Notice Number: NOT-NS-10-009

Key Dates
Release Date:  May 14, 2010

Issued by
National Institute of Neurological Disorders and Stroke (NINDS), (http://www.ninds.nih.gov/)

Purpose

To establish the NINDS Policy for a two phase award process for Investigator-Initiated cooperative agreement phase III Clinical Trial applications submitted under PAR-10-198.

Background
Because of their comparatively large size and long duration, Phase III clinical trials are the most complex and challenging trials to design and implement.  They require extensive planning and proactive oversight for successful completion.  Despite careful planning, numerous factors often extend the time needed to complete a Phase III trial, including delays in start-up, regulatory approval, or in enrollment of trial participants.  Such delays can result in the large carry-over of research dollars and the need for additional years to complete the trial.  Therefore, NINDS has developed this policy for providing an initial funding commitment of 2-3 years for the trial in order to establish feasibility before an administrative decision is made to allow the award of the remaining budget and years within the scope of the original council approved application. 

Policy

All NINDS multi-center phase III clinical trials awarded under the NINDS program announcement for the submission of Phase III multi-center clinical trials (PAR-10-198) will be given an initial award for 2 to 3 years in order to start-up the trial and establish performance feasibility.  Continuation of the award past this feasibility period will be contingent upon a demonstrated ability to meet milestones indicating that the trial can be implemented as planned.  Feasibility milestones will be defined at the start of each trial and will be monitored closely by the Institute-appointed Data and Safety Monitoring Board (DSMB) and NINDS program officer. A decision to either continue with the completion of the trial or to discontinue enrollment of subjects in the trial will be based on some or all of the following factors: (1) implementation feasibility (i.e., ability to start the trial as planned; (2) enrollment feasibility (i.e., establishing an acceptable enrollment rate to at least 80% of projected rate), (3) no safety concerns (i.e., recommendation from the Data and Safety Monitoring Committee to continue the trial), (4) if applicable, interim analysis evaluating the probability that the trial will be futile or inconclusive; (5) other criteria as appropriate to the individual trial.

At the end of the feasibility period, an administrative decision with input from the DSMB will be made by NINDS to continue or terminate the trial. If the trial is approved to continue, the investigators will be permitted to complete a non-competitive (Type 4) extension application to obtain the remainder of the funding and project years specified in budget of the initial application (see below) in order to complete the trial.  During this extension period, the NINDS, with input from the DSMB, will regularly evaluate progress toward enrollment goals, work with investigators to improve enrollment, and will terminate trials if adequate progress is not demonstrated (for example, falling below 50% of the expected enrollment goal).  During both the feasibility and extension phase, funding will be carefully monitored and adjusted appropriately and proportionately to the rate of performance in the trial.  Should performance accelerate faster than planned, NINDS will adjust the funding award to keep pace with the rate of activities.

If after the feasibility assessment or at any point during the initial competitive application it is determined that both additional project years and additional money (i.e., in addition to what was approved and funded in the original competitive application) are going to be needed to complete the trial, the NINDS will determine whether the completion of the trial remains a priority and if so, the investigators will be permitted to submit a competitive renewal (Type 2) application to request the additional funding and project years needed to complete the trial.  Submission of this type 2 application would be planned prior to the end of the type 1 grant to ensure continuity of funding the trial during the peer review process.  

Application

The following section describes the process for either the Type 4 (non-competitive) extension or Type 2 (competitive) renewal applications.

Non-competitive Extension (Type 4)

Before the end of the pre-defined feasibility phase of the award, the Principal Investigator will discuss with the NINDS program officer the status of the trial and the conditions of the feasibility agreement.  If it is determined that the trial is an appropriate candidate for extension, the investigator will be permitted to submit an extension application.  The application will include the following:

1. A letter co-signed by the Principal Investigator and his/her Institution’s Business Official requesting the additional years of support;
2. PHS 398Application Face Page;
3. A progress report summary for the current budget period;
4. A one-page research plan for the additional years; and
5. A budget and justification using Page EE of the PHS 398 (budget for entire proposed remaining period of support; including an accounting of funds awarded but remaining unspent to date).

Competitive Renewal (Type 2)

If it is determined that the trial is an appropriate candidate for continuation and it is determined that additional money and project years are needed to complete the trial, the investigator will be permitted to submit a type 2 competitve renewal application. Standard submission dates will be used. (For submission dates, see http://grants1.nih.gov/grants/funding/submissionschedule.htm).  

Inquiries

Inquiries concerning this policy should be sent to:

Scott Janis, Ph.D.
Office of Clinical Research
National Institute of Neurological Disorders and Stroke
Room 2170, MSC 9525
6001 Executive Blvd.
Bethesda, MD 20892-9525
Telephone: (301) 496-9135
Fax: (301) 410-1080
Email: janiss@ninds.nih.gov

For inquiries about review issues contact:
Chief, Scientific Review Branch
National Institute of Neurological Disorders and Stroke
Room 3201, MSC 9529
6001 Executive Blvd.
Bethesda, MD 20892-9529
Telephone: (301) 496-9223
Fax: (301) 402-0182
Email: nindsreview@ninds.nih.gov

For inquiries about grants management issues contact:
Ms. Tijuanna DeCoster, MPA
Grants Management Officer
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 3258
Bethesda, MD 20892-9529
Telephone: (301) 496-9531
Fax:  (301) 402-0219
Email:  decostert@ninds.nih.gov