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This is a Request for Proposal (RFP) for Behavioral Economics for Abuse Liability Testing. See continuation pages for details.

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2 2 of

Behavioral Economics for Abuse Liability Testing

FDA-SOL-75F40124R00037

REQUEST FOR PROPOSAL

US Food and Drug Administration

Request for Proposal (RFP)

FDA-SOL-75F40124R00037

Behavioral Economics for Abuse Liability Testing

Date Posted: March 14, 2024

Response Date: April 4, 2024, 12PM EST

Classification Code:AJ13 - General Science & Technology R&D Svcs; General Science & Technology; Experimental Development NAICS Code: 541618 – Other Management Consulting Services

SECTION 1 – PRODUCT LIST AND DELIVERY INFORMATION

This is a combined synopsis/solicitation for commercial items prepared in accordance with the Federal Acquisition Regulation (FAR) format in Subpart 12.6, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a written solicitation will not be issued. It is the Government's intent to issue a Firm Fixed Priced Purchase Order in accordance with FAR Part 13.

The solicitation number is FDA-SOL-75F40124R00037. This solicitation is issued as a Request for Proposal (RFP).

The solicitation document and incorporated provisions and clauses in effect through the Federal Acquisition Circular 2023-04, effective 02 June 2023. FAR and HHSAR provisions and clauses referenced in this RFQ can be found on the following website:

https://www.acquisition.gov/browse/index/far

BASIS FOR AWARD AND EVALUATION CRITERIA

The basis for award is Lowest Price Technically Acceptable (LPTA). The Government intends to award this order without clarification or discussions with Offeror. Additional Federal discounts are highly encouraged. Quotes must meet all the salient functional characteristics and requirements of this solicitation in order to be considered technically acceptable. Quotes providing an equivalent solution will not be considered further, if the requisite functionality/compatibility explanation is not provided.

FDA will issue the award to the Quoter whose proposed solution meets all technical requirements, including the Terms and Conditions identified within the solicitation, and whose overall price is lowest.

Quoter’s are advised that additional terms and conditions submitted with their quotation that are in conflict of the terms and conditions of this solicitation may be deemed technically unacceptable and may not be considered for award.

All questions in response to this solicitation shall be submitted on or March 21, 2024, 12:00 noon Washington DC Local Time. All questions shall be submitted via email to Sheron Johnson, Contracting Specialist, sheron.johnson@fda.hhs.gov.

Vendors shall submit quotes electronically to sheron.johnson@fda.hhs.gov. All quotes are due no later than April 4, 2024, 12:00 noon Washington DC Local Time.

https://www.acquisition.gov/browse/index/far https://www.acquisition.gov/browse/index/far

Volume One: Technical

Brief narrative description of Quotor's understanding and approach of this requirement.

Volume One shall not exceed 12 pages in length. The 12 pages do not include the resumes of proposed personnel, which should not exceed 5 pages each. Volume One shall not include any pricing information.

All text shall be Arial font with 11-point size.

Volume Two: Business

The business proposal shall include the following elements:

• A cover letter signed by an official authorized to bind the company.

• This will be a Firm Fixed price contract type.

• Any notes or assumptions.

• Provide a price build up for the tasks using the format below.

• Break out the pricing by all task areas (please see attachment A- Pricing Sheet)

• Clearly state the overall price to the Government.

I. Background

Operant Behavioral Economics is a field of study that began in 1980 (Hursh, 1980, 1984) and has since received exponential growth in interest from both researchers and interventionists (see Hursh, 1991).

Central to that work is the application of the economic concept of demand and demand-curve assessment to determine the strength of behavior maintained by an outcome. A demand curve measures how much of a commodity (e.g., drug, food) is consumed under an escalating series of prices (e.g., responses per infusion for animals, money cost for humans). Consumption generally declines as price increases, and the slope of that curve can be precisely modeled as a gauge of the strength of demand for the substance.

When fit with a well-defined demand model (Hursh & Silberberg, 2008), the rate of change in the point-slope of the curve for drug self-administration is a relatively dose-independent measure of demand strength. When demand is normalized, two additional parameters of demand can be used to compare drugs: Pmax—the price associated with the greatest responding (e.g., drug seeking in the case of drugs of abuse)—and Omax—the level of response output at that price. Those parameters have been found to be meaningful metrics of demand in many subsequent demand studies (Heinz et al., 2012; Cassidy & Kurti, 2018).

