75D301-20-R-67869 00001 -Amendment Doc Final.pdf

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

1. CONTRACT ID CODE

PAGE OF PAGES

1 58

2. AMENDMENT/MODIFICATION NO.

00001

3. EFFECTIVE DATE

05/06/2020

4. REQUISITION/PURCHASE REQ. NO.

00HCVJEE-2020-41184

5. PROJECT NO. (If applicable)

6. ISSUED BY CODE 2543 7. ADMINISTERED BY (If other than Item 6) CODE

Centers for Disease Control and Prevention

Office of Acquisition Services (OAS)

2900 Woodcock Blvd

Atlanta, GA 30341-5539

8. NAME AND ADDRESS OF CONTRACTOR (No., street, county, State and ZIP Code)

X

9A. AMENDMENT OF SOLICITATION NO.

75D301-20-R-67869

9B. DATED (See Item 11)

05/06/2020

10A. MODIFICATION OF CONTRACT/ORDER NO.

10B. DATED (See Item 13)

CODE FACILITY CODE

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

X The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers x is extended, is not extended.

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended, by one of the following methods:

(a) By completing Items 8 and 15, and returning 1 copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted; or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEGMENT

TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT

IN REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted, such change may be made by telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

12. ACCOUNTING AND APPROPRIATION DATA (If required)

13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS,

IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT ORDER NO. IN

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).

C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority)

E. IMPORTANT: Contractor is not, X is required to sign this document and return 1 copies to the issuing office.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

1. See Continuation Page for Details..

Except as provided herein, all terms and conditions of the document referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in full force and effect.

15A. NAME AND TITLE OF SIGNER (Type or print)

16A. NAME OF CONTRACTING OFFICER

Candice L. Simmons

15B. CONTRACTOR/OFFEROR

(Signature of person authorized to sign)

15C. DATE SIGNED

16B. UNITED STATES OF AMERICA

BY ___________________________________________

(Signature of Contracting Officer)

16C. DATE SIGNED

06 May 2020

NSN 7540-01-152-8070 STANDARD FORM 30 (REV. 10-83)

PREVIOUS EDITION UNUSABLE 30-105 Prescribed by GSA

FAR (48 CFR) 53.243

ITEM 10A.

CONTINUATION PAGE

Amendment 00001 to Request for Proposal 75D301-R-67869 is being issued to do the following:

1. Provide all interested offerors with answers to questions submitted on or before April 24, 2020 as required per originally posted solicitation. See attachment titled “Amendment 00001 – Questions and Answers”.

2. Incorporate revised Section C titled “Description/Specification/Work Statement” with the following changes:

a. Incorporate revised Performance Work Statement with bolded and underlined changes in SECTION 2 titled “PURPOSE”.

3. Incorporate revised Section F titled “Deliveries or Performance” with the following changes:

a. Incorporate revised “Delivery Date” verbiage (bolded and underlined) for task

C.4.1,b,ii,a,1 under section F.2 of solicitation titled “Deliverable(s) Schedule”.

b. Incorporate revised “Standards Criteria for Acceptance” verbiage (bolded and underlined) for “Services Required – 2. IRB Approval Package” under section F.2 of solicitation titled “Performance-based Matrix”.

4. Incorporate revised Section J titled “List of Attachments” with the following changes:

a. Add new Attachment J.12 titled “Subcontracting Plan Template”

5. Incorporate revised Section L titled “Instructions, Conditions, And Notices to Offerors” with the following changes:

a. Per L.9 titled “Proposal Format”:

i. Add additional language (bolded and underlined) at section L.9(a).

ii. Revised verbiage (bolded and underlined) at section L.9(d).

iii. Revised verbiage (bolded and underlined) at section L.9(f).

b. Per L.10 titled “TECHNICAL PROPOSAL INSTRUCTIONS”:

i. Revised verbiage (bolded and underlined) at section L.10(b).

ii. Revised verbiage (bolded and underlined) at section L.10(c ).

iii. Revised verbiage (bolded and underlined) at section L.10(d).

iv. Revised verbiage (bolded and underlined) at section L.10(d)(5)(a).

v. Revised verbiage (bolded and underlined) at section L.10(d)(5)(b).

vi. Add Subcontracting Language/Requirement (bolded and underlined) at section L.10(d)(6).

6. Incorporation revised Section M titled “Evaluation Factors for Award” with the following changes:

a. Revise verbiage (bolded and underlined) at M.3 titled “Evaluation of Proposals.

b. Per M.6 titled “Evaluation of Technical Proposals:

i. Add row to Technical Proposal Evaluation Criteria Table for addition of Subcontracting Plan (bolded and underlined) and corresponding “Acceptable’ or “Unacceptable” rating option.

ii. Add Technical Evaluation Criterion (6) titled “Subcontracting Plan” and corresponding “Acceptable” or “Unacceptable” rating option (underliend and bolded).

