SOW_NCCIH OCD Skin Biopsies 2024_draft.pdf

STATEMENT OF WORK (SOW)

1.0 TITLE

Skin Biopsy Analysis for the Study of Small Fiber Neuropathies at the National Institutes of Health.

2.0 BACKGROUND

The Department of Health and Human Services (HHS), National Institutes of Health (NIH), National Center for Complementary and Integrative Health (NCCIH), Division of Intramural Research (DIR), Office of The Clinical Director (OCD) requires skin biopsy analysis for the study of Small Fiber Neuropathies.

NCCIH is currently conducting research into the causes, treatment, and prevention of many medical disorders, with a focus on pain disorders. The NCCIH mission is to seek fundamental knowledge about complex disorders, such as pain applying approach of whole person health.

Investigators in the NCCIH intramural program conduct research in the basic, translational, and clinical neurosciences.

Small fiber neurons play an important role in the regulation of homeostasis and the modulation of organ function. Small fibers mediate manifestation of pain symptoms, autonomic function, blood vessel, sweat gland function, and gastrointestinal peristalsis. Alterations in small fiber nerve density have been documented in neuropathic pain disorders as well as in painless neuropathies. To deeply phenotype patients with these neuropathic pain types of symptoms, the role of small fiber function in the development and maintenance of symptoms requires further exploration.

Small nerve fibers cannot be assessed by conventional means of measuring nerve function, such as nerve conduction velocity and amplitude, and quantitative sensory testing provides only functional status information while biochemical underpinning of those functional findings still require more complete evaluation. Currently, the best scientific approach to studying small fiber neurons is collecting samples through skin punch biopsies and measurement of intraepidermal fiber density (IENFD), but this provides only initial information and is incomplete by itself.

Typical small fiber neuropathies typically follow a length-dependent pattern. However, alterations in small nerve fibers may not always follow such a pattern. For this reason, a two-site punch biopsy is required, with one sample collected from the distal lateral leg and one sample collected from the proximal lateral leg.

As the deep phenotyping protocols are hypothesis-generating studies, the skin biopsy samples shall be used to explore other potential findings beyond standard IENFD measurements. The skin biopsy analysis shall be used in biomarker development.

2.1 OBJECTIVE

The primary objective of this procurement is to obtain skin biopsy analysis containing information about histochemical status of the peripheral nerve terminals, including proteins and peptides that are involved in nociception and neuropathic pain, which would be used to complement functional status of those nerve terminals as a part of deep phenotyping of patients with neuropathic pain. The skin biopsies should be processed in a way that allows for additional future staining and analysis.

3.0 SCOPE

This purchase order includes the procurement of the initial analysis of up to 28 skin samples of which will undergo clinical assessment via skin biopsy, microtomy sectioning and slide collection, immunolabeling and qualitative and quantitative microscopic analysis. The Contractor shall provide all personnel, labor, facilities, materials, and equipment necessary to perform the required tasks described in section 4 below. All data shall be coded and shall not contain any personally identifiable information (PII). All fees related to sample transfer/shipping and the required measurements biomarkers shall be included in this purchase order.

4.0 CONTRACT REQUIREMENTS/ AND PERSONNEL QUALIFICATIONS

The Contractor shall perform the following required tasks:

4.1 The Contractor shall receive up to 28 individual skin samples from the Government.

4.1.1 The skin samples shall be collected by the Government via skin punch.

4.1.2 The Contractor shall coordinate with the NCCIH Technical Point of

Contact a shipment method which shall best preserve the tissue samples, at award.

4.2 The Contractor shall acknowledge receipt of samples.

4.3 The Contractor shall provide histological and biochemical measurements on

Government designated regions of interest and conduct microscopic analysis of intraepidermal fibers for each of the two site skin biopsies.

4.4 The Contractor shall provide histological and biochemical measurements of small fiber innervation for each of the two site skin biopsies as determined by the protocol or if clinically indicated.

4.4.1 The Contractor shall provide histological measurements of the following receptors on small nerve fibers: TRPV1, TRPA1, CGRP, for each of the two site skin biopsies if needed by the protocol or if clinically indicated.

4.5 The Contractor shall provide serial 14u cryostat sectioning of biopsies such that successive sections are rotated over 10 slides producing 3 rows of sections with 5-7 sections per row.

4.5.1 The Contractor shall provide an additional set of 10 slides that will have 3 sections. Each section shall be taken at ¼, ½, and ¾ intervals through the biopsy. This shall result in 20 slides of sections.

4.6 The Contractor shall provide the NCCIH TPOC with a summary of results and accompanying covariate dataset.

4.7 The Contractor shall return processed samples to the Government within a year of receipt.

The following tasks are considered optional scope and shall be executed upon request of the Government as follows:

4.8 The Contractor shall archive the remaining unlabeled slides for future biomarker assessments as desired by the Government at additional cost.

4.9 The Contractor shall provide histological and biochemical measurements for Sodium

(Na+) channels for each of the two site skin biopsies if needed by the protocol or if clinically indicated.

