Task order 2-Attachnent 4.pdf

Request for Task Order Proposal - Task Order 2

Request for Task Order Proposal (RTOP)

TASK ORDER 2 -Attachment 4 RTOP No: FDA-23-RTOP-11750

Study Title: Examining the influence of synthetic cooling agents on cigarette sensory and subjective effects and use behavior.

BRIEF DESCRIPTION OF SERVICES

The primary function of the Food and Drug Administration (FDA) is to promote public health associated with the use of foods, dietary supplements, cosmetics, drugs, tobacco, and other products under its jurisdiction. FDA's Center for Tobacco Products (CTP) implements PL 111-31 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act), which was signed into law on June 22, 2009. The Tobacco Control Act granted FDA important authority to regulate the manufacture, marketing, and distribution of tobacco products to protect public health. The goals of this study are to determine the extent to which consumers perceive the cooling sensation from synthetic cooling agents in non-menthol cigarettes at different concentrations, how this effect influences cigarette sensory and subjective effects (e.g., harshness, cooling, liking) and use behavior (i.e., topography), and how this effect compares to menthol cigarettes.

TASK ORDER TYPE

The Government anticipates the award of a hybrid contract, with a mix of firm-fixed price and time and materials deliverables, as a result of this RTOP.

The Government recommends the following tasks are fixed price deliverables:

• Task 1: Kick off meeting

• Task 2: Non-disclosure of private information (NPI) forms

• Task 3: Biweekly meetings

• Task 4: Monthly progress reports

• Task 7: Final laboratory study protocol

• Task 8: Final clinical study protocol

• Task 10: Investigational tobacco product (ITP) submission and clearance

• Task 11: Obtain clearances for the study

• Task 13: Participant recruitment updates

• Task 14: Draft clinical study report

• Task 15: Final clinical study report

• Task 16: Draft laboratory study report

• Task 17: Final laboratory study report

The Government recommends the following tasks are time and material deliverables:

Request for Task Order Proposal- Task Order 2

• Task 5: Draft laboratory study protocol

• Task 6: Draft clinical study protocol

• Task 9: Perform laboratory study

• Task 12: Perform clinical study

SCOPE OF WORK

The primary objectives of this task order are to 1) evaluate the sensory and subjective effects of WS-3 at different concentrations in cigarettes in adult menthol and non-menthol smokers and

2) evaluate the effect of WS-3 at different concentrations on smoking topography in menthol and non-menthol smokers. A secondary objective of this task order is to determine if menthol and non-menthol users have different sensory effects for menthol and WS-3 in cigarettes.

The Contractor shall produce study cigarettes by modifying SPECTRUM non-menthol (NRC600) research cigarettes with various concentrations of menthol and N-ethyl-p-menthane-3-carboxamide (WS-3) (e.g., as proposed in Jackson et al. 2023).1 The Contractor shall perform chemical analyses (whole cigarette and smoke chemistry) on study cigarettes and participants’ own brand cigarettes to assess nicotine, menthol, and WS-3 content. The Contractor shall produce sufficient quantities of study cigarettes to perform the laboratory study and clinical study.

The Contractor shall recruit current menthol and non-menthol cigarette smokers to test seven

(7) conditions in a randomized, double-blind, within and between-subject crossover study across two (2) study visits. During study visits, participants will take a series of puffs from each of three (3) to four (4) randomly selected test cigarettes as they normally would using a topography device and shall complete subjective questionnaires about each cigarette immediately following sampling. Each cigarette test session will be separated by a rest period (e.g., 15 min).

The Contractor shall perform all data analyses, provide FDA all raw data, and write study reports. All results and source documents shall be submitted to the Contracting Officer’s Representative (COR) and Study Project Lead(s).

PRICING TABLE

Task Deliverable Quantity Price 1 Kick-off Meeting 1 $ 2 NPI Forms 1 for each staff member involved in clinical study

3 Biweekly Meetings 1 meeting every 2 weeks $ 4 Monthly Progress Reports 1 electronic version per month

1 Jackson, KJ, Schroeder MS, Jiu Ai, Jiu, Taylor, KM, Oniyide, O, Viray, LC, Smith, C, Koszowski, B, Butler, JM, Pickworth, WB (2023). A Method to Amend Cigarettes with Menthol for use in Research. Nicotine Tobacco Research, DOI:10.1093/ntr/ntad015

5 Draft Laboratory Study Protocol

1 electronic version;

preliminary drafts may be needed

6 Draft Clinical Study Protocol 1 electronic version;

preliminary drafts may be needed

7 Final Laboratory Study Protocol

1 electronic version $

8 Final Clinical Study Protocol 1 electronic version $ 9 Perform Laboratory Study 1 $ 10 ITP Submission and Clearance 1 electronic version $ 11 Obtain Clearances for the