7. All other terms and conditions remain unchanged and in full force and effect.

Section C - Description/Specification/Work Statement

Performance Work Statement Title: Tuberculosis Trials Consortium (TBTC) Clinical Research Services

Period of Performance: September 18, 2020 – September 17, 2030

SECTION 1 – BACKGROUND

Since the late 1940s the U.S. Public Health Service (USPHS), and the Department of Veterans Affairs have conducted studies of anti-TB medications. Many of the agents studied then are still in use today. In the 1960’s, the U.S. TB control and clinical research programs were transferred from their original location in Washington DC to the National Communicable Disease Center (now CDC) in Atlanta.1 In the 1980s, when funding for TB control was declining, support for TB drug trials also diminished. A key CDC study (USPHS Study 21) was nearly terminated for lack of adequate funding. With the resurgence of TB, strong federal support for TB control was restored in 1992. CDC renewed its engagement with TB clinical trials in 1993; an open competition funded a group of trial-capable sites for a period of 5 years (1993–1998).

Some sites were funded through contracts with CDC, and others under an Inter-Agency Agreement with the Washington DC VA Medical Center (VAMC IAA). Among site characteristics sought were: access to significant numbers of TB patients, experience in the conduct of clinical trials, the presence of a highly qualified clinical team, and a credible plan for recruitment, management, and follow-up of trial participants. In collaboration with experienced staff at CDC, the investigators planned a randomized trial comparing a once-weekly rifapentine-based continuation phase regimen with the then-standard twice-weekly rifampin-based regimen, both given after completion of the first 2 months of intensive treatment for TB. This trial, initially named USPHS Study 22, enrolled 1,075 TB participants from sites in the U.S.

and Canada.2

In 1997 CDC and the investigators from these sites decided to reorganize their activities, creating the TB Trials Consortium, or TBTC. TBTC is based in the Clinical Research Branch (CRB) of CDC’s Division of Tuberculosis Elimination (DTBE). The CRB includes medical officers, epidemiologists, health scientists, clinical research specialists, laboratorians, data analysts, data managers, statisticians, and contract specialists. Formal by-laws for TBTC were adopted in 1998, establishing a central Steering Committee, made up of one representative from each site and one from CDC, as well as several executive committees: the Core Science Group (CSG); the Implementation and Quality Committee (IQC);

Publications and Presentations committee(P&P); and Advocacy and External Relations (AER). An Executive Affairs Group (EAG), composed of committee chairs and CRB leadership, was to serve as the executive arm of the Steering Committee, and was responsible for day-to-day decision-making.

In 1999 the TBTC underwent an open re-competition process; the selected clinical trial sites composed the TBTC during a 10-year cycle, from October 1999 to September 2009. Twenty-three sites were included, located in the United States and Canada. In 2003, the consortium received additional funding

1 Binkin NJ, Vernon AA, Simone PM, et al. Tuberculosis prevention and control activities in the United States: an overview of the organization of tuberculosis services. Int J Tuberc Lung Dis. 1999;3:663-74.

2 Benator D, Bhattacharya M, Bozeman L, et al., and the Tuberculosis Trials Consortium. Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: a randomised clinical trial. Lancet. 2002;360:528-34 https://www.ncbi.nlm.nih.gov/pubmed/?term=Binkin%20NJ%5BAuthor%5D&cauthor=true&cauthor_uid=10460098 https://www.ncbi.nlm.nih.gov/pubmed/?term=Vernon%20AA%5BAuthor%5D&cauthor=true&cauthor_uid=10460098 https://www.ncbi.nlm.nih.gov/pubmed/?term=Simone%20PM%5BAuthor%5D&cauthor=true&cauthor_uid=10460098 https://www.ncbi.nlm.nih.gov/pubmed/10460098 https://www.ncbi.nlm.nih.gov/pubmed/12241657 https://www.ncbi.nlm.nih.gov/pubmed/12241657 https://www.ncbi.nlm.nih.gov/pubmed/12241657 from DTBE, and added international sites in Brazil, Spain, Uganda and South Africa. In 2009 a 3rd open competition was conducted, with awards given to sites in the U.S., Spain, Peru, Brazil, Hong Kong, Vietnam, Uganda, Philippines, Kenya, and South Africa. The Brazil site was closed, and other sites reduced, in 2013, when funding was reduced consequent to the U.S. Congress’s budget sequestration.