4.10 The Contractor shall be capable of assessing the vasculature in the dermis, small fiber nerve innervation of blood vessels, and other potential biomarkers such as TRPV1, CGRP and nociception specific-peptide positive nerve fibers.

4.11 The Contractor shall identify possible other biomarkers not yet specified the government may determine to be worth investigation, so samples should be collected in a format that will allow future staining.

4.12 The contractor shall provide 3 biomarker combinations including PGP. The remaining 2 biomarker combinations shall be determined by the TPOC after award.

5.0 TYPE OF ORDER

This is a firm fixed price purchase order.

6.0 PERIOD OF PERFORMANCE

The period of performance shall consist of one (1) 12-months period from August 26, 2024 – August 25, 2025

The Government may elect to exercise the Optional Quantity CLIN outlined in section 7.0 during the applicable 12-month period of performance. The Optional Quantity CLIN may be exercised in accordance with FAR 52.217-6, entitled “Option for Increased Quantity.”

7.0 PURCHASE ORDER PRICING

The Contractor shall be paid a fixed price for each CLIN (if exercised). In addition to the base requirement, the Government may elect to exercise the optional quantity CLIN outlined below.

If the optional quantity CLIN is exercised, funding will be obligated by modification to the purchase order, by no later than the date specified below.

CLIN# Purchase Order Requirement / Description POP Dates Fixed Price 1 Base Requirement: Skin Biopsy Analysis of up to

28 skin samples 8/26/2024- 8/25/2025

$TBD

2 Optional Quantity Requirement: Additional biomarker immunolabeling and single endpoint assessments The Do Not Exceed ceiling price is $56,000 (Must be exercised in fiscal year (FY) 2024, by no later than 5/30/2024. If exercised, the POP start date will be specified in the modification)

To be determined at time of award

$TBD

8.0 PLACE OF PERFORMANCE

All services shall be performed at the Contractor’s facility.

9.0 REPORT(S)/DELIVERABLES AND DELIVERY SCHEDULE

All written deliverables shall be sent electronically to the NCCIH Technical Point of Contact (TPOC), TBD at award, via Microsoft (MS) Word or PDF format, unless approved by the TPOC.

The TPOC shall review the contents of all draft deliverables. If no comments or requests for revisions are provided to the Contractor within 30 business days, the deliverables shall be considered acceptable. If revisions are required, NCCIH shall respond to the Contractor within five (5) business days of receiving the deliverable, specifying the required changes/revisions.

Final copies of approved drafts shall be delivered to the NCCIH TPOC within five (5) business days after receipt of the Government’s comments.

The Technical Point of Contact (TPOC) is:

TBD as Award

All deliverables shall be sent per the following deliverable schedule:

DELIVERABLE DELIVERABLE DESCRIPTION / FORMAT

REQUIREMENTS DUE DATE

#1 (Task 4.1) Coordinate via email or phone call the appropriate shipping method with NCCIH TPOC

Within X business days of award

#2 (Task 4.2) Acknowledge receipt of skin samples via email to the NCCIH TPOC

Within 24 hours of receipt

#3 (Task 4.3) Lab testing analysis Within 3 months of receipt of samples

#4 (Task 4.4) Summary report detailing the testing analysis results Quarterly

#4 (Task 4.5) Ship the processed samples back to NCCIH Ship the processed samples back to

NCCIH

The Government shall have unlimited rights to and ownership of all deliverables provided under this procurement including reports, analyses, recommendations, briefings, work plans, created SOPs and all other deliverables. In addition, it includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.” FAR clause 52.227-14, “Rights in Data-General,” is hereby incorporated by reference and shall be made a part of any resulting contract/order.

10.0 PAYMENT

Payment shall be made monthly in arears. Payment authorization requires submission and approval of invoices to the NCCIH TPOC and NIH OFM, in accordance with the attached payment provisions listed below:

The following clause is applicable to all Purchase Orders, Task or Delivery Orders, and Blanket Purchase Agreement (BPA) Calls: PROMPT PAYMENT (JUL 2013) FAR 52.232-25. Highlights of this clause and NIH implementation requirements follow:

I. Invoice Requirements A. An invoice is the Contractor's bill or written request for payment under the contract for supplies delivered or services performed. A proper invoice is an "Original" which must include the items listed in subdivisions 1 through 12, below, in addition to the requirements of FAR 32.9. If the invoice does not comply with these requirements, the Contractor will be notified of the defect within 7 days after the date the designated billing office received the invoice (3 days for meat, meat food products, or fish, and 5 days for perishable agricultural commodities, dairy products, edible fats, or oils) with a statement of the reasons why it is not a proper invoice. (See exceptions under II., below.) Untimely notification will be considered in the computation of any interest penalty owed the Contractor.

1. Vendor/Contractor: Name, Address, Point of Contact for the invoice (Name, title, telephone number, e-mail and mailing address of point of contact).

2. Remit-to address (Name and complete mailing address to send payment).

3. Remittance name must match exactly with name on original order/contract. If the Remittance name differs from the Legal Business Name, then both names must appear on the invoice.

