J A_FBO_CS.pdf

Justification for Other than Full and Open Competition

1. IDENTIFICATION OF THE AGENCY AND CONTRACTING ACTIVITY.

a. Federal Agency and Contracting Activity.

HHS, National Institutes of Health (NIH)

b. Sponsoring Organization.

National Heart, Lung, and Blood Institute (NHLBI), Division of Blood Diseases and Resources

c. Project Officer Information.

. Project Offcer (PO):

. Mailing address.

. E-mail address.

. Telephone number. 3

2. NATURE AND/OR DESCRIPTION OF THE ACTION BEING APPROVED.

a. Acquisition purpose and objectives.

The objective of this sole source renewal is to perform long-term clinical, radiographic, and laboratory follow-up of children enrolled in the original Pediatric Hydroxyurea Phase ill Clinical Trial (BABY HUG) and the Follow-Up Study i through the first decade of life. In addition, the Follow-Up Study Ii will provide evaluation for hydroxyurea effects on organ function or toxicity during long term use.

The BABY HUG trial was launched in 2000, and has operated successfully and continuously since initiation. It is critical that the BABY HUG study cohort be preserved for the proposed follow-up and any potential future examinations to maximize the value of the clinical investigation to enhance understanding of the impact of hydroxyurea (HU) on the clinical manifestations of Sickle Cell

Disease (SCD). Initiation of a new cohort would substantially delay the acquisition of new and important medical information that would potentially improve the public health. It is also essential that the clinical data collection methods and data analysis methods are comparable to the previous methods used in the BABY HUG Clinical Trial and Follow-Up Study I to support statistically sound longitudinal analyses.

Specifically, this JOFOC is being requested to award new contracts to all of the incumbent contractors for a period of five (5) years to support the performance of the BABY HUG Follow-Up Study II, with an option period of nine (9) months for data analysis.

b. Project background.

In.2000, the National Heart, Lung, and Blood Institute (NHLBI) competitively awarded contracts to conduct a randomized, double-blind, placebo-controlled trial in young children with SCD to test the hypothesis that Hydroxyurea (HU) can prevent the onset of chronic end organ damage in children recruited before two years of age.

Contracts were awarded under full and open competition to ten Clinical Centers to recruit, enroll, and follow patients to monitor clinical responsiveness to study treatments, to assess growth and development, and to monitor for toxicity from study treatments.

Surrogate markers of end organ damage were used to evaluate pulmonary, renal, splenic, and brain function as well as developmental milestones. One Medical Coordinating Center was awarded, under a small business set-aside, to oversee drug distribution, coordinate central laboratory functions, perform data collection and analysis, and conduct clinical sites visits to monitor study performance. The trial enrolled 193 subjects with SCD between the ages of 9 and 17 months from October 2003 to June 2007.

Subjects remained on study drug for a period of two years. HU demonstrated substantial clinical benefit without serious toxicity in this cohort of very young children. In 2008, a follow-up study was noncompetitively added to the contracts to provide structured follow-up of the children after they completed their two years on study drug.

A JOFOC was approved on the basis that the incumbents were the only sources capable of performing the requirement due to their prerequisite knowledge and experience in performing preliminary and current work on the trial, as well as their accrual of a unique patient population. The purpose of the initial Follow-Up Study is to characterize the long-term toxicities and unexpected risks (if any) associated with treatment with HU at an early age. Information obtained from this follow-up study is vitally important to understanding the risks and benefits of early treatment, and ultimately for creation of an optimal paradigm for HU therapy in young children with sickle cell anemia. The follow-up study ends in December 2011 and is followed by a 6-month data analysis period ending on June 30, 2012. The following is a list of the current contractors:

Contractor Contract #

Children's Research Institute N01-HB-07150 Duke University Medical N01-HB-07151Center Howard University N01-HB-07152

Johns Hopkins University N01-HB-07153 Medical University of South N01-HB-07154Carolina St. Jude Children's Hospital N01-HB-07155

State University of New York N01-HB-07156

University of Miami N01-HB-07157

University of Mississippi N01-HB-07158 University of Texas N01-HB-07159Southwestern Clinical Trials & Surveys N01-HB-07160Corporation

3. Description of the supplies or services required to meet the agency's needs (including the estimated value).

a. Project title.