The remaining sites continued to function productively. For administrative reasons, a set of one-year “bridging” contracts were issued in Sept. 2019.This new funding announcement proposes to award contracts to a new group of TBTC trial sites for the next 10-year cycle, from September 2020 to September 2030. It is the intent of the DTBE that TBTC continue its efforts to conduct therapeutic, diagnostic, and preventive research in support of the CDC goal of TB elimination. Research of the consortium should be relevant to those locations where it is conducted, and programmatically relevant to the TB control program of the United States and the mission of domestic TB elimination.

SECTION 2 – PURPOSE

The purpose of this procurement is to support clinical trials and clinical research on the treatment, diagnosis and prevention of tuberculosis (TB) throughout the ten-year performance period 2020 -2030.

Emphasis will be given to studies of latent TB infection in low- and medium- TB incidence settings, inclusive of but not limited to the United States and Canada, as well as studies of active TB disease both domestically and internationally.

SECTION 3 – SCOPE OF WORK

Awarded contractor(s) shall conduct all phases of clinical trials in patients with TB disease or latent TB infection, including (as needed) screening, diagnosis, enrollment, treatment, observation, clinical testing, data collection, and follow-up after treatment. The scope of activities may range from small laboratory-based and/or single site studies to large Phase 2 and long-term Phase 3 clinical trials to evaluate new TB drugs and drug regimens, diagnostics, and preventive interventions. Contractors shall also participate fully as members of the TBTC. A description of the TBTC is detailed herein and a copy of the current TBTC By-Laws (attachment J.1) are provided in Section J. Note that the TBTC By-Laws are subject to revision and the version provided in attachment J.1 provide the current version as example.

CDC and TBTC vendor research sites have developed infrastructure and methods of operation that seek fully to engage the capacities of the clinical sites. Vendor, must conduct all work under the infrastructure of the TBTC, which currently includes:

1. A network of domestic and international clinical sites funded through direct contracts with CDC, through sub-contracts established by academic medical centers in North America with funding from the CDC, or through the VAMC IAA;

2. CRB-guided study design, implementation, data and information management, microbiology lab oversight, regulatory affairs, and data analysis, with engagement and collaboration from vendor research sites.

3. By-Laws which govern the function of the consortium, and which define a network of committees, protocol teams and working groups to facilitate the accomplishment of the consortium’s objectives;

4. A communications system that includes extensive use of E-mail, teleconferences and web-conferences; and regular in-person meetings in Atlanta;

5. Cooperative relationships with local clinics and TB control programs at recruiting sites, which facilitate the recruitment and management of trial participants;

6. An expert Data & Safety Monitoring Board (DSMB) which convenes at least annually to review ongoing clinical trials;

7. Coordination with and between the CDC Institutional Review Board (IRB) and IRBs from the clinical sites;

8. Support for a contract research organization (CRO), which performs on-site clinical monitoring;

9. A custom-designed web-based study management system (herein referred to as TBTC2), including electronic enrollment and data capture, tracking of regulatory approvals, real-time quality assurance, and drug supply management. Additional details of TBTC2 are:

a. TBTC2 is custom designed and built by CDC staff and contractors solely for TBTC study management;

b. TBTC2 is housed on CDC servers and accessible to all users via a secure URL;

c. A user-role access matrix is implemented such that specific users are granted access only to modules within TBTC2 required for specific tasks;

d. User access and credentialing is managed by CDC staff; and

e. TBTC2 is optimized for computer use on Internet Explorer v11 but can be accessed via other internet browsers and mobile applications via the secure URL. There is not a mobile application for TBTC2.

10. Cooperative relationships with:

a. Key manufacturers of anti-TB drugs;

b. Key public-private partnerships, non-governmental organizations, and international agencies;

c. Mycobacteriology, pharmacology, pharmacokinetic, and genetics laboratories within and outside CDC; and

d. The U.S. National Institutes of Health

11. Collaborative relationships with global experts in TB clinical trials, medical statistics, pharmacology, animal modeling, basic mycobacteriologic science, and other domains.

As noted, several executive committees—composed of CRB representatives, site investigators, and study coordinators— advise CRB and DTBE on the administrative and development work of the TBTC. These committees include:

1. The Core Science Group (CSG), which advises and oversees implementation of the TBTC’s scientific research agenda;

2. The Implementation and Quality Committee (IQC), which provides guidance on the conduct and quality assurance of ongoing studies, and advises on the feasibility of proposed new studies;

3. The Publications and Presentations Committee (P&P), which reviews and accepts materials for public dissemination and advises on the manner in which results of TBTC studies are made public;

4. The Advocacy and External Relations Committee (AER), which offers guidance on TBTC’s relationships with outside institutions and entities; and,

5. The Executive Affairs Group (EAG), which is composed of TBTC leadership (including CRB leadership and chairs of major TBTC committees) and which advises CRB and DTBE on overall execution of the TBTC research agenda.