As a representative example of this method, demand curves fit to consumption of three NMDA-receptor antagonists differing in speed of onset of action (ketamine, PCP, and dizocilpine, ranked from fastest to slowest) have demonstrated that the drug value (based on differences in demand elasticity and Pmax) was a linear decreasing function of time to peak effect onset, implicating reinforcer delay as a key pharmacological factor in determining drug demand strength (Winger, et al., 2002). In these experiments, the exponential model of demand (Hursh & Silberberg, 2008; Hursh & Roma, 2016) provided an excellent fit to the experimental data and permitted the calculation of an Essential Value (EV) for each drug, with EV defined as a normalized value that represents the resistance of consumption to increases in constrain or price. In terms of drug self-administration, drugs with higher EV are less sensitive to the impact of price on consumption. These results confirmed that motivation to consume these drugs can be scaled in terms of EV as a metric of reinforcing strength and abuse liability that is generally less sensitive to drug dose than conventional procedures such as fixed-ratio schedules (Hursh & Roma, 2013).

Abuse Potential Assessment

Many studies of demand for drugs in animal self-administration studies (see Hursh et al. 2005) lay the groundwork for using behavioral economic demand-curve methodology for FDA assessment of pharmaceuticals for purposes of recommending control in a drug schedule under the Controlled Substances Act (CSA). The key improvement offered by behavioral economic assessments is that it assesses the degree of responding and consumption across a wide range of economic prices, creating what is called a demand curve. Using the slope of the demand curve—sensitivity to increasing price—to determine EV as a metric of abuse potential could improve the precision of the assessment, which is a key factor in drug scheduling. If a standardized method of abuse potential assessment based on demand-curve testing using drug-self-administration procedures were developed along with a standardized model for rank ordering drugs by the EV measure of price sensitivity, drugs could be more precisely differentiated based on the likely robustness of demand supported by the drug in the natural marketplace (Banks, et al.

2011; Hursh & Roma, 2013; Gilroy, 2022; Koffarnus, 2023).

While many drugs may support consumption at a very low price (e.g., a fixed-ratio 10 or FR10), drugs studied with demand-curve methodology can be differentiated by the EV measure of price sensitivity across a broad price range (Hursh & Roma, 2013; Reed, et al, 2022). This has important implications for drug control policy. Behavioral economic methods evaluate abuse potential across a range of constraints that are more representative of real-world market prices and real-world constraints on consumption (e.g., effort needed to obtain a drug) than current methods used to evaluate abuse potential. Prior work with primates and rodents illustrates the ability of EVs determined from demand curves to distinguish between the value of different drugs that otherwise appear similar at a low cost. This could have value for evaluating opioid-like substances. Behavioral economic demand curve studies have shown a remarkable ability of EVs to differentiate the reinforcing value of a range of opioids (Hursh & Roma, 2013). Novel opioid-like substances can have beneficial properties for pain relief but have become restricted by the FDA because of abuse potential concerns when evaluated using current methods. An assessment of EVs based on demand could differentiate those drugs from other highly abusable opioids, such as fentanyl.

One outstanding question might be whether the demand-curve method and the estimates of EV are sufficiently robust to be used by the FDA for regulatory purposes. If the method were to be applied across experiments, labs, time, and companies, the FDA would want some assurance that a drug's evaluation would be consistent across all these conditions, provided the methods used were "standardized." In addition, most of the studies evaluating demand across a wide range of self-administered drugs have been conducted with non-human primates, although the basic methods have been demonstrated with rats. Rats are likely to be the species of choice in the regulatory science future, necessitating a review of the current state of demand-curve methods with rats, as well as a discussion of potential laboratory studies with this species that would establish the consistency of the rank ordering of drug EVs when independently assessed at different sites (O’Connor, et al. 2011; Schwartz, et al. 2017; Kim, et al. 2018; McConnell, et

al. 2021).

Furthermore, similar demand studies are required with human subjects to establish species generality and to demonstrate the translational homology between non-human animal studies and human abuse-potential studies. Several behavioral-economic techniques have been developed for humans, necessitating formal comparisons of these methods to the current human standards for abuse potential assessment. Such techniques include hypothetical simulated purchasing tasks and self-administration procedures (see Reed, et al. 2016; MacKillop, et al. 2019). Finally, the novelty of collecting demand-curve data in abuse-potential assessments necessitates a clear comparison of the relative costs and benefits of alternative procedures to justify any added time and expense of these methods. A discussion of what is known about the relationships between demand assessments and scheduling and surveillance data can be used to illustrate the potential value of a more precise and selective method of ranking abuse potential.

II. Objectives

• The first objective of this project is to describe the overall behavioral economic approach to abuse potential assessment using demand-curve analysis and EV determination and to summarize the relevant literature related to behavioral economic demand analysis.

• The second objective is to relate the overall behavioral economic framework to current practices for identifying and mitigating drug abuse risks. As part of this objective, consideration would be given to the potential benefits the framework offers for the FDA and for pharmaceutical companies developing drugs requiring abuse-potential assessment.

• The third objective is to clearly define what studies are needed to demonstrate both the feasibility and replicability of the methods and, in general, how those studies would be undertaken, and how the results would be applied in a broader abuse-potential assessment framework and considerations for drug scheduling.