BABY HUG Follow-Up Study Ii (Data Coordinating Center, RFP NHLBI-HB-12-01 and Clinical Sites, RFP NHLBI-HB-12-02)

b. Project description.

The purpose of the BABY HUG Follow-Up Study II is to provide continued structured follow-up of the children enrolled in the BABY HUG Follow-Up i Study, to characterize the long-term toxicities and unexpected risks (if any) associated with HU treatment at an early age, and to determine if there are clinical benefits from the treatments. Collection and ongoing evaluation of growth and development and clinical cjata are crucial for determination of the long-term effects of HU. The objective is to intensively monitor and assess this unique group of children for growth, development, and clinical status at least through the first decade of life to document any alterations in the natural history of sickle cell disease associated with early HU therapy. The follow-up will include enhanced neuropsychological, brain, cardiac, and pulmonary evaluations. All children enrolled will be followed to a common termination date of December 31,2016. Results from the Follow-up Study Ii will improve understanding of the natural history of SCD in young children and in a cohort receiving HU. Whether or not HU reduces organ damage in these children will be established. If HU has a beneficial effect, the standard of care for children with SCD will be permanently altered.

. Requirement type.

~ Research & development (R&D) o R & D support services o Support services (non-R&D) o Supplies/equipment o Information technology (IT) o Construction o Architect-engineer (A & E) services o Design-build o Other (specify):

. Type of action.

o New requirement x Follow-on o Other (speCify):

· Proposed contracUorder type.

o Firm-fixed-price o Other fixed-price (specify, e.g., fixed-price award-fee, fixed-price incentive-fee):

~ Cost-plus-fixed-fee (Data Coordinatinq Center) o Other cost reimbursement (specify, e.g., cost-plus-award-fee, cost-plus-incentive-fee):

o Time and materials o Indefinite delivery (specify whether indefinite quantity, definite quantity, or requirements):

~ Other (specify): The clinical sites will be a combination of fixed price and cost reimbursement x Completion Form 0 Term form

. Acquisition identification number.

RFP NHLBI HB-12-01 (DCC)

RFP NHLBI HB-12-02 (CS)

c. performance/delivery period.

The period of performance is five years with a 9-month option period for data analysis.

Please see attached for a breakdown of costs.

4. Identification of the statutory authority permitting other than full and open competition.

x This acquisition is conducted under the authority of 41 United States Code (U.S.C.) 253(c)(1) as set forth in Federal Acquisition Regulation (FAR) 6.302-1.

o This acquisition is conducted under the authority of section 4202 of the Clinger-Cohen Act of 1996.

o This acquisition is conducted under the authority of the Services Acquisition Reform Act of 2003 (41 U.S.C. 428a).

5. Demonstration that the proposed contractors unique qualifications or the nature of the acquisition requires use of the authority cited.

a. Name and address of the proposed contractors.

Contractor Children's Research Institute

Duke University Medical Center

Howard University

Johns Hopkins University

Medical University of South Carolina

St. Jude Children's Hospital

State University of New York

University of Miami

University of Mississippi

University of Texas Southwestern

Clinical Trials & Surveys Corporation

b. Nature of the acquisition and proposed unique qualifications of the contractor(s).

The current contractors are the only sources capable of performing the requirements due to their prerequisite knowledge and experience in performing preliminary and current work on this trial, as well as their accrual of a unique patient population. Sickle cell disease is a rare, orphan disease primarily encountered.in African Americans. The number of centers skilled in the care of these patients is limited and the number of health care providers skilled in the care of affected infants, toddlers, and very young children is even fewer. There are only approximately 25 centers in the United States that are capable of participating in this type of project and 14 of them are already participating in this trial (10 current contractors plus 4 subcontractors). If a new center were to participate in the Follow-Up Study, it would not be geographically located close enough to the existing centers, therefore, the patients would have to travel unreasonably long distances for their study visits.

Traveling long distances would be too rnuch of a hardship for patients and families and would effectively prevent them from participating in the study.

