> ![](media/image2.wmf)

> List of Acronyms

  ----------- -----------------------------------------------------------
  JHU         Johns Hopkins University

  MA          Mexican American

  MALD        Mapping Admixture Linkage Disequilibrium

  MLS         Maximum Lod Score

  MOO         Manual of Operations

  MRC         Resource Center

  NCI         National Cancer Institute

  NIDDK       National Institute of Diabetes& Digestive & Kidney Diseases

  NIH         National Institutes of Health

  NIMH        National Institute of Mental Health

  OGTT        Oral Glucose Tolerance Test

  PBL         Peripheral Blood Lymphocytes

  PBMC        Peripheral Blood Monocytes

  PI          Principal Investigator

  PIC         Participating Investigator Center

  PID         Patient Identifier Number

  QC          Quality Control

  QTL         Quantitative Trait Locus

  RBC         Red Blood Cells

  RR          Relative Risk

  S.A.G.E.    Statistical Analysis for Genetic Epidemiology

  S/MIME      Secure Multipurpose Internet Mail Extensions

  SSL         Secure Socket Layer

  TAC         Total Allele Content

  TDT         Transmission/Disequilibrium Test

  UCI         University of California at Irvine

  UNM         University of New Mexico

  URN         Urine

  UTHSCSA     University of Texas Health Sciences Center San Antonio
  ----------- -----------------------------------------------------------

#  INTRODUCTION 

## Overview of the Manual of Operations

The Manual of Operations (MOO) provides detailed instruction of study
procedures, details of each subcommittee, and instructions regarding all
aspects of the study operations, inclusive of human specimen sample
shipping and handling.

## Study Overview

The Family Investigation of Nephropathy and Diabetes (FIND) study will
have prospective subject entry. The National Institute of Diabetes and
Digestive and Kidney Diseases at the National Institutes of Health
(NIDDK/NIH) funds FIND.

FIND is a multi-center consortium, comprising eight (8) Participating
Investigator Centers (PICs) and a Genetic Analysis and Data Coordinating
Center (GADCC), established to study the genetics of Diabetic
Nephropathy. The charge of the consortium is to acquire sets of families
with well-characterized diabetic nephropathy, establish a secure master
FIND database, and perform a genome scan to identify chromosomal regions
linked with diabetic nephropathy. Analytic methods will include a)
affected sibling pair (ASP), discordant sib pair (DSP), affected
relative pair (ARP), and discordant relative pair (DRP) linkage analyses
and b) Mapping by Admixture Linkage Disequilibrium (MALD) analyses. To
expedite the mapping, and eventual cloning, of nephropathy genes,
markers at candidate genes or human chromosomal regions containing
putative renal failure susceptibility genes identified in previous
genome scans, or syntenic to regions of renal susceptibility in model
organisms, will also be examined. For candidate gene analysis both
linkage and association (Transmission Disequilibrium Test (TDT))
methodologies will be used.

There are eight (8) Participating Investigator Centers (PICs). The GADCC
and PICs, inclusive of each personnel directory, together with the
NIDDK/NIH support staff and the External Advisory Committee, are given
in APPENDIX A. This list, updated monthly, can be found on the FIND
website (<http://darwin.cwru.edu/find>).

## Study Objectives

The primary aim of the FIND is to identify genes responsible for
diabetic nephropathy and their linkage relationships, if any, to
nephropathy.

Specific aims are to:

1.  Organize a multi-centered consortium to undertake the recruitment of
    participants of several ethnicities.

2.  Use Affected Relative Pair (ARP), Discordant Relative Pair (DRP),
    and Mapping by Admixture Linkage Disequilibrium (MALD) linkage
    analyses to scan the genome for linked chromosomal regions, and the
    transmission disequilibrium test (TDT) to evaluate candidate genes
    in those regions with evidence for linkage.

3.  Use environmental data as a guide for possible risk factor effects
    on genetic susceptibility.

This is a clinical research cross-sectional study and longitudinal
studies will not be addressed at this time, although may be at some
later date.