The TBTC By-Laws (see example in attachment J.1) codify this committee structure. As previously noted, the By-Laws are subject to revision by CRB and DTBE.

C.4 TASKS TO BE PERFORMED

Each vendor research site shall, as an independent organization and not as an agent of the Government, furnish all the necessary services, qualified personnel, material, equipment, and facilities to concurrently perform multiple clinical trials and/or studies for the treatment of active and/or latent tuberculosis (TB), for the evaluation of new tests or approaches for the diagnosis of TB infection and disease, and for the prevention of TB, using procedures outlined in each trial or study’s applicable protocol. At the study sites, data must be available for external checking against original source documents as required by U.S.

federal regulations. CRB staff and/or external CRO site monitors will evaluate adherence to U.S. and international standards of good clinical practice (GCP), good clinical laboratory practice (GCLP), data collection and reporting, regulatory compliance, accurate protocol implementation, internal quality management, and test product accountability. Site visits will be performed once or twice yearly, or as-needed to review specific protocols, provide training on protocol conduct, review internal quality assurance plans, and document error resolution. Specific requirements are as follows, but at the discretion of CRB other requirements may be imposed, if necessary, to allow alternative methods and mechanisms for the capture of data and information.

The expected duration of these contracts is ten years. During the next decade, the focus of the consortium will be on treatment of latent TB infection (LTBI) and active TB disease.

C.4.1 Specific contract requirements include the following:

a. Participation in clinical research studies:

i. Clinical trial planning and execution:

a. Participate each year in as many active TBTC protocols as is feasible at the site, considering availability of TB patients and staff capacity.

ii. Conduct research studies and/or clinical trials in accordance with each study’s applicable protocol.

a. Each protocol will describe in detail the required procedures, including scheduled clinic visits, required laboratory tests (which must be performed in qualified laboratories), required chest x-rays, required collection of pharmacokinetic or other samples, and other required procedures. Each study will provide specific data collection forms and data entry screens to be used for the vendor to report results. When required by individual protocols, the vendor shall be responsible for secure, safe and timely shipping of specimens (such as bacteriologic isolates or plasma/serum specimens) to designated laboratories or repositories.

b. Transmission of electronic records of all clinical and laboratory data to the sponsor will occur through the web-based study management system, TBTC2.

iii. Recruit, screen, consent, enroll, and follow participants for TBTC studies.

a. The participant population shall reflect the demographics of the local community, and shall, as feasible and appropriate, include minorities, adult men and women, and children. Expected enrollment numbers will depend on the location and on the local prevalence of TB infection and disease and should be estimated using local surveillance data or data from the WHO (reported or estimated incidence rate of smear-positive TB).

If local or regional surveillance data are available and these data are more accurate and relevant than the WHO national rate, the vendor is encouraged to use the local or regional numbers and to add a justification for not using the WHO national rate.

i. Vendors based in areas of low to medium TB incidence (≤ 100 cases per 100,000 population), shall enroll a minimum of 50 latent tuberculosis patients each year across all actively enrolling TB prevention protocols; and a minimum of 3 newly diagnosed active tuberculosis patients each year across all actively enrolling TB treatment protocols.

ii. Vendor based in areas of high TB incidence (>100 cases per 100,000) shall enroll a minimum of 75 newly diagnosed active tuberculosis patients each year across all actively enrolling TB treatment protocols.

Retain, and follow to completion of study, participants enrolled in TB trials and studies.

Vendors are expected to retain a minimum of 85% of all participants, and to make efforts to retain all participants.

iv. Regulatory management

a. As these studies will be funded by the U.S. Government, they must comply with regulatory requirements of the host country, relevant international regulatory bodies, and the United States. Specifically, each vendor research sites must conduct and report on studies according to accepted GCP and in compliance with:

i. Existing U.S. Federal Regulations (including CDC, U.S. Food and Drug Administration, and the Office of Human Research Protections [OHRP]);

ii. Relevant international policies and regulations (including where appropriate guidelines from ICH and from international bodies such as WHO); and

iii. Applicable U.S., international, and host-country national policies concerning the use of investigational agents and the protection of human subjects.

b. Have research records and documents well organized and accessible for monitoring visits and audits by the clinical research organization and/or Federal Regulators.

c. Have procedures in place for study-close out and archiving study records in accordance with Federal Regulations and institutional policy.

v. Personnel

a. Have key personnel with the appropriate qualifications in place for the conduct of each clinical trial.

b. Have a personnel plan that fosters growth in junior staff and that includes a contingency plan to replace key personnel if needed;

vi. Laboratory Capacity

a. Identify a study laboratory or laboratories that will process, store and ship specimens.

