Amendment_2_RFP-NIH-NICHD-OPPT-2017-2_signed.pdf

OMB No.: 0990-0115

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

1. CONTRACT ID CODE

PAGE

OF PAGES

2. AMENDMENT/MODIFICATION NO.

3. EFFECTIVE DATE

01/20/2017

4. REQUISITION/PURCHASE

REQ. NO.

5. PROJECT NO. (if applicable)

6. ISSUED BY CODE

7. ADMINISTERED BY (If other than Item 5) CODE

National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development Contracts Management Branch 6710B Rockledge Drive

BETHESDA MD 20892

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

TO ALL POTENTIAL OFFERORS

9A. AMENDMENT OF SOLICITATION NO.

RFP NIH-NICHD-OPPT-2017-2

X

9B. DATED (SEE ITEM 11)

12/29/2016

10A. MODIFICATION OF

CONTRACT/ORDER NO.

CODE

FACILITY CODE

10B. DATED (SEE ITEM 13)

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

The above numbered solicitation is amended as set forth in item 14. The hour and date specified for receipt of Offers is extended.

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

(a) By completing Items 8 and 15, and returning __1___ copy of the amendment in your business proposal; (b) By acknowledging receipt of this amendment on each copy of the offer submitted; or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted, such change may be made by telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

12. ACCOUNTING AND APPROPRIATION DATA (if required)

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

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

A. THIS CHANGE ORDER IS ISSUED PURSUANT TO FAR 52.243-2. THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT

ORDER NO. IN ITEM 10A.

B.THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b) and Contract ARTICLE B.4.

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

D.OTHER (Specify type of modification and authority)

E. IMPORTANT: Contractor __ is not, X is required to sign this document and return _1_ copy in your business proposal to the issuing office.

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

PURPOSE: To amend RFP NIH-NICHD-OPPT-2017-2, entitled, “Best Pharmaceuticals for Children Act Data Coordinating Center” and to provide clarifications based on inquiries received.

DUE DATE: Until February 13, 2017, 4:00 PM Local Time (Eastern Standard Time (EST) (Unchanged)

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

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

16A. NAME AND TITLE OF CONTRACTING OFFICER

Alice Pagán NICHD Contracts Management Branch, NIH

15B. CONTRACTOR/OFFEROR

BY ______________________________________________

(Signature of person authorized to sign)

15C. DATE SIGNED

16B. UNITED STATES OF AMERICA

BY

(Signature of Contracting Officer)

16C.DATE

SIGNED

pagana Typewritten Text 1/19/17 pagana Typewritten Text pagana Typewritten Text

RFP-NIH-NICHD-OPPT-2017-2

AMENDMENT NO.: 002

CONTINUATION PAGE

A. As a result of this Amendment the RFP is revised as follows:

1. Section J – List of Attachments, Attachment 1 is replaced in its entirety to specify the page limit exclusions for the Technical Proposal as follows:

Technical Proposal – The offeror must submit one (1) electronic PDF file for the Technical Proposal not to exceed 40 pages.*

*The page limitation is inclusive of all attachments, but does not include: bio-sketches/resumes, references, a list of Standard Operating procedures (SOPs), Proposal Cover Sheet, Section Dividers that do not contain information other than title of Section, Title and Back Page, Table of Contents, Technical Proposal Cost Summary, Summary of Related Activities, Planned Enrollment Form, Protection of Human Subject Assurance Identification (OMB Form 0990-0263), Section 508 PATs and the Information Technology Security Plan (IT-SP), RFP Requirements Index, Program Schedule/Milestone Timeline, Tables of Contents for the Initial Transition Plan and Draft User Manual, Program Management Plan (PMP), Running Agenda and Meeting Minutes (RAMM), Data and Safety Monitoring Plan (DSMP), Statistical Analysis Plan (SAP), Site Monitoring Plan (SMP), Clinical Quality Management Plan (CQMP) and Clinical Study Report

(CSR).

2. Section J – List of Attachments, Attachment 24 – Uniform Assumptions, is hereby incorporated to this RFP to assist the offerors in the preparation of the proposal.

