appendix g: look ahead ancillary studies web viewas in all ancillary studies, ... 2010form / please...

CHAPTER 19

Look AHEAD-E Ancillary Study Policy

19.1 Definition..................................................................................................19-2

19.2 Role of Substudies and Ancillary Studies (SAS) Committee..............19-2

19.3 Ancillary Study Review...........................................................................19-2

19.4 Outside Funding Required for Ancillary Studies..................................19-3

19.5 Scientific Review of Ancillary Studies...................................................19-3

19.6 IRB Approval............................................................................................19-4

19.7 Confidentiality..........................................................................................19-4

19.8 Industry-Sponsored Ancillary Studies...................................................19-4

19.9 Procedure for Proposing an Ancillary Study in Conjunction with

Look AHEAD-E.........................................................................................19-4

19.10 Timeline for Submitting Ancillary Study Proposals.............................19-5

19.11 Data Issues...............................................................................................19-6

19.12 Publications and Presentations.............................................................19-6

Appendix A: Coordinating Center Fee Schedule for Providing Non-Look

AHEAD-E Investigators with Look AHEAD-E data for Ancillary

Studies......................................................................................................19-7

Appendix B: Look AHEAD-E Ancillary Study Proposal Template.........................19-9

Appendix C: Request Letter for Transfer of Ancillary Study Data to Coordinating

Center......................................................................................................19-14

19-1Chapter 19 Ancillary Studies – August 2016

19.1 Definition

In Look AHEAD, an ancillary study is defined as one that derives support from sourcesother than the cooperative agreement grant funds awarded by NIH for support of the main trial.

An ancillary study's objectives are not duplicative of and do not interfere with the Look AHEAD parent study but use Look AHEAD participants, samples, or data collected by Look AHEAD.

Look AHEAD represents a large and uniquely well characterized population sample of obese individuals with type 2 diabetes. To make the best possible use of this extraordinary resource, Look AHEAD encourages investigators to develop ancillary studies in conjunction with the trial and to involve other investigators, within and outside of Look AHEAD, in this process. An ancillary study may involve data collection from one or more Look AHEAD Centers for one or more cohorts.

19.2 Role of Substudies and Ancillary Studies (SAS) Committee

The Steering Committee must approve all ancillary studies to ensure that they do notimpose an unacceptable burden to staff or participants or conflict with the aims of Look AHEAD. The Steering Committee designates the SAS Committee to conduct a preliminary review of all proposed ancillary studies. Data collection may not proceed without the approval of the SAS Committee.

If any SAS member proposes an ancillary study, collaborates with an investigator who proposes an ancillary study, or is affiliated with the institution of an investigator who proposes an ancillary study, he or she will be recused from considering that ancillary study proposal, similar to NIH peer review policies for avoidance of actual or perceived conflicts of interest.

19.3 Ancillary Study Review

The SAS Committee will conduct a preliminary review and provide recommendations tothe Steering Committee for approval of ancillary studies concepts through the process described in this chapter. Proposals will be assessed to evaluate whether they would interfere with other parts of the protocol, would hamper continued recruitment or participation in Look AHEAD-E, or would be inconsistent with the Look AHEAD-E aim of facilitating a broad range of research.

If an ancillary study proposal meets the test of non-interference with Look AHEAD-E, it may still compete with other proposed ancillary studies for limited additional participant or staff time and/or biological resources (e.g., blood). To maximize efficiency, the SAS recommends that several similar and potentially competing proposals be combined.


Highest priority will be given to studies which best fit the following criteria:

1. Have the highest scientific merit.2. Do not interfere with or duplicate the main Look AHEAD-E objectives.3. Produce the least burden on Look AHEAD-E participants and the least demand on

Look AHEAD-E resources such as blood samples4. Require the unique characteristics of the Look AHEAD-E cohort5. Contribute to the aim of examining a broad range of research questions.

If a change occurs in the design or concept of the ancillary study after it has been approved, the SAS committee should be notified. The Steering Committee will be asked to approve the alterations, based on the recommendation of the SAS Committee.

The Data and Safety Monitoring Board (DSMB) may also be asked to judge the demands the proposed study places on participants and the priority in relation to Look AHEAD-E objectives.

19.4 Outside Funding Required for Ancillary Studies

Investigators proposing ancillary studies must seek funding from outside sources toconduct their research. Examples include funding obtained through investigator-initiated NIH research grant awards (R01s), grants from academic institutions, or private sources (e.g., drug companies, non-profit health organizations).