## Committee Structure

> ![](media/image3.png){width="6.49375in" height="4.8805555555555555in"}

## Constitutional Policy

The Steering committee is the governing body that has the authority to
approve and amend the protocol, subcommittee membership, and manual of
operations with a six out of ten majority vote. The Steering Committee
is made up of the PI's of each center (the eight PICs and the GADCC),
and the NIDDK representative (Appendix G). It will meet at least twice a
year to establish any changes to the manual of operations, including
subcommittee memberships.

#  intellectual Property and Archive Policies

## Function and purpose

> The Intellectual Property and Archive Subcommittee will develop and
> propose policies relating to ownership and storage for data and
> biological specimens generated by the F.I.N.D.

## Duties of the Intellectual Property and Archive Subcommittee

> Develop policies relating to ownership and storage for data and
> biological specimens generated by the F.I.N.D., and to the
> distribution of these to non-F.I.N.D. investigators (in the latter
> regard, the duties may overlap with the Subproject Evaluation
> Subcommittee). These policies will require approval by the Steering
> Committee.
>
> Evaluate and make recommendations for use of data or biologicals by
> specific outside (i.e. non-F.I.N.D.) investigators. (This duty may
> overlap with the Subproject/Ancillary Studies Subcommittee.)
>
> Serve as the initial forum for decision and appeal of intellectual
> property issues. Decisions in this regard are to be recommended to the
> Steering Committee for final decision.
>
> All policies and recommendations need to be in accordance with the
> arrangements made with the specific population involved (e.g. Native
> American groups), and in accordance with NIH and federal guidelines,
> and when possible in accordance with individual institutional
> guidelines. Policies and recommendations \[internal and external\]
> will be dictated by the nature of the informed consents signed by the
> subjects.

## Categories of Materials

There are several categories of data, as follows:

######## Category 1: {#category-1 .unnumbered}

> Data are project wide, e.g., phenotypes being recorded on all
> participants, genotyping data for genome scans. In general these are
> data specified in the MOO (Manual of Operations).

######## Category 2: {#category-2 .unnumbered}

> Data that are part of the designed study, but generated by a limited
> number of centers (e.g. 2 PIC's, or 1 PIC and the GADCC).

######## Category 3:  {#category-3 .unnumbered}

> Data that are the results of an approved subproject (ancillary) study
> that is funded by the NIDDK as a supplement to the F.I.N.D. or
> formally in collaboration with the F.I.N.D. (e.g. the NEI retinopathy
> study).

######## Category 4: {#category-4 .unnumbered}

> Data that are the result of an approved subproject (ancillary study)
> not funded by the NIDDK.

######## Category 5: {#category-5 .unnumbered}

> Data that are generated independently from F.I.N.D., but utilizes in
> part F.I.N.D. subjects, whether conducted by F.I.N.D. investigators or
> non-F.I.N.D. investigators.

## Biological Specimens

There are two basic categories:

######## Category 1: Material in finite supply. {#category-1-material-in-finite-supply. .unnumbered}

> a\. DNA
>
> b\. Serum/plasma
>
> c\. Urine

######## Category 2: Material of unlimited supply. {#category-2-material-of-unlimited-supply. .unnumbered}

This can include but is not limited to:

> a\. Immortalized cell lines
>
> b\. DNA from immortalized cell lines

## Ownership

The basic concept here is that ownership of material is vested in the
participating investigators (and their institutions), limited by
agreements with, and the rights of, participating populations, NIH and
federal polices, and policies of the individual funding agencies.
Confidentiality of individual participants will be maintained with all
data shared between centers and with all releases of data. Furthermore,
it is deemed advisable that, after some period of time, certain
categories of data and possibly biologic materials be made available to
non-FIND investigative teams.

