Amendment__1_final.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

05/29/2013

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 6100 EXECUTIVE BLVD., Suite 7A07, MSC 7510

BETHESDA MD 20892-7510

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-DESPR-2013-12

X

9B. DATED (SEE ITEM 11)

May 15, 2013

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 off ice.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF sect ion headings, including solicitat ion/contract subject mat ter w here feasible.)

PURPOSE: To answ er tw o quest ions and replace Task Order 2 in its ent irety on RFP NIH-NICHD-DESPR-2013-12 – Biomedical Analysis of Human Biospecimens for the Division of Epidemiology, Statistics, and Prevention Research

DUE DATE: June 18, 2013 4:00 PM Local Time (Unchanged)

Except as provided herein, all terms and condit ions 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

Megan Gnall, Contracting Off icer NICHD Contracts Management Branch, NIH

15B. CONTRACTOR/OFFEROR

BY ______________________________________________

(Signature of person authorized to sign)

15C. DATE

SIGNED

16B. UNITED STATES OF AMERICA

/S/

BY ________________________________________

(Signature of Contract ing Off icer)

16C.DATE

SIGNED

05/29/2013

RFP-NIH-NICHD-DESPR-2013-12 – Amendment #1

Biomedical Analysis of Human Biospecimens for the Division of Epidemiology, Statistics, and Prevention Research

Question 1: There are two tables in the technical requirements that specify the types of assays for measurement. The first table is on page 2 (Markers to be measured) and the other is on 4-5 (Specific tests required).

The information contained in these two tables differ. The table on page 2 includes CRP, Ascorbic acid, CTRPs 1, 3, 5, 6, 7, 9 and 15, triglycerides, LDL, HDL, VLDL, total cholesterol, glucose, creatinine, urea nitrogen, ACR, AST, ALT, albumin, gamma-glutamyltransferase, alkaline phosphatase, bilirubin, bile acids, ferritin, Vitamin B6, Uric Acid, and F2 Isoprostanes. These assays are not found in the table on page 4-5 (specific tests required). We would like some direction on whether we should restrict our bid to those listed in the Table found on page 4-5, or to include the additional assays listed in the table on page 2 and specified above in bold.

Answer 1: The RFP is amended to change Task Order 2 – Statement of Work – Additional Metabolomic Profiles for Exposome by adding the above listed assays in the table. See revised Task Order 2 below.

Question 2: Specified in the technical requirements is that measurements are on serum samples. However, in the table defining the markers to be measured, Urine albumin-to-creatinine ratio (ACR) is also requested. Does this task order also include urine samples?

Answer 2: Yes, see revised Task Order 2 Statement of Work below.

As shown in the RFP, Task Order 2 Statement of Work – Additional Metabolomic Profiles for Exposome is replaced in its entirety. Section J., Attachment 3, Task Order 2, Additional Metabolomic Profiles for Exposome, is replaced in its entirety with the attached Task Order 2 – Statement of Work.

Attachment 3

Biomedical Analysis of Human Specimens for the Division of Epidemiology, Statistics, and Prevention Research (DESPR)

Task Order 2 – Statement of Work

Additional Metabolomic Profiles for Exposome

BACKGROUND

Pregnancy represents the initial state of human development, and is a sensitive window characterized by considerable epigenetic reprogramming of the conceptus in response to environmental stimuli. To this end, pregnancy and its inherent intrauterine environment represents an ideal window for exploration of the exposome. Definition of the exposome offers promise for designing research capable of identifying environmental factors relevant for health and disease across the lifespan. This premise builds upon growing evidence that health and disease originates at conception or in utero with overarching implications for fecundity and later onset adult diseases (Skakkebaek et al. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects.

Human Reproduction 2001; 16:972-978. Buck Louis et al. The ovarian dysgenesis syndrome. Journal of Developmental Origins of Health and Disease 2011; 2(1) 25-35). To this end, the exposome paradigm including this proposed proof-of-concept offers promise for identifying signals about the impact of environmental exposures on the epigenome, which in turn affects gene expression in various cell types.

