary study data require approval of the MESA P&P committee. All the publications, presentations and abstracts from an ancillary study must be reviewed and approved by the MESA Publications Committee and the Steering Committee prior to submission or presentation, in accordance with the general rules for publications and presentations.
    

MESA Ancillary Study Review Procedures

1. 
   Investigators wishing to propose studies that pose participant, clinic, or Blood Lab burden are encouraged to discuss their studies with the NHLBI Project Office for MESA before submitting a proposal to the Ancillary Studies Committee.
   
   
   
2. 
   Principal Investigator submits ancillary study proposal using the template provided on the MESA website via an email to the MESA Coordinating Center (CC) Assistant.
   
   
   
3. 
   MESA CC Assistant reviews proposal for administrative compliance (assures that all questions have been answered) and to determine involvement of MESA labs and/or reading centers. If the proposal is not complete, it will be returned by email to the investigator for revision and resubmission.
   
   
   
4. 
   MESA CC Assistant forwards the proposal by email to the MESA Ancillary Studies Committee (ASC) (see Appendix 1 for list of members), the MESA Steering Committee (SC) (Appendix 1), and to relevant subcommittees (e.g., Laboratory, Genetics, CT committees). The chair of the ASC will decide whether to convene a conference call, generally one week prior to the monthly SC call, or handle the review by email. Chairs of all relevant subcommittees communicate their reviews to all members of the ASC and SC by email (or in conference call). The ASC review and recommendation for approval are communicated to all SC members, including the ASC comments and the comments of relevant subcommittees.
   
   
   
5. 
   Proposals will be discussed by the SC, generally during their regular monthly conference calls. The chair of the ASC is invited to be present for that portion of the SC conference call. In some cases, as determined by the chair of the SC, email reviews will be conducted. The SC may also invite the PI (and/or the PI’s MESA sponsor) to present the proposal and answer questions and absent him/herself during discussion and voting.
   
   
   
6. 
   If the proposal requires revisions, the comments of the ASC (and LC, GC or SC, if applicable) are sent to the PI by the CC Assistant (with a copy to ASC and SC chairs and NHLBI Project Officer). The PI must address these comments in a separate letter that accompanies the revised proposal and send these to the CC Assistant who forwards them to the appropriate committee(s).
   
   
   
7. 
   Proposals that are approved by the SC but involve no participant burden (though they may use scans or repository samples), and minimal clinical implications are sent by the CC Assistant to the NHLBI Project Officer who sends the formal letter of approval to the PI. (Copies of these communications are sent to the ASC and SC chairs and CC Project Director.)
   
   
   
8. 
   Proposals that are approved by the SC and involve participant burden are sent by the CC Assistant to the NHLBI Executive Secretary and the NHLBI Project Officer, together with all review materials plus updated study and burden tables. (Copies are sent to the ASC and SC chairs, and CC Project Director) The CC Assistant also notifies the PI of the progress in the review process.
   
   
   
9. 
   The Executive Secretary of the MESA Monitoring Board forwards the final proposal, any relevant review materials, and the modified Burden Table to the Monitoring Board for review (allow three weeks).
   
   
   
10. 
    The results of the Monitoring Board review are communicated by formal letter to the PI by the Executive Secretary. The results are also communicated by email to the chairs of the Steering Committee and Ancillary Studies Committee, and the PI and Administrator of the Coordinating Center.
    
    
    
11. 
    In addition to the NHLBI letter of approval, and if the PI of the ancillary study requests it, the SC Chair will write a letter of support that may be included in the PI’s grant application.
    

MESA Ancillary Studies Committee:

1. 
   Susan Heckbert, MD, PhD (Chair)
   
2. 
   Suzette J. Bielinski, PhD
   
3. 
   David Bluemke, MD, PhD
   
4. 
   J. Jeffrey Carr, MD, MSCE
   
5. 
   Joseph Chris Delaney, PhD
   
6. 
   Philip Greenland, MD
   
7. 
   Hanyu Ni, PhD, MPH
   
8. 
   Nels C. Olson, PhD
   

MESA Steering Committee:

1. 
   Greg Burke, MD, MS (Chair)
   
2. 
   David Bluemke, MD, PhD
   
3. 
   Diane Bild, MD, MPH
   
4. 
   Matthew Budoff, MD
   
5. 
   Aaron Folsom, MD
   
6. 
   Richard Kronmal, PhD
   
7. 
   Joao Lima, MD
   
8. 
   Kiang Liu, PhD
   
9. 
   Robyn McClelland, PhD
   
10. 
    Daniel O’Leary, MD
    
11. 
    Wendy Post, MD, MS
    
12. 
    Steven Shea, MD, MS
    
13. 
    Russell Tracy, PhD
    
14. 
    Karol Watson, MD, PhD
    

MESA Executive Committee:

1. 
   Diane Bild, MD, MPH
   
2. 
   Greg Burke, MD, MS
   
3. 
   Richard Kronmal, PhD
   

MESA Coordinating Center Manager: