J.1 - TBTC Bylaws.pdf

Approved by the TBTC Steering Committee on June 11, 2012

The Bylaws of the TBTC were initially approved in April 1998, with subsequent revisions later in 1998 and in 1999, 2005, and 2009.

BY-LAWS

OF THE

TUBERCULOSIS TRIALS

CONSORTIUM

(TBTC)

IIE3

Typewritten Text Attachment J.1 - Solicitation # 75D301-20-R-67869

Tuberculosis Trials Consortium (TBTC) By-Laws Page 2

TUBERCULOSIS TRIALS CONSORTIUM (TBTC)

BY-LAWS

I. Introduction ................................................................................................................. Page 3 II. TBTC Mission.............................................................................................................. Page 3

III. Purpose....................................................................................................................... Page 3 IV. General Principles....................................................................................................... Page 4 V. Roles and Responsibilities of DBTE and TBTC.......................................................... Page 4

VI. Structure and Function of the TBTC............................................................................ Page 6 A. Membership of the TBTC................................................................................. Page 6 B. TBTC Steering Committee............................................................................... Page 6 C. Executive Affairs Group (EAG) ........................................................................ Page 9 D. Executive Committees of the TBTC................................................................. Page 10

Core Science Group (CSG) ....................................................................... Page 12 Implementation and Quality Committee (IQC)............................................ Page 13 Publications and Presentations Committee (P&P)...................................... Page 14 Advocacy and External Relations Committee (AER) .................................. Page 15

E. Working Groups............................................................................................... Page 16 F. Task Forces..................................................................................................... Page 16 G. Community Research Advisory Group (CRAG) ............................................... Page 16

VII. Administrative Group................................................................................................... Page 17 A. TBTC Data Coordinating Center (DCC) ........................................................... Page 17 B. Monitoring and Support Center (MSC)............................................................. Page 18 C. Financial Management Office (FMO) ............................................................... Page 19

VIII. Review and Oversight................................................................................................. Page 19 A. DBTE Scientific Advisory Group of Experts (SAGE) ........................................ Page 19 B. Data and Safety and Monitoring Board (DSMB)............................................... Page 20 C. CDC and Local Institutional Review Boards..................................................... Page 20 D. Advisory Committee for the Elimination of Tuberculosis (ACET)...................... Page 21

IX. Appendices Appendix A: Process for the Development and Approval of New

TBTC Protocols ........................................................................... Page 23 Appendix B: Process for the Approval of TBTC Protocol Amendments, Informed Consent Amendments, and Embedded Substudies ..... Page 27 Appendix C: Process for the Evaluation and Approval of a Secondary

Analysis...................................................................................... Page 29 Appendix D: Publications and Presentations (P&P) Committee Policies and

Procedures ................................................................................. Page 33 Appendix E: Implementation and Quality Committee (IQC) Policies and

Procedures................................................................................. Page 38 Appendix F: Management of Grants and Contracts from Outside

Organizations ............................................................................. Page 40

Tuberculosis Trials Consortium (TBTC) By-Laws Page 3

BY-LAWS

of the

TUBERCULOSIS TRIALS CONSORTIUM (TBTC)

I. Introduction

The United States Public Health Service (USPHS) and the U.S. Department of Veterans Affairs (VA) have a distinguished history of conduct of clinical trials to evaluate new drug regimens for both the treatment and prevention of tuberculosis. In 1960, the Centers for Disease Control and Prevention (CDC) assumed a major role in these studies when the USPHS Tuberculosis Division was transferred to CDC. Subsequently, CDC coordinated a series of multi-center clinical trials which helped to establish rifampin-based, short-course therapy as the standard for tuberculosis treatment in the U.S. It also conducted studies to provide the scientific basis for preventive chemotherapy, which remains a major component of the CDC tuberculosis elimination strategy.

Currently, new drugs and regimens for tuberculosis treatment and prevention, new diagnostic tests, and new vaccine candidates are becoming available for clinical investigation. Concurrently, the challenges posed by the goal of TB elimination are increasing, as rates of drug resistance increase and as the costs associated with assuring high rates of adherence rise.

In 1993, the CDC established the Tuberculosis Trials Consortium (TBTC) for the purpose of conducting clinical trials of new drugs and regimens for the treatment and prevention of tuberculosis. The TBTC is comprised of clinical investigators from academic medical centers and health departments in North America and internationally, and Veterans Affairs (VA) medical centers in the United States of America, working closely with staff from the CDC's Division of Tuberculosis Elimination (DTBE).

II. TBTC Mission

The mission of the TBTC is to conduct programmatically relevant clinical, laboratory and epidemiologic research concerning the diagnosis, clinical management, treatment and prevention of tuberculosis infection and disease.

III. Purpose

Conduct research that expands clinical and epidemiologic knowledge of tuberculosis and facilitates the diagnosis, clinical management, treatment and prevention of tuberculosis infection and disease.

Integrate research into the care of persons with tuberculosis infection and disease.

Develop research questions that are relevant to program settings in general.

Promote research within local tuberculosis control programs through collaboration and collaboration on clinical research of relevance to public health settings.