Study (OMB and IRB) 1 electronic version each $

12 Perform Clinical Study 1 $ 13 Participant Recruitment

Updates 1 electronic version per week

14 Draft Clinical Study Report 1 electronic version;

additional drafts may be needed

15 Final Clinical Study Report 1 electronic version $ 16 Draft Laboratory Study Report 1 electronic version of final draft; additional drafts may be needed

17 Final Laboratory Study Report 1 electronic version Total $

SPECIFIC TASKS

Task 1 – Kick-off Meeting Within ten (10) business days of award, the Contractor shall set up and host a kick-off teleconference with the Study Project Lead(s), COR, and other FDA personnel to discuss roles, expectations, and deliverables associated with the task order requirements.

Task 2 – Non-disclosure of Private Information (NPI) Forms All Contractor staff shall sign NPI forms prior to commencing work. All signed forms shall be submitted electronically to the COR within thirty (30) business days of award. If additional staff are added to this contract after contract award, Contractor staff shall sign the NPI form immediately, and the COR shall be notified.

Task 3 – Biweekly Meetings The Contractor shall set up biweekly teleconferences, for the duration of the task order, with the Study Project Lead(s), COR, and other FDA personnel (as necessary) to discuss study progress, challenges, and other study details every two (2) weeks. Within five (5) business days following each teleconference, the Contractor shall submit teleconference meeting minutes to FDA that include a detailed summary of the discussion.

Task 4 – Monthly Progress Reports The Contractor shall submit monthly progress reports on the 10th calendar day of each month, for the duration of the task order, to the Study Project Lead(s), COR, and Contract Specialist detailing study progress, challenges (and solutions to those challenges), contract budget status, recruitment status, study deviations, adverse events, and other study details pertaining to the prior month’s progress. Progress reports shall indicate which deliverables or percentages of deliverables were completed during the month and overall progress of the task order and budget.

Task 5 – Draft Laboratory Study Protocol The Contractor shall develop a Draft Laboratory Study Protocol for the study titled “Examining the influence of synthetic cooling agents on cigarette sensory and subjective effects and use behavior” based on the following study objectives and protocol requirements:

Laboratory Study Objectives:

1. The Contractor shall prepare study cigarettes by adding 0.5 and 3 mg/cigarette (cig) menthol and 0.5, 1, 1.5, and 2 mg/cig N-ethyl-p-menthane-3-carboxamide (WS-3) to SPECTRUM non-menthol (NRC600) cigarettes. Concentrations in the study cigarettes must be within 20% of the target concentration.

2. The Contractor shall conduct chemical characterization of SPECTRUM study cigarettes and participants’ own brand cigarettes to measure nicotine, menthol, and WS-3 content. The Contractor shall conduct chemical characterization in the whole cigarette and in machine-generated cigarette smoke.

3. The Contractor shall select the laboratory and research facilities which are equipped to perform the study.

Whole Cigarette and Smoke Characterization The Contractor shall recommend methods and conduct chemical characterization of SPECTRUM study cigarettes and participants’ own brand cigarettes to measure nicotine, menthol, and WS- 3 content in the whole cigarette. The Contractor shall also measure nicotine, menthol, and WS- 3 smoke yields using a machine-based puffing regimen (e.g., via CORESTA methods under intense and non-intense use conditions such as Health Canada Intense (HCI) and International Standards Organization (ISO) or via a customized regimen based on topography data collected from clinical study participants).

Stability The Contractor shall conduct stability testing of the stock solutions and study cigarettes prior to their use in the Clinical Study (as required by the Investigational Tobacco Product [ITP] submission). FDA will review and approve stability data. Stability testing will include: nicotine (in study cigarettes only), menthol, and WS-3 content. Stock solutions shall be tested for stability prior to clinical study use and every three (3) months for the duration of the clinical study. Study cigarette batches shall be tested for stability prior to clinical study use and at the 10%, 25%, 50%, and 75% clinical data collection points. If a stock solution or cigarette batch is not within stability specifications, the Contractor will be required to re-test the samples. If after re-testing, the solution or batch is still outside the stability specifications, then it shall be remanufactured and/or require additional testing, and the FDA shall be consulted as soon as possible before remanufacture and/or continuance of the study.

Protocol Requirements:

1. The Contractor shall provide a detailed step-by-step description of the analytical methods and procedures used to produce the stock solutions and study cigarettes, analyze whole cigarettes and stock solutions, and generate machine yield data.