III. Scope

This proposed project will take the form of a white paper that is composed of three publishable units (scientific manuscripts) for inclusion in peer-reviewed journals. The white paper will include a comprehensive review of all relevant drug self-administration literature evaluating behavioral economic demand, with specific focus on demand-curve assessments as applicable to abuse potential testing conducted over the last 30 years. The white paper will establish the implications and benefits of applying such methodologies to abuse potential assessment. The white paper will discuss the feasibility of behavioral economic methods for determining abuse potential by evaluating opioids across a range of regulatory controls under the CSA (Schedules I–V) in both preclinical tests and human trials.

The white paper will define a framework for conducting preclinical self-administration experiments in rats with special emphasis on the applications for evaluation of opioids of varying efficacy to evaluate the potential and validity of demand-curve analysis and EV determinations to differentiate degrees of abuse potential above and beyond traditional dose-effect curves under simple schedules of reinforcement. The white paper will outline the statistical methods for determining an EV-based drug scheduling framework to increase drug-scheduling precision and thereby enhance the quality of evidence used in agency decisions. The white paper will also discuss the potential for extended drug exposure to potentiate or escalate EVs. The white paper will discuss a method to identify the relative dose levels and duration of exposure that could significantly alter the behavioral economic demand for a drug.

The white paper will also describe the necessary clinical arm of a program including the behavioral economic demand approach to human drug abuse potential testing including templates for human abuse potential testing for use by industry sponsors. The white paper will also outline a program of trials to establish the feasibility of human drug abuse potential studies with opioids of varying intrinsic activity (efficacy) to evaluate the sensitivity and specificity of demand curve analysis for determining abuse potential above and beyond traditional human abuse potential metrics such as visual analog scale (VAS) scores for 'drug liking'. The white paper will conclude with a summary of the benefits of the behavioral economic framework for the FDA drug assessment as it relates to the drug scheduling process, pharmaceutical drug development and testing, and ultimately improving the efficacy and safety of new drugs to improve the health of the general public.

References

Banks, M. L., Roma, P. G., Folk, J. E., Rice, K. C., & Negus, S. S. (2011). Effects of the delta-opioid agonist SNC80 on the abuse liability of methadone in rhesus monkeys: a behavioral economic analysis. Psychopharmacology, 216(3), 431–439. https://doi.org/10.1007/s00213-011-2235-2

Cassidy, R. N., & Kurti, A. N. (2018). Behavioral Economic Research in Addiction as an Area of Growth for the Experimental Analysis of Behavior. Behavior analysis (Washington, D.C.), 18(4), 333–

339. https://doi.org/10.1037/bar0000105

Gilroy S. P. (2022). Hidden equivalence in the operant demand framework: A review and evaluation of multiple methods for evaluating nonconsumption. Journal of the experimental analysis of behavior, 117(1), 105–119. https://doi.org/10.1002/jeab.724

Heinz, A. J., Lilje, T. C., Kassel, J. D., & de Wit, H. (2012). Quantifying reinforcement value and demand for psychoactive substances in humans. Current drug abuse reviews, 5(4), 257–272.

https://doi.org/10.2174/1874473711205040002

Hursh, S.R. (1980) Economic concepts for the analysis of behavior. Journal of the Experimental Analysis of Behavior, 34, 219-238.

Hursh, S.R. (1984) Behavioral Economics. Journal of the Experimental Analysis of Behavior, 42, 435- 452.

Hursh, S.R. (1991) Behavioral economics of drug self-administration and drug abuse policy. Journal of the Experimental Analysis of Behavior, 56, 377-393.

Hursh, S. R., Galuska, C. M., Winger, G., and Woods, J.H. (2005) The economics of drug abuse: a quantitative assessment of drug demand, Molecular Interventions, 5, 1, 20-28.

Hursh, S. R., & Silberberg, (2008) A. Economic demand and essential value. Psychological Review, 115, 186-198.

Hursh, S. & Roma, P., (2013) Behavioral Economics and Empirical Public Policy, Journal of the Experimental Analysis of Behavior, 99, 98–124.

Hursh, S. R., & Roma, P. G. (2016). Behavioral Economics and the Analysis of Consumption and Choice.

Managerial and Decision Economics, 37, 224-238.

Kim, J. S., Gunawan, T., Tripoli, C. S., Silberberg, A., & Kearns, D. N. (2018). The effect of economy type on demand and preference for cocaine and saccharin in rats. Drug and alcohol dependence, 192, 150–157. https://doi.org/10.1016/j.drugalcdep.2018.08.005

Koffarnus, M., (2023) Recommendations for the Use of Behavioral Economic Demand as an Abuse Liability Assessment for Drug Scheduling, Policy Insights from the Behavioral and Brain Sciences, Vol. 10(1) 113–120

MacKillop, J., Goldenson, N. I., Kirkpatrick, M. G., & Leventhal, A. M. (2019). Validation of a behavioral economic purchase task for assessing drug abuse liability. Addiction biology, 24(2), 303–314. https://doi.org/10.1111/adb.12592

