SOW_for_Creation_and_Curation_Database.pdf

Statement of Work (SOW)

A. GENERAL INFORMATION

1. Title of Project:

Creation and curation of database for efficient data mining and analysis to support NCATS projects

2. Background Information:

The National Center for Advancing Translational Sciences (NCATS) Division of Preclinical Innovation (DPI) is a translational science center that prides itself on its tremendously productive pipeline and is innovative in a number of ways. First, our quantitative high throughput screening (qHTS) paradigm, which tests all compounds at multiple concentrations in the primary screen, is unique.

However, more and more academic and pharmaceutical groups are now adopting it in their own operations due to the enhanced data generation that enable compound bioactivity assessment and probe production efficiency. This efficiency derives not only from savings in post-screen cherry-picking, reconfirmation, dose-response testing, and initial SAR assessment, but also from the ability to perform reliable “virtual counter screens,” thus allowing us to make more informed decisions on which scaffolds to pursue for probe development.

Second, the NCATS is distinctive in its focus on collaboration with outside investigators to produce high-quality chemical probes to define new biology. This focus is reflected in our unprecedented Outreach program, which reaches hundreds of potential new investigators every year, and accounts for much of the new science being done at the NCATS. Third, the NCATS is uniquely focused on new technologies and paradigms to improve the process of probe development, typified by qHTS, our informatics platform, our utilization of structural biology to accelerate probe development, development of new synthetic and analytical chemistry paradigms.

3. Purpose or Objective of the Requirement:

NCATS requires the creation and curation of a database to support some of NCATS projects, such as NPC, Inxight, NPACT, and Pharos.

4. Period of Performance The contractor shall provide services for one (1) year after receipt of award.

B. CONTRACTOR REQUIREMENTS (SCOPE OF WORK)

The contractor shall provide the following services:

1. Therapeutics (Approved Drugs)

a. The contractor shall provide drug ingredients with Code of Federal Regulations (CFR) (including inactive ingredients status).

b. The contractor shall provide pre-1982 drugs/OTC drugs/drugs called out in the CFR, specifically the vendor shall provide

i. Initial data/jurisdiction of marketing

ii. Old Physicians’ Desk Reference (PDRs)

iii. New Drug Applications (NDA) Number

iv. Sponsor and product name

v. DESI (drug efficacy study implementation) status

vi. US Pharmacopeia Status [especially pre-1950s drugs]

c. The contractor shall indicate whether ingredient has been used markets abroad and shall match old, international pharmacopeias to GINAS (The Global Ingredient Archival System)

d. The vendor shall provide raw materials for drug synthesis and curate the NCATS provided abstracted data from Pharmacology Manual Encyclopedia

2. Therapeutics (Approved and Investigational Drugs; Combination Therapeutics)

a. The contractor shall provide the following information for approved and investigational drugs and combination therapeutics:

i. Peak therapeutic plasma concentrations (from pharmacokinetics (PK) studies published)

ii. Halftime (T1/2) data

iii. Tissue distribution --- not systemically available/distributes preferentially into tissues/CNS exposure

iv. Tissue site of action

v. Indication

vi. Max dose in man

vii. Max status

viii. First date of publication

ix. Last date of clinical development

x. Tolerable dose in preclinical animal models (rodent and non-rodent)

xi. Dose-limiting toxicity

xii. Biochemical, cellular (including ex vivo), and in vivo potency in model systems

xiii. Clinical trials prior to 2001 (Clinicaltrials.gov approx. start date)

xiv. Taking Medical Subject Headings (MESH) and generating ---compound, indication, phase, sponsor, paper reference

xv. Is therapeutic present in NCGC pharmaceutical collection?

3. Off-label Use of Worldwide Therapeutics

a. The contractor shall provide the following metrics on off-label use of worldwide therapeutics

i. Indication

ii. Dose regimen

iii. Established standard of care

iv. Clinical trials

v. Case reports

vi. Preclinical studies

4. Clinical Trials

a. The contractor shall map and curate ClinicalTrials.gov trials to Unique

Ingredient Identifier (UNIIs)

b. The contractor shall map and curate World Health Organization (WHO) trials to UNIIs

5. FDA Orphan Product

a. The contractor shall map orphan therapeutics to accurate UNIIs

6. Therapeutic Hypotheses

a. The contractor shall write short narratives for all approved and investigational therapeutics

i. The narratives describe how a therapeutic works in terms of pharmacological action, pathway, and mechanism

ii. Narratives is specific to each indication therapeutic is used for

b. All therapeutics must be linked to public databases including: clinical trials, UNIIs, pathways, genes, proteins, disease models

7. NCATS Pharmacologically Active Chemical Toolbox (NPACT) Annotations

a. The contractor shall curate annotations for all compounds in the NCATS

NPACT chemical library

b. Annotations include biological targets, mechanisms, pathways, diseases, therapeutic categories

c. Compounds include over 10,000 natural products, approved and investigational drugs, tool compounds, lipids, small peptides

d. Annotations include brief narrative on how to use compound in vitro

e. Annotations include brief narrative on how to use compound in vivo, if applicable

B. GOVERNMENT RESPONSIBILITIES

The Government shall provide NCATS owned data as needed for the Curation.

D. DELIVERY OR DELIVERABLES

The contractor shall provide a curated database.