B. This Amendment provides answers to questions received regarding this RFP, please note that individual questions may have been combined or reworded. The responses are provided for information only as guidance to potential offerors and do not supersede any terms of the RFP and do not revise or become part of this RFP. The responses to inquiries are as follows:

1. Question: In addition to the attachments exempted from the Technical Proposal 40-page limit in

Amendment 01, please confirm that the following sections and attachments are also exempt from the page limit:

• Bio-sketches/resumes

• References

• List of Standard Operating procedures (SOPs),\

• Proposal Cover Sheet

• Section Dividers that do not contain information other than title of Section

• Title and Back Page

• Table of Contents

• Technical Proposal Cost Summary

• Summary of Related Activities

• Protection of Human Subject Assurance Identification Form (OMB Form 0990-0263)

• Planned Enrollment Form

• Section 508 PATs

• Information Technology Security Plan (IT-SP)

• RFP Requirements Index

• Program Schedule/Milestone Timeline

• Tables of Contents for the Initial Transition Plan and Draft User Manual

• Program Management Plan (PMP)

• Running Agenda and Meeting Minutes (RAMM)

• Data and Safety Monitoring Plan (DSMP)

• Statistical Analysis Plan (SAP)

• Site Monitoring Plan (SMP)

• Clinical Quality Management Plan (CQMP)

• Clinical Study Report (CSR)

Answer: All documents listed above are excluded from the page limitation. Facilities, Equipment, and Resources shall be addressed as part of the technical proposal. See Attachment 1 of the RFP.

2. Question: Section L.1.d., Estimate of Effort (page 49), states offerors should “assume one (1) new study during the period of performance of the contract in addition to the ongoing 25 studies. We ask that the Government provide a list of the one (1) new study and 25 ongoing studies that includes the following information for each study:

• Study Drug

• Type of Study

• Primary Clinical Site

• Number of Sites

• Site Locations

• Total Number of Subjects

• Current Activity

• Status of Regulatory Documents

• Future Plans and Responsibilities for the BPCA-DCC

Answer: See Attachment 24 – Uniform Assumptions.

3. Question: We ask that the Government provide Uniform Budget Assumptions in an Additional

Business Proposal Instructions attachment.

Answer: See Page 49, letter d. Estimate of Effort under Section L – Instructions, Conditions, and Notices to Offerors of the RFP and Attachment 24 – Uniform Assumptions.

4. Question: Attachment 3, page 2 (Statement of Work, Objective and Scope of the Contract) states that approximately twenty percent (20%) of the studies will be conducted at international sites. Please confirm the following:

• All international site locations for ongoing studies

• International site locations for future anticipated studies, if applicable

Answer: See Attachment 24 - Uniform Assumptions for current locations for international sites. The number and locations of the sites are determined by the Pediatric Trials Network at the time of protocol development. At this time there is only one "new" study slated for next year. At this time the number of future sites cannot be determined as it will depend on future studies.

RFP Number: NIH-NICHD-OPPT-2017-2

Packaging and Delivery of Proposal RFP Attachment 1, Revised 1-19-17

PACKAGING AND DELIVERY OF PROPOSAL

A. PROPOSAL SUBMISSION:

Proposals must be submitted by email to the following electronic mail addresses:

nichdoaedelivery@mail.nih.gov, deborah.brock@nih.gov and alice.pagan@nih.gov

1. Use the following subject line:

“RFP-NIH-NICHD-OPPT-2017-2: TO BE OPENED BY AUTHORIZED GOVERNMENT

PERSONNEL ONLY”

2. The body of email must include the following:

a) Offeror’s name and address

b) Offeror’s Point of Contact with name, telephone number and email address

c) Listed Government Points of Contract for the solicitation

i. Primary – Deborah Brock

ii. Secondary – Alice Pagán

3. Attachments

a) There is an expectation of three (3) attachments to the email. A Technical Proposal, a Business Proposal, and the Excel Workbook (Budget).

b) It is required that the filenames for both your Technical Proposal, Business Proposal, and Excel Workbook include the name of the offeror, the solicitation number, and the type of proposal (i.e., Technical, Business).

Examples:

Technical Proposal: XYZ Company_NICHD-OPPT_2017-2_Technical.pdf Business Proposal: XYZ Company_ NICHD-OPPT-2017-2_Business.pdf Excel Workbook: XYZ Company_ NICHD-OPPT-2017-2_Business.xlsx

TECHNICAL PROPOSAL BUSINESS PROPOSAL

The offeror must submit one (1) electronic PDF file for the Technical Proposal not to exceed 40 pages.