The current contractors not only have the requisite expertise but also have built a relationship with the patient cohorts of the BABY HUG Trial and Follow-Study I that will be crucial to the success of the Follow-Up Study 11. Due to the fact that the patients for the original intervention trial were infants and toddlers, recruitment was very difficult for the existing contractors. Parents and guardians were very hesitant to have their very young children participate in this type of a drug treatment trial and their relationship with the centers was critical in reassuring the caretakers that their children were receiving the most cautious and thoughtful care. Recruitment for the Follow-Up Study Ii will heavily depend on the relationship that has been built with the existing patients and families. The existing centers have also established highly knowledgeable patient/family advocates at each site who have played a critical role in ensuring full disclosure to participants and explaining the risks/benefits of participation in the study. In addition, information from study participants has been gathered in confidential records that protect the identities of the subjects. Transfer of this information from the current contractors would raise critical issues about disclosure of patient identifying information that is not ethically acceptable. Therefore, continuation of the current study centers into the follow-up study is imperative. Information obtained from this follow-up study is vitally important to understanding the risks and benefits of early and continued treatment, and ultimately for creation of an optimal paradigm for hydroxyurea therapy in young children with sickle cell disease.

The current Data Coordinating Center (DCC) is the only source capable of performing the requirements for Follow-Up Study II due to their prerequisite knowledge and experience in performing initial and current work on the two prior studies. The DCC developed or participated in the development of all study documents including protocols, manuals of operation, safety reports to FDA, and periodic clinical study reports for regulatory filing and for review by the Data and Safety Monitoring Board. The DCC has acquired skills and experience that cannot be replaced for the conduct of a study in very young children of minority racial-ethnic background participating in a sickle cell disease research study. In addition, the DCC has created a dependable and secure record system that ensures the confidentiality of all subjects and their associated test results and biospecimens. Transfer of this.information to a new DCC would create serious logistic problems and place subject confidentiality at great risk. Creation of a secure data transfer system would require many months and add substantial additional costs to the project. Furthermore, the current DCC is uniquely qualified to ensure the comparability of the newly obtained to the previously collected data. Comparability of the data is crucial to the success of the study. If the data collected by a new organization are not comparable, it could dramatically reduce the value of all previously collected data, which would be very detrimental to the study.

6. Description of the efforts made to ensure that offers are solicited from as many potential sources as practicable. Indicate whether a FedBizOpps notice was or will be publicized as required by FAR Subpart 5.2 and, if not, which exception under FAR 5.202 applies.

Multiple discussions took place between the Project and Contracts Offices' staff and internal and external NHLBI scientific experts to determine if it was in the government's best interest to negotiate on a non-competitive basis with the incumbent contracts, for both the DCC and the CS. As mentioned in item 8, an R&D sources sought notice was issued for the CS, whereas, both an R&D and Small Business sources sought notices were issued for the DCC. It was determined based upon discussions and the responses to the FBO sources sought synopses that the incumbent contractors were uniquely qualified for the work scope requirements both in the scientific and management aspects of the study. Therefore, the pre-solicitation notices notifying the public of our intent to negotiate on a non-competitive, sole source basis were issued in FBO on September 24, 2010. Only one email dated September 25, 2010, was received from a company in India, in response to the pre-solicitation notices for both the DCC and CS. The company did not submit a capability statement for either notice, rather inquired about obtaining additional information that is not available (i.e., budgetary information, bill of materials, etc.) before they "purchased" the document. An email dated September 27,2010 was sent in response, indicating that the requested information was not available and that the notices were to announce NHLBI's intent to negotiate on a sole-source basis with the incumbent contractors, but that if they felt capable of performing the requirement, they should submit a capability st"tement by the due date of October 8,2010. No capability statements were received.

7. Determination by the Contracting Officer that the anticipated cosUprice to the Government will be fair and reasonable.

An independent government cost estimate (IGCE) has been developed based on the cost history of the original BABY HUG clinical trial and current Follow-Up study with the contractors over the past 10 years. As such, the IGCE and historical costs will be used as a reference point to conduct a cost analysis to establish the fairness and reasonableness of costs. In addition, a cost realism analysis will be performed to determine if the proposed costs are realistic and consistent with the scope of work. The contractors will be required to certify their cost and pricing data. Based on the above, the Contracting Offcer will be able to negotiate fair and reasonable costs and therefore, an audit will not be performed.

8. Description of the market research conducted (see FAR Part 10) and the results, or a stàtement of the reasons market research was not conducted.

