N01CN05014-69.pdf

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SOLICITATION

SECTION A - SOLICITATION/CONTRACT FORM

1. Requisition or other Purchase Authority:

2. Request for Proposal (RFP) Number:

N01CN05014-69

3. Issue Date:

March 25, 2011

4. Set Aside:

[X] No

[ ] Yes See Part IV Section L

5. Title : Cancer Prevention Agent Development Program: Early Phase Clinical Research

6. ISSUED BY:

NCI, Office of Acquisitions

National Institutes of Health

7. SUBMIT OFFERS TO:

See Part III, Section J, "Packaging and Delivery of the Proposal," ATTACHMENT 1 of this Solicitation.

8. Proposals for furnishing the supplies and/or services in THE SCHEDULE will be received at the place specified in, and in the number of copies specified in Attachment 1, "Packaging and Delivery of the Proposal," until 3:00 PM local time on July 25, 2011. Offers will be valid for 120 days unless a different period is specified by the offeror on the Attachment entitled, "Proposal Summary and Data Record, NIH 2043.

9. This solicitation requires delivery of proposals as stated in ATTACHMENT 1, "PACKAGING AND DELIVERY OF THE PROPOSAL." If proposals are requred to be delivered to two different locations, the OFFICIAL POINT OF RECEIPT for determining TIMELY DELIVERY is the address provided for the OFFICE OF ACQUISITIONS.

IF YOUR PROPOSAL IS NOT RECEIVED BY THE CONTRACTING OFFICER OR HIS DESIGNEE AT THE PLACE AND TIME SPECIFIED FOR THE OFFICE OF ACQUISITIONS, THEN IT WILL BE CONSIDERED LATE AND HANDLED IN ACCORDANCE WITH subparagraph (c)(3) of FAR Clause 52.215-1, Instructions to Offerors--Competitive Acquisition," LOCATED IN SECTION L.1. OF THIS SOLICITATION.

10. Offeror must be registered in the Central Contractor Registry (CCR) prior to award of a contract. http:// www.ccr.gov

11. FOR INFORMATION CALL: Donna Perry-Lalley

PHONE: 301-435-3776

e-MAIL: perryd@mail.nih.gov

COLLECT CALLS WILL NOT BE ACCEPTED.

A Pre-Proposal Conference/teleconference will be held in Bethesda, MD on April 27, 2011 from 11am -2pm. See details in Section L, item 1.d.

Also, note the additional instructions in Section L: Additional Technical Proposal Instructions and Additonal Business Proposal Instructions in preparing proposals.

Virginia DeSeau Contracting Officer Office of Acquisitions http://www.ccr.gov http://www.ccr.gov

RFP Number : N01CN05014-69

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RFP TABLE OF CONTENTS

PART I - THE SCHEDULE

SECTION A - SOLICITATION/CONTRACT FORM

SECTION B - SUPPLIES OR SERVICES AND PRICES/COSTS

SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

SECTION D - PACKAGING, MARKING AND SHIPPING

SECTION E - INSPECTION AND ACCEPTANCE

SECTION F - DELIVERIES OR PERFORMANCE

SECTION G - CONTRACT ADMINISTRATION DATA

SECTION H - SPECIAL CONTRACT REQUIREMENTS

PART II - CONTRACT CLAUSES

PART III - LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACHMENTS

SOLICITATION ATTACHMENTS

TECHNICAL PROPOSAL ATTACHMENTS

BUSINESS PROPOSAL ATTACHMENTS

INFORMATIONAL ATTACHMENTS

PART IV - REPRESENTATIONS AND INSTRUCTIONS

SECTION K - REPRESENTATIONS, CERTIFICATIONS AND OTHER STATEMENTS OF OFFERORS

SECTION L - INSTRUCTIONS, CONDITIONS, AND NOTICES TO OFFERORS

1. GENERAL INFORMATION

a. INSTRUCTIONS TO OFFERORS--COMPETITIVE ACQUISITION

b. NAICS CODE AND SIZE STANDARD

c. TYPE OF CONTRACT AND NUMBER OF AWARDS

d. PRE-PROPOSAL CONFERENCE

e. ESTIMATE OF EFFORT

f. COMMITMENT OF PUBLIC FUNDS

g. COMMUNICATIONS PRIOR TO CONTRACT AWARD

h. RELEASE OF INFORMATION

i. PREPARATION COSTS

j. SERVICE OF PROTEST

2. INSTRUCTIONS TO OFFERORS

a. GENERAL INSTRUCTIONS

1. Contract Type and General Clauses

2. Authorized Official and Submission of Proposal

3. Proposal Summary and Data Record (NIH-2043)

4. Separation of Technical and Business Proposals

5. Alternate Proposals

6. Evaluation of Proposals

7. Potential Award Without Discussions

8. Use of the Metric System of Measurement

9. Standards for Privacy of Individually Identifiable Health Information

10. Privacy Act - Treatment of Proposal Information

11. Selection of Offerors

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12. Institutional Responsibility Regarding Conflicting Interests of Investigators

13. ROTC Access and Federal Military Recruiting on Campus

14. Past Performance Information

15. Electronic and Information Technology Accessibility, HHSAR 352.239-73(a)

16. Solicitation Provisions Incorporated by Reference

b. TECHNICAL PROPOSAL INSTRUCTIONS

1. Technical Discussions

2. Other Considerations

3. Technical Evaluation

4. Human Subjects

Notice to Offerors of Requirements of 45 CFR Part 46, Protection of Human Subjects, HHSAR 270-4(a)