As such, this research is an important first step in trying to understand how the epigenome and exposome affects phenotype inclusive of disease susceptibility.

Pregnancy cohorts provide an excellent platform for characterizing the pregnancy exposome, for exploration of pregnancy physiology and length of gestation, and for the eventual understanding of the etiology of pregnancy complications and adverse birth outcomes. This design encompasses an untargeted or unbiased methodology aimed at the characterization of environmental exposures, proteins, metabolism and, possibly, reactive electrophiles or adductomics (Rubino et al. Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds. Mass Spectrometry Reviews 2009; 28(5):725- 784).

The Exposome Project is a proof-of-concept study that has two overarching research aims: 1) to characterize and quantify the “normal” pregnancy exposome using an existing pregnancy cohort study, and 2) to determine its utility and feasibility for design and implementation on a larger scale. This is an on-going endeavor. The original Exposome study was conducted on samples collected from 50 control subjects from the calcium in peritonology and preeclamsia (CPEP) trial. This study will expand the number of samples, allowing for a better understanding of how changes in utero exposure correlate with changes in metabolomic profiles.

TECHNICAL REQUIREMENTS

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, as needed to successful perform the following work as specified in the statement of work (SOW) provided below.

This task requires the ability to measure a wide variety of biomedical markers from banked serum or urine samples from 10 women. This measurement will use biospecimens collected at three time points:

at < 13 weeks; at 26-27 weeks; and at 36-37 weeks of gestation. Thus, there will be a total of 30 samples. Markers to be measured are defined in the table below:

Category of Exposure Assays to be Measured Targeted Inflammation

CRP, tumor necrosis factor-α (TNF-α), MCP-1, E-selectin, ICAM-1, VCAM-1, PAI-1, fibrinogen, VEGF, interleukin 6 and 10

Antioxidants Ascorbic acids, tocopherols, carotenoids Sex hormones

Anti-mullerian hormone, inhibin-b, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, testosterone, DHEAS, intact hCG

Adipogenesis, lipolysis, and lipogenesis

Adiponectin, high molecular weight adiponectin; leptin; soluble leptin receptor; CTRPs 1, 3, 5, 6, 7 ,9, and 15; RBP-4; vaspin;

omentin-1; FABP4; triglyceride; HDL; LDL; VLDL; total cholesterol;

free fatty acids; Apo B; lipoprotein (a); ox-LDL

Angiogenesis Soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), soluble endoglin

Glucose hemeostasis C-peptide, insulin, glucose Renal function

Creatinine, urea nitrogen, cystatin-C Urine albumin-to-creatinine ratio (ACR)

Liver function Asparate aminotransferase (AST), alanine aminotranferase (ALT), Albumin, gamma-glutamyltransferase, alkaline phosphatase bilirubin, bile acids

Thyroid function Thyroid stimulating hormone, triiodothyronine free (FT3), thyroxine free (FT4), thyroid peroxidase antibodies (TPO-Ab), thyroglobulin, TSH R Abs, TG-Ab, Total T3, Total T4

Others 25-(OH) vitamin D2 and D3, ferritin, transferrin receptor, hepcidin, ANA, AT1-AA; insulin-like growth factor 1, insulin-like growth factor and binding proteins, vitB6, vitB12, homocysteine, uric acid, F2 isoprostanes, acylcarnitines, amino acids, nephrin, podocalyxin, cystatin C

Non-targeted Metabolomics Proteomics

1) Samples will be sent to the laboratory in batches of agreed upon size, with batches sent at agreed upon intervals. Please see Deliverables Schedule.

2) Upload all assay results, quality control data, and other data deliverables into the web-based data management system maintained by the NICHD data center contract, as directed by the Contracting Officer’s Representative (COR) within a week of obtaining the data. Maintain the specimen identification numbering system provided on the sample labels, and report results linked to the identification number.

3) Return all residual specimens to the NICHD Repository in Rockville, Maryland or elsewhere at the direction of the COR. Residual specimens must be identifiable by the study identification numbers shipped to the laboratory. All applicable Federal regulations for shipping biological specimens will be followed.