A small business sources sought (SBSS) was issued in the FedBizOpps on September 3, 2010 to assess the availability of small business to perform as the DCC. At the same time, a research and development sources sought (RDSS) was also issued to assess the availability of all qualified sources to perform as the DCC. Within the RDSS, it was noted that a SBSS was being issued simultaneously and if 2 or more small businesses were found to be capable of performing the requirement, it would be set-aside. Furthermore, a RDSS was issued on September 3,2010, to assess the availability of all qualified sourced to perform as Clinical Sites. Upon the September 17, 2010 expiration date of these notices, one capability statement was received for the CS and two capability statements were received for the DCC under the SBSS notice. The capability statements that were received in response to the DCC SBSS were submitted by and

. The capability statement received in response to the CS RDSS was submitted by

. Reviews of these statements were conducted by a team of 3 experts (including the PO, NHLBI), and it was determined that they did not have the capability of performing these requirements.

9. Any other facts supporting the use of other than full and open competition.

Due to the inherent duplication of cost and unacceptable delays in performance, noncompetitive awards are in the best interest of the Government. It would take a new center at least 12 months to initiate and implement the study. These tasks would include, but not be limited to, transferring and reviewing all of the data gathered to date, training of clinical site staff, recruiting patients, and obtaining IRB approval of the Follow-Up Study II protocol. Since the current clinical sites already have IRB approval for the interventional trial and Follow-Up Study I, the approval of the Follow- Up Study II will require less than half the time it would take for a new center to get IRB approval. This delay for newly selected sites would severely impact the chances of recruiting the majority of patients who are enrolled in Follow-Up Study i. There are 161 participants enrolled in Follow-Up Study i that are being actively followed by the current clinical sites. If subjects cannot be recruited in a timely manner, there is a greater risk that they will be lost to follow-up. Low recruitment numbers of existing subjects will severely limit the scientific integrity and utility of the study. Therefore, it is essential that the current contractors perform the study to ensure a seamless and timely transition from Follow-Up Study I to Follow-Up Study Ii.

In addition, it would cost approximately for initiation of each new center and for initiation of a new coordinating center. Since the funding for this project is limited, these additional costs would make the study not viable. These costs are based on the additional time and effort it would take for a new organization to get up to speed to implement the study.

10. Listing of sources, if any, that expressed, in writing, an interest in the acquisition.

a woman-owned small business, submitted a capability statement in response to the Clinical Site R&D sources sought notice.

Two businesses expressed interest in writing by submitting capability statements in response to the DCC Small Business sources sought notice, and are as follows:

· a small business . a privately-owned small business

All capability statements were reviewed by a team of 3 experts (including the PO, NHLBI). The three businesses were assessed and based on the findings from the reviewers, it was determined that they did not have the capability of performing the statement of work related to this requirement.

Reviews of these capability statements were provided to the Contracts Office in writing (see attached).

11. Statement of the actions, if any, the agency may take to remove or overcome any barriers to competition before any subsequent acquisition for the required supplies or services.

At this time, the NIH knows of no action that it can take to encourage competition because of the uniqueness of these resources. At the end of the requested renewal, the Government will reevaluate the need for this study and survey the market to determine if other sources are capable of performing this requirement.

12. Program office certification.

This is to certify that the portions of this justification that have been developed by the undersigned program office personnel, including supporting information and/or data verifying the Government's minimum needs, schedule requirements and other rationale for other than full and open competition, are accurate and complete.

Official Name & Title Signature Date

PO

PO's Immediat Supervisor

Head of the Sponsoring

Program Office

13. Contracting Officer Certification.

This is to certify that the justification for the proposed acquisition has been reviewed and that to the best of my knowledge and belief the information and/or data provided to support the rationale and recommendation for approval is accurate and complete.