Instructions to Offerors Regarding Protection of Human Subjects

Required Education in the Protection of Human Research Participants

Inclusion of Women and Minorities in Research Involving Human Subjects

Inclusion of Children in Research Involving Human Subjects

Research Involving Prisoners as Subjects

Research Involving Human Fetal Tissue

Data and Safety Monitoring in Clinical Trials

Registration and Results Reporting for Applicable Clinical Trials in ClinicalTrials.gov

5. Obtaining and Disseminating Biomedical Research Resources

6. Information and Physical Access Security

7. ADDITIONAL TECHNICAL PROPOSAL INSTRUCTIONS

c. BUSINESS PROPOSAL INSTRUCTIONS

1. Basic Cost/Price Information

2. Proposal Cover Sheet

3. Information Other than Cost or Pricing Data

4. Requirements for Cost or Pricing Data or Information Other than Cost and Pricing Data

5. Salary Rate Limitation in Fiscal Year 2009

6. Small Business Subcontracting Plan

7. Mentor Protege Program, HHSAR 352.219-70

8. HUBZone Small Business Concerns

9. Extent of Small Disadvantaged Business Participation

10. Total Compensation Plan

11. Other Administrative Data

12. Qualifications of the Offeror

13. Subcontractors

14. Proposer's Annual Financial Report

15. Travel Costs/Travel Policy

16. ADDITIONAL BUSINESS PROPOSAL INSTRUCTIONS

SECTION M - EVALUATION FACTORS FOR AWARD

1. GENERAL

2. COST/PRICE EVALUATION

3. HUMAN SUBJECT EVALUATION

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4. EVALUATION OF OPTIONS

5. EVALUATION OF DATA SHARING PLAN

6. TECHNICAL EVALUATION CRITERIA

7. EVALUATION OF ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY- SECTION

8. PAST PERFORMANCE FACTOR

9. EXTENT OF SMALL DISADVANTAGED BUSINESS PARTICIPATION

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PART I - THE SCHEDULE

THE INFORMATION SET FORTH IN SECTION A - SOLICITATION/CONTRACT FORM, HEREIN CONTAINS IMPORTANT INFORMATION FOR ANY OFFEROR INTERESTED IN RESPONDING TO THIS SOLICITATION.

ANY CONTRACT RESULTING FROM THIS SOLICITATION WILL INCLUDE IN ITS SECTION A - SOLICITATION/ CONTRACT FORM, ACCOUNTING, APPROPRIATION AND GENERAL INFORMATION APPLICABLE TO THE

CONTRACT AWARD.

THE CONTRACT SCHEDULE SET FORTH IN SECTIONS B THROUGH H, HEREIN, CONTAINS CONTRACTUAL INFORMATION PERTINENT TO THIS SOLICITATION. IT IS NOT AN EXACT REPRESENTATION OF THE CONTRACT DOCUMENT THAT WILL BE AWARDED AS A RESULT OF THIS SOLICITATION. THE CONTRACT COST OR PRICE AND OTHER CONTRACTUAL PROVISIONS PERTINENT TO THE OFFEROR (i.e., those relating to the organizational structure [e.g., Non-Profit, Commercial] and specific cost authorizations unique to the Offeror's proposal and requiring Contracting Officer Prior Approval) WILL BE DISCUSSED IN THE NEGOTIATION PROCESS AND WILL BE INCLUDED IN THE RESULTANT CONTRACT. THE ENCLOSED CONTRACT SCHEDULE IS

INTENDED TO PROVIDE THE OFFEROR WITH THE NECESSARY INFORMATION TO UNDERSTAND THE

TERMS AND CONDITIONS OF THE RESULTANT CONTRACT.

SECTION B - SUPPLIES OR SERVICES AND PRICES/COSTS

ARTICLE B.1. BRIEF DESCRIPTION OF SUPPLIES OR SERVICES

The Contractor shall provide essential clinical trials infrastructure and laboratory support to assess the cancer preventive potential of various agents. The goals of the program are:

1. To efficiently design and conduct early phase clinical trials to assess various classes of potential cancer preventive agents.

2. To characterize the biological effects of new cancer preventive agents on their defined molecular targets as well as on multiple endpoints associated with carcinogenesis, such as proliferation, apoptosis, growth factor expression, oncogene expression, and others.

3. To correlate the biological effects with clinically relevant endpoints.

4. To develop scientific insights into the mechanisms of cancer prevention by the agents examined and to continue to develop novel potential markers as determinants of response.

ARTICLE B.2. ESTIMATED COST - OPTION

a. The estimated cost of the Base Period of this contract is $ .

b. If the Government exercises its option pursuant to the OPTION PROVISION Article in SECTION H of this contract, the Government's total estimated contract amount represented by the sum of the estimated cost plus the fixed fee will be increased as follows:

Estimated Cost

Base Period:

Option Periods:

Option 1

Option 2

Option Quantities: Subjects

Option 1: 12 subjects

Option 2: 12 subjects

Option 3: 13 subjects

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Estimated Cost

Option 4: 13 subjects

Total

[Base Period and Option(s)]

ARTICLE B.3. ESTIMATED COST - INCREMENTALLY FUNDED CONTRACT, HHSAR

352.232-71 (June 2010)

a. The total estimated cost to the Government for full performance of this contract, including all allowable direct and indirect costs, is $ .

b. The following represents the schedule* by which the Government expects to allot severable funds to this contract:

CLIN, Task, Number, or Description Start Date of Period or

Increment of Performance

End Date of Period or Increment of Performance Estimated Cost ($)

TBD

[Total]

*To be inserted after negotiation

c. Total funds currently obligated and available for payment under this contract are $ .

d. The Contracting Officer may issue unilateral modifications to obligate additional funds to the contract and make related changes to paragraphs b. and/or c., above.

e. Until this contract is fully funded, the requirements of the clause at FAR 52.232-22, Limitation of Funds, shall govern. Once the contract is fully funded, the requirements of the clause at FAR 52.232-20, Limitation of Cost, shall govern.