Assure laboratory capacity and adhere to performance standards as specified in each study protocol. Specific laboratory requirements include:

i. Having standard operating procedures in line with GCLP and GCLP training;

ii. Concurrence with Key Elements for Mycobacteriology Laboratories (Attachment

J.6);

iii. Designated point person (laboratory study coordinator) who is responsible for case report forms, and communication with study coordinator, site staff, and CRB, regarding test results;

iv. Participation in TBTC’s designated External Quality Assessment (EQA) program for relevant testing, including proficiency testing, rechecking and retesting, and/or on-site evaluations;

v. Documented laboratory technical certification (College of American Pathologists certification, ISO 15189, or equivalent), proficiency testing, and quality management systems, including validation of all relevant tests updated annually;

vi. Accept site visits from CDC and provide support for CRO monitoring of laboratory data; and

vii. Availability of BACTEC MGIT automated systems for all study specimens to ensure legitimacy of results of high-volume mycobacteria growth, detection and susceptibility testing.

vii. Investigational Product Management

a. Serve as, or delegate function of, importing agent for investigational study products, as applicable, including obtaining proper permits for import, liaising with customs agents, and responding to requests from CRB and pharmaceutical partners within five (5) business days of receipt. Importation of study products can take no longer than six (6) months from date of submission of request for products to CRB

b. Maintain documentation of accountability procedures for study drug, device, or agent.

c. Conduct studies in compliance with any protocol-specific requirements including those contained in protocol-related CRADAs or other agreements, regarding use and management of supplied products or devices.

i. The product supplied by any manufacturer will not be used for any purpose other than the conduct of studies as outlined in the protocol.

ii. The product supplied by any manufacturer will not be transferred to anyone other than research personnel or participants and will not undergo any analysis (compositional, structural, functional or other) without written permission from the manufacturer.

viii. Data Management

a. Collect and report to CDC all study data according to the requirements of the specific protocol (see attachments J.5.1, J.5.2, and J.5.3). Each vendor research site shall provide completed participant data forms to CRB through the TBTC2 study management system within 14 days of participant visit, event, or report, and at intervals specified within each protocol and its related manual of operating procedures (see attachments J.5.1, J.5.2, and

J.5.3). In instances where electronic access to TBTC2 study management system is not available submission of scanned or paper forms may be necessary.

b. Protect the confidential nature of proprietary information provided, including information related to the product used for any study. The precautions should be at least as stringent as those observed by their own organizations to protect their own confidential information.

c. Report adverse experiences of study participants according to specific protocols and in compliance with applicable national, international, U.S. regulatory, and pharmaceutical partner requirements.

d. Respond within five (5) days of receipt to data queries and requests emailed from CRB.

e. Review and respond to data query and quality assurance reports available on the TBTC2 study management system at least weekly.

f. Utilize the drug management module available on the TBTC2 study management system for requesting study drugs, confirming receipt of study drugs, and documenting any challenges with study drugs.

g. Utilize administrative modules of the TBTC2 study management system for the following activities, in support of each study in which the site participates:

i. Maintenance of study staff contact information;

ii. Reporting of Federal-Wide Assurance (FWA) number and expiration;

iii. Reporting of study laboratories; and

iv. Confirmation of IRB approval dates.

v. Have functioning administrative systems in place for receiving clinical research funding from U.S.-government contracts.

h. Send required administrative reports to DTBE-CDC:

i. Annual Progress Report- At a minimum the Annual Progress report must include an overview of the one-year contract period, study activities, committee work and participation at TBTC semi-annual meetings, work plan for next quarters, and a fiscal summary.

ii. Final Report – At a minimum the Final Report must include a summary of the ten--year contract period, study activities, committee work and participation at TBTC semi-annual meetings, and a total fiscal summary.

iii. Reports must be submitted on annual basis by December 30th of the base and all option years

i. Invoices must be provided on a monthly basis and costs stated in invoices must be converted to U.S. dollar currency.

j. Vendors must be able to reliably connect to a U.S. telephone line for scheduled conference calls.

k. Vendors must have Microsoft Office 365 including Power BI, or a transition date to O365 within 1 year of contract award, for data quality report provision.

b. Complete and adhere to the following start-up requirements within 60 days of contract award, with specific addenda for every protocol, as applicable, and whenever site changes occur that impact these requirements:

i. Study Management Plans:

a. Pharmacy Plan

1. All sites will be required to submit a pharmacy plan using the template that is provided (Attachment J.9).

2. Each pharmacy plan will address template in its entirety and include at a minimum, pharmacy address and contact person; temperature control mechanism; drug storage plans; and plans for provision of study drugs to participants including directly observed therapy, if required and specified by study protocol. A review of directly observed therapy process by the principal investigator is required by protocol.

b. Regulatory Compliance and Quality Management Plan

1. Sites will be required to complete and submit an overall Regulatory

Compliance and Quality Management Plan and will be required to submit protocol-specific addenda for each protocol using the template

(Attachment J.10) that is provided.