The offeror must submit one (1) electronic PDF file Business Proposal.

In addition, the Offerors must include the Excel Spreadsheet with the Breakdowns of the Proposed Estimated Costs

*The page limitation is inclusive of all attachments, but does not include: bio-sketches/resumes, references, a list of Standard Operating procedures (SOPs), Proposal Cover Sheet, Section Dividers that do not contain information other than title of Section, Title and Back Page, Table of Contents, Technical Proposal Cost Summary, Summary of Related Activities, Planned Enrollment Form, Protection of Human Subject Assurance Identification (OMB Form 0990-0263), Section 508 PATs and the Information Technology Security Plan (IT-SP), RFP Requirements Index, Program Schedule/Milestone Timeline, Tables of Contents for the Initial Transition Plan and Draft User Manual, Program Management Plan (PMP), Running Agenda and Meeting Minutes (RAMM), Data and Safety Monitoring Plan (DSMP), Statistical Analysis Plan (SAP), Site Monitoring Plan (SMP), Clinical Quality Management Plan (CQMP) and Clinical Study Report (CSR).

mailto:nichdoaedelivery@mail.nih.gov mailto:deborah.brock@nih.gov mailto:alice.pagan@nih.gov

Packaging and Delivery of Proposal RFP Attachment 1, Revised 1-19-17

B. PROPOSAL FORMATTING

1. The PDF files should be created in a format that enables word searches to the maximum extent practicable.

2. Each of the proposals, Technical and Business, must be separate and complete in itself, so that evaluation of one may be accomplished independently of, and concurrently with, evaluation of the other.

3. Proposals shall not include links to internet web site addresses (URLs) or otherwise direct readers to alternate sources of information.

4. Font size must be 10 to 12 points.

5. Spacing should be no more than 15 characters per inch. Within a vertical inch, there must be no more than six lines of text.

6. Print margins must be at least one-inch on each edge of the paper.

7. Print setup shall be on standard letter size paper (8.5 x 11").

8. Signatures may be electronic, or scanned, but must be merged into the respective file.

Uniform Assumptions

Attachment 24

Uniform Assumptions

I. Clinical Trials Assumptions

STUDY PRIMARY

OUTCOME/ TYPE

OF STUDY

NUMBER

OF

PATIENTS

NUMBER

OF SITES

CURRENT PLANS * (as of December 2016)

CLOSED LEGACY STUDIES

Sodium Nitroprusside

Control of blood pressure

Study 1: 200

Study 2: 43

10 CSR submitted to FDA 11/29/11 and 3/12/13.

Label changed 12/14/13.

De-identified data submitted to DASH 2015.

Meropenem Intra-abdominal infections

N=200 25 CSR submitted to FDA 8/25/11. Label changed 12-24-14. De-identified data submitted to DASH 2015.

Baclofen Spasticity N=61 10 CSR submitted to FDA 12/20/13. No label change expected.

Submission to DASH pending.

Hydroxyurea Safety and efficacy in children with sickle cell

N=200 15 Draft CSR to FDA in May 2014. Final data sets to FDA anticipated in spring 2017. *Note: separate DCC responsible for this study and submission.

Lithium PK, safety and efficacy in pediatric mania

Study 1: 61

Study 2: 81

10 CSRs submitted to FDA 11/13/15 and 12/15/15.

FDA review ongoing.

Label change and De-identified data submissions pending.

Lorazepam Status

PK, safety and efficacy in seizures

Study 1: 69

Study 2: 303

12 CSR submitted to FDA June 2014. Label changed June 2016.

Additional submissions and discussions with FDA underway about label revisions.

Lorazepam Sedation

PK, safety and efficacy in sedation in ICU

N=180 10 Draft CSR submitted to FDA December 2012.

Additional information and revised CSR submission pending and scheduled for Q4 2016.

Metronidazole PK, safety study of use in intra-abdominal infections

N=24 4 Draft CSR submitted to FDA. No current plans for DASH or Docket submissions until completion of SCAMP study (*see below)

PTN-lead Closed Studies

Hydroxyurea Bioequivalence study

N=42 5 CSR submitted to FDA 2/24/14. Awaiting final BabyHUG submission for Docket and DASH submissions.