######## Category 1 {#category-1-1 .unnumbered}

> These data will be owned jointly by the individual PIC's and the
> GADCC. They will be kept at the GADCC, and at each PIC that desires
> them. While each group is free to examine and evaluate the data for
> informal/internal purposes, the formal use of these data will be
> dictated by the Steering Committee via the Analysis, Protocol, and the
> Publication Subcommittees. The GADCC and PIC's will not disclose the
> data to other parties except as specified by the above committees and
> the Manual of Operations.
>
> After each F.I.N.D. publication that involves major data, the GADCC
> will make the data used in that publication available to the public
> (the exact method to be proposed by the GADCC) as soon as is
> reasonably possible, but no later than within one year. These data
> will be anonymized, i.e. identifiers (e.g. birthdates) will be
> removed, and ethnic group identified by only one of 4 categories
> (Caucasian, African-American, Hispanic, Native American). This
> anonymization must be done before any data are released to the public.
>
> When the GADCC (or equivalent successor) ceases to function as the
> data coordinator and analytic resource to the F.I.N.D., it will
> release a fully documented copy of all F.I.N.D. data to each PIC
> (limiting identifiers to the PIC from which the data were derived),
> and an anonymized data set to the NIDDK. One to Two years after the
> termination of the F.I.N.D. and/or this release (whichever comes
> first), the anonymized data set will be made public (this will
> probably require an archiving mechanism, to be discussed). Decisions
> regarding any other disclosure of data to other parties will be
> brought to the Intellectual Property Subcommittee, which will make
> recommendations for decision by the Steering Committee.
>
> Note: The responsibilities of any users (e.g. the GADCC) to return
> these data to the central database will continue, the data being sent
> to the archives/repository mechanism established after the GADCC
> ceases to function.

######## Category 2  {#category-2-1 .unnumbered}

For the most part these are to be treated in the same way as category 1
data, but ownership of the data is to be vested in the individual
participating centers (e.g. the GADCC and a PIC or 2 PICs). The location
of the data should be in the GADCC and participating centers.

######## Category 3  {#category-3-1 .unnumbered}

These are to be treated as category 1 or category 2 data, depending on
the number of Centers involved.

######## Category 4  {#category-4-1 .unnumbered}

These data are to be owned by the responsible investigators. Data
analysis is the responsibility of those investigators, with whatever
involvement of the GADCC the Subproject and Steering Committee will have
designated. Since this is an approved project of the F.I.N.D., even if
the GADCC is not involved in analysis, the data (e.g. the primary
molecular genotyping data) should be immediately available to the GADCC
and the Steering Committee upon publication. However any public release
of these data will be at the discretion of the responsible
investigators, but will be included in the full public data release.

######## Category 5  {#category-5-1 .unnumbered}

The responsible investigators own these data, and their analysis. After
publication, the data are to be made available to the GADCC central
database (and/or successor) within 3 months. Public distribution of
these data is at the discretion of those investigators but will be
included in the full public data release.

## Biological materials

> The basic principal here is that the first priority is the desire of
> populations, second the needs of the study, third that of the
> investigators, and fourth posterity.

### Finite Supply

> PIC\'s will have the option of receiving a sample of DNA (quantity to
> be determined) from all FIND participants recruited at that site
> during the initial 5 year enrollment period. Within one to two years
> of the conclusion of the study, any remaining biological materials in
> this category (e.g. DNA, serum) residing at the GADDCC or other
> central laboratory (e.g. assay laboratory) will be treated as follows:

a.  If a given population has requested return of samples, that request
    will be honored.

b.  Of the remaining material at the GADCC (or other central core), half
    will be returned to the individual PIC, and half will be archived
    for the NIDDK (mechanism to be determined).

c.  The ownership of these samples will reside with the possessors (e.g.
    the NIDDK and the individual PICs, respectively).

Note, excess materials that have been accumulated at a given PIC will be
owned by that PIC, subject to restriction (a) above.

