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Adolescent Medicine Trials Network for HIV/AIDS Interventions
Policy for Study Concept Plan Development
Step 1: Initiation of a Protocol Concept
1. The proposing investigator(s) develop(s) a Protocol Concept Capsule (PCC), a brief
description of the proposed study. The PCC is no longer than two single-spaced typewritten
pages and includes the following:

Study title

Lead investigator

Basic study objectives

Significance

Study population

Intervention

Outcome measures

Approximation of sample size, e.g., <20, >100 (formal sample size calculation not
required)

Potential resources or collaborative network
2. The proposing investigator submits the PCC to the co-chair of the appropriate group, the
Behavioral Leadership Group, the Community Prevention Leadership Group, or the
Therapeutics Leadership Group (BLG/CPLG/TLG), in electronic form. For a capsule to move
forward for Protocol Concept Sheet development, it must relate to the group’s current
prioritized scientific research agenda. The co-chair of the BLG/CPLG/TLG receives the PCC
and after preliminary review may 1) accept or reject the PCC for further development, or 2)
may request review by the individual leadership group for approval or disapproval for further
development. If the PCC is consistent with the scientific agenda, but there are feasibility
concerns regarding the number of subjects, a statistical consult may be made available per
the discretion of the BLG/CPLG/TLG as a whole.
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3. If the PCC is approved for further development, the co-chair:

Notifies the proposing investigator of the decision

Forwards the PCC to the ATN Coordinating Center (ACC) for assignment of a
Protocol Concept Sheet number (PCS_#_).

Establishes a link with the sponsoring BLG/CPLG/TLG through a liaison
BLG/CPLG/TLG investigator to work with any proposing investigator external to the
ATN; a liaison BLG/CPLG/TLG investigator is available to any Adolescent Medicine
Trials Unit principal investigator who propose a PCC, if requested.
4. Any questions, concerns, or disputes regarding the initial review of a PCC will be brought
to the ATN Executive Committee for discussion and resolution.
5. The approved PCC is submitted to the Adolescent Medicine Trials Units Principal
Investigators (ATP) for review and feedback on feasibility as it moves to concept sheet
development. The PCC is included on the agenda of the next conference call for this group
and the lead investigator joins this call to present the capsule and answer any
questions/concerns.
6. The BLG/CPLG/TLG are informed monthly of decisions concerning any PCCs that have
been reviewed (via E-mail or conference call). ATN members are notified of all PCCs
approved for PCS development in a weekly/monthly newsletter.
Step 2: Development of a Protocol Concept Sheet
1. Proposing investigator(s) develop(s) the Protocol Concept Sheet (PCS) that includes the
following in page/line numbering format:

Study title

Proposing investigator(s)

-
Lead investigator
-
Team members
Study objectives and aims
-
Brief study overview and objective
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-
Aims and/or hypotheses

Study rationale/background

Study design

Study population with inclusion and exclusion criteria

Treatment regimen, if applicable

Analytic section
-
Sample size estimate

Feasibility section detailing collaborative resources or connections

Proposed assessment measures (in an appendix) if developed in a pilot study or if the
measures have never been used with HIV-infected youth

Budget (on PHS 398 forms) with budget justification

Accrual timeframe
If the proposed study will be using a subset (<12-15 sites) of the Adolescent Medicine
Trials Units (AMTUs), the PCS includes:

Site selection criteria (obligatory and desirable)
-
Attach an appendix describing criteria necessary or desirable for site selection
and external constraints (e.g., school program, STD clinic, detention center).

Study numbers: minimum and maximum number of subjects per site;
minimum and maximum number of sites

Rationale/basis for site restriction that may include but not be restricted
to

Staffing (existing staff expertise and availability, space, capacity,
and/or funding needs for additional staff)

Already extant site partnerships, CBO characteristics; locale
(inner city, rural, school; GLBT or street youth specific program;
venue based outreach in place or doable; cultural competence;
GCRC; correctional facility)

Training needs/capacity (for intervention, data collection,
procedure, need to train CBO’s or youth)