Ampicillin PK and safety study in neonates

N=75 20 CSR submitted to FDA December 2014. De-identified data submitted to FDA Docket October 2015. Awaiting FDA negotiations with aNDA holders. DASH submission pending.

Acyclovir PK and safety study in neonates

Study 1=32

Study 2=49

20 CSR submitted to FDA 7/2015. Additional submissions 9/2016.

Awaiting FDA feedback.

FDA Docket and DASH submissions pending.

Lisinopril PK and safety study in children with renal transplants

N=26 10 CSR submitted to FDA December 2014. Label change April 2016.

No Docket submission anticipated. DASH submission pending.

Anti-Staph PK and safety of 3 antibiotics in neonates

N=63 30 Plan is for CSR development in 2016

TAPE 1 Pediatric weight estimation device

N=624 12 Study report submitted to FDA, device approved May 2015.

Clindamycin (obesity)

PK study of dose in obesity

N=22 4 CSR submitted to FDA 12/2015. Awaiting FDA feedback.

PTN-Lead Active Studies*

Antibiotic Safety

(*SCAMP)

PK and safety study of three drugs in pre-term neonates

N=182 40 Plan is for CSR development in 2017.

Data from Metronidazole study to be combined with this study data for FDA submission.

Pantoprazole PK study in children

N=41 10 CSR development underway, plan for submission by end 2016

Methadone PK study in neonates

N=26 10 CSR development underway, plan for submission by mid-2017

Sildenafil PK study in neonates

Study 1=32

Study 2=12

10 Study 1 report in development. Plans for study 2 enrollment in early 2017.

Opportunistic PK sampling of drugs of interests (DOI) to develop

N=~1800

Approx. 30

40 Each drug of interest developed into a data report and/or used for

PK models DOIs future studies

Caffeine PK, safety and efficacy study for apnea in neonates

N=400

(data review)

20 Data validation and cleaning underway.

Anticipate CSR submission in Spring 2017.

Timolol PK, safety and efficacy study for hemangioma in children

N=100 10 Enrollment starting Spring/2017.

Furosemide PK and safety study of 2 drugs in neonates

Study 1=679 (data review)

Study 2 Target=120 Current=35

4 Enrollment ongoing for study 2. Plans for submission to FDA in Winter 2017.

Anti-psychotics in Children

Long-term Safety study of 3 drugs used in children

N=800 ~60 Protocol finalization complete. Meeting request to FDA submitted Oct. 2016

Tape 2 Pediatric weight estimation device in infants

N=~2000 20 CSR in development.

Antiepileptic Study

PK of anti-seizure drugs in obese children

N=96 10 Protocol finalization underway. No enrollment to date.

Other Collaborative Studies with Children’s Oncology Group: Daunomycin, Actinomycin-D.

Daunomycin, Methotrexate, 13-Cis Retinoic Acid, Vincristine. Anticipate study reports for each drug planned for submission to the FDA in the future after data review for quality. Anticipated submission dates range from Fall 2017 to Spring 2019.

*For active studies, DCC support includes data management, site monitoring, regulatory support and submissions, safety reporting and monitoring, and statistical leadership.

a. The following assumptions should be made for Proposed Pediatric Study Requests

(PPSRs)—which are outlines of new studies submitted to the FDA:

i. Assume three (3) PPSRs will be submitted annually from the NICHD and/or the PTN to the FDA.

ii. Assume three (3) new clinical trials will be initiated annually (which includes studies done with our without PPSRs).

iii. Assume participation in three (3) new investigatory meetings annually, which includes the submission of three new IND submissions annually.

iv. The DCC will be responsible for the regulatory submissions, statistical support and medical writing for the clinical study submissions to the FDA.

b. The following assumption should be made for pre-clinical studies: the NICHD plans to conduct approximately one (1) preclinical studies each year—pre-clinical studies can include formulation or device related research. The DCC will be responsible for the regulatory submissions, statistical support and medical writing for the pre-clinical study.

c. The following assumption should be made for clinical study sites: the NICHD anticipates that approximately twenty percent (20%) of the studies will be conducted at international sites. Current international sites include Canada, Europe, Japan and Israel.