### Infinite Supply

> First, as cell lines are created from any samples from one or more
> PICs, the individual PICs will be given the opportunity to receive
> viable aliquots of those lines as soon as feasible by the central
> laboratory, but no later than 3 months after establishment of the
> lines.
>
> Within one to two years of the conclusion of the study, any biological
> materials in this category residing at the GADDCC or other central
> core laboratory will be treated as follows:
>
> If a given population has requested return of the samples, that
> request will be honored. A viable aliquot of the material will be
> provided to each individual PIC that generated it. A viable aliquot
> will be archived for the NIDDK (mechanism to be determined). Ownership
> of the samples will reside with the possessors (e.g. the NIDDK and the
> individual PICs, respectively).
>
> It is currently the intention of the NIDDK to establish a repository
> of cell lines with accompanying data to be available to outside, i.e.
> non-F.I.N.D., investigators. The [full sample repository]{.underline}
> (final phase repository) will be established within 1 to 2 years,
> after the termination of the F.I.N.D. These samples must be
> anonymized, i.e. all identifiers removed. Ethnic groups will be
> identified by only one of 4 categories: Caucasian, African-American,
> Hispanic, Native American.
>
> There may be a desire to establish an early phase repository based on
> relevant publications (e.g. the initial genome scan). Such an [early
> phase repository]{.underline} would include the relevant publication
> data and samples available at that time. They would be anonymized. The
> desire/need for such a repository will be assessed by a
> to-be-established committee (such could include representatives from
> the F.I.N.D. Steering Committee, EAC, NIDDK, and non-F.I.N.D.
> representatives).
>
> Access to the sample repository(ies) would be decided by a
> to-be-established committee, likely to consist of F.I.N.D. Steering
> Committee members, EAC members, NIDDK, and possibly outside
> (non-F.I.N.D.) representatives. This will require an application
> process, and formal commitments by the requested investigators
> (whether in academia or industry) to commit to utilize the samples
> only for the F.I.N.D. purposes (i.e. to find the genes for kidney
> disease, diabetes, and associated diseases, e.g. retinopathy and
> atherosclerosis), and to deliver to the central database the primary
> data of any publication within 3 months after publication. Provision
> of these samples and accompanying data will require a funding
> mechanism to be developed, ranging from peer reviewed funding to a
> fee-per-sample mechanism.

## Funding

All activities that are mandated by these policies will receive
appropriate funding for the responsible parties to carry them out,
otherwise these parties will not be held responsible for the tasks (i.e.
there are to be no unfunded mandates).

# PUBLICATIONS

## Overview and Objectives of the Publications Subcommittee

The Publications Subcommittee will coordinate, monitor, review, and
assume responsibility for, arranging the preparation of all study-wide
press releases, interviews, presentations, and publications relating to
the scientific aspects of FIND. During the planning, conduct, and
analysis of FIND, there will be no communications of study plans or
results that have not been reviewed and approved following the
procedures as described below.

## Duties of the Publications Subcommittee

Recommend policy and procedures for review and approval of all
scientific communications regarding FIND to outside groups.

Identify publications to be written and presentations to be made during
the course of the study, with target dates for each. The Publications
Subcommittee will also review proposals for FIND-related publications or
presentations. These will include publications related to the main study
and those resulting from projects previously approved by the Subprojects
Evaluation Subcommittee.

Propose policy guidelines for authorship of FIND publications and
appoint writing groups.

Monitor the writing of each paper to ensure publication in a timely
fashion.

Suggest appropriate journals for FIND publications and monitor the
process of publication.

Perform other writing, reviewing, or editing tasks assigned by the
Steering Committee.

Assist writing groups in publishing papers of the highest quality and
clarity. Review and edit all FIND publications and presentations prior
to submission (see section 13.4), enlisting the special assistance of
other members of FIND Research Group and subcommittees whenever
appropriate. The activities of the Publications Subcommittee will be
conducted pursuant to the following policy regarding publications and
presentations from FIND:

1.  ensure accurate, uniform, timely, and high quality reporting of FIND
    activities and results;

2.  preserve the scientific integrity of the study;

3.  safeguard the rights and confidentiality of participants;

4.  ensure that the timing of publications and presentations serves the
    right of the public to know the results of the study without
    jeopardizing the privacy of the participants.

In all of these matters, the Publications Subcommittee will, by majority
vote, make recommendations to the Steering Committee. Final decisions
will be by majority vote of the Steering Committee.