McConnell, S. Brandner, A., Blank, B. Kearns, D. Koob, G. Vendruscolo, L. Tunstall, B. (2021) Demand for fentanyl becomes inelastic following extended access to fentanyl vapor self-administration Neuropharmacology, 182, 108355

O'Connor, E. C., Chapman, K., Butler, P., & Mead, A. N. (2011). The predictive validity of the rat self-administration model for abuse liability. Neuroscience and biobehavioral reviews, 35(3), 912–

938. https://doi.org/10.1016/j.neubiorev.2010.10.012

Reed, D. Kaplan, B. Becirevic, A, Roma, P, Hursh, S. (2016) Toward Quantifying the Abuse Liability of Ultraviolet Tanning: A Behavioral Economic Approach to Tanning Addiction, Journal of The Experimental Analysis of Behavior, 106, 93–106

Reed, D. D., Strickland, J. C., Gelino, B. W., Hursh, S. R., Jarmolowicz, D. P., Kaplan, B. A., & Amlung, M. (2022). Applied behavioral economics and public health policies: Historical precedence and translational promise. Behavioural processes, 198, 104640.

https://doi.org/10.1016/j.beproc.2022.104640

Schwartz, L. P., Kim, J. S., Silberberg, A., & Kearns, D. N. (2017). Heroin and saccharin demand and preference in rats. Drug and alcohol dependence, 178, 87–93.

https://doi.org/10.1016/j.drugalcdep.2017.04.031

Winger, G., Hursh, S.R., Casey, K.L., and Woods, J.H. (2002) Relative reinforcing strength of three n-methyl-D-Aspartate antagonists with different onsets of action. J. Pharmacol Exp Ther 301: 690- 697, 2.

IV. Tasks

Overview

1. Explain Behavioral Economic (BE) concepts and the application of demand metrics to drug self-administration.

2. Review modeling methods used to determine dose independent essential value (EV).

3. Review the use of demand curve methods to provide a method for statistical comparison and rank ordering of relative EV of drugs based on the extensive literature on primate drug self-administration. Highlight how these methods complement current operant methods for determining pre-clinical abuse potential.

4. Describe prior work showing the feasibility of the same BE methods with rodents, based on existing data. Outline how the rodent model could be used to screen new drugs for relative abuse potential, with draft guidelines for conducting such studies.

5. Describe BE methods for use with human clinical studies for determination of human demand, both intensity of demand and price sensitivity. Develop a draft protocol for conducting behavioral economic human abuse potential studies.

6. Develop draft guidance to sponsors for how BE could be used to estimate relative pre-clinical and clinical abuse potential of new compounds.

7. Discuss data gaps relative to this guidance that requires additional research.

8. Discuss how these methods would integrate with other existing methods as part of the abuse-potential assessment framework. Describe the overall benefit of BE methods for drug scheduling, both from the point of view of the FDA and industry sponsors.

The overall scope of work describes the topics to be included in the white paper deliverable. Each task defines a specific topic to be included in the white paper.

Task 1: Review the literature on drug self-administration as applied to determine operant demand.

The Contractor shall explain the concept of behavioral economic demand as relevant to substance use and abuse-potential testing. The literature review shall also illustrate demand-curve analysis based on the field’s current knowledge to include standardized procedures validated for non-human and human research. The Contractor shall explain the methodology for assessing drug demand using drug self-administration with non-human subjects or hypothetical demand in human subjects. The Contractor shall also review the published literature regarding the rank-ordering method based on demand elasticity and essential value (EV) value relative to a standard.

Task 2: Preclinical studies.

The Contractor shall describe how preclinical studies will (a) define self-administration (SA) experiments with opioids of varying efficacy to evaluate the sensitivity and specificity of demand curve analysis for determining abuse potential beyond traditional dose-effect curves and (b) describe how an essential value (EV)-based analytic framework can be used to increase drug-scheduling precision and enhance the quality and rigor of evidence used in agency decisions, and (c) describe how studies can be conducted to evaluate the relationship between repeated opioid administration and EV to identify the relative dose levels and exposure durations that increase OUD risk. The preclinical arm shall be divided into three phases.

Task 2.1: The Contractor shall describe the methods to be used to develop a standardized preclinical demand assessment as an extension of the standard SA paradigm in rats. The Contractor shall determine (a) the range and increments of costs (ratio values) to be assessed, (b) dose selection procedures based on standard SA dose effect curves1, (c) appropriate training and drug delivery methods, and (d) optimal analysis pipelines.

Task 2.2: The Contractor shall describe the procedures to be used to apply the standardized method to a range of opioids with varying efficacy, including representative drugs from each schedule of the CSA, to establish an EV-based scheduling framework to enhance the quality and rigor of evidence used in drug scheduling recommendations. The Contractor shall justify the choice of parameters in quantitative methods, and when uncertainty exists related to one or more parameters, explain how the best parameters must be chosen. The Contractor shall also describe a method for statistical comparison of parameters between drugs.