d. The following assumptions should be made for clinical trials conducted under the BPCA:

i. The NICHD anticipates an additional twenty five (25) NEW clinical trials for the BPCA Consortium will be performed for the life of the contract (this excludes the existing studies). The clinical trials may include primarily Phase 1 and 2, pharmacokinetic (PK), pharmacodynamic (PD), efficacy, and safety studies. The data from these studies will be used to inform the labeling of drugs in children.

i. Assume a minimum of twelve (12) clinical sites per study for smaller PK related studies with a maximum of one hundred (100) clinical sites per study for larger safety and/or efficacy studies.

ii. The BPCA clinical trials are primarily conducted within four (4) age groups:

1. Birth-<90 days

2. 91 days—<2 years

3. 2 years—10 years

4. >11 years

iii. Pharmacokinetic determinations are conducted with at least twelve (12) children per dose group in each of the four age groups.

iv. Each clinical study will have designated study teams that consist of the study PI, PTN project lead, DCC project manager, DCC data manager, DCC statistician.

v. Data acquisitions from outside sources (i.e., other NIH Institutes or Centers) are another mechanism for obtaining study data in the BPCA program. For budgeting purposes, assume labor hours for the development of one additional CSR from data from an outside source once every other year for the life of the contract. The government anticipates this to occur for thirty percent (30%) of the overall BPCA studies.

II. Data Management System Assumptions

a. If a commercial off-the-shelf product is available and meets the necessary specifications, it may be used. Alternatively, tools available from the National

Cancer Institute (NCI) Center for Bioinformatics program (publically available and modifiable) may be consulted. Please refer to the following website for reference: http://ncicb.nci.nih.gov/NCICB/site_map/

III. Regulatory Requirements and Support Assumptions

a. The Contractor shall prepare and provide support for all BPCA-related regulatory activities. This includes the preparation and submission of all regulatory documents and other communications associated with the CSRs, Investigational New Drugs (INDs) and New Drug Applications (NDAs) or Supplemental NDAs (sNDAs), for NICHD COR’s review and submission to FDA on behalf of the NICHD and in support of the IND sponsor (if not NICHD but supported by BPCA).

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPar t=312&showFR=1&subpartNode=21:5.0.1.1.3.2

b. Expectations for the Data Monitoring Committee (DMC):

i. The DMC is selected, approved, and reports to the NICHD. The NICHD holds the charter for the DMC. The role of the DMC is to provide guidance and recommendations to the NICHD that ensure the safety and welfare of the patients enrolled in the various BPCA trials. The DCC is responsible for assisting the NICHD with the management of and logistical support for the DMC which includes hosting DMC meetings, developing all DMC reports, payments to the DMC for their services, and submitting all DMC recommendations to the NICHD and the respective clinical site investigators.

ii. The DCC will be responsible for maintaining all necessary documentation of the DMC activities, actions, deliberations, and recommendations of the committee that will be distributed to clinical sites/investigators.

iii. The Contractor shall provide, implement, and maintain a plan for reporting SAEs and AEs to the DMC in accordance with federal regulations.

IV. Site Monitoring, Protocol Training, and Audits Assumptions

a. The following assumptions should be made for site monitoring and audits under the BPCA:

i. Assume a minimum of four (4) site visits per clinical trial that will consist of the following: a site initiation visit, a visit after the first enrolled patient, an interim visit, and a close out visit. Site visits may occur in-person and/or remotely.

ii. Uniform Assumption for Travel Cost:

Year1: $173,680, Year 2: $171,825, Year 3: $171,825, Year 4: $171,825 Year 5: $172,480, Year 6: $184,925, Year 7: $184,925, Year 8: $185,580, Year 9: $205, Year 10: $204,575.

iii. Site monitoring plans must be developed for each study and the number of visits can be altered from the above structure for cost containment in order to accommodate the type of study and the needs of the safety evaluations for the participants.

http://ncicb.nci.nih.gov/NCICB/site_map/ http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=312&showFR=1&subpartNode=21:5.0.1.1.3.2 http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=312&showFR=1&subpartNode=21:5.0.1.1.3.2

iv. Laboratory audits for GLP will be conducted at the end of each study for labs where PK and other lab values are the primary outcomes.

v. At each study close out visit, the DCC shall provide a mechanism for the review and appropriate storage for all study-related data at the site. Each site should be prepared for potential FDA audits in the future.

vi. If an FDA audit should occur, the DCC shall provide materials and a staff member to assist the clinical site in preparing for an FDA audit.