Official Name & Title Signature Date

Contracting lOfficer

14. Chief of the Contracting Office and Head of the Contracting Activity signatures.

Official Name & Title Signature Date

Chief of the Contracting

Office

Head of the Contracting

Activity

15. Competition Advocate signature.

Official Name & Title Signature Date

Competition Advocate

16. HHS Senior Procurement Executive signature.

Official Name & Title Signature Date

HHS Senior Procurement

Executive

Statement of Work – CS Page 1

STATEMENT OF WORK

BABY HUG – Follow-Up Study II: Clinical Sites (CS)

Background Information

In 2000, t he National Heart, Lung, and Blood I nstitute (NHLBI) awarded contracts to conduct a randomized, double-blind, placebo-controlled trial in young children with sickle cell disease (SCD) to test the hy pothesis that Hy droxyurea (HU) can prevent th e onset of chronic end organ damage in children recruited before two y ears of age. Con tracts were awarded to ten Clinical Centers to recruit, enroll, and follow patients to monitor clinical responsiveness to study treatments, to assess growth and development, and to monitor for toxicity from study treatments. Surrogate markers of end o rgan damage were used to evaluate pulmonary, renal, splenic, and brain function as well as developmental milestones. One Medical Coordinating Center was awarded to oversee drug distribution, coordinate central laboratory functions, perform data collection and analy sis, and conduct clinical sites visits to monitor study performance. The trial enrolled 193 subjects with SCD between the ages of 9 and 17 m onths from October 2003 to June 2007. Subjects remained on study drug for a perio d of two years. HU dem onstrated substantial clinical benefit without serious toxicit y in this cohort of very young children. In 200 8, a follow-up stud y was added to the contracts to provide structured follow-up of the children after they completed their two years on study drug. The purpose of the initial Follow-Up St udy is to characterize th e long-term toxicities and unexpected risks (if any ) associated with treatment with HU at an early age. Information obtained fr om this follow-up study is vit ally important to understa nding the risks and benefits of early treatment, and ultimately for creation of an optim al paradigm for HU therapy in young children with sickle cell anemia.

The follow-up study ends in December 2011.

Objectives

The purpose of the Baby Hug Follow- Up Stud y II is to provi de continued st ructured foll ow-up of the children enrolled in the Baby Hug F ollow-Up Study I, to characterize th e long-term toxicities and unexpected risks (if any ) associated with HU treatment at an early age, and to determ ine if there ar e clinical benefits from the treatments. Collection and ongoing evaluation of growth and development and clinical data are crucial fo r determination of the l ong-term effects of HU. The objective is to intensively monitor and assess this unique group of children for gr owth, development, and clinical s tatus at le ast through the first decade of life to document any alterations in the natural history of sickle cell diseas e associated with early HU therapy . The follow-up will include enhanced neurops ychological, brain, cardiac, and pulmonary evaluations. All children enr olled will be followed to a common termination date of December 31, 2016. Results fro m the Follow-up Study II will im prove understanding of the natural history of SCD in y oung children and in a cohor t receiving HU. Whether or not HU reduces organ damage in these children will be established. If HU has a beneficial effect, the st andard of care for children with SCD will be permanently altered.

Detailed Description of Requirements

Independently, and not as an agent of the Governme nt, the Contractor shall furnish all the necess ary services, qualified personnel, material , equipm ent, and facilities, not othe rwise provided by the Government as needed to perform the Statement of Work below. Specifically , the Contractor shall serve as a clinical site for the Follow-Up Study II to the Pediatric Hy droxyurea Phase III Clinical Trial (Baby Hug).

A Data Coordinating Center, to be awarded under a separate co ntract, will support the cl inical sites through active participation in the development of study documents, organization of periodic face-to-face

Statement of Work – CS Page 2 and telephone meetings, performance of quality site visits, filing of regulatory documents, collection and analysis of data, and support of manuscript development and writing.

The study schedule is estimated to be as follows:

Phase I - Planning (January 10, 2012 – April 30, 2012): Study protocol will be finalized, forms will be designed, the manual of operations will be prepared, and IRB approval of the protocol will be obtained by the clinical sites and the data coordinating center (DCC).

Phase II - Active Follow-Up (May 1, 2012 - December 31, 2016): The observational study will occur.

OPTION: Phase III – Data Analy sis (January 1, 2017 – September 30, 2017) – Phase III will be an option period that may be exercised at the discretion of the Government. The Clinical Site shall ensure resolution of all data queries and participate in final site visits from the DCC.

The Contractor shall perform the following specific tasks:

1. Participate in the finalization of t he pr otocol as a mem ber of the Steering Co mmittee. Th e protocol for Baby Hug Follow-Up Study II, “P ediatric Hy droxyurea Phase III Clinical Trial (Baby Hu g) --Follow-Up Observational Stud y II” is hereby incorporated in the contract. It is mutually agreed that future revisions of this protocol are considered to be incorporated by reference into the contract without fu rther cont ract modification. The final protocol and all revisions must be approved by the NHLBI. The final protocol and all revisions must be approved by the NHLBI prior to enrollment of patients into the follow-up study.