4) Before conducting any assays, the COR shall review and approve the proposed assay method, the laboratory’s standard operating procedures (SOPs) and the procedures for Quality Assurance and Quality Control including adherence to Westgard Rules Violations.

5) For each assay batch, provide the NICHD with quality assurance and quality control data including the values for the standard curve, blanks, and duplicate or triplicate values as performed; provide all instrument-observed values including negative values, values below the limit of detection and/or quantification, values above the standard curve (that is, above the limit of quantification that might require dilution and re-assay), values that require repetition of the assay, values from entire batches that need to be repeated, etc; provide files with data on the limit of detection and limit of quantification for that batch. Note that some software programs, such as Excel, round numbers less than 0.0001 to a value of 0 and care should be taken to prevent such rounding. NICHD shall receive the actual instrument values.

6) Prior to conclusion of this Task, DESPR personnel will conduct an on-site visit with the primary investigator/research scientist at the assay laboratory to ensure quality standard and SOP are as stated.

7) The final decision of all assay methods will be made by the COR.

8) For all assays requested under this Task Order, the Offeror must provide to the government for review copies of their SOPs, Quality Assurance, and Quality Control documents, including Westgard Rules, when applicable.

9) The primary investigator/laboratory scientist must meet requirements for authorship and participate in the preparation of scientific publications for peer reviewed journals.

The period of performance for this Task Order is one year.

Specific tests required are detailed in the table below. Each test will be performed on 30 samples.

Labor % Effort Fixed Price Loaded Rates Total Price

Principal Investigator 8% Administrative Assistant 20%

Analytes Number of Samples

Cost per Sample Total Cost

Untargeted Metabolomics 30 Untargeted Proteomics 30

AMH 30

Inh B 30 Thyroglobulin 30 Intact hCG 30 Leptin 30

FABP4 30

Phospholipid Fatty Acids 30 Total Free Fatty Acids 30 Homocysteine 30 Amino Acids 30 Testosterone 30 Carotenoids/Tocopherols 30 25-(OH) Vitamin D2 and D3 30 Acylcarnitines 30 TNF-alpha 30

MCP-1 30

E-selectin 30

ICAM-1 30

VCAM-1 30

Fibrinogen (Clauss) 30

IL-10 30

IL-6 30

Estradiol 30 Progesterone 30

LH 30

FSH 30

SHBG 30

Adiponectin, total 30 Adiponectin, high molecular weight 30 soluble leptin receptor 30

RBP-4 30

ox-LDL 30 C-peptide 30 Insulin 30

Cystatin-C 30 Thyroid Stimulation Hormone

((TSH) 30

Triiodothyronine free (FT3) 30 Thyroxine free (FT4) 30 TPO-Ab 30 Transferrin receptor 30 Anti-Nuclear Antibody (ANA) 30

AT1-AA 30

Vitamin B12 30

VEGF 30

Plasminogen Activator Inhibitor (PAI-1) 30

Vaspin 30 Omentin-1 30 sFlt-1 30 PlGF 30 soluble Endoglin 30 Insulin-like growth factor

(IGF-1) 30

IGF binding protein 2 30 IGF binding protein 3 30 Nephrin 30 Podocalyxin 30 TSH receptor antibodies 30 Thyroglobulin Antibodies (TG-Ab) 30

Hepcidin 30

DHEAS 30

ApoB 30 Lipoprotein(a) 30 Total T3 30 Total T4 30

CRP 30

Ascorbic acid 30 CTRP (1,3,5,6,7,9,and 15) 30 Triglycerides 30

LDL 30

HDL 30

VLDL 30

Total Cholesterol 30 Glucose 30 Creatinine 30 Urea nitrogen 30 Albumin/Creatinine Ratio 30 Aspartate aminotransferase 30 Alanine aminotransferase 30

Albumin 30 Gamma-glutamyltransferase 30 Alkaline phosphatase 30 Bilirubin 30 Bile acids 30 Ferritin 30 Vitamin B6 30 Uric acid 30 F2 isoprostanes 30

Urine albumin-to-creatinine ratio (ACR)