Provide a forum for international collaborative research of importance to both domestic and international tuberculosis control.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 4

IV. General Principles

The TBTC performs research on tuberculosis issues of clinical and public health interest.

This may include but will not be limited to clinical, preventive, epidemiologic, diagnostic, prognostic, cost-benefit, operational and vaccine studies. All studies are performed with careful attention to scientific validity and relevance to tuberculosis control programs in both the developed and the developing world.

The investigators are careful stewards of the funds entrusted to them for this research, endeavoring to provide the most useful knowledge at a reasonable cost and being committed to continuous improvement in the quality of research performed.

The TBTC is governed by the TBTC Steering Committee, with all major decisions reached by a majority vote of the steering committee, except where specifically noted, by a two-thirds majority. CDC DTBE will share responsibility and authority for these decisions with the Steering Committee through its representation on the Steering Committee and subcommittees and in its role in funding TBTC investigations. CDC also provides oversight and concurrence through the DTBE Scientific Advisory Group of Experts.

All scientific activities of the TBTC are performed in a spirit of open communication and mutual respect. In addition to providing knowledge that increases the ability to control TB, the TBTC seeks to develop and maintain clinical and investigative skills in persons working in TB investigation, care and control. All activities of the TBTC are guided by the knowledge that participation in the TBTC is an important manifestation of public service and that these activities must be of the highest integrity, justifying the public trust that accompanies this responsibility.

V. Roles and Responsibilities of DBTE and TBTC

The Centers for Disease Control and Prevention (CDC) is the funding agency for the TBTC and bears ultimate fiscal, regulatory, and scientific accountability for all TBTC activities. The DTBE communicates DTBE priorities and perspectives to the TBTC Steering Committee. The TBTC maintains an accountable governance process that shares decision-making between the TBTC and DTBE concerning the science and management of the TBTC.

A. The DTBE has three primary responsibilities in relation to the TBTC

1. DTBE promotes its scientific research agenda by:

a. Providing broad framework of DTBE research priorities and the role of TBTC research, particularly as it relates to other DTBE-sponsored research.

b. Communicating in a timely manner any substantive changes in DTBE priorities or plans for the TBTC.

c. Serving as an information resource on activities related to TBTC research and functioning.

2. DTBE provides support and direction by:

Tuberculosis Trials Consortium (TBTC) By-Laws Page 5

a. Providing resources to support TBTC research and related activities, as well as appropriate scientific and operational support for development of the TBTC scientific agenda and for specific protocols.

b. Providing review and approval of all TBTC research.

c. Providing review and approval of TBTC Steering Committee decisions based on merit, scientific mission, and priorities of the DTBE.

d. Managing the overall TBTC budget issues.

e. Facilitating meetings between the TBTC and DTBE staff to review the research priorities to ensure development of studies that contribute to the overall research agenda of the DTBE.

3. DTBE ensures the quality of TBTC research by:

a. Ensuring activities are conducted in accordance with appropriate Federal regulations and provides contract management guidance.

b. Participating in performance assessment of the TBTC using mutually agreed upon performance standards.

c. Ensuring that the TBTC meets the performance standards described in the contracts with each TBTC site and the responsibilities listed below by adjustment of funding, withholding of support, or suspension or termination of the award.

B. Responsibilities of the TBTC

1. The TBTC develops its research program by:

a. Meeting with DTBE staff to review DTBE priorities.

b. Developing a research agenda consistent with the mission of the TBTC and priorities of DTBE.

2. The TBTC conducts high quality research by:

a. Developing specific protocols that address appropriate scientific questions consistent with the scientific mission of the TBTC.

b. Initiating, conducting, and concluding individual studies in exemplary fashion (i.e., ensuring studies can be completed given current capacity, collecting accurate data, following patients for the length of the study, monitoring the status of ongoing studies).

c. Initiating and implementing an education/training program that supports the TBTC investigators' conduct of scientifically sound research.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 6

d. Disseminating interim and final results of research in a prompt fashion, using an equitable process for authorship, presentation and recognition with full and appropriate involvement of TBTC and DTBE staff.

3. The TBTC provides oversight and quality assurance for its research by:

a. Initiating and implementing quality control procedures that meet mutually agreed upon standards, and take corrective actions when necessary.

b. Initiating and implementing a performance evaluation procedure that meets mutually agreed upon standards.

c. Conducting research in accordance with Federal regulations and coordinate with DTBE staff on scientific decisions.

d. Submitting required fiscal and performance reports from each unit to

DTBE.

VI. Structure and Function of the TBTC

A. Membership of the TBTC

Full Membership in the TBTC is open to persons who participate in TBTC activities at TBTC sites, the DTBE, the Monitoring and Support Center and CRAG.

Associate Membership in the TBTC is open to other individuals working with and collaborating with the TBTC. Examples of associate members are collaborating scientists, individuals from collaborating laboratories, pharmaceutical companies, and other medical research organizations.

B. TBTC Steering Committee

The Steering Committee serves as the central decision making body for the TBTC.

1. Functions of the Steering Committee

a. Develop a long-term comprehensive scientific agenda for the TBTC with the assistance of the Core Science Group and the DTBE Scientific Advisory Group of Experts.