(End of Clause)

ARTICLE B.4. PROVISIONS APPLICABLE TO DIRECT COSTS

This article will prohibit or restrict the use of contract funds, unless otherwise approved by the Contracting Officer. The following is a list of items that may be included in the resultant contract as applicable. 1) Acquisition, by purchase or lease, of any interest in real property; 2) Special rearrangement or alteration of facilities; 3) Purchase or lease of any item of general purpose office furniture or office equipment regardless of dollar value; 4) Travel Costs; 5) Consultant Costs; 6) Subcontract Costs; 7) Patient Care Costs; 8) Accountable Government Property; and 9) Research Funding.

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ARTICLE B.5. ADVANCE UNDERSTANDINGS

Specific elements of cost, which normally require prior written approval of the Contracting Officer before incurrence of the cost (e.g., foreign travel, consultant fees, subcontracts) will be included in this Article if the Contracting Officer has granted his/her approval prior to contract award.

a. Complexity Model Table 1

The following table sets forth the rates for the Per Subject Costs for the first year that budgets for protocols are approved, tentatively 2013. Each subsequent year from 2014 - 2017, a revised table will be calculated factoring in an escalation factor of 2% to be applied to the rates.

Stage Base Cost x 1.5 x 2.0 x 2.5 x 3.0 Screening 1 $ x $ 1.5x $ 2x $ 2.5x $ 3x Screening 2 $ y $ 1.5y $ 2y $ 2.5y $ 3y Intervention $ z $ 1.5z $ 2z $ 2.5z $ 3z

SECTION C - DESCRIPTION/SPECIFICATIONS/WORK STATEMENT

ARTICLE C.1. STATEMENT OF WORK

a. Independently and not as an agent of the Government, the Contractor shall be required to furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, as needed to perform the Statement of Work, dated March 16, 2011, attached hereto and made a part of this Solicitation (See SECTION J - List of Attachments).

b. The applicable Privacy Act System of Records Number will be specified and shall be used in any design, development, or operation work to be performed under the resultant contract. Disposition of records shall be in accordance with SECTION C of the contract, and by direction of the Contracting Officer's Technical Representative (COTR).

ARTICLE C.2. REPORTING REQUIREMENTS

All reports required herein shall be submitted in electronic format. In addition, one hardcopy of each report shall be submitted to the Contracting Officer.

All reports submitted shall be compliant with Section 508 of the Rehabilitation Act of 1973. Additional information about testing documents for Section 508 compliance, including specific checklists, by application, can be found at:

http://www.hhs.gov/web/508/index.html under "Helpful Resources."

a. Technical Progress Reports

1. In addition to the required reports set forth elsewhere in this Schedule, the preparation and submission of regularly recurring Technical Progress Reports will be required in any contract resulting from this solicitation. These reports will require descriptive information about the activities undertaken during the reporting period and will require information about planned activities for future reporting periods. The frequency and specific content of these reports will be determined prior to contract award. [Note: Beginning May 25, 2008, the Contractor shall include the applicable PubMed Central http://www.hhs.gov/web/508/index.html

- 8 -or NIH Manuscript Submission reference number when citing publications that arise from its NIH funded research.]

For proposal preparation purposes only, it is estimated that in addition to the required electronic versions 1 hard copy of these reports will be required as follows:

[X] Monthly Data Reporting - Protocol Specific [X] Quarterly [ ] Semi-Annually [X] Annually [ ] Annually (with a requirement for a Draft Annual Report) [ ] Final - Upon final completion of the contract [X] Final - Upon final completion of the contract (with a requirement for a Draft Final Report)

1.1 Monthly Data Reporting - Protocol Specific

The Contractor shall report individual protocol-specific information including, but not limited to, participant accrual and characteristics, agent dosing, adverse events, and endpoint, response, and/or outcome data.

The Contractor shall provide all data to the Division of Cancer Prevention (DCP) electronically using DCP's secure file transfer site. This submission method requires the Contractor to develop and/or implement computer programs to download data from the Contractor's current clinical trials management system/clinical data management system to DCP's secure file transfer site. All data elements used in the collection of data for DCP-sponsored clinical trial must be Common Date Element (CDE)-compliant. (Note: These data elements may change as Government requirements evolve.) Acceptable file transfer formats include: MS Excel (saved as CSV file), XML, and Text delimited flat file.

DCP will evaluate the submitted data files for completeness and accuracy. The Contractor will be notified of any problems with a data submission. The Contractor shall be required to make corrections and resubmit the entire data set within 2 weeks following receipt of DCP comments.

Select clinical trials may require the reporting of data in addition to that required for the routine Monthly Data Reporting. Those specific additional data elements will be determined and defined during the development of the trial and as needed during the conduct of the trial to address changing scientific and safety concerns.

The monthly data submissions are due by the 10th calendar day of each month and should reflect the status of data as of the end of the preceding month. The first submission is due the month after the protocol has received Final Study Approval. These submissions are required for all approved studies until they reach a status of 'complete' or 'administratively complete'.