Information on the analytical procedures shall include (but not be limited to):

a. Analytical instrument

b. Apparatus

c. Laboratory consumables

d. Reagents

e. Test standards

f. Qualified personnel

g. Method calibration range, limit of detection (LOD), and limit of quantitation

(LOQ)

h. Sample preparation for the tobacco products and standards with any other pertinent protocol(s) including but not limited to extraction protocol

i. System suitability criteria

j. Data analysis (calculation applied to process data) and criteria in handling the outliers

k. Management systems

2. Verification of analytical methods to demonstrate that the methods are acceptable and suitable for their intended use. If the test methods are standard or international standards, identify any deviation from those standards and provide scientific justification. This includes, but is not limited to, the evaluation of the following parameters:

a. Accuracy

b. Precision

c. Specificity

d. Matrix effects

3. If the methods are developed by the Contractor, validation of analytical methods detailing testing plans for the following parameters, if applicable:

a. Sample preparation (derivatization, extraction, concentration, etc.)

b. Reference sample

c. Accuracy

d. Precision (repeatability, intermediate precision and/or reproducibility)

e. Linearity

f. LOD

g. LOQ

h. Range

i. Specificity

4. Details of the stock solution and study cigarette storage conditions, including how the stock solutions and study cigarettes are prepared and pulled for analytical testing and clinical use.

Multiple iterations of the protocol draft may be necessary to address feedback from all FDA review processes, but this process shall not exceed three (3) protocol iterations. Methods and results from the laboratory study shall be submitted for ITP clearances (See Task 10).

The Contractor shall be responsible for working with the FDA Study Project Lead(s) to obtain ITP clearance to perform the study. Stability data for the study cigarettes modified with WS-3 and menthol will be required before the ITP submission can be submitted for review/clearance, to include a five (5) day-time course of stability testing. Multiple time points over the course of shall be assessed to determine menthol and WS-3 stability in the study cigarettes (e.g., 1 hr, 2 hr, 5 hr, 8 hr, 12 hr, 24 hr, 48 hr, 72 hr, up to five days).

Task 6 – Draft Clinical Study Protocol The Contractor shall develop a Draft Clinical Study Protocol for the study titled “Examining the influence of synthetic cooling agents on cigarette sensory and subjective effects and use behavior” based on the following study objectives and protocol requirements:

Clinical Study Objectives:

1. Evaluate the sensory and subjective effects of WS-3 in cigarettes in adult menthol and non-menthol smokers.

2. Evaluate the effect of WS-3 on smoking topography in menthol and non-menthol smokers.

3. Determine whether menthol and non-menthol users have different sensory and subjective effects and use behaviors for menthol and WS-3 in cigarettes.

Puff Topography The Contractor shall recommend a validated laboratory-based puff topography data collection instrument (e.g., CReSS, Sodim). Software accompanying the topography data collection instrument shall be used to configure, initialize, and download data.

Protocol Requirements:

1. The study shall be a single-site, double-blind, within and between-subject crossover design with seven experimental cigarette conditions (i.e., non-menthol, 0.5 mg/cig menthol, 3 mg/cig menthol, 0.5 mg/cig WS-3, 1 mg/cig WS-3, 1.5 mg/cig WS-3, 2 mg/cig WS-3). There will be two (2) cohorts of participants: 1) current adult menthol cigarette smokers and 2) current adult non-menthol cigarette smokers. Full eligibility criteria will be proposed by the Contractor. The study shall consist of a screening visit and two (2) experimental visits. At the screening visit, if participants are deemed eligible, demographic information shall be collected and participants will receive training on the topography device using their own brand cigarette. Participants shall be randomized into double-blinded groups to determine the order of experimental conditions. The number of cigarettes presented at each session shall be counterbalanced so that some participants receive three randomly selected study cigarettes presented at the first session and others receive four.

2. Study visits shall be approximately sixty-five (65) minutes. At each visit, inclusion and exclusion criteria shall be reviewed to ensure participants remain qualified for the study.

Participants will be asked to refrain from smoking/tobacco product use, eating, or drinking anything other than water for two (2) hours prior to arrival. During study visits, participants will take a series of puffs from each of three (3) or four (4) randomly selected study cigarettes as they normally would using the topography device.

Participants shall complete sensory and subjective questionnaires (e.g., Duke Sensory Questionnaire [DSQ], Product Specific Questionnaire (PSQ)-Visual Analog Scale [VAS]) about each cigarette immediately following sampling. Specific sensory and subjective questionnaires to be used for assessment will be determined in conjunction with FDA.