In assessing the acceptability of an ancillary study proposal, the Steering Committee will be concerned with both the explicit and the hidden costs to Look AHEAD-E entailed by the proposal (e.g., costs to the Coordinating Center for coordinating the additional data collection, costs to Clinical Centers for notification of alert values). The PI of the ancillary study should provide evidence that adequate support for carrying out these functions is available at his/her institution; if not, the Coordinating Center will conduct the activities required using resources that must be included in the ancillary study budget. (See, “Look AHEAD-E Reimbursement Costs” for details of the general policy for charges in providing investigators with Look AHEAD-E data, Attachment A.)

19.5 Scientific Review of Ancillary Studies

For proposals submitted to the NIH, either in response to an RFA or as investigator-initiated R01 applications, scientific review is through the regular NIH peer review system. For other proposals, if no other acceptable peer review has taken place, the scientific merit of a proposal will be reviewed by the SAS, supplemented with additional experts as necessary.


19.6 IRB Approval

All ancillary studies must receive necessary approvals from IRBs at the individualinstitutions involved. Documentation of IRB approval is required to be submitted to the Look AHEAD-E Coordinating Center before an ancillary study can be initiated in conjunction with Look AHEAD.

19.7 Confidentiality

Confidentiality of individually identifiable data about Look AHEAD-E participants must be assured. Look AHEAD-E provides no assurances that ancillary studies will be able to identify and contact participants in the future, particularly after Look AHEAD-E ends.

19.8 Industry-sponsored Ancillary Studies

Proposals for industry-sponsored ancillary studies are evaluated in accordance with the Look AHEAD-E procedures used for all other ancillary studies. As in all ancillary studies, conduct of industry-sponsored ancillary studies must comply with all existing Look AHEAD-E and NIDDK practices and guidelines. This includes the stipulation that all data relevant to the ancillary study must be submitted and shared with the Coordinating Center and the Steering Committee.

In addition, for industry-sponsored Ancillary Studies, it is the responsibility of the PI to work with the Coordinating Center and the sponsor, NIDDK, to obtain agreement with the industry sponsor describing how all data, biospecimens, and results will be used and how all publications will be developed. NIDDK practice includes the following requirement: that the industry sponsor (recipient) also must agree not to use material for any commercial purposes to include selling, commercial screening, and manufacturing.

19.9 Procedure for Proposing an Ancillary Study in Conjunction with Look AHEAD-E

Each ancillary study must include a Look AHEAD-E Principal Investigator or Co- investigator or Investigator, (or at minimum the Principal Investigator must endorse the project). The investigator on the proposal must also be approved by the NIH and LookAHEAD-E Executive Committee and must have the approval of the Principal Investigator at each Look AHEAD-E site proposed. The Principal Investigator of the ancillary study is responsible for submitting the study proposal to the SAS Committee, monitoring the study to ensure continuing compatibility with Look AHEAD-E, and serving as a liaison to the Look AHEAD-E Steering Committee, including attendance as requested at SAS and Steering Committee meetings

The “Look AHEAD-E Ancillary Study Proposal Template” (see Attachment B) must be completed and submitted to Carrie Williams ([email protected]) at the Coordinating Center and the Chair of the Ancillary Studies Committee, Helen P. Hazuda,


mailto:[email protected]

PhD ([email protected]). To assess the proposal, the SAS and Steering Committees need to know what additional information will be collected at any of the Look AHEAD-E clinic visits, the expected burden to participants, and the amount of time needed to complete the measurement. If Look AHEAD core data, staff, and/or analyses are needed for the ancillary study, this information should be provided.

The “Look AHEAD-E Ancillary Study Proposal Template” should be filled out before submitting an application for funding to a funding agency. The proposal will be reviewed during one of three predetermined cycles, as agreed upon by the Steering Committee and in correlation with the NIH submission cycle (see Timeline below). During the SAS review process, the investigator may be asked to respond in writing to concerns that may arise during review process. An approval by the SAS committee will not be concluded until the concerns are satisfactorily addressed. After SAS approval, the proposal will next require a final vote and approval by the Steering Committee. Once approved, the Principal Investigator will receive an official letter from the SAS Committee signed by either the Chair of the SAS Committee or the Coordinating Center representative on this Committee. A copy of the final funded proposal should be submitted to the SAS Committee.

19.10 Timeline for Submitting Ancillary Study Proposals

Ancillary Study Proposals will be accepted during an established SAS cycle thatcorrelates with the NIH cycle, which is three time periods in a calendar year. Basically, ancillary study proposals should be submitted to the SAS 8 weeks prior to the quarterly NIH cycle.