2. At a minimum the plan must provide documentation of how site staff will ensure participant interactions are conducted with adherence to GCP regulations and describe activities to verify and validate data completeness and accuracy.

c. Recruitment, Screening, and Retention Plan

1. Sites will be required to complete and submit a Recruitment, Screening, and Retention Plan for each protocol using the template (Attachment J.11) that is provided.

2. At a minimum the plan must address the template in its entirety and provide documentation of how site staff will ensure the required high levels of recruitment and retention for validity of the studies.

ii. Regulatory:

a. IRB Package for Registration, Approvals and Continuations

1. As a recipient of US federal funding participating in clinical investigations, sites are required to comply with the United States Code of Federal

Regulations Title 45: Public Welfare, part 46 (45 CFR 46) and where applicable, FDA Regulations (21 CFR Parts 50 and 56). The site must ensure that their institution has a valid Federal Wide Assurance (FWA) and maintain Institutional Review Board (IRB) approval for all protocols conducted under this contract. This provision allows a domestic site to rely on the CDC IRB. Sites must adhere to the IRB Registration instructions and provide evidence of FWA and IRB approvals for each protocol before enrolling participants.

b. Essential documents

1. Each contracted site shall have in place a system for organization, storage and updating of essential documents.

2. Following award, each site shall verify presence of resumes/CVs for all staff, completed FDA forms 1572 for all active protocols, and required financial disclosures.

c. Delegation of Authority Log

1. The log provides documentation of study related tasks that have been delegated by the site principal investigator for each protocol.

2. Sites will be required to complete and keep the log current using the provided template.

3. The log must be submitted upon request or as specified for each study.

d. Education, Training, and Experience Documentation

1. Site staff must have training in Human Subjects Protection, Good Clinical

Practice, Good Clinical Laboratory Practice, and study specific training for each protocol, as applicable to staff- and study-specific roles, per delegated authority.

2. All trainings, except the study specific trainings, must be completed once every three years.

3. Sites should maintain all certifications of completed training and document trainings on the delegation of authority logs for each study.

iii. Laboratory:

a. The protocol and related materials must be shared with the laboratory director (or director’s designee) of the site’s designated laboratory.

b. The principal investigator and study coordinator must discuss laboratory participation with the laboratory director (or designee) at the time the site is informed of the study

c. The laboratory director (or designee) must confirm they are prepared to participate; confirm adherence to study testing and harmonized methods; provide documentation of validation of new methods/testing specific to the study; assure all lab-specific IRB documents are submitted and approved; assure any MTA required by the host site is submitted and approved; and complete and return lab surveys by the deadline.

iv. Drug Management:

a. Sites will be required to use the Drug Management Module to place stocking orders for study medication, confirm receipt of study medication, and document challenges with study drugs. A user guide for the module will be made available in the Manual of Operating Procedures for each protocol.

b. Sites must provide a description of the process for study drug importation and management and inform CRB of changes in the process (once known by sites) that would materially impact the site’s ability to timely and effectively import and manage study drugs.

v. Data Management:

a. Have reliable internet access and perform the following tasks related to the TBTC2 web-based study management system. Training will be provided by CRB staff, and one-on-one assistance can be provided upon request:

1. Vendor must request access to the TBTC2 system within 60 days following award and complete all steps required to obtain log-in credentials for

TBTC2.

2. Vendor must review, confirm accuracy, or update as required, site-specific information in the TBTC2 Study Management System Site Module. This module is a repository for all site-specific information, including Federal-

Wide Assurance and laboratory information.

3. Vendor must review, confirm accuracy, or update as required, site specific information in the TBTC2 Study Management System Member Module.

This module is a repository for all site staff contact information.

c. Participate fully as a member of the TB Trials Consortium (TBTC)

Throughout the duration of the contract, the vendor shall participate fully as an active member of the TBTC in compliance with the TBTC By-Laws (example in attachment J.1). This will include, the first year of performance and all subsequent phases, attendance at TBTC group meetings. The primary purpose of these meetings is to review progress and implementation of current trials, to learn from outside experts, conduct discussion about possible new studies, conduct discussions related to trial implmentation, regulatory compliance and/or quality assurance. These meetings will be held up to twice a year and generally in Atlanta, GA.