## Categories of Papers 

[Definitions]{.underline}

> [Paper]{.underline}: a paper written for publication in a journal,
> monograph, or book, whether initiated by the group or invited.
>
> [Writing group]{.underline}: the individuals directly responsible for
> writing a paper, even though many others in the research group may be
> involved in review and approval before the paper is submitted. A
> writing group will usually be composed of three to seven people and
> include representatives from all the disciplines involved in the paper
> (e.g., clinicians, molecular geneticists, genetic epidemiologists, or
> statisticians).
>
> [Research Group]{.underline}: all investigators at the PICs, GADCC,
> NIDDK project office, and any subcontracting units, such as central
> laboratories. Investigators are considered those working at
> professional levels (and usually trained at the doctoral level),
> regardless of professional discipline (e.g., clinicians, molecular
> geneticists, genetic epidemiologists, or statisticians). The program
> coordinator at each PIC might be included regardless of degree or
> professional credentials.
>
> Each paper will be categorized before the analysis and writing are
> undertaken. Categories are determined by the scope and content of each
> paper, rather than by the particular protocol or protocol(s) under
> which the data were obtained. Results obtained under the full protocol
> followed by all centers will probably be designated as category A
> (defined below), whereas results obtained in ancillary or sub-studies
> may be of any category, depending on their scope and content.

###### A. Full group papers  {#a.-full-group-papers .unnumbered}

These papers represent the work of the entire consortium, including the
PICs, GADCC, NIDDK project office, and any subcontracting units, such as
central laboratories. Examples of topics are: overall study design and
methods, descriptions of recruited populations, and findings
representing all study subjects and PICs.

Authorship will be by the FIND Research Group. Group members will be
listed in a footnote or appendix (depending on editorial policy of the
journal). The list may designate certain roles of individuals, such as
PIs, chairs of the Steering Committee and subcommittees, and members of
the writing group. The corresponding author will be the GADCC, with no
individual named, unless required by the journal, in which case the PI
of the GADCC will be named. The appendix may also acknowledge by name or
by group the nonprofessional staff, external advisors and consultants,
and others as appropriate.

> B. Subgroup papers

These papers represent the work of part of the consortium, consisting of
at least one center, which may include the PICs, GADCC, NIDDK project
office, and any subcontracting units, such as central laboratories.
Examples of topics are: study design, methods, subjects, and findings
pertaining to a subset of PICs or a single PIC; or methods (but not
study results) used by the GADCC alone.

The involved centers may be a single PIC (including affiliated
laboratories or consultants) if the services of the GADCC were not used
in the substudy, the single center plus the GADCC, or more than one (but
not all) PICs, with or without the GADCC. Depending on the roles of the
GADCC in the substudy (i.e. statistical analysis or genotyping), the
authorship list may include only some members of the GADCC.

Authorship will be the investigators of the centers involved. A
subtitle, footnote, acknowledgment, or appendix will indicate that this
represents a subgroup of FIND, and if possible, a FIND paper (category
A) will be referenced.

> C. Miscellaneous papers

These papers represent work funded by FIND but not central to the FIND
consortium. Examples are: development of statistical or genotyping
methods not illustrated by FIND results (even if subsequently used in
FIND), descriptions of aspects of the study populations not directly
related to FIND analyses (such as correlations among study variables).
These papers may emanate from a single center (PIC or GADCC) or from a
combination of one or more PICs, with or without the GADCC.

Authorship will be by the investigators of the centers involved. A
subtitle, footnote, acknowledgment, or appendix will indicate how this
paper is related to FIND, and if possible, a FIND paper (category A)
will be referenced.

Abstracts and meeting presentations will be classified and approved as
above. When required by the organization sponsoring the meeting, a
corresponding author can be named, e.g. in a footnote or in the authors
line, such as A. B. Member, for the FIND Research Group. If any member
of the FIND Research Group receives an invitation to make a FIND
presentation, the invitation should be forwarded to the Publications
Subcommittee. The Publications Subcommittee will recommend whether the
invitation should be accepted, and may suggest that the presentation be
given by a member of the Research Group other than the person originally
invited (to spread the workload of presentations and facilitate public
recognition of members who may not be frequently invited).