1) Ensures consistency with the overall TBTC mission and the research priorities of DTBE.

2) Reviews and updates the overall TBTC scientific agenda on an ongoing basis.

b. Maintains overall responsibility for development of TBTC scientific studies:

1) Receives updates from the Core Science Group on status of new research ideas.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 7

2) Approves/disapproves concepts for protocol development

3) Makes decisions on initiation of protocols taking into account capacity, priority, feasibility in terms of staffing and cost, and status of ongoing research.

c. Oversees the work of the Executive Committees (Core Science Group, Implementation and Quality Committee, Publications and Presentations Committee, and Advocacy and External Relations Committee):

1) Receives recommendations from the Executive Committees.

2) Makes decisions based on these recommendations.

3) Ensures equitable membership on Executive Committees and protocol teams, and provide arbitration, if problems occur.

4) Approves any recommended changes in executive committee missions and functions.

d. Evaluates the progress of ongoing protocols (with the assistance of the Implementation and Quality Committee (IQC)):

1) Reviews accrual data provided by IQC.

2) Assures timely completion of protocols.

3) Enforces quality standards recommended by IQC for protocols.

4) Makes decisions on continuation or termination of protocols, based on recommendations from the Executive Committees and protocol teams.

e. Reviews in an ongoing manner the mission of the TBTC and the priorities of DTBE and ensures that the operations of the TBTC are consistent.

2. Membership of the Steering Committee

a. Voting members of the Steering Committee:

Principal Investigator from each TBTC Site One representative from CRAG One DTBE representative

b. Non-voting members of the Steering Committee:

One Monitoring and Support Center representative Chairs of the Executive Committees (however, an executive committee chair would have a vote if they also represent a TBTC unit)

Executive Coordinator of the Steering Committee

Tuberculosis Trials Consortium (TBTC) By-Laws Page 8

3. Officers of the Steering Committee

a. The Steering Committee has a chair and vice-chair. The chair is a voting member of, and elected by, the Steering Committee from one of the TBTC sites. The vice-chair is the DTBE representative.

b. Terms of Office

The term of office for the chair and vice-chair is two years for each position.

The chair is chosen through a process of nominations from the field, followed by a vote of the Steering Committee, with runoff votes as necessary to achieve a majority. The chair and vice-chair may be re-elected/appointed, as appropriate.

4. Functions of Officers and Staff

a. Chair Organizes and chairs Steering Committee meetings Meets with key DTBE personnel on a regular basis, provides a liaison between DTBE and the Steering Committee, and is a spokesperson for the TBTC with DTBE

Provides a liaison between the TBTC and other research organizations and government agencies

Represents the TBTC as required Provides oversight of the Executive Committees

b. Vice-chair Serves as chair when chairperson is unable to do so Collaborates with the chair to assure that Steering

Committee responsibilities are being met Provides a liaison to the Executive Committees from the

Steering Committee Attends meetings, and chairs meetings, in the absence of the chair

c. Executive Coordinator of the Steering Committee

The chair of the Steering Committee is supported by an Executive Coordinator from DTBE who:

Provides a contact point for DTBE, the Administrative Group, and others

Assists the chair to plan meetings, contact individuals, plan agendas, track the work of the Steering Committee, etc.

Serves as liaison from the chair to the Executive Committees through participation in conference calls and face-to-face meetings to gather information for the chair and to provide information from the chair to the conference call/meeting participants

Tuberculosis Trials Consortium (TBTC) By-Laws Page 9

5. Meetings of the Steering Committee

a. The Steering Committee convenes during periodic conference calls, at each semi-annual meeting of the full Consortium, and at other times as deemed necessary by the chair of the Steering Committee.

b. The following rules govern Steering Committee meetings:

1) The Steering Committee chair, or in his/her absence the vice-chair, oversees the meeting.

2) Robert's Rules of Order is used to govern meetings; each chair/vice-chair is provided a summary of the rules.

Variances are approved by a simple majority vote.

3) Steering Committee meetings are open to all TBTC members and DTBE staff, but it is expected that most of the discussion of issues are by members of the committee.

4) Prior to voting, the chair asks members to state their views.

It is expected that input from nonmembers of the Steering Committee are primarily through participation on Executive Committees.

5) Issues voted on by the Steering Committee are decided by a simple majority. The two exceptions are:

A two-thirds majority of the voting membership of the Steering Committee is required to start or stop TBTC studies

A two-thirds majority of the voting membership of the Steering Committee is required to change the TBTC By-Laws

6) If a Steering Committee member is unable to attend a meeting, he/she may appoint an alternate from the same site to attend the meeting and vote his/her proxy on behalf of the site.

C. Executive Affairs Group (EAG)

The EAG is a Working Group of the Steering Committee that meets on a regular basis to implement Steering Committee decisions; oversees details of concept and protocol development and implementation following Steering Committee approval; identifies problems in the day-to-day operation of the TBTC that require the attention of the Steering Committee; provides whatever administrative support is required to accomplish Steering Committee goals; provides a forum for chairs of Executive Committees to discuss issues; and plans plenary sessions/speakers for TBTC group meetings.