Correlating NIH submission dates with Look AHEAD-E SAS Committee are as follows:

NIH submission deadline Ancillary Studies Committee deadline June 5 April 5October 5 August 5 February 5 December 5

When submissions are received by the SAS in irregular intervals, i.e., additional reviews for applications responding to specific RFA’s, these submissions should be received by the SAS two months prior to the published deadline. With the receipt of these applications, the SAS committee will determine the feasibility of a timely review process, taking into account the requirement that both the SAS and Steering Committees are required to give approval.

Submissions involving access to stored samples will be reviewed one time per year and due on April 5. The SAS committee recommends that the study group should require all assays be conducted at the Central Laboratory, unless specialty analysis is not available at the lab.



19.11 Data Issues

The release of any Look AHEAD-E data from the Coordinating Center to an ancillary study investigator is subject to the rules regarding release of data defined in the Look AHEAD-E Publications Policy. The Coordinating Center will establish a projected cost for data they are asked to provide to the Investigator(s) and notify her/him of the charges. The Coordinating Center will release the requested data at which time payment has been received. See Attachment A for the Table of Charges. Data collected by the ancillary study must be provided electronically to the Look AHEAD-E Coordinating Center for integration into the main database. In return, ancillary study investigators receive an analysis file containing their data and approved data from the main study. The ancillary study PI is given the first opportunity to analyze, present, and publish data collected for the specific aims of the ancillary study.

After a reasonable time (in general, 18 months after the ancillary study PI has received the cleaned data), the ancillary study data are made available for additional uses by Look AHEAD-E investigators, in collaboration with the ancillary study investigators. It is the responsibility of the ancillary study PI to state in writing in advance to the Steering Committee any special circumstances that would mitigate against these guidelines for data sharing. Reasonable and justified requests for limiting Steering Committee access to the data will be considered. (See “Request Letter for Transfer of Ancillary Study Data to Coordinating Center”, Attachment C.)

19.12 Publications and Presentations

Proposals must be submitted for all publications, presentations and abstracts from anancillary study for review and approval by the Publications Committee prior to submission or presentation, in accordance with the general rules for publications and presentations.

Each manuscript and abstract is generally expected to include a Look AHEAD-E investigator as co-author, except under circumstances that should be stated and justified as part of the original submission to the SAS Committee.


Appendix A

Coordinating Center Fee Schedule for Providing Non-Look AHEAD-E Investigators with Look AHEAD-E data for Ancillary Studies

January 2016

Background: The Look AHEAD-E study has generated substantial data that may serve as resources for ancillary studies. Current funding is focused on the conduct of Look AHEAD-E. Providing data and support for ancillary studies involves effort that individually may appear to be modest, but which added together can over-tax the resources of the Coordinating Center. Look AHEAD-E has developed a general policy regarding fees that must be included in ancillary studies that utilize Look AHEAD-E data. The following table provides a description of charges that must be included in grant applications to support Coordinating Center activities for grants submitted beginning March 1, 2016.

Table of ChargesCost Categories

Simple Request

Moderate Request

Advanced Request

Data set preparation $10,000 $15,000 $20,000Summary table preparation for a meta-analysis $5,000 $10,000 $15,000Receive data, archive, track and distribute to PIs Required of all studies; no additional

The Look AHEAD-E Coordinating Center will determine the category of the data set or request and will increase charges appropriately for large or complicated data sets or analyses. The following is a guideline for determining request cost categories:

Si m p l e = one visit, < 100 variables (variables outlined with Look AHEAD-E variable names)

M o d e r ate = multiple visits and/or outcome data <100 variables (variables outlined with Look AHEAD-E variable names).

A d v a n ce d = multiple visits and/or outcome data > 100 variables.

Exceptions can be made (up or down, including higher than the "advanced" level) by the Coordinating Center, as determined by the request. Conditions to consider are if the Coordinating Center has to develop an IRB application or report, create derived variables, or do other administrative tasks.

Contact person: Carrie Williams (Project Manager)[email protected]


Wake Forest Health Sciences Department of Biostatistical Sciences Medical Center BoulevardWinston-Salem, NC 27157Phone: (336) 716-6321Fax: (336) 713-5249


Appendix B

Look AHEAD-E ANCILLARY STUDY Proposal Template

(02/06/2014)

The following areas are to be addressed in the proposal. The proposal is limited to 5 pages or less (using 11 point font). Submit your proposal to Carrie Williams ([email protected]) and the Chair of the Ancillary Studies Committee, Helen P. Hazuda, PhD ([email protected]).

NOTE: The submission is to be received at least 3 months in advance of any planned grant submission deadline. Submissions received <3 months in advance are not guaranteed to be reviewed and a decision made prior to the grant submission deadline.