1.2. Quarterly and Annual Progress Reports

The purpose of the Quarterly and Annual Progress Reports is to provide a description of the activities during the reporting period, the adverse events table, a discussion of any problems encountered, and to detail the activities planned for the ensuing reporting period. The Quarterly and Annual Progress Reports summarize the progress of the contract and provide specific information on each individual clinical trial including expenditure summaries. The format for these progress reports shall be specified by DCP.

All Quarterly and Annual Progress Reports shall be submitted electronically to the Contracting Officer (CO) and Contracting Officer's Technical Representative (COTR). In addition, reports will be submitted electronically to the Protocol Information Office at: nci_dcp_pio@mail.nih.gov. The first reporting period consists of the first full three calendar months of performance plus any fraction of the initial month. Thereafter, the Quarterly Progress Report shall be due 30 calendar days following each

- 9 -quarter. At the end of each contract year an Annual (cumulative) Progress Report shall be submitted within 42 calendar days following the end of each contract year in lieu of the Quarterly Progress Report.

If applicable, the Government will act as Sponsor of the Investigational New Drug (IND) under the Code of Federal Regulations §312. The Code specifies that the Investigator shall furnish reports to the Sponsor who is required under §312.33 to submit annual reports to FDA on the progress of the clinical investigations. It is noted for informational purposes that CFR 312.60 requires the Principal Investigator, who has committed by signing Form FDA 1572, to personally conduct or supervise the described investigations under applicable regulations, to report the conduct and progress of the clinical investigation to the authorized representative(s) of the Government and the Sponsor of the clinical investigation, in this case the National Cancer Institute, Division of Cancer Prevention.

1.3. Human Subject Education Certification

The Principal Investigator and all Key Personnel shall submit documentation of the required education to DCP's Regulatory Contractor within sixty (60) calendar days of contract award. Prior to the substitution of the principal investigator or any other individuals responsible for the design and conduct of the research under contract, the contractor shall provide the following written information to the Contracting Officer: the title of the education program and a one sentence description of the program that has been completed by the replacement.

1.4. Draft Final and Final Contract Report

The Final Report summarizes work performed and results obtained for the entire contract period of performance. The report shall be prepared according to the document "NCI Requirements for Final Reports for Clinical Trials" as found at: http://dcp.cancer.gov/Files/clinical-trials/final-report.pdf. A Draft of the Final Report, including all calculated and raw data, shall be submitted to the Division of Cancer Prevention for review by the COTR. This Draft is due at least 60 calendar days before the end of the contract. The DCP COTR will review and respond with approval or comments to the draft Final Report within 30 calendar days of submission. The Final report is due by the date of contract expiration. An Annual Report will not be required for the period when the final report is due.

The Draft Final Report and the Final Report shall be submitted electronically to the Protocol Information Office to: nci_dcp_pio@mail.nih.gov, the COTR, and the CO. The Contractor shall also provide a disc of the Final Report to the COTR and the CO.

2. Summary of Salient Results

The Contractor will be required to prepare and submit, with the final report, a summary (not to exceed 200 words) of salient results achieved during the performance of the contract. This report will be required on or before the expiration date of the contract.

3. Annual Technical Progress Report for Clinical Research Study Populations

The Contractor shall submit information about the inclusion of women and members of minority groups and their subpopulations for each study being performed under this contract. The Contractor shall submit this information in the format indicated in the attachment entitled, "Inclusion Enrollment Report," which is set forth in SECTION J of this contract. The Contractor also shall use this format, modified to indicate that it is a final report, for reporting purposes in the final report.

The Contractor shall submit the report in accordance with the DELIVERIES Article in SECTION F of this contract.

In addition, the NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research, Amended, October, 2001 applies. If this contract is for Phase III clinical trials, see II.B of these guidelines. The Guidelines may be found at the following website:

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Include a description of the plans to conduct analyses, as appropriate, by sex/gender and/or racial/ ethnic groups in the clinical trial protocol as approved by the IRB, and provide a description of the progress in the conduct of these analyses, as appropriate, in the annual progress report and the final report. If the analysis reveals no subset differences, a brief statement to that effect, indicating the subsets analyzed, will suffice. The Government strongly encourages inclusion of the results of subset analysis in all publication submissions. In the final report, the Contractor shall include all final analyses of the data on sex/gender and race/ethnicity.

b. Other Reports/Deliverables

1. Information Security and Physical Access Reporting Requirements

The Contractor shall submit the following reports as required by the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract. Note: Each report listed below includes a reference to the appropriate subparagraph of this article.

a. Roster of Employees Requiring Suitability Investigations

The Contractor shall submit a roster, by name, position, e-mail address, phone number and responsibility, of all staff (including subcontractor staff) working under the contract who will develop, have the ability to access, or host and/or maintain a Federal information system(s). The roster shall be submitted to the Contracting Officer's Technical Representative (COTR), with a copy to the Contracting Officer, within 14 calendar days of the effective date of the contract. (Reference subparagraph A.e. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

b. Reporting of New and Departing Employees

The Contractor shall notify the Contracting Officer's Technical Representative (COTR) and Contracting Officer within five working days of staffing changes for positions that require suitability determinations as follows:

a. New Employees who have or will have access to HHS Information systems or data: Provide the name, position title, e-mail address, and phone number of the new employee. Provide the name, position title and suitability level held by the former incumbent. If the employee is filling a new position, provide a description of the position and the Government will determine the appropriate security level.

b. Departing Employees: 1) Provide the name, position title, and security clearance level held by or pending for the individual; and 2) Perform and document the actions identified in the "Employee Separation Checklist", attached in Section J, ATTACHMENTS of this contract, when a Contractor/Subcontractor employee terminates work under this contract. All documentation shall be made available to the COTR and/or Contracting Officer upon request.