1. Responsibilities of the EAG

a. Assists in overseeing development of concepts and development and implementation of protocols.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 10

b. Decides on the timeframe for concepts and protocols to be submitted to sites and DTBE for review.

c. Reviews summaries of comments from sites and DTBE to ensure that they have been addressed by the protocol team.

d. Approves protocol team members recommended by the Core Science Group.

e. Assists in the evaluation of the progress of ongoing protocols.

f. Identifies issues requiring the attention of the Steering Committee.

g. Assists DTBE in strategic planning toward developing productive partnerships and gaining external funding.

h. Plans meetings of the full Consortium.

i. Explores and evaluates opportunities to collaborate with other research organizations.

j. Meets with SAGE annually to provide a report of TBTC accomplishments, goals and needs.

k. With the assistance of the administrative Centers, provides general administrative support for the Steering Committee and the TBTC.

2. Membership of the EAG

a. Chair and Vice-Chair of the Steering Committee

b. Chairs of the Executive Committees

c. Representative of the VA-funded consortium

d. Executive Coordinator of the Steering Committee

e. Representative of the Monitoring Center

f. Other TBTC and DTBE staff as appropriate

D. Executive Committees of the TBTC

Four Executive Committees have been established by the Steering Committee: 1) Core Science Group; 2) Implementation and Quality; 3) Publications and Presentation;

and 4) Advocacy and External Relations. These executive committees report to, and are accountable to, the Steering Committee. Each Committee has a specific mission that is an integral part of the function of the entire TBTC, and these functions are

Tuberculosis Trials Consortium (TBTC) By-Laws Page 11 coordinated by the Steering Committee, eliminating duplication of effort. Each committee is aware of the current tasks for the others through the chairs' attendance as non-voting members at Steering Committee and EAG meetings, and via receipt of communications.

1. Responsibilities of the Executive Committees of the TBTC

a. The Executive Committees convenes via regularly scheduled conference calls and periodically during face-to-face meetings at semi-annual meetings of the full Consortium.

b. Recommendations from the Executive Committees are presented to the Steering Committee during periodic conference calls and face-to-face meetings. The recommendations are discussed and voted upon by the Executive Committee prior to presentation to the Steering Committee.

c. Executive Committees may create Working Groups to focus on specific functions and short-term Task Forces to deal with specific tasks. Both of these will report back to the parent Committee with recommendations for action.

2. Executive Committee Elections and Related Issues

a. Terms of membership and office are two years on a rotating basis.

These terms are staggered so that half (or approximately half) the voting members rotate off (or run for re-election) every year.

b. The Steering Committee chooses the members from the slate of applicants who submitted a brief description of their interests and qualifications for membership (i.e., past and potential contributions to the mission and purpose of the specific committee and to the TBTC.)

c. If a vacancy occurs, the position is filled as soon as possible by an electronic announcement and voting process. The new incumbent will complete the term of the prior incumbent.

3. Election Process and Functions of the Executive Committee Chair/Vice-Chair

a. The chair and vice-chair of each executive committee is nominated and elected by members of that committee.

b. The chair is nominated and elected first, followed by nomination and election of the vice-chair.

c. The term of office is two years for the chair and vice-chair. Individuals may be re-elected to multiple terms.

d. An individual may not be chair/vice-chair of more than one committee;

however, an individual may be a member of more than one committee.

e. The vice-chair will not automatically succeed the chair.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 12

f. The chair of each executive committee attends Steering Committee meetings as a nonvoting member and reports on the activities of the committee that he/she chairs. The chair of each Executive Committee may also represent his/her unit on the Steering Committee.

1) Each committee sets a standard for participation and makes that standard known to its membership. The chair of each committee may request that a member who is not meeting the standard for participation resign from the committee and may request that a replacement be chosen either by special Steering Committee election or special Steering Committee appointment.

2) Each committee will have a representative from the Data Coordinating Center who will be a non-voting member. The Data Coordinating representative and the DBTE representative (a voting member on each committee) may be the same person.

4. Mission, Role, and Membership of Respective Executive Committees

a. Core Science Group (CSG)

1) Mission: The CSG develops research related to the treatment, prevention and diagnosis of tuberculosis and recommends research to the Steering Committee for approval and further development.

2) Role of the Core Science Group:

a) Identifies scientific opportunities, gaps in current knowledge, and research questions relevant to the diagnosis, treatment and prevention of tuberculosis.

b) Reviews the literature and confers with, and seeks collaborations with, other research organizations.

c) Gathers and disseminates information about various diagnostic tests, new drugs and other therapeutic interventions, including new methods to prevent tuberculosis in infected persons, and new vaccines.

d) Coordinates research information within the TBTC

e) Guides the development of TBTC research:

i. Receives research ideas developed by TBTC members and/or generates research ideas consistent with the overall TBTC scientific agenda.

ii. Prioritizes research ideas and determines which are developed into concepts (see TBTC concept/protocol development process for details).