Each cigarette session will be separated by a rest period (e.g., fifteen (15) min). At the second study visit, participants will be randomly presented with the three or four study cigarettes they did not receive at the first study visit.

3. The Draft Clinical Study Protocol shall include: study procedures, human subjects’ protection documentation (e.g., consent form, adverse event reporting), data handling and record keeping, publication plan (if applicable), quality assurance plan, and administrative information.

4. A Proposed Statistical Analysis Plan document, which shall include:

a. Details regarding data collection, organization, analysis, and interpretation as well as information on the personnel who shall conduct the statistical analyses and their credentials (e.g., training and courses completed).

b. The statistical model(s) and software program(s) that shall be used to analyze the data.

c. Methods and criteria for outlier detection and removal, where applicable.

d. Information on the selection of the significance level and post- hoc analysis, when applicable.

Special Government Employee (SGE) and FDA Internal Review Once the Contractor submits the first version of the draft protocol, FDA and the Contractor shall not exceed three (3) rounds of edits. Following these edits, the clinical study protocol will undergo SGE review. The Project Lead(s) and Contractor will edit the protocol based on SGE feedback and then the clinical study protocol will undergo an FDA internal review process. The Project Lead(s) and Contractor may need to edit the protocol based on this internal FDA review process. Together, these two review processes will take up to 2-3 months.

Data Monitoring A preliminary clinical study data monitoring plan shall be submitted as part of the Contractor’s study proposal (i.e., bid proposal).

The draft and final clinical study protocols shall include a section describing the proposed plan for interim data monitoring. This section shall explain who is to be responsible for interim monitoring, what data will be monitored (e.g., performance, risk assessment), the timing of the first data review, and the frequency of interim reviews (which will depend on such factors as the study design, interventions, and anticipated recruitment rate). The plan shall specify "stopping guidelines" and other criteria, if appropriate, for the monitors/auditors to follow in their review of the interim data. Guidance on these topics is available at:

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127073.pdf.

In addition to the study data monitoring plan described above, CTP has a supplemental separate monitoring program in which the Study Project Lead(s) and CTP Study Monitoring Point of Contact will provide additional oversight of data and human subject protection monitoring, ensuring that monitoring systems are in place, that the quality of the monitoring activity is appropriate, and that the Principal Investigator (PI) or designee and COR are informed of recommendations and actions resulting from monitoring activities. All study data may be reviewed, and data sources verified, on site or remotely.

CTP monitoring will be in place for each research study, to safeguard the well-being of study participants and to ensure scientific integrity. CTP monitoring may include the reports of adverse events, unexpected events, non-compliance, protocol deviations, recruitment issues, other reported human subjects’ protection (HSP)/data integrity issues. CTP monitoring may be performed throughout subject accrual, while study procedures are being conducted, and during follow-up periods. Information regarding data and safety monitoring shall be included in the clinical study protocol.

The specific approach to CTP monitoring will depend on features of the research study to be conducted. CTP monitoring activities will be appropriate to the study, study population, research environment, and degree of risk involved.

In addition to CTP Study Monitoring, FDA/CTP/Office of Compliance and Enforcement has the authority to audit this study at any time, with appropriate notification. Federal or state laws may require FDA to show information to university or government officials (or sponsors), who are responsible for monitoring the safety of this study. To the extent possible, directly identifying information (e.g., names, addresses) will be safeguarded and maintained under controlled conditions as appropriate.

Task 7 – Final Laboratory Study Protocol The Contractor shall incorporate FDA feedback from the Draft Laboratory Study Protocol development phase and deliver a Final Laboratory Study Protocol for FDA approval.

The Final Laboratory Study Protocol shall include: study procedures; data handling and record keeping, a statistical analysis plan; quality assurance plan, publication plan (if applicable), and administrative information.

Task 8 – Final Clinical Study Protocol The Contractor shall incorporate FDA feedback (including SGE and FDA Internal Review feedback) from the Draft Clinical Study Protocol development phase and deliver a Final Clinical Study Protocol for FDA approval. This version of the clinical study protocol will then be http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127073.pdf submitted for internal CTP HSP and IRB review and approval and may require additional edits after all human subjects’ protections reviews have concluded in Tasks 10 and 11.

Task 9 – Perform Laboratory Study The Laboratory Study shall begin after FDA approval of the Final Laboratory Study Protocol. The Contractor shall perform the Laboratory Study according to the procedures in the Final Laboratory Study Protocol developed in Task 7. The Contractor shall submit any relevant source documents to the Study Project Lead(s). The Contractor shall provide laboratory technicians and other staff to perform the laboratory tests as required.