C.4.2 Study Initiations by Year

BASE YEAR

The vendor shall perform start-up/preparation activities in accordance with the procedures and guidelines outlined in detail in the enclosed examples of a Phase 2 clinical trial, a Phase 3 clinical trial, and/or a pharmacokinetic protocol. Examples of protocols for TBTC Studies are provide as Attachments in Section J. Enrollment into a study may not begin until the relevant ethical committees or Institutional Review Boards (IRBs) have granted approval.

Upon IRB approval the vendor shall start the enrollment, treatment, testing, follow-up, observation, data collection, specimen collection, and compliance activities for the studies chosen to be implemented. The government estimates that new studies may be initiated during this phase.

OPTION PERIOD 1:

The vendor shall start or continue the enrollment, treatment, testing, follow-up, observation, data collection, specimen collection, and compliance activities for the studies chosen to be implemented.

The government estimates that 0-2 new studies may be initiated during this phase.

OPTION PERIOD 2:

The vendor shall start or continue the enrollment, treatment, follow-up, observation, data collection, and specimen collection, and compliance activities for the studies chosen to be implemented. The government estimates that 0-2 new studies may be initiated during this phase.

OPTION PERIOD 3:

The vendor shall start or continue the enrollment, treatment, follow-up, observation, data collection, and specimen collection, and compliance activities for the studies chosen to be implemented. The government estimates that 0-2 new studies may be initiated during this phase.

OPTION PERIOD 4:

The vendor shall start or continue the enrollment, treatment, follow-up, observation, data collection, and specimen collection, and compliance activities for the studies chosen to be implemented. The government estimates that 0-4 new studies may be initiated during this phase.

OPTION PERIOD 5:

The vendor shall start or continue the enrollment, treatment, follow-up, observation, data collection, and specimen collection, and compliance activities for the studies chosen to be implemented. The government estimates that 0-2 new studies may be initiated during this phase.

OPTION PERIOD 6:

The vendor shall start or continue the enrollment, treatment, follow-up, observation, data collection, and specimen collection, and compliance activities for the studies chosen to be implemented. The government estimates that 0-2 new studies may be initiated during this phase.

OPTION PERIOD 7:

The vendor shall start or continue the enrollment, treatment, follow-up, observation, data collection, and specimen collection, and compliance activities for the studies chosen to be implemented. The government estimates that 0-2 new studies may be initiated during this phase.

OPTION PERIOD 8:

The vendor shall start or continue the enrollment, treatment, follow-up, observation, data collection, and specimen collection, and compliance activities for the studies chosen to be implemented. The government estimates that 0-2 new studies may be initiated during this phase.

OPTION PERIOD 9:

The vendor shall start or continue the enrollment, treatment, follow-up, observation, data collection, and specimen collection, and compliance activities for the studies chosen to be implemented. The government estimates that 0-2 new studies may be initiated during this phase.

There are no clauses/provisions included in this section.

Section F - Deliveries Or Performance

F.1 FAR 52.252-2 Clauses Incorporated By Reference (Feb 1998)

This contract incorporates one or more clauses by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. Also, the full text of a clause may be accessed electronically at this/these address(es):

https://www.acquisition.gov https://www.gsa.gov/policy-regulations/regulations/federal-acquisition-regulation-far

(End of Clause)

FAR SOURCE TITLE AND DATE

52.242-15 Stop-Work Order (Aug 1989)

52.242-15, Alternate I Stop-Work Order, Alternate I (Apr1984)

F.2 Deliverable(s) Schedule

Base Year: September 18, 2020 through September 17, 2021

The Contractor shall deliver, within the time frames specified, Item(s) No. 1 through 11

Task Description Quantity of Copies

Delivery Date Format Deliver To

C.4.1, b, ii, a,1 IRB Registration Package

1 Within 75 days after award for current protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, a,1 IRB Approval

1 Within 30 days after receiving approval of a protocol locally or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

https://www.acquisition.gov/

C.4.1, b, ii, a,1 IRB Continuation

1 Within 30 days before expiration for current protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, b, 2 Essential Documents

1 Within 30 days after award, and within 14 days of any change in personnel

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a, vi, a, v Laboratory Certification Documentation

Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, a Pharmacy Plan 1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol .

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, iv, b Drug Management Procedures

1 Within 30 days of award, or as specified in protocols, or start-up instructions.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, b Regulatory Compliance and Quality Management Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1., b, i, c Recruitment, Screening, and Retention Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, c Delegation of Authority Log

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol, and when key personnel changes.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a,vii,h,i Annual Progress Report

1 30 days after the end of each 12-month period.