4. Invoice date.

5. Unique invoice #s for all invoices per vendor regardless of site.

6. NBS document number formats must be included for awards created in the NBS: Contract Number; Purchase Order Number; Task or Delivery Order Number and Source Award Number (e.g., Indefinite Delivery Contract number; General Services Administration number);

or, BPA Call Number and BPA Parent Award Number.

7. Unique Entity Identifier (UEI) which is in the System for Award Management (SAM) and replaces the Dun & Bradstreet Data Universal Numbering System (DUNS) number.

8. Federal Taxpayer Identification Number (TIN). In those rare cases where a contractor does not have a UEI number or TIN, a Vendor Identification Number (VIN) must be referenced on the invoice.

The VIN is the number that appears after the contractor’s name on the face page of the award document.

9. Identify that payment is to be made using a three-way match.

10. Description of supplies/services that match the description on the award, by line billed.

11. Freight or delivery charge must be billed as shown on the award. If it is included in the item price do not bill it separately. If identified in the award as a separate line item, it must be billed separately.

12. Quantity, Unit of Measure, Unit Price, Extended Price of supplies delivered or services performed, as applicable, and that match the line items specified in the award.

NOTE: If your invoice must differ from the line items on the award, please contact the Contracting Officer before submitting the invoice. A modification to the order or contract may be needed before the invoice can be submitted and paid.

Shipping costs will be reimbursed only if authorized by the Contract/Purchase Order. If authorized, shipping costs must be itemized. Where shipping costs exceed $100, the invoice must be supported by a bill of lading or a paid carrier's receipt.

B. The Contractor shall submit invoices to the Department of Treasury’s Invoice Processing Platform (IPP) at https://www.ipp.gov with a copy to the approving official, as directed below.

The Contractor shall submit a copy of the electronic invoice to the following NCCIH TPOC:

Name- TBD at Award Email Address- TBD at Award https://www.ipp.gov/

For inquiries regarding the status of invoices, contact OFM Customer Service via email at ofm_customer_service@incontactemail.com or via phone at 301-496-6088. To send your inquiries via other available communication methods refer to the OFM Customer Service website at https://ofm.od.nih.gov/Pages/Customer-Service.aspx.

Note: The OFM Customer Service is open Eastern Standard Time Monday – Friday from 8:30 a.m. to 5:00 p.m. and is closed between 12:00 p.m. to 1:00 p.m.

II. Invoice Payment

A. Except as indicated in paragraph B., below, the due date for making invoice payments by the designated payment office shall be the later of the following two events:

1. The 30th day after the designated billing office has received a proper invoice.

2. The 30th day after Government acceptance of supplies delivered or services performed.

B. The due date for making invoice payments for meat and meat food products, perishable agricultural commodities, dairy products, and edible fats or oils, shall be in accordance with the Prompt Payment Act, as amended.

III. Interest Penalties

A. An interest penalty shall be paid automatically, if payment is not made by the due date and the conditions listed below are met, if applicable.

1. A proper invoice was received by the designated billing office.

2. A receiving report or other Government documentation authorizing payment was processed and there was no disagreement over quantity, quality, or contractor compliance with a term or condition.

3. In the case of a final invoice for any balance of funds due the contractor for supplies delivered or services performed, the amount was not subject to further settlement actions between the Government and the Contractor.

B. Determination of interest and penalties due will be made in accordance with the provisions of the Prompt Payment Act, as amended, the Contract Disputes Act, and regulations issued by the Office of Management and Budget.

mailto:ofm_customer_service@incontactemail.com https://ofm.od.nih.gov/Pages/Customer-Service.aspx

IV. PROVIDING ACCELERATED PAYMENT TO SMALL BUSINESS

SUBCONTRACTORS, FAR 52.232-40 (November 2021)

(a) Upon receipt of accelerated payments from the Government, the Contractor shall make accelerated payments to its small business subcontractors under this contract, to the maximum extent practicable and prior to when such payment is otherwise required under the applicable contract or subcontract, after receipt of a proper invoice and all other required documentation from the small business subcontractor.

(b) The acceleration of payments under this clause does not provide any new rights under the Prompt Payment Act.

(c) Include the substance of this clause, including this paragraph (c), in all subcontracts with small business concerns, including subcontracts with small business concerns for the acquisition of commercial products or commercial services.

V. HHSAR 352.232-71 Electronic Submission of Payment Requests (February

2, 2022)

(a) Definitions. As used in this clause— Payment request means a bill, voucher, invoice, or request for contract financing payment with associated supporting documentation. The payment request must comply with the requirements identified in FAR 32.905(b), ‘‘Content of Invoices’’ and the applicable Payment clause included in this contract.

(b) Except as provided in paragraph (c) of this clause, the Contractor shall submit payment requests electronically using the Department of Treasury Invoice Processing Platform (IPP) or successor system. Information regarding IPP, including IPP Customer Support contact information, is available at www.ipp.gov or any successor site.

(c) The Contractor may submit payment requests using other than IPP only when the Contracting Officer authorizes alternate procedures in writing in accordance with HHS procedures.

(d) If alternate payment procedures are authorized, the Contractor shall include a copy of the Contracting Officer’s written authorization with each payment request.

http://www.ipp.gov/