Tuberculosis Trials Consortium (TBTC) By-Laws Page 13

iii. Reports to the Steering Committee the status of research ideas reviewed and the rationale for decisions made.

iv. Assists the development of study concepts, and following review by Steering Committee, designates protocol team chairs and protocol team members for the development of concepts into full protocols, including protocol-specific consent and case report forms.

v. Reviews protocols and recommends to the Steering Committee whether or not implementation should take place.

vi. Maintains a repository of concept proposals.

vii. Tracks concept proposals from submission to approval, rejection, or withdrawal.

e) Tracks protocols from development to enrollment, analysis, and publication.

3) Membership of the Core Science Group (CSG)

The CSG consists of 11 voting members, of whom 8 are elected TBTC members. The other 3 voting members are the vice-chair of the Steering Committee or (a DTBE staff member appointed by the vice-chair of the Steering Committee), a member from IQC and a member appointed by CRAG. The chair of CSG may select other individuals to be ad-hoc members as he/she deems appropriate.

b. Implementation and Quality Committee (IQC)

Mission: The IQC ensures plans for implementing TBTC protocols are appropriate and feasible, and assures research performance and data within the TBTC are highest possible quality.

1) Role of the IQC

a) Ensures plans for implementing TBTC protocols are appropriate and feasible.

b) Ensures education, training, and other resources are provided that support the “day-to-day” conduct of quality TBTC study work; generally; this is done in collaboration with the Monitoring and Support Center.

c) Monitors ongoing protocols in terms of quality assessment reviews and maintains/fosters good communications with the Data Center, TBTC sites, and

Tuberculosis Trials Consortium (TBTC) By-Laws Page 14 the Monitoring and Support Center:

i. Works with protocol teams to regularly identify, evaluate, and monitor actual and potential problems/barriers to recruitment, accrual, and retention throughout the life of a protocol and recommends resolutions.

ii. Provides reports, as needed, to the Steering Committee on accrual into ongoing protocols by site.

iii. Assesses and monitors site capacity, as needed, and reports to the Steering Committee.

iv. Refines capacity assessment tools, as needed.

2) Membership of the IQC

The IQC consists of 12 voting members, 8 of whom are elected TBTC members. Each must be identified as a study coordinator or is responsible for doing the work of a study coordinator (vs.

the work of an investigator) for overseeing/ managing study work. The other 4 voting members are the DTBE staff member appointed by the vice-chair of the Steering Committee, a representative from the Monitoring and Support Center, a member from the Core Science Group, and a representative from CRAG.

c. Publications and Presentations Committee (P&P)

Mission: The P&P Committee encourages timely and accurate dissemination of designs, methods, and results of research performed by the TBTC; ensures a high standard of scientific quality; allows freedom for individual creativity; and appropriately acknowledges the efforts of professional persons involved in the planning, conduct, and analysis of TBTC studies.

1) Role of the P&P Committee

a) Ensures and expedites the orderly and timely presentation to clinicians, TB patients, and the scientific community of all pertinent data and conclusions resulting from TBTC studies.

b) Ensures all scientific publications and presentations involving TBTC studies are accurate, scientifically sound, and consistent with the mission of the TBTC.

c) Ensures all TBTC investigators and collaborating clinicians, professional and scientific support staff and DTBE staff has the opportunity to participate and is

Tuberculosis Trials Consortium (TBTC) By-Laws Page 15 recognized in TBTC scientific publications and presentations, as appropriate.

d) Ensures all scientific publications and presentations summarizing TBTC study results receive DTBE clearance/approval.

e) Maintains record of submissions to the P&P Committee, as well as scientific publications and presentations.

2) Membership of the P&P Committee

The P&P Committee consists of 6 voting members, of whom 4 are from TBTC sites, including a preferred minimum of two Principal Investigators and one study coordinator. The other voting members are a DTBE staff member appointed by the vice-chair of the Steering Committee and a representative from

CRAG.

d. Advocacy and External Relations Committee (AER)

Mission: The AER promotes the TBTC as a research organization contributing importantly to the goal of tuberculosis elimination.

1) Role of the AER Committee

a) Coordinates activities with other research organizations, including pharmaceutical and biologics companies.

b) Develops and implements an advocacy plan to promote recognition of the TBTC, especially among national decision makers.

c) Identifies opportunities for obtaining financial support for TBTC activities.

d) Represents the TBTC externally and articulates the accomplishments of the TBTC to the larger research community.

e) Ensures that TBTC secures appropriate representation of community interests, for example, through engaging activists and other advocates for those affected by tuberculosis.

2) Membership of the AER

The AER Committee consists of 8 voting members, 5 from TBTC sites, including a preferred minimum of two principal investigators and one study coordinator. The other voting members are a DTBE staff member appointed by the vice-chair

Tuberculosis Trials Consortium (TBTC) By-Laws Page 16 of the Steering committee, a representative from CRAG, and a representative from the Monitoring and Support Center.

E. Working Groups

1. Responsibilities of Working Groups

a. Working Groups are long-term groups with specific objectives and tasks assigned by the Steering Committee or an Executive Committee. The performance of Working Groups requires regular review by the parent Committee.

b. Working Groups convene periodically, via conference calls and face-to-face meetings. The group selects a chair who conducts the business of the group during conference calls and face-to-face meetings.

c. Recommendations from the Working Group are presented to the parent Committee during periodic conference calls and face-to-face meetings.