Task 10 – ITP Submission and Clearance The Contractor shall be responsible for working with the FDA Study Project Lead(s) to obtain ITP clearance to perform the study. This requires approval of the Human Subjects Protection-ITP checklist by CTP leadership and the CTP-ITP Subject Matter Expert.

Regarding ITP submission, Section 910(g) of the FD&C Act states, “The Secretary may exempt tobacco products intended for investigational use from the provisions of this chapter under such conditions as the Secretary may by regulation prescribe.” FDA intends to propose regulations establishing conditions for exempting ITPs from certain FD&C Act requirements.

Until then, ITPs are not exempt from applicable FD&C Act requirements, including premarket submission requirements and tobacco product standards.

Researchers may seek to study tobacco products that do not have marketing authorization or that do not comply with an applicable tobacco product standard. Until regulations governing the use of ITPs are issued and finalized, FDA intends to evaluate specific uses of ITPs according to potential public health concerns or other impacts on public health. In making enforcement decisions, FDA generally intends to consider:

1. Whether there are controls on how and to whom the tobacco products intended for investigational use are distributed.

2. Whether the protocol for the clinical investigation or the procedures used during the clinical investigation adequately provide for the protection of human subjects.

3. Whether the study is designed to ensure the quality and integrity of the study data and permit other investigators to replicate the findings.

4. Whether there are adequate procedures in place to ensure that ITPs are not commercialized.

The Contractor may reference the ITP Draft Guidance for further recommendations on the types of information to include in the ITP submission. For any questions, please contact CTP-OS-ITP@fda.hhs.gov.

The Contractor shall discuss ITP elements with the Study Project Lead(s) prior to ITP submission.

The Contractor shall submit all information relevant to the ITP process in electronic format to the Study Project Lead(s).

Time to ITP clearance is variable, is subject to regulations, and can take 1-2 months.

http://www.fda.gov/downloads/TobaccoProducts/Labeling/RulesRegulationsGuidance/UCM463953.pdf mailto:CTP-OS-ITP@fda.hhs.gov

Task 11 – Obtain Required Human Subjects Clearances for the Study The Contractor shall work with the FDA to submit proper human subjects’ clearance documents and obtain necessary human subjects’ clearances to perform the study, including:

1. Office of Management and Budget (OMB) approval, if applicable

a. Approval from the OMB, consistent with the Paperwork Reduction Act, is necessary for data collection from ten (10) or more individuals. Some studies may be granted exemption from OMB based on study procedures. The Contractor shall be responsible for providing the COR and Study Project Lead (s) with the necessary information about the Contractor’s procedures for data collection.

2. Institutional Review Board (IRB) approval

a. For research exempt from the requirements of 45 CFR Part 46:

The Contractor will submit to FDA a letter from their IRB or human subjects protection entity that the proposed research is exempt (see 45

CFR 46.104).

In accordance with SMG 9001.4, FDA will follow its procedures for exempt research determination. Data collection from human subjects cannot commence under this contract until the FDA COR provides the Contractor with the outcome of the FDA determination.

b. For nonexempt human subjects research:

The Contractor agrees to protect the rights and welfare of human subjects involved in research under this contract by complying with 45 CFR Part 46 and the clause at HHSAR 352.270-4b.

Initial proof of compliance with 45 CFR Part 46 shall consist of:

• A copy of a current Federal-wide Assurance on file with the Office of Human Research Protections (https://www.hhs.gov/ohrp/federalwide-assurances-fwas.html).

The copy of a current Federal–wide Assurance shall be included with the Contractor’s proposal.

• A letter from the Contractor’s local IRB (the IRB specified in the Offeror’s Assurance of Compliance) stating that it has reviewed and approved the proposed research protocol. The letter from the local IRB shall be submitted to the COR.

• In accordance with SMG 9001.4, the FDA will determine if FDA is considered engaged in the research for purposes of 45 CFR part

46. Data collection from human subjects cannot commence under this contract until the FDA COR provides the Contractor with the outcome of the FDA determination. When that determination is made, the FDA will confirm the extent to which the terms of “352.270-11 Protection of Human Subjects— Research In Human Subjects Committee Approval of Research Protocols Required” apply.

The Contractor shall obtain all necessary internal approvals, such as determination from its own IRB prior to any human subject data collection. All staff working with human subjects or having https://www.hhs.gov/ohrp/federalwide-assurances-fwas.html access to human subjects’ data must complete human subjects training appropriate for this type of clinical study.

