Notice Number: NOT-AR-16-015

Key Dates
Release Date: April 4, 2016 (This notice will be rescinded on January 9, 2018) - RESCINDED

Issued by
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Purpose

The purpose of this Notice is to update existing NIAMS Clinical Trials policy (NOT-AR-14-021) regarding submission of Clinical Trials applications via the Parent R01 Funding Opportunity Announcement (FOA). In light of the recently revised NIH definition of a clinical trial (NOT-OD-15-015), NIAMS is revising current policy in order to allow R01 applications that include a clinical trial if the primary endpoint is mechanistic. In addition, the NIAMS Clinical Trials policy is being extended to the Parent R21 FOA.

Effective immediately, NIAMS will accept applications submitted in response to either the NIH Parent R01 (PA-16-160) or Parent R21 FOA (PA-16-161) that include a clinical trial in which the primary objective is mechanistic, rather than a clinical outcome. This revised policy applies not only to the current Parent FOAs, but also to subsequent reissuances. Note that NIAMS will not accept applications submitted in response to the NIH Parent R01 FOA or the Parent R21 FOA that include a clinical trial in which the primary objective is to test a clinical outcome: such trials will only be accepted through NIAMS-specific FOAs specifically designed for clinical trials.

• A mechanistic study is defined as one designed to understand a biological process, the pathophysiology of a disease, or the mechanism of action of an intervention.
• A clinical outcome study is defined as one with the objective of determining the clinical safety, tolerability, efficacy and/or effectiveness of pharmacologic, behavioral, biologic, surgical, or device (invasive or non-invasive) interventions.

This policy will allow applications for studies where the primary objective is mechanistic, but where it would be appropriate to analyze a clinical outcome as a secondary objective. For example, in a study of the effect of an intervention on a mechanistic pathway in humans with a specific disease, this would allow for concurrent measurement of disease activity. However, other considerations may apply. For example, an early-phase study of a new drug or device in human subjects must include analyses of safety and tolerability as primary objectives, which would constitute important clinical outcomes that NIAMS would not accept in an application submitted in response to either the Parent R01 or Parent R21 FOA.

Additional Considerations
Consultation with NIAMS staff is strongly recommended for investigators planning a clinical trial. Such consultation is particularly important for those considering an R01 or R21 application that includes a clinical trial with a mechanistic outcome. If NIAMS determines after submission that a clinical outcome is a primary objective of the study, NIAMS will not accept the application.

Inquiries

Please direct all inquiries to:

Laura K. Moen, Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Telephone: 301-451-6515
Email: [email protected]