## Implementation of Policy and the Review Process

Topics for papers and members of writing groups may be proposed by the
Publications Subcommittee or any member of the Research Group. The
Publications Subcommittee will either reject the proposal or assign each
proposal a category and writing group. A log of such decisions will be
maintained on the FIND website accessible to all members of the Research
Group. Any members disagreeing with a Publications Subcommittee decision
on categorization of a paper, membership in the writing group, or
approval of a paper should express their concerns to the Chair of the
Publications Subcommittee, who will relay them to the full Publications
Subcommittee, if necessary, for resolution. Unresolved disagreements
within the Publications Subcommittee will be referred to the Steering
Committee for resolution. A decision of the majority of the Steering
Committee will be binding.

The Publications Subcommittee will review a completed paper of any
category. The review will include attention to scientific accuracy,
clarity, and style. If a majority does not approve it, suggestions for
revision will be given to the writing group for revision, after which
the Publications Subcommittee again reviews the paper. When the majority
of the Publications Subcommittee approves a paper, it will be forwarded
to the Steering Committee for further suggested revisions or final
approval by majority vote.

## Use of Data

For purposes of publication and presentation policies, study data are
defined as all data specified in the MOO pertaining to enrolled
participants. Subjects evaluated for eligibility but not enrolled (for
whatever reason) can be used by the individual PICs for other studies.

Study data will be owned jointly by the individual PICs and the GADCC,
but will be kept at the GADCC. The GADCC and PICs will make no use of
study data nor disclose them to any other parties except as specified in
the Protocol or MOO, unless such use or disclosure is approved by a
majority of the Steering Committee.

Final disposition of the data is covered by the policies developed by
the Intellectual Property and Archives Subcommittee.

## Presentations to Volunteer Participants

Presentation of results with clinical significance determined by the
steering committee will be offered to the volunteer participants in an
appropriate manner before they are presented to the public or the
professional communities.

# Subprojects and Ancillary Studies

## Objectives of the Subprojects and Ancillary Studies Subcommittee

Subprojects and ancillary studies will be evaluated with regard to
scientific merit and the potential impact on the objectives of FIND.
Projects that complement the objectives of FIND will enhance the value
of the study and, therefore, are encouraged. The Subproject Evaluation
Subcommittee will evaluate each proposal and make a recommendation to
the Steering Committee. The Steering Committee's final approval is
necessary before the sub-study can begin. In addition, the customary
approval of the relevant Institutional Review Board(s) must be obtained.

## Definition

Subprojects and ancillary studies are defined as investigations that are
not set forth in the primary FIND protocol, but which require resources
that are shared by all of the PICs (including analytic resources and
genotypic data), or which relate to the molecular genetics of
nephropathy. These include the following types of proposals:

1.  Proposals that the GADCC conduct analyses of data collected by one
    or more individual PICs which are not part of the analyses proposed
    by the overall FIND protocol.

2.  Proposals that the GADCC type candidate genes, which are not
    proposed in the FIND protocol, in samples collected by one or more
    individual PICs.

3.  Proposals that individual PICs, or other collaborators, type
    candidate genes in samples obtained from more than one PIC, which
    are collected for the primary FIND protocol.

4.  Analyses conducted by individual PICs or other collaborators, which
    employ genotypic data generated by the main FIND.

5.  Proposals that all PICs collect data that is not specified in the
    primary protocol.

6.  Proposals that an individual PIC investigate the molecular genetics
    of nephropathy (*e.g.,* by association or linkage studies utilizing
    candidate genes or genomic segments), in data collected by the
    individual PIC under the FIND protocol.

Analyses, conducted by an individual PIC, of clinical phenotypic data
collected by that PIC or of molecular genetic data that are unrelated to
nephropathy, do not require evaluation by the Subproject Evaluation
Subcommittee. (Note that any such studies using data in FIND subjects
are limited by the participants' consent.)