In addition, internal CTP human subjects protection reviews may be required prior to IRB review for packages including the initial protocol package, amendments, adverse event reporting and study closure. The Project Lead(s) and Contractor may need to edit the protocol based on this internal CTP review process. For each review, the process can take up to twenty

(20) business days.

ITP and IRB approval are required prior to obtaining SPECTRUM non-menthol research cigarettes (NRC600) for the clinical portion of this study. The Contractor shall follow the necessary guidelines and prepare the required Request Package for ordering research cigarettes: https://nida.nih.gov/research/research-data-measures-resources/nida-drug-supply-program/nicotine-research-cigarettes-nrcs.

Task 12 – Perform Clinical Study Clinical study recruitment should begin within five (5) business days of IRB approval or after FDA has reviewed and accepted the required study product stability data, whichever occurs last. The Contractor shall perform the clinical study using the Final Clinical Study Protocol developed in Task 8 and the Final Laboratory Study Protocol developed in Task 7. The Contractor shall submit any relevant source documents to the Study Project Lead(s) upon request.

The Contractor shall select the laboratory and clinical research facilities which are equipped to perform the study. The Contractor shall provide laboratory technicians and clinical staff to perform the screening, behavioral assessments, and laboratory tests.

The Contractor shall recruit healthy, volunteer, adult male and female current menthol and non-menthol cigarette smokers for the study and assess their inclusion and exclusion criteria to satisfy the Final Clinical Study Protocol. The Contractor is responsible for proactively ensuring recruitment can be achieved and for identifying measures to increase recruitment, if needed.

The Contractor shall inform the FDA for the measures taken to ensure the confidentiality of data.

The Contractor will be compensated incrementally for this task as participants complete the clinical study (i.e., after reaching 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% and 100% of the participant completion goal agreed upon by both parties).

Task 13 – Clinical Recruitment Updates The Contractor shall deliver informal weekly updates via email to the COR and Study Project Lead(s) on the status of recruitment and progress of research for the duration of recruitment.

Recruitment updates shall begin one week after the start of recruitment and shall be delivered on the same day of the week throughout the duration of the study.

https://nida.nih.gov/research/research-data-measures-resources/nida-drug-supply-program/nicotine-research-cigarettes-nrcs https://nida.nih.gov/research/research-data-measures-resources/nida-drug-supply-program/nicotine-research-cigarettes-nrcs

Recruitment updates shall include the number of participants scheduled/completed for the prior week’s duration, the number of participants scheduled/completed from the start of recruitment, the number of participants who are deemed ineligible during pre-screening and screening, and reasons for ineligibility.

Task 14 – Draft Clinical Study Report Within two (2) months of completing the final study participant, the Contractor shall deliver a Draft Study Report to the COR and Study Project Lead(s) containing: the background and purpose of the project, summary of recruiting, data collection techniques and procedures, sensory and subjective effects analyses, puff topography analyses, adverse events, data preparation and processing, any information necessary to reproduce statistical results and reanalyze datasets (e.g., coding procedures, statistical/analytic code), any significant problems encountered during the clinical study and their solutions, and conclusions.

All raw data and data analysis files will be submitted in Statistical Analysis System (SAS) transport format and Microsoft Excel. The Contractor shall submit all documents relating to study monitoring to the COR. The Contractor shall write up the results of the study in the form of an expanded American Psychological Association (APA; http://www.apastyle.org) format introduction section. The Contractor shall write these documents in MS Word (Office 2010) compatible software.

Data files shall be prepared and delivered according to the following specifications:

1. Each record shall be uniquely identified and shall correspond to one respondent's data

2. All data values shall be numeric rather than character

3. Adverse events description with the time in the event table

4. One (1) electronic copy of a finalized, complete, and correct Coding Book with descriptions of the respective variables

5. One (1) electronic copy of the data analyses report, including files, tables and figures, and appropriate statistical analyses of the results.

The Contractor should estimate FDA review of the data and draft clinical study report will take 3 months.

Task 15 – Final Clinical Study Report The Contractor shall address all feedback and deliver a Final Study Report to the COR and Study Project Lead(s) within one (1) month after receiving comments from the FDA on the Draft Study Report. All biospecimens should be properly stored until FDA confirms receipt and approval of the final clinical study report.

Should the FDA have any additional comments on the Final Study Report, the Contractor shall respond to any comments from the FDA in a revised report to be submitted within one (1) month after receipt of FDA comments.

Task 16 – Draft Laboratory Study Report Within two (2) months of the completion of the laboratory study, the Contractor shall deliver a draft laboratory study report to the COR and Study Project Lead(s) containing: the background and purpose of the project, analytical methods and results, validation protocols and reports, if applicable, verification protocols and reports, if applicable, deviation protocols for any or all analytical methods used, data preparation and processing, any information necessary to reproduce statistical results and reanalyze datasets (e.g., coding procedures, statistical/analytic code), any significant problems encountered during the laboratory study and their solutions, and conclusions.