Task 2.3: The Contractor shall describe the methods to be used to evaluate the most frequently prescribed opioids before and after their repeated administration to investigate how opioid dependence and withdrawal changes their EV to quantify abuse potential-related risks associated with extended exposure.

Task 3: Clinical studies.

The Contractor shall (a) describe the behavioral economic approach to human drug abuse potential (HAP) testing, including templates for purchase-task experiments for use by industry sponsors, and (b) define how studies of HAP with opioids of varying efficacy can be conducted to evaluate the sensitivity and specificity of demand-curve analysis for determining abuse potential beyond traditional metrics such as visual analog scale (VAS) scores for ”drug-liking.”

Task 3.1: The Contractor shall describe the methods to be used to formulate a procedure for conducting clinical purchase-task experiments as an extension of HAP studies (see Assessment of Abuse Potential of Drugs - Guidance for Industry [https://www.fda.gov/media/116739/download]) and evaluations of abuse-deterrent opioid formulations (see Abuse-Deterrent Opioids — Evaluation and Labeling Guidance for Industry [https://www.fda.gov/media/84819/download]) in humans. This task must define (a) step-by-step procedures including a standardized instruction sheet and questionnaire, (b) dose-selection procedures1, and (c) optimal analysis pipelines.

Task 3.2: The Contractor shall describe the methods to be used to define how to conduct HAP studies of opioids with varying efficacy to (a) evaluate the sensitivity and specificity of purchase-task experiments for determining abuse potential beyond VAS scores, and (b) compare outcomes to current schedules of tested drugs. The Contractor shall also develop a supplemental protocol that is a regulatory ready protocol (i.e., IRB documentation) for the conduct of the proposed work.

Task 4: Translational framework.

The Contractor shall describe in general terms how these studies must provide a translational link

1 The models for determining EV are relatively insensitive to dose within the reinforcing range, but the reinforcing range must be determined using standard procedures.

between preclinical and clinical studies with an EV-based framework for the FDA’s evaluations of drug abuse potential. The Contractor shall discuss the conceptual overlaps between preclinical and clinical studies’ methods and describe how such overlaps or discrepancies in approaches influence interpretations and implications of the work, particularly in terms of essential value.

The Contractor shall draft guidance to sponsors describing how behavioral economics methods could be used to estimate relative preclinical and clinical abuse-potential metrics of new compounds.

Task 5: Summary of the benefits of behavioral economic approach.

The Contractor shall justify the value of this approach as an addition to the current abuse potential methodology and explain the need for additional research to establish the robustness of the method across laboratories. The Contractor shall summarize gaps in knowledge relative to proposed guidance for applying these methods in preclinical rat studies and clinical human studies. The Contractor shall describe the necessary research to address these gaps, using a multi-laboratory approach to establish the replicability of findings across laboratories based on a standard research protocol and across species for translational homology.

The Contractor shall provide a clear explanation of how the use of these behavioral economic methods may enhance the precision of the drug scheduling process. The Contractor shall discuss how these methods would integrate with other existing methods as part of the drug evaluation and scheduling process. The Contractor shall describe the potential overall benefit of BE methods for drug scheduling, from the point of view of both the FDA and industry sponsors. The Contractor shall define how any added burden on the sponsors could be minimized and offset by the benefits of greater scheduling precision.

Delivery

• The Contractor shall submit a final white paper deliverable in the form of an electronic document in

.DOCX format that covers all topics described in the SOW tasks.

• The Contractor shall ensure that the length of the final white paper is consistent with the pages number ranges tabulated below, excluding all tables, figures, and references, unless otherwise mutually agreed upon with the FDA

• The Contractor shall submit all deliverables with Arial font, 11 pt. font size, single spaced line spacing (with 0 pt. before each line and 0 pt. after each line; don’t add space between paragraphs of the same style), and 1-inch margins (top, bottom, left, and right) in .DOCX format.

• The Contractor shall ensure that all in-text and bibliographic citations in the final white paper are in American Psychological Association (APA) 6th format.

• The Contractor shall use original language in the final white paper. In general, the use of quotes should be kept to a minimum and must not exceed 5% of the total length of the final white paper.

• The Contractor shall not use artificial intelligence or any implementation of large language models to generate the final white paper.

• During the period of performance, the Contractor shall hold internal monthly progress teleconferences between 30 and 60 minutes in length with the team preparing the final white paper to discuss deliverable progress and FDA feedback (see below).

• The Contractor shall submit drafts of individual sections for FDA review and comment according to the milestone schedule.

• During the period of performance, the Contractor shall meet with the FDA monthly for between 30 and 60 minutes per occurrence to discuss deliverable progress and feedback on FDA comments on draft documents to ensure that the white paper is responsive to FDA needs.