The recommendations are discussed and voted upon prior to presentation to the Steering Committee for recommendations and/or approval.

d. Working Groups are dissolved, when appropriate, by the executive committee that convened the workgroup.

F. Task Forces

1. Responsibilities of Task Forces

a. A Task Force is a short-term group with a specific objective assigned by the Steering Committee or an Executive Committee. It is anticipated that a Task Force complete its assignment(s) within several months. Membership on a Task Force is assigned by the parent Committee, based on interest, availability, and expertise in specific areas.

b. A facilitator is selected who conducts the business of the group during conference calls and face-to-face meetings, with the goal of completing assigned tasks as efficiently and quickly as possible.

c. Recommendations from the Task Force are presented to the parent Committee membership during conference calls and face-to-face meetings.

The recommendations are discussed and voted upon prior to presentation to the Steering Committee. When parent Committee members agree to accept the task force report, and the Steering Committee has accepted the recommendation, the Task Force is dissolved.

G. Community Research Advisory Group (CRAG)

The mission of CRAG is to enhance the value and impact of CDC’s Tuberculosis Trials Consortium’s (TBTC) research for the benefit of TB-affected communities. The goals are to provide a voice for the affected and traditionally underserved populations in TB clinical research processes; provide the TBTC with community-based perspectives on the development, implementation and translation of TBTC research; and support and

Tuberculosis Trials Consortium (TBTC) By-Laws Page 17 participate in TB education and awareness, thus enabling TB-affected communities to become better advocates for improved TB research.

1. Responsibilities of CRAG Members

a. Participate in local and national policy discussions impacting TB.

b. Strengthen and enhance TBTC’s awareness of the relevant concerns of the local communities about its clinical studies.

c. Participate in TBTC internal committees to ensure community priorities are addressed in research.

d. Work with the local TBTC site to communicate TBTC research priorities and increase local understanding of its research.

e. Solicit input from communities and bring back to the TBTC.

f. Build community support for TBTC research.

g. Advocate for increased support for TB research.

h. Continually build TB and research literacy skills.

2. Membership of the CRAG

The CRAG is a diverse group with regard to race, gender, age, and country of origin. Members have personal or professional experience with latent or active TB, and/or HIV, and/or live or work in settings where there is a high burden of TB. The group may include those who are TB clinic staff or educators (whose work is not funded by, or involved with TBTC research).

There are no less than 8 and no more than 10 CRAG members. Potential members must live/work in communities where TBTC study sites are located. CRAG members elect their Chair and Vice-Chair. Voting is by simple majority of CRAG members.

3. CRAG’s Relationship to the TBTC

CRAG is an autonomous group and is an advisory body to TBTC as a whole, to its Executive Committees, and to local sites. CRAG reports to the AER Executive committee, as well as the Steering Committee at the biannual meetings.

VII. Administrative Group

A. TBTC Data Coordinating Center (DCC)

The TBTC DCC is based in the Centers for Disease Control and Prevention, Clinical Research Branch, Division of TB Elimination, National Center for HIV, STD, and TB Prevention, in Atlanta, Georgia.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 18

1. Functions of the TBTC DCC

Staff from the Clinical Research Branch, the Data Management and Statistics Branch, the International Research and Programs Branch, and the Laboratory Branch, participates in or oversees TBTC data activities that include provisions of statistical and epidemiologic study design expertise; design of data collection forms; enrollment of study participants and study-based treatment assignment;

receipt of completed forms; data entry and verification; data cleaning; data analysis; provision of statistical analyses; and preparation and maintenance of master datasets for all TBTC protocols.

2. Responsibilities of the TBTC DCC

a. Provides administrative support to the TBTC and houses CDC project officers for all TBTC studies, and is responsible for tracking and confirming endpoint events and deaths in all TBTC protocols.

b. Serves as liaison with the CDC DTBE Laboratory Branch, and is responsible for tracking receipt of study isolates and confirmation of susceptibility profiles.

c. Represents CDC's interest in the TBTC to external agencies or institutions, such as the U.S. Food and Drug Administration and the National Institutes of Health.

d. Serves as liaison between the TBTC and the CDC Institutional Review Board to assure compliance of all TBTC sites with CDC IRB requirements and tracks approval of relevant documents.

e. Stores official versions of all TBTC documents, including protocols, consent forms, and data collection forms.

f. Is responsible for analyses prepared for DSMB meetings.

g. Stores hard-copy of all completed data collection forms unless and until TBTC moves toward a paperless system.

h. Ensures that TBTC complies with all recordkeeping requirements under federal law and human subjects research regulations.

B. Monitoring and Support Center (MSC)

The TBTC Monitoring and Support Center (MSC) is based in the offices of a contract research organization.

1. Functions of the MSC

a. Conducts site monitoring visits at each of the clinical sites to evaluate site performance within TBTC protocols to document data reported to the TBTC Data Coordinating Center.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 19

b. Assures compliance with applicable FDA and IRB regulations.

c. Provides relevant training or updates in study procedures

d. Assists sites in their efforts to participate productively in the work of the consortium.