(Reference subparagraph E.2.a-c. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

c. Contractor - Employee Non-Disclosure Agreement(s)

The contractor shall complete and submit a signed and witnessed "Commitment to Protect Non-Public Information - Contractor Agreement" form for each contractor http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm

- 11 -and subcontractor employee who may have access to non-public Department information under this contract. This form is located at: http://ocio.nih.gov/docs/public/ Nondisclosure.pdf.

(Reference subparagraph E.2.d. of the INFORMATION AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract.)

2. Section 508 Annual Report

The contractor shall submit an annual Section 508 report in accordance with the schedule set forth in the ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY Article in SECTION H of this contract. The Section 508 Report Template and Instructions for completing the report are available at: http://www.hhs.gov/od under "Vendor Information and Documents."

3. Deliverables Required Prior to Initiating Any Clinical Trial

a. Multi-Institution Monitoring Plan The Multi-Institution Monitoring Plan is due within 30 calendar days of the contract effective date.

The Contractor shall submit a Plan describing implementation of appropriate procedures to ensure compliance with the DCP Multicenter Guidelines (see http://prevention.cancer.gov/clinicaltrials/ management/consortia/step-1/multi). The Plan shall be sent to the PIO for distribution to the COTR.

The Multi-Institution Monitoring Plan shall be approved by the COTR prior to initiation of any clinical trial.

b. Master Data and Safety Monitoring Plan A Master Data and Safety Monitoring Plan (DSMP), reflecting procedures to be implemented across all studies within the Contractor's network, is due within 60 calendar days of the contract effective date. It shall be approved by DCP before it can become effective. Additionally, a protocol-specific DSMP is required with the submission of each protocol and must be approved by the DCP before the clinical trial may commence. The protocol-specific DSMP should reference the approved Master DSMP and only needs to contain information that customizes the DSMP to a specific protocol or differences from the Master DSMP. The NIH policy reference, purpose, essential elements and other requirements for this Plan can be found at http://prevention.cancer.gov/clinicaltrials/management/consortia/step-3/guide; http://www.cancer.gov/ clinicaltrials/conducting/dsm-guidelines.

4. Deliverables Required Prior to Initiation of Each Clinical Trial

a. Letters of Intent (LOIs) The Letter of Intent (LOI) is a document prepared and submitted by the Principal Investigator to declare interest in conducting a particular clinical trial. The LOI process is further defined in the Statement of Work (SOW, Section 2.a, "The Letter of Intent Process"). The LOI Guidelines and Form are available at: http://prevention.cancer.gov/clinicaltrials/management/consortia/step-1/protocol#loi

b. Contract Work Assignment The Contract Work Assignment will be completed and submitted with the Protocol Document in accordance with Article G in the contract.

c. Protocol Document LOIs approved by the DCP LOI Review Committee shall be developed into complete protocol documents by the Principal Investigator. The protocol document with informed consent document, and all Additional Study Related Documents are due to DCP within 60 calendar days of the Principal http://ocio.nih.gov/security/Nondisclosure.pdf http://ocio.nih.gov/security/Nondisclosure.pdf http://www.hhs.gov/od

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Investigator's notification of LOI approval. The protocol shall include the essential elements and follow the template on the DCP web site http://prevention.cancer.gov/clinicaltrials/management/ consortia/step-1/protocol. The Protocol Document shall also include the budget based on the number of subjects to be accrued, protocol-specific costs, and proposed biomarker analyses (see d. below).

The protocol shall incorporate required changes from the LOI review committee. The protocol and attachments shall be submitted to the DCP PIO as an electronic attachment (MS Word). Any further revisions requested by DCP shall be submitted as a revised protocol according to the format and time lines specified by the PIO.

d. Biomarker and Pharmacokinetic Method Development Document

All pharmacokinetic and biomarker laboratory techniques, assays, and procedures shall be validated according to the parameters described in the URL under the Protocol Document above (see section in URL entitled "Protocol Process"; document entitled "Additional Study Related Documents") and a report prepared for Division of Cancer Prevention approval within 60 calendar days of approval of an LOI (as part of the Additional Study Related Documents submitted with the protocol).

A budget for the techniques, assays, and procedures to be used for each specific protocol shall be submitted with the LOI. Each technique, assay, and procedure shall be budgeted on a per specimen, per test basis and shall be separately negotiated per protocol.

e. Protocol-related administrative and regulatory documents

DCP or its contractors will notify the investigator of the specific regulatory and administrative documents required for FDA submission and/or protocol initiation. Documents include, but are not limited to:

i) Principal Investigator Form FDA 1572, biosketch and sub-investigator biosketches

ii) Any additional documentation required by a pharmaceutical partner

iii) IRB approval of protocol, consent, promotional materials, data and safety monitoring plan

iv) IRB committee membership roster

v) Lab certifications (CLIA, CAP)

vi) List of lab normal ranges

vii) Delegation of authority form, as appropriate

viii) Human Subjects Education verification

5. Deliverables Required During the Conduct of Each Clinical Trial

a. Participants Data Clinical trial data for each participant using paper based or electronic reporting as specified by DCP will be required. Reportable data shall include, but may not be limited to: administrative data elements, treatment administration details, adverse events, response data, demographic data.

b. Adverse Event Reports All serious adverse events (SAEs), whether judged to be drug related or not, must be reported to the DCP Medical Monitor according to the guidelines below. Adverse events shall be graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Studies will be conducted under the latest version of the CTCAE or as required by DCP. A complete set of the CTCAE and instructions for use are available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm In addition to reporting these events on the Case Report Form a cumulative table describing all adverse events is required in the Quarterly, Annual, and Final reports.