1. Date:

2. Title of Ancillary Study:

3. Principal Investigator:Institution:Address:E-mail Address:Phone Number:

4. Look AHEAD-E PI who is a Co-Investigator on this Project:

5. Additional Co-Investigators and E-mail Addresses:

6. Science Background, Rationale, Significance:

7. Main Hypothesis, Aims:

8. Methods:a. Existing data you anticipate requestingb. If requesting biological samples (stored blood), provide details on the

number of samples, time periods requested, amount of sample to be used, and details on how the samples will be used.

c. New data you anticipate collectingd. Sample size and power justification

9. Burden (include plan to support burden and costs):a. Participantsb. Clinicc. Coordinating Center




10. Resourcesa. State clearly any resources you may need from the Coordinating

Center (limited to data transfer from WFUHS)b. State clearly any identifiable needs from the clinics

11. Safety: a. Risk to participantsb. Steps to mitigate or minimizec. Complete the Look AHEAD Ancillary Study Data Monitoring & Safety

Form (below)

12. Funding Mechanism:a. Granting agencyb. Submission Deadlinec. RFA/PA is applicable

13. Cost for data analysis by Coordinating Center


Ancillary Study - Data Safety Monitoring Report Request

April 30, 2010 - 1stRevision March 23, 2007 -Original

The Look AHEAD Safety Committee requests from you a report about new data already developed (or to be developed) in your Ancillary Study. The Safety Committee adopted this safety reporting procedure in March 2007.

The re port should in c lu d e the f ollowin g :

(1) a list of all new variables developed by your Ancillary Study;

(2) your reasoning about which of these variables are possibly meaningful clinically; and

(3) your plans to report clinically meaningful results back to participants and their physicians. This information could be provided in the form of a table and a brief cover memo (see model table attached). The completed Data Table with brief cover letter should be sent to the attention of Ms. Carrie Williams at the Coordinating Center.

Case that Originally Prompted this RequestThe case involves an NIH funded ancillary study that involves questionnaires and storedblood samples. The goal of the study is to study biomarkers of oxidative stress in relation to weight loss. The study PI and the local site PI’s all judged that the biomarkers of interest were so novel as to not warrant reporting to participants or their physicians. However, to accurately estimate biomarker levels, the protocol required measurement of circulating immunoglobulins-IgG, IgM, and IgA. These were measured on stored specimens, months after the specimens were drawn. After the study had been in the field for several years, the following question arose: How should the immunoglobulin levels is addressed? Unlike the biomarkers that were the focus of the study, these were clinically available assays that could be important. For example, very high levels of IgG could indicate an underlying bone marrow cancer. Since Hopkins was one of the clinical sites involved, we had to deal with this question directly. Our judgment was that, although most immunoglobulin level ‘abnormalities’ are non-specific (e.g. due to transient infection or genetic variation) and hence not used for screening in standard practice; we should nonetheless investigate the data, with particular attention to marked or progressive abnormalities, and report those back to participants and physicians, couched in appropriately non-alarmist language.

19-11

Chapter 19 Ancillary Studies – May 2016

Deliberations of Safety CommitteeThe case in point above was addressed locally. The Safety Committee developed a study-wide response, to reduce the likelihood that other ancillary PIs and clinic PIs would be surprised by a similar circumstance?

The c ommittee f o r med c onse n sus a r ound the f ol l owing opinions:

(1) the Parent Study already has adequate monitoring and reporting mechanisms in place for clinically relevant data developed in ‘real time’ (e.g. ECG, GXT, DEXA, A1c, lipids, BP, etc.);

(2) the parent study should consider monitoring and reporting concerns as data are developed from banked specimens (e.g. serum, DNA);

(3) individual Ancillary Studies might not be as well prepared as the Parent Study, especially those that rely on delayed assay of banked specimens;

(4) data monitoring and safety in Ancillary Studies is inherently the responsibility of the Ancillary Study PI and their collaborating PI’s at Look AHEAD clinics, under the direction of the relevant IRBs; and

(5) the role of the Look AHEAD Safety Committee vis a vis the Ancillary Studies should not be to micro-manage data monitoring and reporting, but rather to insure that such plans are in place and appear reasonable.

Considerations in Writing ReportWith opinion #5 in mind, the Safety Committee requests a brief report from eachAncillary Study PI regarding data monitoring and safety. Please use the form included and keep the following considerations in mind:

D a ta A lre a d y D e v e loped You should already be acting on a plan for monitoring and reporting already developed data that you consider ‘clinically significant’. If you’re not sure about clinical significance after reading this memo and completing the form, the Safety Committee is glad to help you deliberate.