2. Responsibilities of the MSC

a. Assists protocol teams, the TBTC Data Coordinating Center, and IQC, in the development of study forms and the definition of study procedures.

b. Helps prepares study documents.

c. Assures required logistics and supplies.

d. Participates on all protocol teams and in relevant Working Groups.

e. Provides assistance in arranging and attending TBTC group meetings.

C. Financial Management Office (FMO)

1. Responsibilities of the FMO

Supervisory fiscal management for the TBTC is the responsibility of fiscal and administrative staffs in the Division of TB Elimination, in cooperation with the relevant other CDC fiscal offices.

2. Functions of the FMO

a. In managing contracts or agreements with each of the non-Veterans

Affairs sites, CDC fiscal staff communicate with appropriate fiscal officers of the respective sites.

b. In managing funds that support the VA sites, fiscal staff in DTBE arrange the initial issuance and subsequent modifications of a federal Interagency Agreement between the CDC and the U.S. Department of Veterans Affairs, via the VA Medical Center of Washington DC, which serves as the administrative hub for the VA-Affiliates of the TBTC.

VIII. Review and Oversight

A. DTBE Scientific Advisory Group of Experts (SAGE)

1. Functions of SAGE

a. Provides the TBTC with broad framework of DTBE research priorities and the role of TBTC research, particularly as it relates to other DTBE-sponsored research.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 20

b. Communicates in a timely manner any substantive changes in DTBE priorities or plans for the TBTC.

c. Provides periodic review of the TBTC plan of work and of Steering Committee decisions based on merit, scientific mission, and priorities of

DTBE.

d. Through the Associate Director for Science, DTBE provides approval of all TBTC research protocols and publications.

2. Membership of the SAGE

a. Membership on SAGE consists of the DTBE Director, Associate Director for Science and Branch/Activity Chiefs, and the vice-chair of the TBTC Steering Committee and other individuals selected by CDC.

b. The SAGE meets at least yearly. At these meetings, the chair of the TBTC Steering Committee and the EAG present the current plan of work and recent decisions by the Steering Committee. When requested, other TBTC members, e.g., chairs of subcommittees or working groups, will give presentations to the SAGE.

B. Data and Safety Monitoring Board (DSMB)

1. For each trial, an appropriately constituted DSMB should intermittently examine accumulating data in order to make recommendations to the protocol team, CSG, TBTC Steering Committee and DTBE concerning continuation, termination or other modification of studies. These examinations are based on the observed beneficial or adverse effects of the therapeutic or preventive interventions under study and should include a review of the general progress of the study and adhere to good scientific practice. The monitoring process can often be facilitated by early involvement of a DSMB in assessing the design of studies, through the timely review of new protocols for studies to be monitored by the DSMB.

2. Additional and extraordinary review of study progress, changes in study protocols, and/or of other information of relevance to ongoing studies may be required as determined by the DSMB in consultation with the chair and vice-chair of the protocol team and the CSG and the EAG.

C. CDC and Local Institutional Review Boards

1. Each site must hold a valid Federal-wide assurance (FWA) with the U.S. Office for Human Research Protections and must certify IRB approval for each nonexempt research study in which the site is engaged.

2. All study protocols are reviewed and approved by CDC’s IRB, as well as by local IRB’s of participating study sites. Local sites may rely on review of TBTC protocols by the CDC IRB.

3. The primary role of the IRB is to protect the rights and welfare of human

Tuberculosis Trials Consortium (TBTC) By-Laws Page 21 participants in the research. In accordance with the United States Federal Regulations, an IRB may approve research only after it has determined that all of the following requirements are satisfied:

a. Risks to participants are minimized by using procedures that are consistent with sound research design, and that do not unnecessarily expose participants to risks, and whenever appropriate, researchers should employ procedures that are performed on participants for prevention, diagnostic or treatment purposes.

b. Risks to participants are reasonable relative to anticipated benefits, if any, to participants, and the importance of the knowledge that may reasonably be expected to results from the research.

c. The selection of participants is equitable taking into account the purposes of the research and the setting in which it is conducted. The protocol must be particularly attentive to the special problems that may arise when research involves vulnerable populations, such as children, pregnant women, fetuses, prisoners, mentally disabled persons, economically or educationally disadvantaged persons. If any of the participants are likely to be susceptible to undue influence or coercion, the protocol should provide additional safeguards in the study to protect such participants.

d. Informed consent is sought from each prospective participant, or the participant's legally authorized representative, generally by means of a written consent document.

e. The research plan makes adequate provisions for monitoring the data collected to ensure the safety of participants.

f. There are adequate provisions protecting the privacy of participants and maintaining the confidentiality of data.

4. When a study protocol is approved by the TBTC Steering Committee, it is submitted to the CDC IRB. With EAG approval, some protocols are submitted to the CDC IRB sooner, to help expedite implementation.

Following approval at CDC, the protocol is submitted for local review.