IRB / Legal Issues
o IRB registration and FWA approval
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o Permissive interpretations of state law or regulation
-
If a team has specific site preferences, an addition to the above appendix must
include: 1) their request in writing with a justification addressed to the Executive
Committee and 2) statements from the AMTU PIs at those preferred sites
stating their interest, availability of staff, and immediate availability of the
populations required for the proposed study.
If needed, a team may request a consultation review with the TLG/CPLG/BLG to discuss
issues related to development of the proposed concept before the full PCS is submitted to
the BLG/CPLG/TLG for formal review and vote.
2. Proposing investigators submit the PCS to the ACC in electronic form within eight weeks
of PCS number being assigned. If the PCS is not submitted within eight weeks, the PCS
team is responsible for setting a timeline for submission of the PCS and discussing reasons
for delay with the appropriate group (BLG/CPLG/TLG). The chair of the group
(BLG/CPLG/TLG) notifies the Executive Committee of any delays.
3. ACC distributes the PCS to the appropriate group (BLG/CPLG/TLG) for review.
4. BLG/CPLG/TLG co-chair assigns two reviewers from the BLG/CPLG/TLG within 3 days;
reviewers are assigned on a rotating basis. Occasionally outside reviewers may be consulted
at the discretion of the BLG/CPLG/TLG. Reviewers provide written reviews of the PCS noting
major and minor points within 6 working days. A PCS is reviewed on the basis of scientific
merit, priority within the BLG/CPLG/TLG objectives, and placement within the ATN’s scientific
agenda. The review must be a separate document and should include major points (if any),
minor points (if any), and general comments (if any) on each of the PCS context areas listed
above. All recommendations and comments must refer to a specific page and line number
when applicable. Line-by-line edits in the text of the PCS are not acceptable. Reviews are
sent to the ACC for distribution to the investigators and the BLG/ CPLG/TLG.
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5. When reviews are completed, the PCS is included on the agenda of the next monthly
BLG/CPLG/TLG conference call. BLG/CPLG/TLG members carefully review the PCS and
the reviews prior to the call.
6. Proposing investigator(s) present(s) a brief overview of the PCS on the conference call.
The two BLG/CPLG/TLG reviewers present their reviews. Other BLG/CPLG/TLG members
add any additional comments. Discussion with the BLG/CPLG/TLG ensues and the
proposing investigators have an opportunity to clarify and discuss issues and answer queries
and concerns.
7. Proposing investigator(s) leave the conference call and the BLG/CPLG/TLG further
discusses the PCS if needed at the co-chair’s discretion. Following the call the ACC
distributes an E-mail ballot for group members to vote 1) to approve or disapprove the PCS
to move forward to be developed into a protocol, and 2) to approve or disapprove a
recommendation for the Executive Committee concerning the requested ATN resources. An
approval vote of two-thirds of eligible voters is required to approve the concept and to
approve the recommendation for the Executive Committee concerning the requested
resources. Eligible voters are NIH science collaborators in attendance (one vote per institute)
and supported members of the BLG/CPLG/TLG. A BLG/CPLG/TLG member is not eligible to
vote if they are a proposing investigator or collaborator for the PCS under review.
If approved and no revisions are required, the PCS moves forward to the next step in the
review process. If the PCS is approved but revisions are needed per the BLG/CPLG/TLG
discussion, the BLG/CPLG/TLG will specify if the reviewers alone can approve the revised
PCS for minor modifications or if full BLG/CPLG/TLG review is required for major ones. If the
latter occurs, revisions are made and the PCS is re-submitted to the ACC within three weeks
of notification of the first review results. The PCS is then submitted to the BLG/CPLG/TLG for
full re-review and an approval vote.
8. When a PCS is approved for protocol development by the BLG/CPLG/TLG, it is
distributed to AMTU site personnel for feedback on feasibility, subject issues, etc. as follows:
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a. Therapeutic protocols – AMTU PIs (ATP) and Study Coordinators (SC)
b. Community protocols – AMTU PIs (ATP) and Connect to Protect (C2P )
Coordinators
c. Behavioral protocols – AMTU PIs (ATP) and either Study Coordinators (SC) or
C2P Coordinators: to be determined case-by-case based on the content of the
protocol
The PCS is included on the agendas of the next conference call for each of these assigned
groups and the lead investigator or a designee joins these calls to present an overview, hear
the reviews, and answer any questions/concerns.
9. If the PCS team is requesting either restricted or specific sites, the site selection process
is initiated when the AMTU reviews are completed:
a. A site interest query will be implemented by the ACC. For the query, the PCS team
may choose 1) for the site selection criteria from the PCS appendix to be included,
and/or 2) to develop a set of questions for the sites based on their site selection
criteria that will help in determining site eligibility for participation; these questions
will be submitted to the ACC within one week of team notification of
BLG/CPLG/TLG approval. The ACC distributes the query to the sites for review
and for a response if they are interested in being considered as a site for the
proposed study.
b. The ACC then submits to the Executive Committee’s Site Performance Committee
for review 1) the collated responses from the sites interested in being considered
as sites for the proposed study, and 2) if the PCS team has specific site
preferences, the PCS appendix with the team’s request in writing with a justification
addressed to the Executive Committee and statements from the AMTU PIs at
those preferred sites stating their interest, availability of staff, and immediate
availability of the populations required for the proposed study.
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The Site Performance Committee reviews the responses from sites that express
interest and the request, if any, from the PCS team for specific sites. Eligibility
based on the criteria, equity in research opportunity, available site resources,