• The Contractor shall prepare and submit, with FDA co-authors, three publishable units (scientific manuscripts) for inclusion in peer-reviewed journals within 12 months of the end of the period of performance.

• Specific deliverables are listed in the deliverable schedule table below.

Task Number Work Milestones Projected Completion Date

Page Number Estimates (less figures, tables, and references)

1 Review the literature on drug-self administration as applied to determine operant demand.

4 months post award 15-20

2 Describe Preclinical studies.

5 months post award 15-20

3 Describe Clinical Studies

5 months post award 15-20

4 Describe Translational Framework

6 months post award 15-20

5 Summary of Benefit of Behavioral Economic Approach and Final Submission

8 months post award 15-20

Deliverable Schedule

Deliverable Description Quantity/Media Date Completed Kickoff Meeting An initial telecon with the Contractor team shall be conducted to ensure common understanding of deliverables and schedule

Web-meeting using Teams or Zoom

Within one month of award

1 Milestone 1: Task 1 One electronic document in .DOCX file format for FDA review

Milestone 1 completion

1.1 Government review of

Task 1 submission

One electronic document in .DOCX file format for FDA review

Three weeks after Milestone 1 submission

2 Milestone 2: Task 2 One electronic document in .DOCX file format for FDA review

Milestone 2 completion

2.1 Government review of One electronic Three weeks after

Task 2 submission document in .DOCX file format for FDA review

Milestone 2 submission

3 Milestone 3: Task 3 One electronic document in .DOCX file format for FDA review

Milestone 3 completion

3.1 Government review of

Task 3 submission

One electronic document in .DOCX file format for FDA review

Three weeks after Milestone 3 submission

4 Milestone 4: Task 4 One electronic document in .DOCX file format for FDA review

Milestone 4 completion

4.1 Government review of

Task 4 submission

One electronic document in .DOCX file format for FDA review

Three weeks after Milestone 4 submission

5 Milestone 5: Task 5 One electronic document in .DOCX file format for FDA review

Milestone 5 completion

5.1 Government review of

Task 5 submission

One electronic document in .DOCX file format for FDA review

Three weeks after Milestone 5 submission

Final Delivery Meeting

The Contractor will meet with the FDA to present the final white paper and provide a summary

One electronic document in .DOCX format and one slide deck in .PPTX format

Within one month of receipt of FDA comments

Government-Furnished Property, Material, Equipment, or Information (GFP, GFM, GFE, or GFI)

During monthly telecons or via email, the FDA will provide the Contractor with guidance on which drugs and schedules are to be included in the white paper discussion.

Travel

At the conclusion of the contract, the Contractor shall meet with the FDA to present the final white paper, deliver a summary presentation, and answer questions.

Other Unique Requirements

The organization conducting this work (i.e., the “Contractor”) must be led by an individual who is a widely recognized expert in behavioral economics with publications that include both non-human primates and rodents, as well as human experimentation and hypothetical demand. The Contractor must have demonstrated experience working with regulatory agencies to translate behavioral science into practical empirical policy. The team must include several laboratories conducting rodent drug self-administration work because a key requirement is for the validation of a model for determining behavioral economic demand in rodents that could be used by pharmaceutical companies. The Contractor must also include in their team one or more individuals with demonstrated experience conducting behavioral economic work with humans with experimental drug administration because a key requirement is the development of a protocol for human abuse potential assessment using behavioral economics.

Period of Performance

The period of performance shall be 12 months, with the Contractor anticipating providing deliverables within 9 months, and 3 months for any necessary revisions.

Contract Type

This order is a firm-fixed-price order.

Place of Performance

The Contractor must perform the work at the site of the Contractor institutions. The final meeting shall be conducted at a place determined by the FDA.

Administrative Contacts

Contracting Officer Representative (COR):

TBD

Contract Specialist (CS):

Sheron Johnson Sheron.johnson@fda.hhs.gov

Contracting Officer (CO):

Ian Weiss Ian.Weiss@fda.hhs.gov

Contracting Officer’s Authority

The Contracting Officer (CO) is the only person with authority to act as agent of the Government under this contract. Only the Contracting Officer has authority to: (1) direct or negotiate any changes in the RFQ; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimbursement to the Contractor any costs incurred during the performance of this contract;

or (5) otherwise change any terms and conditions of this contract. No statement, whether oral or written, by anyone other than the Contracting Officer, shall be interpreted as modifying the terms and conditions of this award. It is the Contractor’s responsibility to contact the CO immediately if there is even the appearance of any technical direction that is or may be outside the scope of the award. The Government will not reimburse the Contractor for any work not authorized by the Contracting Officer, including work outside the scope of the award.

mailto:Sheron.johnson@fda.hhs.gov mailto:Ian.Weiss@fda.hhs.gov

The Contracting Officer’s Representative (COR) is responsible for: (1) monitoring the Contractor's technical progress, including the surveillance and assessment of performance and recommending to the Contracting Officer changes in requirements; (2) interpreting the contract and any other technical performance requirements; (3) performing technical evaluation as required; (4) performing technical inspections and acceptances required by this contract; and (5) assisting in the resolution of technical problems encountered during performance.

