The National Institute of Mental Health (NIMH) proposes to issue a Request for Proposals (RFP) No. HHS-NIH-DA-2012-241 entitled "New Experimental Medicine Studies: Fast-Fail Trials in Autism Spectrum Disorders (FAST-AS)" under Full and Open Competition.

This is a Research and Development initiative. The overall goal of this initiative is to implement an experimental medicine paradigm of "fast fail" Proof of Clinical Mechanism (POCM) and Proof of Concept (POC) trials in order to expeditiously test and analyze the molecular and/or clinical targets of novel interventions. The emphasis is upon treating clinical dimensions of psychopathology across traditional autism spectrum disorder diagnoses (e.g., social engagement, rigidity or inflexibility) embedded in the current DSM diagnostic entities, but not typically identified as the primary target of current clinical therapeutics. The intent of the NIMH Research Domain Criteria Project (RDoC) is to accelerate the pace of new discoveries by fostering research that translates findings from basic science into new treatments addressing fundamental mechanisms that cut across current diagnostic categories (see the Research Domain Criteria (RDoC) webpage http://www.nimh.nih.gov/research-funding/rdoc/nimh-research-domain-criteria-rdoc.shtml for more details).

The initiative will focus on the analyses of novel molecular and clinical targets, engaged by both new and re-purposed compounds. The outcome of this initiative is expected to lead to an enhanced understanding of underlying mechanisms and development of innovative, pharmacological treatment approaches for autism spectrum disorders.

The general approach required for this initiative will be to establish a small organization of clinical trial sites and to test selected novel pharmacological interventions in adequately powered (i.e., to successfully address the primary aim/s) clinical trials (e.g., First in Human, Proof of Clinical Mechanism, Proof of Concept) in humans. Trials will be initiated after promising interventions are identified by the FAST-AS organization, NIMH (which may include the NIMH Intramural Research Program), and outside scientific experts (as needed), and approved by the FAST-AS Steering Committee and the NIMH Government Program Officer (GPO; sometimes also referred to as the COTR).

The primary objectives of resultant contract(s) are:

1) To expeditiously perform small-scale Phase I and/or Phase IIa clinical trials (e.g., First in Human, Proof of Clinical Mechanism, Proof of Concept) to demonstrate target engagement, safety, and early signs of efficacy of promising interventions in healthy child, adolescent, and adult subjects and/or a well-characterized cohort of patients with clinical dimensions of psychopathology across traditional autism spectrum disorder diagnoses (see information regarding RDoC, above).

2) Depending on pilot data available for interventions selected for testing, each trial may be a single-site or multisite study with a number of subjects adequate to successfully address the primary aims (e.g., pharmacologic dose range, safety in humans, molecular and/or clinical target engagement, potential biomarkers, biological effects, early signs of efficacy) and inform a judgment whether the particular intervention warrants further evaluation.

3) The objective of this initiative is to expeditiously perform small-scale Phase I and/or IIa clinical trials with an approximate range of 8-30 subjects per trial. The Government does not anticipate that any preclinical (i.e., Phase 0) studies or any larger scale (e.g., Phase IIb, Phase III, IV) clinical trials will be performed under this contract.

Important Considerations:

The offeror should also have the capability to:

1) Establish a small group of clinical trials sites that will focus on identifying and testing promising pharmacological interventions for the treatment of autism spectrum disorders.

2) Experience performing a range of clinical trials, Phase I-IIa (e.g., First in Human, Proof of Clinical Mechanism, Proof of Concept) of pharmacological clinical trials in children, adolescents, and adults with autism spectrum disorders.

3) Perform multi-site clinical trials including provide scientific oversight, facilitate collaboration among the investigators, integrate complex protocol management, acquire data, analyze bio-statistical data, and report results from clinical trials involving subjects with autism spectrum disorders.

4) Experience obtaining access to study interventions and previous experience(s) of productive interactions with pharmaceutical companies.