D a ta Y ou Plan to D e v e lop These are data you already specified in your approved Ancillary Study proposal, but you haven’t developed yet (e.g. assays on banked specimens).

T y pe o f D a t a Use your judgment in terms of lumping. For example, you might show “complete blood

19-12


count” rather than listing individual components. But please split where you think questions might arise. For example, for heavy metals, you might lump arsenic, mercury, and lead together as recognized toxins that require monitoring and split out chromium, selenium, and zinc as trace minerals of uncertain significance that do not require reporting.

Clinic a l l y R e lev a nt? Please consider this carefully. In the trigger case, none of the investigators considered serum immunoglobulins as ‘clinically relevant’ because they’re not used for screening purposes in primary care. But, upon more careful consideration, the committee thought it was possible that an abnormal result could be a clue to an underlying malignancy. It is likely that most tests done in clinical laboratories could have some clinical relevance, even if only in selected individuals. For example, fasting insulin level is not typically the object of medical attention. However, highly elevated fasting insulin could indicate the presence of an insulinoma. If you’re not sure, please pose the question to the Safety Committee and they will give you their consensus advice.

I f re le v a nt, how do y ou monitor a nd r e port? ( or f or d a ta y e t to d e v e loped, how w i ll y ou monitor a nd r e port ? ) Here, the committee would like you to say something about time frame, who reviews, and something general about how you flag abnormal results. At this point, keep it brief. They will follow up with you if needed to know more details.

19-13


Look AHEAD Ancillary Study Data Monitoring & Safety FormMarch 31, 2010Form / Please and fill out using MS Word and add more rows and space as needed

If you’re filling this form out as part of a ‘new Ancillary Study’ application, then please ignore the ‘data already developed’ section

Today’s Date: Name of Ancillary Study: Ancillary Study PI:Collaborating Look AHEAD Sites: Total Number of Participants:

Type of Data ClinicallyRelevant? (Yes, Maybe, No)

Does yourconsent form comment about monitoring or

If clinically relevant, how do/will you monitor and report?

Data You’ve Already Developed

Data You Plan to Develop

Comments:

19-13 Chapter 19 Ancillary Studies – 12/05/2017

Appendix C

Re q uest L e tter f o r T r a n s f er o f Anci l lary St u dy Data t o C o ordin a t i ng Cent e r

Date:To: Ancillary Study Principal Investigator Re:Look AHEAD-E Ancillary Study:

Dear:

The Look AHEAD-E Coordinating Center is soliciting help from Look AHEAD-E Ancillary Study Principal Investigators to facilitate the transfer of their data to our central archive of study databases. As you’ll recall, ancillary studies are subject to data transfer requirements, which was part of your agreement with the Look AHEAD-E study group. This requirement is outlined in the Ancillary Studies Policy document (see excerpt from the policy below).

We have determined that the data transfer can most easily be accomplished if the data file is saved in a standard file format such as .xls or .csv. The data dictionary should accompany the data so that we will be aware of any variables that may have been created. Ms. Lea Harvin ([email protected]) will coordinate our efforts. We are requesting that you or one of your staff please contact Ms. Harvin in the next few weeks to initiate the process of data transfer. We also request that you send confirmation to Ms. Carrie Williams (CCWillia@WakeH ealth.edu ) that you have either previously transferred your data or you have made initial contact with Ms. Harvin to arrange the data transfer.

Best regards,

Mark Espeland, PhDPrincipal Investigator, Look AHEAD-E Coordinating Center

cc: Mary Evans, PhDLook AHEAD-E Project Director, NIDDK

“The release of any Look AHEAD data from the Coordinating Center to an ancillary study investigator is subject to the rules regarding release of data defined in the Look AHEAD Publications Policy.

Data collected by the ancillary study must be provided electronically to the Look AHEAD Coordinating Center for integration into the main database. In return, ancillary study



investigators receive an analysis file containing their data an approved data from the main study. The ancillary study PI is given the first opportunity to analyze, present, and publish data collected for the specific aims of the ancillary study.

After a reasonable time (in general, 18 months after the ancillary study PI has received the cleaned data), the ancillary study data are made available for additional uses by Look AHEAD investigators, in collaboration with the ancillary study investigators. It is the responsibility of the ancillary study PI to state in writing in advance to the Steering Committee any special circumstances that would mitigate against these guidelines for data sharing. Reasonable and justified requests for limiting Steering Committee access to the data will be considered.”


appendix g: look ahead ancillary studies web viewas in all ancillary studies, ... 2010form / please...

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