2. Follow the procedures specified in the Manual of Operations that will be devel oped by the DCC.

The manual of operations, upon its completion, is made part of the contract by reference.

3. Obtain Institutional Review Board (IRB) approval of the study protocol and informed consent forms.

4. Enroll patients into the Follow-Up Study who have co mpleted the “Phase II I Clinical Trial -

Follow-Up Observational Stud y I”, whose parents or legal g uardians con sent to have their children participate in this study . Obtain info rmed consent and assent as appropriate for patient enrollment.

5. Ensure execution and secure storage of all study regulatory and clinical documents. File periodic study reports to evaluate data quality.

6. Participate in yearly Clinical Site visits by the DCC and/or NHLBI.

7. Forward biological specimens collected to the Blood and Chemistry Laboratory and Cytogenetics

Laboratory as described in the protocol.

[Note to Offerors: For cost proposal purposes, assume no shipment costs at this time.]

8. As a Steering Committee with the support of the DCC, apply to BioLINCC

(https://biolincc.nhlbi.nih.gov/home/) fo r storage of biospecim ens and if approved, for ward specimens to the biorepository at BioLINCC.

Statement of Work – CS Page 3

[Note to Off erors: For cost proposal purposes, assume one shipment a year over the 5-year period of performance.]

9. Participate in the development of a data analysis plan by the DCC within one year of the contract award. Submit data as requested from the DCC.

10. Perform tests as indicated by the study protocol.

11. Enter and edit case report forms as requested by the Data Coordinating Center as indicated by the protocol and /or Manual of Operations.

12. Follow and monitor patients as outlined per procedures in the protocol.

13. Provide administrative oversight of the Clinical Site and transmit complete and accurate patient clinical data to the Data Coordinating Center in accordance with the procedures set forth in the protocol and Manual of Operations. Provide timely study data to the DCC prior to the Dat a Analysis Period.

14. Oversee exit of the subjects from the study.

15. Attend and participate i n Steering Co mmittee (SC) meetings and Publi cations Co mmittee meetings. The clinical site shall participate in other duly constituted comm ittees as need ed to ensure study operations and timely communication of study results. Participation in the m eetings of other committees shall be based on interest and/ or appointment by the SC or lead investigator when such committees are constituted.

[Note to Offerors: For cost proposal purposes, assume travel costs for two (2) staff members at a

1-day in-person meeting to be held on ce per ye ar in Bethesda, Maryland an d participati on i n monthly Steering Committee and Publications Committee teleconferences.]

16. At the request of the DCC, attend scientific meetings to present interi m results o f the Baby Hug study.

[Note to Offerors: For cost proposal purposes, assume no travel at this time].

17. Participate in the analysis of data and the writing of manuscripts and reports for publication.

OPTION for Phase III – Data Analysis Period

If this option is exercis ed by the Government, the Contrac tor shall perform the f ollowing the following tasks:

1. Participate in the analysis of data and the writing of manuscripts and reports for publication.

2. As requested by the DCC, attend scientific meetings to present final results of the Baby HUG study.

3. Attend and participate i n Steering Co mmittee (SC) meetings and Publi cations Co mmittee meetings. T he clinical si te shall parti cipate in other duly constituted commi ttees as ne eded to ensure study operations and timely communication of study results. Participation in the m eetings of other committees based shall be based on inte rest and/or appointm ent by the SC or lead investigator when such committees are constituted.

Statement of Work – CS Page 4

[Note to Offerors: For cost proposal purposes, assume travel costs for two (2) staff members at a 1-day in-person meeting to be held for one day in Bethesda, M aryland and participati on in monthly Steering Committee and Publications Committee teleconferences.]

4. Ensure execu tion and secure storage of all study regulatory and clinical documents. Co mplete periodic study reports to evaluate data quality.

5. Participate in a final Clinical Site visit by the DCC and/or NHLBI.

6. Provide administrative oversight of the Clinical Site and transmit complete and accurate patient clinical data to the Data Coordinating Center in accordance with the procedures set forth in the protocol and Manual of Operations.