All raw data and data analysis files shall be submitted in SAS transport format and Microsoft Excel. The Contractor shall write up the results of the study in the form of an expanded American Psychological Association (APA; http://www.apastyle.org) format introduction section. The Contractor shall write these documents in MS Word (Office 2010 or later) compatible software.

Data files shall be prepared and delivered according to the following specifications:

1. All data values shall be numeric rather than character

2. One (1) electronic copy of a finalized, complete, and correct Coding Book with descriptions of the respective variables

3. One (1) electronic copy of the data analyses report, including files, tables and figures, and appropriate statistical analyses of the results.

The Contractor should estimate FDA review of the data and draft laboratory study report will take 3 months.

Task 17 – Final Laboratory Study Report The Contractor shall address all feedback and deliver a Final Laboratory Study Report to the COR and Study Project Lead(s) within one month after receiving comments from the FDA on the Draft Study Report. All laboratory products/samples should be properly stored until FDA confirms receipt and approval of the final laboratory study report.

Should the FDA have any additional comments on the Final Study Report, the Contractor shall respond to any comments from the FDA in a revised report to be submitted within one (1) month after receipt of FDA comments.

PERIOD OF PERFORMANCE

Three (3) years from date of task order award.

DELIVERABLE SCHEDULE

Task Number

Deliverable Quantity Delivery Date after Task Award

1 Kick-off Meeting 1 Within the (10) business days of task order award.

2 NPI forms 1 per staff member

Within thirty (30) business days of task order award.

3 Biweekly Meetings Biweekly for contract duration

Biweekly. Start within ten

(10) business days of Kick-off Meeting.

4 Monthly Progress Reports 1 electronic version per month for contract duration

Electronically submit to the COR by the 10th calendar day of each month for each thirty-day period prior to the report due date.

5 Draft Laboratory Study Protocol

1 electronic version

Initial draft within thirty

(30) business days of task order kick-off meeting.

Multiple iterations (no more than 3 each) may be necessary to address feedback from all FDA review processes.

6 Draft Clinical Study Protocol 1 electronic version

Initial draft within thirty

(30) business days of task order kick-off meeting.

Multiple iterations (no more than 3) may be necessary to address feedback from all FDA review processes.

7 Final Laboratory Study Protocol 1 electronic version

Within five (5) business days of receiving final Government comments on Draft Laboratory Study protocol.

8 Final Clinical Study Protocol 1 electronic version

Within five (5) business days of receiving approval from the SGE and FDA Internal Review process.

9 Perform Laboratory Study 1 Upon FDA approval of the Final Laboratory Study Protocol, approximately three (3) months after contract award.

10 ITP Submission 1 electronic version

Within five (5) business days of SGE and FDA Internal Review approval.

11 Obtain Clearances for the Study (OMB and IRB)

1 each Variable, approximately 4 months is anticipated. All clearances must be obtained prior to any data collection.

12 Perform Clinical Study 1 Within five (5) business days of final IRB approval, or after FDA has reviewed and accepted the required study product stability data, whichever occurs last.

13 Participant Recruitment Updates

1 electronic version per week

Weekly for the duration of the clinical study.

14 Draft Clinical Study Report 1 electronic version

Within two (2) months after completion of the last participant.

15 Final Clinical Study Report 1 electronic version.

Within one (1) month after receiving FDA comments on the Draft Clinical Study Report.

16 Draft Laboratory Study Report 1 electronic version

Within two (2) months after completion of the laboratory portion of the study.

17 Final Laboratory Study Report 1 electronic version

Within one (1) month after receiving FDA comments on Draft Laboratory Study Report.

INSPECTION AND ACCEPTANCE

The COR shall review and inspect all deliverables furnished under this task order in accordance with the deliverables cited herein.

CONFLICT OF INTEREST

The Contractor warrants that it is in compliance with the base award.

OTHER REQUIREMENTS

FDA considers the sharing of FDA-funded research, including digital data, an important means to enhance its value and support future research. When the findings associated with research developed with FDA funds are published, they are required to be made readily available to the public. In addition, investigators seeking FDA funding, in whole or in part, via a contract, grant, or assistance agreement must have an FDA-approved Data Management Plan – a plan for digital data management and sharing – prior to commencing any related services or work.