Subprojects are defined as proposals, meeting the above definition, that
are to be conducted using FIND resources. Ancillary studies are studies
that require supplemental funding or resources in addition to FIND
resources. (For example, ancillary studies may be conducted with funding
obtained from an RO1 grant from NIH. Since approval from FIND will be
necessary before proceeding with such studies, it will generally be to
the investigators' advantage to obtain approval for such studies from
FIND prior to applying for supplemental funding.)

## Criteria

The Subproject Evaluation Committee will evaluate proposals with regard
to the following:

1.  Impact on the objectives of FIND (no subproject should compromise
    the scientific integrity of FIND, adversely effect its public image,
    or cause a significant diversion of Find's resources. In addition,
    subprojects should not compete with or duplicate the main results of
    FIND).

2.  Scientific merit (proposals should test an important hypothesis and
    the design and power of the proposal should be adequate to ensure a
    reasonable test of this hypothesis).

3.  Feasibility (both from a practical and ethical standpoint- the input
    of the Consent and Ethics Subcommittee will be sought when necessary
    to ensure that the proposed project is within the scope of
    participants' consent).

## Procedures

The Subproject Evaluation Subcommittee will meet at each FIND
Investigators' meeting. Proposals for subprojects or ancillary studies
should be submitted at least one month prior to each meeting to ensure
that sufficient time is available for review.

A written request for approval of a proposed subproject or ancillary
study should be submitted to the Chair of the Subproject Evaluation
Subcommittee. The request should be brief (no more than 5 pages), but
should contain sufficient detail so that scientific merit can be
assessed. It should contain the following elements in order:

A.  description of the hypothesis(es) to be evaluated.

B.  background and significance of the study.

C.  the proposed methods.

D.  analysis strategy.

E.  plans for publication.

F.  source of funding.

If funds are being sought from outside FIND, the proposed source of such
funds should be clearly identified. If additional data from subjects are
to be collected (*e.g.*, by collection of additional samples or by
clinical examination), full details need to be provided. It should also
be specified whether molecular or statistical analyses are to be
conducted by the GADCC.

Proposals may be assigned to have a detailed or abbreviated review. Any
proposals that utilize genotypic data, clinical data or analytic
resources common to more than one PIC (study types 1-5 above) will
receive a detailed review; proposals that relate to the molecular
genetics of diabetic nephropathy, but in which all of the work,
including genotyping and data analysis, will be done by a single PIC
(study type 6) will receive an abbreviated review. If a detailed review
is necessary, the Chair of the Subproject Evaluation Subcommittee will
assign a primary and secondary reviewer from among the committee members
for each proposal. The opinions of outside experts will be sought at the
discretion of the committee. A statistical review by the GADCC will also
be conducted. The Subproject Evaluation Subcommittee will vote on
approval or disapproval; approval is based on a simple majority of
committee members. The Chair will then prepare a written summary of the
committee's decision and forward this to the investigator(s). Copies of
proposals designated for an abbreviated review will be forwarded by the
Chair to the Subcommittee, which will vote on whether the proposal is
consistent with the objectives of FIND. Since such proposals will not
utilize the shared molecular or analytical resources of FIND, they will
not require a detailed review by primary, secondary and statistical
reviewers.

If the Subproject Evaluation Subcommittee approves the proposal, the
proposal will be forwarded to the Steering Committee, along with the
summary and recommendation of the Subproject Evaluation Subcommittee.
Final approval of the proposal will be based on a majority vote of the
Steering Committee. If the Steering Committee approves a subproject, it
will proceed. If the proposal is an ancillary study, it may proceed with
Steering Committee approval once funding is obtained.

The Subproject Evaluation Subcommittee may not initially approve the
proposal, but may request further information from the investigators
before rendering a final decision. In such cases, the investigators will
be invited to submit a revised proposal.

If the Subproject Evaluation Subcommittee disapproves the proposal, the
investigators may appeal to the Steering Committee, which may override
the decision of the Subcommittee. If the Steering Committee also
disapproves the subproject, it will not be conducted.

## Publication

Publication of data from all subprojects and ancillary studies must
comply with the policies of the FIND Publications Subcommittee.