Adverse Event Reporting Chart:

Summary of Investigator's Obligations for Reporting Adverse Events in Phase 0-

II Clinical Trials to the National Cancer Institute, Division of Cancer Prevention (DCP) http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm

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Reaction Reporting Obligation

a. ALL SERIOUS ADVERSE EVENTS

(Fatal, all life-threatening events, any adverse event drug experience occurring at any dose that results in the following: inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

b. ALL ADVERSE EVENTS (SERIOUS, NON-SERIOUS) 3

Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a serious adverse event when, based upon appropriate medical judgement, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

REPORT BY PHONE TO DCP WITHIN 24 HOURS. 1

(written report to follow within 48 hrs 2)

REPORT in the Adverse Event Case Report Form and Quarterly/Annual Progress Reports.

1. Report to Medical Monitor for the specific trial

2. Use Common Terminology Criteria for Adverse Events (CTCAE), most recent version.

3. A list of all known toxicities can be found in the Investigator's Brochure of package insert of agent.

An Investigator shall promptly report to the Sponsor (National Cancer Institute, Division of Cancer Prevention, Medical Monitor) any adverse effect that may reasonably be regarded as caused by, or probably caused by the drug. If the non-serious adverse event is alarming, the Investigator shall report the adverse effect immediately.

c. Protocol Amendments Administrative and Scientific amendments must be submitted to DCP PIO for review and approval by the COTR and the Medical/Scientific Monitor.

6. Deliverables Required Following Completion of Each Clinical Trial

a. Draft and Final Study Manuscript: A 'draft' or 'submission' manuscript shall be submitted within 120 calendar days of the time that all participants have met the primary study endpoint. All submitted manuscripts shall be clearly labeled on the cover page as either draft or submission version. Final Study Manuscripts shall be provided to DCP PIO and the NIH Library of Medicine one month after publication.

b. Data set for analysis: final clinical and safety data should be submitted to DCP's regulatory contractor within 120 calendar days of the last patient's exit from the clinical protocol; biomarker data may follow. The data provided should be a copy of the final, complete, cleaned, audited, locked data set used for analysis.

c. Biomarker and Other Laboratory Study Analyses: The results of secondary biomarker analyses may not be available until after the primary manuscript is written. The due date of the report regarding biomarker analyses not included in the primary study manuscript will be negotiated with the Medical/ Scientific Monitor.

d. Biologic Specimens: Biologic specimens collected during the conduct of each clinical trial that are not used during the course of the study will be considered deliverables under the contract and thus be the property of the NCI. At study completion, NCI reserves the option to either retain or relinquish ownership of the unused biologic specimens. If NCI retains ownership of specimens, the Contractor shall collect, verify, and transfer the requested biologic specimens from the site to an NCI-specified repository or laboratory at NCI's expense.

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SECTION D - PACKAGING, MARKING AND SHIPPING

All deliverables required under this contract shall be packaged, marked and shipped in accordance with Government specifications. At a minimum, all deliverables shall be marked with the contract number and Contractor name. The Contractor shall guarantee that all required materials shall be delivered in immediate usable and acceptable condition.

SECTION E - INSPECTION AND ACCEPTANCE

a. The Contracting Officer or the duly authorized representative will perform inspection and acceptance of materials and services to be provided.

b. For the purpose of this SECTION, the Contracting Officer's Technical Representative is the authorized representative of the Contracting Officer.

c. Inspection and acceptance will be performed at:

National Cancer Institute Bethesda, Maryland

Acceptance may be presumed unless otherwise indicated in writing by the Contracting Officer or the duly authorized representative within 30 days of receipt.

FAR Clause 52.246-8, Inspection of Research and Development - Cost-Reimbursement (May 2001).

SECTION F - DELIVERIES OR PERFORMANCE

ARTICLE F.1. PERIOD OF PERFORMANCE

a. The period of performance of this contract shall be from June 16, 2012 through June 15, 2017.

b. If the Government exercises its option(s) pursuant to the OPTION PROVISION Article in Section H of this contract, the period of performance will be increased as listed below:

Option Option Period

ARTICLE F.2. DELIVERIES

Satisfactory performance of the final contract shall be deemed to occur upon performance of the work described in the Statement of Work Article in SECTION C of this contract and upon delivery and acceptance by the Contracting Officer, or the duly authorized representative, of the following items in accordance with the stated delivery schedule:

a. The items specified below as described in the REPORTING REQUIREMENTS Article in SECTION C of this contract will be required to be delivered F.o.b. Destination as set forth in FAR 52.247-35, F.o.b. DESTINATION, WITHIN CONSIGNEES PREMISES (APRIL 1984), and in accordance with and by the date(s) specified below [and any specifications stated in SECTION D, PACKAGING, MARKING AND SHIPPING, of this contract]:

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Item No.