5) Appropriate capability, expertise, and equipment to assess molecular and/or clinical target engagement, test clinical mechanism, and identify and validate biomarkers, using measures such as PET, fMRI, clinical electrophysiology, emotional reactivity, neurocognitive performance, and biospecimen assays.

6) Both the Contract-PI and Site-PI(s) should have the capability to select and coordinate a team of investigators and support staff who have the capability to conduct research on the safety and efficacy of pharmacological interventions in patients with autism spectrum disorders, assess molecular and/or clinical target engagement using appropriate measures (e.g., PET, fMRI, clinical electrophysiology, emotional reactivity, neurocognitive performance, biospecimens assays) and identify and validate biomarkers.

7) To function as a Coordinating Center (FAST-AS-CC) responsible for conducting multiple concurrent trials.

8) Access to a standing IRB with a Federalwide Assurance (FWA) from the United States Department of Health and Human Services Office for Human Research Protections.

9) Access to a pharmacy experienced in the preparation of materials for randomized clinical trials.

10) Appropriate staff with experience in training, following, and conducting research protocols.

11) Adequate computing resources and support staff, including necessary electronic communication capabilities.

12) Adequate capabilities and staff for data collection, entry, editing, electronic transfer, quality control, database management (maintaining security and accessibility), and data backup (on site and off site).

13) Proposed Contract-PI and Site-PI(s) should be established researchers in autism spectrum disorders and actively publishing in the field.

General information:

This is a Presolicitation Notice in advance of the Request for Proposal (RFP), and the Government is not committed to award a contract pursuant to this announcement. The RFP, HHS-NIH-DA-2012-241, detailing the specifics of the project as well as information pertinent to the development of an offeror's proposal will be available electronically on or about January 09, 2012 and may be accessed through the Internet at the Federal Business Opportunities website at: http://www.fedbizopps.gov. No paper copies will be available. Offerors are responsible for downloading their own copy of the solicitation and amendments and for routinely checking the Internet site for any possible solicitation amendments that may be issued by the Government. Proposals will be due on or about February 23, 2012. It is anticipated that one or more cost-reimbursement contracts award will be made for a period of three years beginning on or about September 15, 2012. Contract(s) will be Indefinite Delivery Indefinite Quantity (IDIQ) and the number of interventions to be tested over the contract period is indefinite.

Concept Review: Please be advised that this project has not been reviewed. Such review will occur prior to technical evaluation. Thus potential offerors are cautioned that cancellation of the RFP due to disapproval is a possibility.

This pre-solicitation notice corresponds to the Small Business Sources Sought notice #HHS-NIH-DA-SBSS-12-241, previously titled: Small Clinical Trials to Test Feasibility and Specific Target Engagement of Novel Pharmacological Treatments in Autism Spectrum Disorders (FAST-AS), which was previously posted on November 10, 2011 and Research and Development Sources Sought notice#: NIH-DA-RDSS-12-241 posted on November 15, 2011. Additionally, this notice corresponds to the Request for Information Special Notice #HHS-NIH-DA-RFI-12-001 entitled: "New Experimental Medicine Studies: Fast-fail trials (FAST)" posted on www.fbo.gov on December 16, 2011.

All responsible sources are encouraged to submit a proposal that will be considered by the NIMH. This advertisement does not commit the Government to award a contract.

No additional details will be provided until after such time that the Request For Proposal is published.

Points of contact are: Marla Jacobson, Contract Specialist at jacobsonmj@mail.nih.gov and Bruce Anderson, Contracting Officer at banderso@mail.nih.gov.

 

The following is a summary of the Solicitation/Request For Proposal (RFP)

Note: Offerors are responsible for reviewing the entire RFP and submitting all information and documentation with their proposal as instructed within the solicitation document.

There are two parts of the proposal that are due, the technical and the business proposal. The RFP is separated into various sections as listed below. Some sections provide information as to what will be required post-contract award, other sections provide information on the proposal process and what is required with the proposal submission. It is very important to review Attachments 1 - 9 carefully as they pertain directly to submission of the proposal. It is also very important to review Sections L. and M. carefully.