subject availability, and other commitments at each interested clinical site are
considered as well as the rationale for any specific site requests by the PCS team.
From this review, the Site Performance Subcommittee determines a
recommendation concerning sites for the proposed study.
10. The ACC forwards the PCS and the BLG/CPLG/TLG resource recommendation to the
Executive Committee for approval. The ACC also forwards the PCS and resource
recommendation to the other two leadership groups for their information; if any member of
those two groups has concerns about the PCS or resource recommendation, they will send a
formal memo outlining their concerns to the PCS team and the Executive Committee.
The PCS and resource recommendation are included on the agenda of the next Executive
Committee conference call. The Executive Committee chair presents the PCS and resource
recommendation. The ATP, SC, and/or C2P representatives on the Executive Committee are
responsible for presenting any lingering feasibility concerns or subject issues. If completed
and if the study will be site restricted, the Site Performance Subcommittee chair (or
designated representative) presents a brief report on responses from the sites that
expressed interest in being considered for the study and the subcommittee’s
recommendation concerning sites for the proposed study. Following the call the ACC
distributes an E-mail ballot for committee members to vote 1) to approve or disapprove the
PCS/resource recommendation, and 2) the recommended sites, if applicable. A simple
majority vote is required for approval.
If the Site Performance Subcommittee’s recommendation of sites for the proposed study is
not completed when the PCS/resource recommendation comes forward for the EC approval
vote, a plan is determined for finalizing the EC’s recommendation of sites for the protocol
team. If the PCS is approved by Program for protocol development, the EC makes a final
recommendation to the PCS team for site selection before protocol development begins.
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11. When a PCS is approved for protocol development by the Executive Committee, it is
submitted for Program scientific review by the ACC.
a. Program distributes the PCS to the review committee
b. Primary and secondary reviewers are assigned
c. The PCS lead investigator sends a PowerPoint overview presentation of the PCS
to Program for distribution to the committee
d. The PCS lead investigator joins at the beginning of the review committee call and
presents the overview
e. The PCS lead investigator interacts with the review committee to answer questions
and clarify issues
f. The PCS lead investigator leaves the call and the review committee conducts the
review of the PCS
g. Program synthesizes the written reviews and notes from the committee discussion
into one scientific review summary with a recommendation; the review summary is
distributed to all reviewers for approval (5-7 days are allotted for a response)
h. Revisions to the written scientific review summary are made if requested by the
reviewers and it is then distributed to the PCS lead investigator and the ACC
i.
The PCS lead investigator with the PCS team responds to any concerns in the
review within three weeks.
j.
When Program determines that concerns have been responded to sufficiently,
notification of approval for protocol development is distributed to the lead author
and the ACC, and the PCS number becomes the protocol number (ATN #).
k. The ACC then notifies the Data and Operations Center (DOC); the ACC
notification also includes a decision by Program of any DSMB requirement for the
protocol.
Step 3: Full Protocol Development
1. In general, the protocol chair will be the person initiating the PCS within the network or the
person taking the lead on writing an application for funding.
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2. When the PCS is approved by the EC and Program for protocol development, a protocol
team is organized to include the proposing investigators, an AMLG liaison if the proposing
investigators are from outside the ATN, a Protocol Specialist from the DOC, an AMTU PI,
and a Study Coordinator or C2P representative (dependent upon the context of the protocol).
Other interested AMTU PIs, Study Coordinators, or C2P Coordinators who desire to devote
time and effort to the development of the protocol may contact the protocol team directly
regarding their involvement through a written communication outlining their proposed
contribution. CAB input on developing protocols is solicited as appropriate.
3. Procedures for protocol development depend upon whether the protocol is to be
developed within the ATN or within a collaborating network:
a. If protocol development is to be within the ATN, a Protocol Specialist will be
assigned to assist in full protocol development including full detailing of study
procedures, visit schedules, timelines, IRB materials, and data monitoring safety
issues. Please refer to the ATN Procedure for Protocol Development, Approval,
and Implementation for details of this process.
b. If protocol development is to be within a collaborating network, issues of logistical
support will be negotiated with the appropriate network. A Memorandum of
Understanding will be signed by the PIs of both Networks and by the protocol chair.
4. The Network is committed to the most efficient development of the studies that it
endorses and therefore, the performance of the protocol team is monitored closely.
Reassignment of a protocol chair could be considered by the Executive Committee if there is
lack of leadership or an inattention to timelines during protocol development, protocol
implementation, or manuscript production.
Records will be kept on how protocol concept plan development proceeds and what
precedents are set each year of the study. These will be reviewed and the policy amended
as needed annually.
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Concept Sheet Development Process
Protocol Concept Capsule
BLG, CPLG, or TLG Co-Chair Review
or Full Individual Group Review
(Approval)
PCS number assigned
ATP feasibility review
Team develops Protocol Concept Sheet
BLG, CPLG, or TLG
Review
(Approval)
ATP and SC or C2P Review
(Feedback on feasibility and
other issues)
Site Selection Process
Executive Committee Review
(Approval)
Program Scientific Review
(Approval)
Protocol Development
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