Deliverable Description Addressee Due Date

1 Multi-Institution Monitoring Plan PIO, COTR 30 calendar days after contract award 2 Master Data and Safety

Monitoring Plan PIO, COTR 60 calendar days after contract award

3 Protocol-specific Data and Safety Monitoring Plan

PIO To be provided with the submission of each protocol

4 Human Subjects Education certification

DCP's regulatory contractor

Within 60 calendar days of award and yearly thereafter

5 Letter of Intent (LOI) PIO 60 calendar days after DCP announcement of the request for LOIs

6 Contract Work Assignment COTR With submission of Protocol 7 Protocol with informed consent document, appendices, and all Additional Study Documents

PIO First submission due 60 calendar days from DCP approval of LOI, and Revisions due as specified in the Consensus Review document

8 Protocol Amendments PIO As necessity determines after protocol is initiated

9 Biomarker and Pharmacokinetic Method Development Document

PIO First submission due 60 calendar days from DCP approval of LOI, and Revisions due as specified in the Consensus Review document

10 Monthly Data Reporting- Protocol Specific

DCP's secure file transfer site

10th calendar day of the month after Final Study Approval

11 Protocol-related administrative and regulatory documents

DCP's regulatory contractor

Prior to Final Study Approval, in consultation with COTR

12 Adverse Events Reports Study Medical Monitor Due in accordance with DCP Adverse Event Reporting Chart

13 Biological specimens

DCP's specimen biorepository (site to be determined)

Prior to or upon expiration of contract, as requested by COTR

14 Draft and Final Study Manuscript

PIO, Study Medical/ Scientific Monitor

Draft: 120 calendar days after completion of study Final: one month after publication

15 Biomarker and Other Laboratory Study Analyses

PIO, Study Medical/ Scientific Monitor

After completion of study and as agreed upon with study Medical/Scientific Monitor

16 Complete, cleaned, audited, locked data set (on disc)

DCP's regulatory contractor (to be determined)

120 calendar days after completion of study

17 Quarterly Progress Reports including expenditure summary for each clinical trial

PIO, COTR, CO 30 calendar days following the end of each quarter

18 Annual Progress Report PIO, COTR, CO 42 calendar days following the end of each contract year

19 Inclusion Enrollment Report PIO, COTR, CO Annually 20 Draft Final Contract Report PIO, COTR, CO 60 calendar days prior to the expiration date of the contract 21 Final Contract Report

PIO, COTR, CO By Contract expiration date

22 Roster of Employees Requiring Suitability Investigations

COTR, CO Fourteen (14) calendar days after award

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Item No.

Deliverable Description Addressee Due Date

23 Reporting of New and Departing Employees

COTR, CO Within five working days of staffing changes for positions that require suitability determinations

24 Contractor - Employee Non- Disclosure Agreement(s)

COTR, CO Prior to commencing work on the contract

25 Section 508 Report COTR, CO Sixty (60) calendar days prior to the end of each contract year.

b. The above items shall be addressed and delivered to:

Addressee Contracting Officer's Technical Representative (COTR)

Division of Cancer Prevention

National Cancer Institute

Executive Plaza North, Room

6130 EXECUTIVE BLVD

BETHESDA, MD 20892

DCP Protocol Information Office (PIO)

Division of Cancer Prevention

National Cancer Institute

Executive Plaza North, Room 2050

6130 EXECUTIVE BLVD

BETHESDA, MD 20892

Preferred electronic delivery to: nci_dcp_pio@mail.nih.gov Contracting Officer (CO)

Research Contracts and Acquisition Branch

National Cancer Institute

Executive Plaza South, Room 603

6120 EXECUTIVE BLVD MSC 7220

BETHESDA, MD 20892-7220

DCP's Regulatory Contractor - Will be provided

Study Medical/Scientific Monitor - Will be provided

ARTICLE F.3. CLAUSES INCORPORATED BY REFERENCE, FAR 52.252-2 (FEBRUARY

1998)

This contract incorporates the following clause(s) by reference, with the same force and effect as if it were given in full text. Upon request, the Contracting Officer will make its full text available. Also, the full text of a clause may be accessed electronically at this address: http://www.acquisition.gov/comp/far/index.html

FEDERAL ACQUISITION REGULATION (48 CFR CHAPTER 1) CLAUSE:

52.242-15, Stop Work Order (August 1989) with Alternate I (April 1984).

SECTION G - CONTRACT ADMINISTRATION DATA

http://www.acquisition.gov/comp/far/index.html

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ARTICLE G.1. CONTRACTING OFFICER'S TECHNICAL REPRESENTATIVE (COTR)

The following Contracting Officer's Technical Representative (COTR) will represent the Government for the purpose of this contract:

To be specified prior to award

The COTR 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 statement of work 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.

The alternate COTR is responsible for carrying out the duties of the COTR only in the event that the COTR can no longer perform his/her duties as assigned.

The Contracting Officer 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 statement of work; (2) modify or extend the period of performance; (3) change the delivery schedule; (4) authorize reimbursement to the Contractor for any costs incurred during the performance of this contract; or (5) otherwise change any terms and conditions of this contract.

The Government may unilaterally change its COTR designation.

ARTICLE G.2. KEY PERSONNEL, HHSAR 352.242-70 (January 2006)

The key personnel specified in this contract are considered to be essential to work performance. At least 30 days prior to diverting any of the specified individuals to other programs or contracts (or as soon as possible, if an individual must be replaced, for example, as a result of leaving the employ of the Contractor), the Contractor shall notify the Contracting Officer and shall submit comprehensive justification for the diversion or replacement request (including proposed substitutions for key personnel) to permit evaluation by the Government of the impact on performance under this contract. The Contractor shall not divert or otherwise replace any key personnel without the written consent of the Contracting Officer. The Government may modify the contract to add or delete key personnel at the request of the Contractor or Government.