Upon acceptance for publication, researchers are also responsible for submitting the author’s final manuscript of any peer-reviewed scientific publication resulting from research supported, in whole or in part, with FDA funds to the NIH National Library of Medicine's (NLM) PubMed Central (PMC). FDA defines the author's final manuscript as the final version accepted for journal publication, which includes all modifications resulting from the publishing peer review process. The PMC archive is the designated repository for these manuscripts for use by the public, health care providers, educators, scientists, and FDA. FDA expects timely release and sharing of final research data from FDA-funded studies for the research community’s use in accordance with the submitted Data Management Plan. Please see the FDA Public Access Policy (provided as Attachment/Exhibit XXYY; or, available at http://www.fda.gov/downloads/aboutfda/reportsmanualsforms/staffmanualguides/ucm47926 8.pdf).

INSTRUCTIONS TO CONTRACTORS

The Contractor shall include a project timeline to accompany the technical proposal. The timeline shall depict how all contract milestones will be accomplished during the period of performance including, but not limited to: protocol development and review (FDA and Contractor review timelines), human subject protections review (FDA and External), purchase of study product(s), laboratory study, clinical study, data analysis and reporting. Specifically, the Contractor shall provide in weeks or months, how long they anticipate each deliverable will take to complete as well as a visual timeline.

EVALUATION CRITERIA

For overall evaluation purposes, technical and all other non-price factors are considered more important than price. As technical scores become more equal, price may become the determining factor.

http://www.fda.gov/downloads/aboutfda/reportsmanualsforms/staffmanualguides/ucm479268.pdf http://www.fda.gov/downloads/aboutfda/reportsmanualsforms/staffmanualguides/ucm479268.pdf

EVALUATION FACTORS

Factor 1 - TECHNICAL APPROACH

a. TECHNICAL APPROACH

The Contractor shall provide a narrative description of the approach to performing the work described in the SOW. The narrative should describe the Contractor's understanding of the project (both from a business and technical standpoint) and its relevance to CTP regulatory activities, how the Contractor intends to satisfy the technical requirements, any risks it foresees in carrying out its approach, along with mitigation strategies for those risks. This shall also include a project timeline for the life of the contract. The timeline will be evaluated on reasonableness and the Contractors ability to complete the project within the specific period of performance. The Contractor shall demonstrate when each deliverable will be completed and all target milestones.

The Contractor's technical approach will be evaluated by how the Contractor demonstrates in-depth knowledge, expertise, and experience in screening and selecting participants; administering tobacco products; collecting behavioral, subjective, physiological, pharmacological, and biological data; and performing data analyses. This includes, but is not limited to, subject evaluation, laboratory tests, computer-assisted-self-administered interviewing, and use topography.

b. STAFFING PLAN

The Contractor shall provide a narrative description of the approach to staffing the project. This should include discussion of how it shall ensure that the project is adequately staffed. Representative resumes of proposed personnel for the contract shall be included.

The Contractor shall provide a Staffing Plan that shows the positions to be used to support this effort. The plan should conform to the following requirements:

• Shows all proposed positions by labor category.

• Indicate with a “Yes” or “No”, whether it is a key position.

• Lists the number of hours for each proposed position, per task.

• Calculates subtotals, segregated by the CLINs delineated.

• Calculates total hours.

• Describes the functional/technical role corresponding to each position.

c. KEY PERSONNEL

The Contractor shall provide a narrative in which the Contractor identifies key personnel. The narrative should describe the roles of key personnel and expected contributions of each individual identified. The following labor categories are considered key personnel: Senior Scientist, Project Manager, Subject Matter Expert, Chemist.

The Contractor shall submit a resume for each proposed key personnel describing experience, education, work history, professional certifications, and any other relevant information regarding their qualifications. Each resume shall be limited to three (3) 8.5 x 11 inch pages (anything over this limit shall be ignored).

The Contractor shall submit a letter of commitment on company letterhead for each key person proposed who is not already an employee of the proposed prime or subcontractor. This includes any key person that is a 1099/consultant/or subcontractor employee. Date the letter, list the named individual and position, show dates of committed employ, and have the letter signed by both parties. Any salary amounts shall be redacted from the letter.

Factor 2: PRICE

The Contractor shall include a price per deliverable and a detailed price breakdown to demonstrate how each price was developed. The Contractor shall include their methodology for how they determined the price for each deliverable.

AWARD DECISION

Award will be made based on a best value tradeoff. When combined, all non-price factors are considered significantly more important than price.

CLAUSES

All clauses included in your master contract flow down to this task order and remain in effect.

LIST OF ATTACHMENTS

Attachment 5: Jackson et al. (2023) paper Attachment 6: Flowchart with Study Timeline Visual