Procurements Requiring Information Security and/or Physical Access Security

1) Baseline Security Requirements

a) Applicability. The requirements herein apply whether the entire contract or order (hereafter

“contract”), or portion thereof, includes either or both of the following:

i) Access (Physical or Logical) to Government Information: A Contractor (and/or any subcontractor) employee will have or will be given the ability to have, routine physical (entry) or logical (electronic) access to government information.

ii) Operate a Federal System Containing Information: A Contractor (and/or any subcontractor) will operate a federal system and information technology containing data that supports the HHS mission. In addition to the Federal Acquisition Regulation (FAR) Subpart 2.1 definition of “information technology” (IT), the term as used in this section includes computers, ancillary equipment (including imaging peripherals, input, output, and storage devices necessary for security and surveillance), peripheral equipment designed to be controlled by the central processing unit of a computer, software, firmware and similar procedures, services (including support services), and related resources.

b) Safeguarding Information and Information Systems. In accordance with the Federal Information

Processing Standards Publication (FIPS)199, Standards for Security Categorization of Federal Information and Information Systems, the Contractor (and/or any subcontractor) shall:

a. Protect government information and information systems in order to ensure:

• Confidentiality, which means preserving authorized restrictions on access and disclosure, based on the security terms found in this contract, including means for protecting personal privacy and proprietary information;

• Integrity, which means guarding against improper information modification or destruction, and ensuring information non-repudiation and authenticity; and

• Availability, which means ensuring timely and reliable access to and use of information.

b. Provide security for any Contractor systems, and information contained therein, connected to an FDA network or operated by the Contractor on behalf of FDA regardless of location. In addition, if new or unanticipated threats or hazards are discovered by either the agency or contractor, or if existing safeguards have ceased to function, the discoverer shall immediately, within one (1) hour or less, bring the situation to the attention of the other party. This includes notifying the FDA Systems Management Center (SMC) within one (1) hour of discovery/detection in the event of an information security incident.

c. Adopt and implement the policies, procedures, controls, and standards required by the

HHS/FDA Information Security Program to ensure the confidentiality, integrity, and availability of government information and government information systems for which the Contractor is responsible under this contract or to which the Contractor may otherwise have access under this contract. Obtain the FDA Information Security Program security requirements, outlined in the FDA Information Security and Privacy Policy (IS2P), by contacting the CO/COR or emailing your ISSO.

d. Comply with the Privacy Act requirements and tailor FAR clauses as needed.

c) Information Security Categorization. In accordance with FIPS 199 and National Institute of

Standards and Technology (NIST) Special Publication (SP) 800-60, Volume II: Appendices to Guide for Mapping Types of Information and Information Systems to Security Categories, Appendix C, and based on information provided by the ISSO or other security representative, the risk level for each Security Objective and the Overall Risk Level, which is the highest watermark of the three factors (Confidentiality, Integrity, and Availability) of the information or information system are the following:

Confidentiality: [ ] Low [ ] Moderate [ ] High Integrity: [ ] Low [ ] Moderate [ ] High Availability: [ ] Low [ ] Moderate [ ] High Overall Risk Level: [ ] Low [ ] Moderate [ ] High

Based on information provided by the Privacy Office, system/data owner, or other privacy representative, it has been determined that this solicitation/contract involves:

[X ] No PII [ ] Yes PII

Personally Identifiable Information (PII). Per the OMB Circular A-130, “PII is information that can be used to distinguish or trace an individual's identity, either alone or when combined with other information that is linked or linkable to a specific individual.” Examples of PII include, but are not limited to the following: Social Security number, date and place of birth, mother’s maiden name, biometric records, etc.

PII Confidentiality Impact Level has been determined to be: [ ] Low [ ] Moderate [ ] High

d) Controlled Unclassified Information (CUI). CUI is defined as “information that laws, regulations, or Government-wide policies require to have safeguarding or dissemination controls, excluding classified information.” The Contractor (and/or any subcontractor) must comply with Executive Order 13556, Controlled Unclassified Information, (implemented at 3 CFR, part 2002) when handling CUI. 32 C.F.R. 2002.4(aa). As implemented the term “handling” refers to “…any use of CUI, including but not limited to marking, safeguarding, transporting, disseminating, re- using, and disposing of the information.” 81 Fed. Reg. 63323. All sensitive information that has been identified as CUI by a regulation or statute, handled by this solicitation/contract, shall be:

i) marked appropriately;

ii) disclosed to authorized personnel on a Need-To-Know basis;

iii) protected in accordance with NIST SP 800-53, Security and Privacy Controls for Federal