5. Ongoing study protocols require continuing IRB review, at least annually, and approval by the appropriate IRBs.

D. Advisory Council for the Elimination of Tuberculosis (ACET)

1. The role of the ACET is to provide advice and recommendations regarding the elimination of tuberculosis to the Secretary of HHS, the Assistant Secretary for Health of HHS, and the Director of CDC.

a. Makes recommendations regarding policies, strategies, objectives, and priorities.

b. Addresses the development and application of new technologies.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 22

c. Reviews the extent to which progress has been made in eliminating tuberculosis.

2. In this capacity, TBTC will request that ACET review the work plan and accomplishments of the TBTC at least yearly. Based on this review, ACET will make recommendations on current and future TBTC activities, helping ensure that the work of the TBTC is consistent with CDC's tuberculosis elimination strategy.

IX. Appendices (below)

Tuberculosis Trials Consortium (TBTC) By-Laws Page 23

Appendix A Process for the Development and Approval of New TBTC Protocols

Part One: Seeking Approval of Research Concept

I. Research Idea A two- to three-page summary/concept sheet (including target population, proposed intervention, and proposed primary endpoint) is sent to the CSG chair. Research ideas may be submitted by TBTC members or associate members.

II. Core Science Group (SCG) – Initial Review and Vote

A. A primary reviewer assigned by the CSG chair leads the discussion of the proposal on a CSG conference call. Proposals are reviewed according to a) scientific rigor and merit; b) how the proposal fits within the scientific priorities of the TBTC, and c) feasibility and logistics of the study. The proposing investigator or representative will join the call and answer questions. Proposals will be scored by all CSG members, and the proposing investigator will receive the composite score and written comments.

B. Vote (3 possible outcomes):

Forward to EAG with recommendation for development Return to proposing investigator/coordinator with suggestions for changes

(following resolution of issues, resubmission to CSG; CSG forwards to EAG, as above)

Reject research idea

III. Executive Affairs Group (EAG) – Initial Review and Vote

A. Identify resources (i.e., funding, data center, laboratory, TBTC site resources) that would be needed for the proposed study.

B. Vote (3 possible outcomes):

Forward to Steering Committee with recommendation for development Return to proposing investigator/coordinator with suggestions for changes

(following resolution of outstanding issues, resubmission to EAG; EAG forwards to Steering Committee, as above)

Reject research proposal

IV. Steering Committee – Initial Review and Vote

A. The Steering Committee has the responsibility for taking final action on the proposal.

B. The written concept will be presented to the Steering Committee for their review. EAG may request a presentation by proposing investigator/coordinator to the Steering Committee.

C. The Steering Committee is allotted time to submit questions/comments to the proposing investigator/coordinator.

D. The proposing investigator/coordinator responds to questions/comments.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 24

E. Vote by the Steering Committee; simple majority required.

Part Two: Following Concept Approval

V. Protocol Team Formation

A. CSG selects/designates a protocol team after a broad announcement for volunteers.

From volunteers who have submitted their names for consideration EAG approves protocol team members recommended by CSG

B. Protocol chair – proposing investigator/study coordinator.

C. Protocol team includes TBTC investigators, study coordinators, DCC, CDC, Monitoring and Support Center, laboratory, and pharmaceutical company representatives, etc., as appropriate. A balance of senior and junior investigators and coordinators will be sought.

D. Protocol team develops the concept into a detailed protocol.

E. When general outlines of the proposed protocol have been developed, protocol team sends draft version to CSG for review.

VI. Core Science Group (CSG) – Review and Vote

A. Reviews draft version of the protocol; review will focus on a) scientific rigor and merit;

b) how the proposal fits within the scientific priorities of the TBTC, and c) feasibility and logistics of the study d) possible collaborations with other research organizations.

B. Sends score/comments/recommendations to the protocol team.

C. Protocol team incorporates comments/recommendations or explains reasons for not doing so and returns modified protocol back to CSG.

D. CSG reviews protocol team’s response; votes to accept or reject protocol.

E. Sends their vote to protocol team and EAG.

F. If CSG votes to accept protocol, protocol team sends it to IQC for review (though IQC review may occur concurrently in some cases).

VII. Implementation and Quality Control (IQC) – Review and Vote

A. Reviews draft protocol for implementation, recruitment and retention issues.

B. Reviews consent forms to identify areas that might hinder patient understanding and IRB approval.

C. Sends comments/recommendations to the protocol team.

D. Protocol team incorporates comments/recommendations or explains reasons for not doing so.

Tuberculosis Trials Consortium (TBTC) By-Laws Page 25

E. IQC reviews protocol team’s response; votes to accept or reject protocol.

F. Sends their vote to protocol team and EAG.

If ultimately accepted by Steering Committee, IQC reviews case report forms for implementation issues; sends comments/recommendations to the DCC and the protocol team for consideration/inclusion

VIII.Executive Affairs Group (EAG) Review and Approval

A. EAG reviews the protocol for its effect/impact on:

The TBTC as a whole Human resources Financial resources The DCC Possible collaboration with other research organizations

B. EAG may send protocol back to CSG, IQC, and/or protocol team for clarifications, if necessary.

C. Feasibility survey may be done (i.e.,…