TBTC Data Center

CO and COR

Option 1 Option Period One Items: September 18, 2021 through September 17, 2022

C.4.1, b, ii, a,1

IRB Registration protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, IRB Approval Package of a protocol locally or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, a,1

IRB Continuation Package

1 Within 30 days before expiration for current protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, b, 2

Essential Documents 1 Within 30 days after award, and within 14 days of any change in personnel

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a, vi, a, v

Laboratory Certification specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, a Pharmacy Plan 1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol .

TBTC Data Center

TBTC Data

C.4.1, b, iv, b

Drug Management Procedures

1 Within 30 days of award, or as specified in protocols, or start-up instructions.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, b Regulatory Compliance and Quality Management Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1., b, i, c

Recruitment, Screening, and Retention Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, c

Delegation of Authority Log

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol, and when key personnel changes.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a,vii,h,i

Annual Progress Report 1 30 days after the end of each 12-month period.

TBTC Data

Option 2 Option Period Two Items: September 18, 2022 through September 17, 2023 protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data of a protocol locally or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, a,1

IRB Continuation Package

1 Within 30 days before expiration for current protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, b, 2

Essential Documents 1 Within 30 days after award, and within 14 days of any change in personnel

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a, vi, a, v

Laboratory Certification specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, a Pharmacy Plan 1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol .

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, iv, b

Drug Management Procedures

1 Within 30 days of award, or as specified in protocols, or start-up instructions.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, b Regulatory Compliance and Quality Management Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1., b, i, c

Recruitment, Screening, and Retention Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data c

Delegation of Authority Log

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol, and when key personnel changes.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a,vii,h,i

Annual Progress Report 1 30 days after the end of each 12-month period.

TBTC Data

Option 3 Option Period Three Items: September 18, 2023 through September 17, 2024 protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, of a protocol locally or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, a,1

IRB Continuation Package

1 Within 30 days before expiration for current protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, b, 2

Essential Documents 1 Within 30 days after award, and within 14 days of any change in personnel

TBTC Data Center

TBTC Data

C.4.1, a, vi, a, v

Laboratory Certification specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, a Pharmacy Plan 1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol .

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, iv, b

Drug Management Procedures

1 Within 30 days of award, or as specified in protocols, or start-up instructions.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, b Regulatory Compliance and Quality Management Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1., b, i, c

Recruitment, Screening, and Retention Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, c

Delegation of Authority Log

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol, and when key personnel changes.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a,vii,h,i

Annual Progress Report 1 30 days after the end of each 12-month period.

TBTC Data

Option 4 Option Period Four Items: September 18, 2024 through September 17, 2025 protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, of a protocol locally or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, a,1

IRB Continuation Package

1 Within 30 days before expiration for current protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, b, 2

Essential Documents 1 Within 30 days after award, and within 14 days of any change in personnel

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a, vi, a, v

Laboratory Certification specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, a Pharmacy Plan 1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol .

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, iv, b

Drug Management Procedures

1 Within 30 days of award, or as specified in protocols, or start-up instructions.

TBTC Data Center

TBTC Data

C.4.1, b, i, b Regulatory Compliance and Quality Management Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1., b, i, c

Recruitment, Screening, and Retention Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, c

Delegation of Authority Log

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol, and when key personnel changes.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a,vii,h,i

Annual Progress Report 1 30 days after the end of each 12-month period.

TBTC Data

Option 5 Option Period Five Items: September 18, 2025 through September 17, 2026 protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, of a protocol locally or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data

IRB Continuation Package

1 Within 30 days before expiration for current protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, b, 2

Essential Documents 1 Within 30 days after award, and within 14 days of any change in personnel

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a, vi, a, v

Laboratory Certification specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, a Pharmacy Plan 1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol .

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, iv, b

Drug Management Procedures

1 Within 30 days of award, or as specified in protocols, or start-up instructions.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, i, b Regulatory Compliance and Quality Management Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data Center and

COR

C.4.1., b, i, c

Recruitment, Screening, and Retention Plan

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol.

TBTC Data Center

TBTC Data c

Delegation of Authority Log

1 Within 60 days after award or as specified in each protocol or start-up requirements for each protocol, and when key personnel changes.

TBTC Data Center

TBTC Data Center and

COR

C.4.1, a,vii,h,i

Annual Progress Report 1 30 days after the end of each 12-month period.

TBTC Data

Option 6 Option Period Six Items: September 18, 2026 through September 17, 2027 protocols or as specified in start-up requirements for each protocol

TBTC Data Center

TBTC Data Center and

COR

C.4.1, b, ii, of a…