Section A. Provides important identifying information (introductory)

Section B. Provides brief description about what services are needed, information on budget, etc...

Section C. Description/Specifications/Work Statement - This refers to Attachment 3 (detailed Statement of Work); provides information on the various reporting requirements that will be applicable post-contract award.

Section D. - Packaging, Marking and Shipping - provides information on post-contract award, e.g. instructions for biomaterials collection

Section E. Inspection and Acceptance - provides information on post-contract award - (deliverables will be reviewed for acceptance)

Section F. - Provides information on post-contract award; e.g. contract deliverables due during performance of any resultant contract

Section G. Contract Administration Data- provides information on post-contract award; required contract administration - e.g. task order procedures, invoicing, key personnel, information security system requirements, etc...

Section H. - Provides information on the special contract requirements that will pertain to any resultant contract, e.g. human subjects, data and safety monitoring, registration of trials, OMB clearance, small business subcontracting matters, information and security matters, conflicts of interest, etc...(post-contract award)

Section I. References general contract clauses (post-contract award)

Section J. (Proposal) Lists the attachments to the RFP and provides links to those that are not physically attached at the end of the RFP.

Section K. Representations and Instructions - (Proposal) discusses one of the steps required if proposal will be submitted

Section L. - (Proposal) Provides Instructions to Offerors for the proposal (both on the development of the technical proposal and of the business proposal

Section M. Evaluation Factors for Award - (Proposal) - Informs of what the peer reviewers will evaluate (technical approach, personnel, etc...)

Abbreviated list of Attachments at end of solicitation document: (Refer to Section J. for complete listing and links) (Proposal)

Attachment 1 - provides instructions about the packaging and delivery instructions of the proposals

Attachment 2 - Is Intent to propose document

Attachment 3 - Statement of Work - discusses the scientific requirements that the Government is seeking

Attachment 4 - Background (scientific)

Attachment 5 - Sample Tasks - (discusses what budgets need to be submitted and the cost assumptions for those; also discusses what protocols need to be submitted)

Attachment 6 - Additional Technical and Business Proposal Instructions - Important to review carefully

Attachment 7 - Past Performance Survey

Attachment 8 - Sample Task Order form

Attachment 9 - Technical Evaluation Criteria (Refer to Section M.)

Concept Review was conducted on January 20, 2012 and concept was approved.

Submit questions in writing to jacobsonmj@mail.nih.gov. Subsequent Amendments will be posted as necessary.

This Solicitation (Request For Proposal) corresponds to the following previously published notices:

Small Business Sources Sought Notice: HHS-NIH-DA-SBSS-12-241, posted on 11/10/11 (previously titled: Small Clinical Trials to Test Feasibility and Specific Target Engagement of Novel Pharmacological Treatments in Autism Disorders (FAST-AS).

Research and Development Sources Sought Notice: HHS-NIH-DA-RDSS-12-241, posted on 11/15/11(previously titled: Small Clinical Trials to Test Feasibility and Specific Target Engagement of Novel Pharmacological Treatments in Autism Disorders (FAST-AS).

Request For Information (RFI): HHS-NIH-DA-RFI-12-001, posted on 12/16/11, Titled: "New Experimental Medicine Studies: Fast-fail trials (FAST)"

Pre-solicitation Notice: HHS-NIH-DA-12-241, posted on 12/22/11, Titled: New Experimental Medicine Studies: Fast-Fail Trials in Autism Spectrum Disorders (FAST-AS)

 

The due date is extended to March 28, 2012.

REMINDER: Questions regarding this solicitation (RFP) may be submitted in writing through March 7, 2012

REMINDER: Attachment 2, Proposal Intent Sheets are requested by March 07, 2012.

Amendment #02 to Solicitation to address Offeror's questions. Amendment #03 to the Solicitation Document (RFP) is attached. Amendment #04 to RFP which includes an additional Attachment to the RFP. Amendment #5 to RFP and revised Attachment #7 are attached. Any Past Performance Surveys already received by the contract specialist do not have to be resubmitted. The revised Attachment #7 extends the due date for receipt of the surveys.