Information Systems and Organizations applicable baseline if handled by a Contractor system operated on behalf of the agency, or NIST SP 800-171, Protecting Controlled Unclassified Information in Nonfederal Information Systems and Organizations if handled by internal Contractor system; and http://csrc.nist.gov/publications/nistpubs/800-60-rev1/SP800-60_Vol2-Rev1.pdf http://csrc.nist.gov/publications/nistpubs/800-60-rev1/SP800-60_Vol2-Rev1.pdf http://csrc.nist.gov/publications/nistpubs/800-60-rev1/SP800-60_Vol2-Rev1.pdf http://csrc.nist.gov/publications/nistpubs/800-60-rev1/SP800-60_Vol2-Rev1.pdf http://csrc.nist.gov/publications/nistpubs/800-60-rev1/SP800-60_Vol2-Rev1.pdf

iv) returned to FDA control, destroyed when no longer needed, or held until otherwise directed.

Destruction of information and/or data shall be accomplished in accordance with NIST SP 800- 88, Guidelines for Media Sanitization and the FDA IS2P Appendix T: Sanitization of Computer- Related Storage Media.

e) Protection of Sensitive Information. For security purposes, information is or may be sensitive because it requires security to protect its confidentiality, integrity, and/or availability. The Contractor (and/or any subcontractor) shall protect all government information that is or may be sensitive in accordance with OMB Memorandum M-06-16, Protection of Sensitive Agency Information by securing it with a FIPS 140-2 validated solution.

Confidentiality and Nondisclosure of Information. Any information provided to the contractor (and/or any subcontractor) by FDA or collected by the contractor on behalf of FDA shall be used only for the purpose of carrying out the provisions of this contract and shall not be disclosed or made known in any manner to any persons except as may be necessary in the performance of the contract. The Contractor assumes responsibility for protection of the confidentiality of Government records and shall ensure that all work performed by its employees and subcontractors shall be under the supervision of the Contractor. Each Contractor employee or any of its subcontractors to whom any FDA records may be made available or disclosed shall be notified in writing by the Contractor that information disclosed to such employee or subcontractor can be used only for that purpose and to the extent authorized herein.

The confidentiality, integrity, and availability of such information shall be protected in accordance with HHS and FDA policies. Unauthorized disclosure of information will be subject to the HHS/FDA sanction policies and/or governed by the following laws and regulations:

a. 18 U.S.C. 641 (Criminal Code: Public Money, Property or Records);

b. 18 U.S.C. 1905 (Criminal Code: Disclosure of Confidential Information); and

c. 44 U.S.C. Chapter 35, Subchapter I (Paperwork Reduction Act).

f) Internet Protocol Version 6 (IPv6). All procurements using Internet Protocol shall comply with

OMB Memorandum M-05-22, Transition Planning for Internet Protocol Version 6 (IPv6).

g) Government Websites. All new and existing public-facing government websites must be securely configured with Hypertext Transfer Protocol Secure (HTTPS) using the most recent version of Transport Layer Security (TLS). In addition, HTTPS shall enable HTTP Strict Transport Security (HSTS) to instruct compliant browsers to assume HTTPS at all times to reduce the number of insecure redirects and protect against attacks that attempt to downgrade connections to plain HTTP.

For internal-facing websites, the HTTPS is not required, but it is highly recommended.

h) Contract Documentation. The Contractor shall use FDA-provided templates, policies, forms and other agency documents to comply with contract deliverables as appropriate.

i) Standard for Encryption. The Contractor (and/or any subcontractor) shall:

i) Comply with the HHS Standard for Encryption of Computing Devices and Information to prevent unauthorized access to government information.

ii) Encrypt all sensitive federal data and information (i.e., PII, protected health information [PHI], proprietary information, etc.) in transit (i.e., email, network connections, etc.) and at rest (i.e., servers, storage devices, mobile devices, backup media, etc.) with FIPS 140-2 validated encryption solution.

iii) All devices (i.e.: desktops, laptops, mobile devices, etc.) that store, transmit, or process non-public FDA information should utilize FDA-provided or FDA information security authorized devices that meet HHS and FDA-specific encryption standard requirements. Maintain a complete and current inventory of all laptop computers, desktop computers, and other mobile devices and portable media that store or process sensitive government information (including

PII).

iv) Verify that the encryption solutions in use are compliant with FIPS 140-2. The Contractor shall provide a written copy of the validation documentation to the COR.

v) Use the Key Management system on the HHS Personal Identification Verification (PIV) card or establish and use a key recovery mechanism to ensure the ability for authorized personnel to encrypt/decrypt information and recover encryption keys. Encryption keys (PIV card) shall be provided to the COR upon request and at the conclusion of the contract. Upon completion of contract, contractor ensures that COR is able to access and read any encrypted data.

j) Contractor Non-Disclosure Agreement (NDA). Each Contractor (and/or any subcontractor) employee having access to non-public government information under this contract shall complete the FDA non-disclosure agreement (3398 Form), as applicable.