(End of Clause)

The following individual(s) is/are considered to be essential to the work being performed hereunder:

Name Title

When Multiple Principal Investigators are named, the "Contact PI" MUST be specified

ARTICLE G.3. WORK ASSIGNMENT PROCEDURES

In providing support under this contract, the Contractor shall initiate work only when so directed by a Work Assignment (Attachment provided in SECTION J). Approval of a Work Assignment shall not constitute approval to exceed any item listed in the contract or general clauses of the contract. Work Assignment amounts shall not exceed the total amounts listed in the contract (time, dollars, effort, consultants, travel, etc.). The Contracting Officer's Technical Representative (COTR) with Contracting Officer approval, is authorized to initiate Work Assignments and to sign Work Assignments indicating satisfactory performance/delivery of the services/product required in each Work Assignment. The Contractor shall assure, prior to commencing work on any Work Assignment, that written approval of the COTR and the Contracting Officer has been obtained. A Work Assignment which does not contain both Contracting Officer and COTR approval signatures shall be considered invalid and costs incurred for such work shall be considered unallowable. The Contractor shall not exceed the estimated labor hours, estimated Work

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Assignment amount, or change the Work Assignment leader without prior written approval of the COTR and the Contracting Officer by modification of the Work Assignment. The day-to-day operational and administrative details of the Work Assignment system will be established by the COTR with input from the Contractor. The Work Assignment system will operate within the following general guidelines:

a. Work Assignment (W.A.) Information

1. All work to be assigned under this contract shall relate directly to one or more of the task areas listed in the Statement of Work.

2. Each W.A. shall be written for the conduct of a specific, finite task.

3. Each new W.A. shall be numbered serially beginning with 01.

4. Each W.A. shall be completed on the form entitled "Sample Contract Work Assignment" and listed as an Attachment in Section J of this contract.

5. Upon award of the contract, an Administrative Work Assignment as shown in SECTION J, Attachments, shall be issued on a yearly basis. This Work Assignment will cover the time and expenditures necessary for the administration of the contract.

b. Initiation of a W.A.

1. The COTR will initiate Part I of the W.A.

2. The Contractor shall complete Part II and obtain the appropriate signature. The Contractor shall forward the proposed W.A. to the COTR.

3. Upon receipt of the proposed W.A. and after determining that the proposed W.A. is acceptable, the COTR will sign Part II to indicate recommendation for approval and forward to the Contracting Officer.

4. Upon receipt, the Contracting Officer will review the proposed W.A.

a. If approved, the Contracting Officer will sign Part II to indicate approval and will forward the W.A. to the Contractor with a copy to the COTR.

b. If not approved, the Contracting Officer will notify the COTR, stating the reasons for disapproval.

5. After receipt of the approved W.A., the Contractor shall begin work. The period of performance shall never precede the Contracting Officer Approval date.

c. Modification to a W.A.

1. Each amendment to an existing Work Assignment shall contain the original W.A. number and shall designate a modification number. Modification numbers for each W.A. shall be serially numbered beginning with 01 (for example, Work Assignment 01, Modification No. 01).

2. Each W.A. modification shall set forth in specific detail which portion(s) of the W.A. is to be modified. All Cost/Labor modifications shall be in the following format:

Authorized to Date This Modification Revised Estimate

Labor Hours

Cost Elements

(List Each Element)

d. Conclusion of a W.A.

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1. For each W.A. performed, the Contractor shall prepare PART III of the Work Assignment for submission to the Contracting Officer.

2. This PART III submission shall include all actual information (cost, effort, and deliverables) relative to the W.A.

3. PART III of the W.A. shall be submitted as soon as possible and not to exceed three months after the closing date of the W.A. For those Work Assignments which expire within three months prior to the contract expiration date, PART III of the Work Assignment shall be submitted on the final contract day.

4. After verification that all work is complete and deliverables have been received and accepted, the COTR will sign Part III of the W.A. to indicate recommendation for approval and forward the W.A. to the Contracting Officer.

5. After verification that the W.A. has been satisfactorily completed, the Contracting Officer will approve completion of the W.A. by signing Part III of the W.A. and forward to the Contractor.

ARTICLE G.4. INVOICE SUBMISSION/CONTRACT FINANCING REQUEST AND CONTRACT

FINANCIAL REPORT

a. Invoice/Financing Request Instructions and Contract Financial Reporting for NIH Cost-Reimbursement Type Contracts NIH(RC)-4 are attached and made part of this contract. The Contractor shall follow the attached instructions and submission procedures specified below to meet the requirements of a "proper invoice" pursuant to FAR Subpart 32.9, Prompt Payment.

1. Payment requests shall be submitted to the offices identified below. Do not submit supporting documentation (e.g., receipts, time sheets, vendor invoices, etc.) with your payment request unless specified elsewhere in the contract or requested by the Contracting Officer.

a. The original invoice shall be submitted to the following designated billing office:

National Institutes of Health Office of Financial Management Commercial Accounts 2115 East Jefferson Street, Room 4B-432, MSC 8500 Bethesda, MD 20892-8500

b. One copy of the invoice shall be submitted to the following approving official:

Contracting Officer Office of Acquisitions National Cancer Institute Executive Plaza South Room 6002 6120 Executive Blvd. MSC 7195 Bethesda, Maryland 20892- 7195

E-Mail:

The Contractor shall submit an electronic copy of the payment request to the approving official instead of a paper copy. The payment request shall be transmitted as an attachment via e-mail to the address listed above in one of the following formats: MSWord, MS Excel, or Adobe Portable Document Format (PDF). Only one payment request shall be submitted per e-mail and the subject line of the e-mail shall include the Contractor's name, contract number, and unique invoice number.

[Note: The original payment request must still be submitted in hard copy and mailed to the designated billing office to meet the requirements of a "proper invoice."]

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2. In addition to the requirements specified in FAR 32.905 for a proper invoice, the Contractor shall include the following information on the face page of all payment requests:

a. Name of the Office of Acquisitions. The Office of Acquisitions for this contract is…