Key Dates

Related Announcements

• December 21, 2023 - Investigator Initiated Clinical Trials of Complementary and Integrative Interventions Delivered Remotely or via mHealth (R01 Clinical Trial Required). See NOFO PAR-24-086. 

Issued by

National Center for Complementary and Integrative Health (NCCIH)

Purpose

The purpose of this Notice is to correct the instructions for PHS Human Subjects and Clinical Trials Information under Application and Submission Information in applications for PAR-24-086, "Investigator Initiated Clinical Trials of Complementary and Integrative Interventions Delivered Remotely or via mHealth (R01 Clinical Trial Required)”. The correction will take effect on June 21, 2024.

The Notice of Funding Opportunity (NOFO) currently reads:

Section IV. Application and Submission Information

PHS Human Subjects and Clinical Trials Information

Section 4 - Protocol Synopsis

4.3 Statistical Design and Power

Applicants must describe the Statistical Analysis Plan (SAP). If the SAP is not a part of the DCC application, both the CCC and the DCC applications will be deemed incomplete and will not proceed to peer review. The SAP should correspond to major aims of the study, and include plans for randomization, final statistical analyses; and methods for handling missing data. The power calculations must be linked to the study endpoints and to the hypothesis(es) being tested. The power calculation description should be detailed enough to allow replication of the analysis by an independent statistician. NCCIH requires a minimum of 90% power for the primary outcome. Multiplicity adjustment should be made if there are multiple primary outcomes. The effect size used in power calculations should be clinically meaningful.

Plans for interim analyses should be described in detail and include plans to assess futility based on the inability of successfully completing the trial, due to poor enrollment or poor adherence to the intervention; conditions for early stopping due to such futility or early achievement of primary clinical outcomes; plans to assess safety; and while not common, any plans to reassess or recalculate power, or modify sample size (e.g., confirm expected event rate during the trial or confirm expected Intra-class Correlation (ICC) for cluster-randomized trials). If the application is not proposing interim analyses, the application should justify why they are not planned. For phase III clinical trials, the SAP must address plans for the analysis of intervention effect differences required by the policy unless there is clear evidence that such differences are unlikely to be seen (https://grants.nih.gov/policy/inclusion/women-and-minorities.htm). Studies with adaptive designs should include a pre-specified adaptation plan that specifies design type, adaptable element(s), clear decision rules and pre-specified statistical analysis boundaries.  

The NOFO has been modified to read:

PHS Human Subjects and Clinical Trials Information

Section 4 - Protocol Synopsis

4.3 Statistical Design and Power

Applicants must describe the Statistical Analysis Plan (SAP).  The SAP should correspond to major aims of the study, and include plans for randomization, final statistical analyses; and methods for handling missing data.The power calculations must be linked to the study endpoints and to the hypothesis(es) being tested. The power calculation description should be detailed enough to allow replication of the analysis by an independent statistician. NCCIH requires a minimum of 90% power for the primary outcome. Multiplicity adjustment should be made if there are multiple primary outcomes. The effect size used in power calculations should be clinically meaningful.

Plans for interim analyses should be described in detail and include plans to assess futility based on the inability of successfully completing the trial, due to poor enrollment or poor adherence to the intervention; conditions for early stopping due to such futility or early achievement of primary clinical outcomes; plans to assess safety; and while not common, any plans to reassess or recalculate power, or modify sample size (e.g., confirm expected event rate during the trial or confirm expected Intra-class Correlation (ICC) for cluster-randomized trials). If the application is not proposing interim analyses, the application should justify why they are not planned. For phase III clinical trials, the SAP must address plans for the analysis of intervention effect differences required by the policy unless there is clear evidence that such differences are unlikely to be seen (https://grants.nih.gov/policy/inclusion/women-and-minorities.htm). Studies with adaptive designs should include a pre-specified adaptation plan that specifies design type, adaptable element(s), clear decision rules and pre-specified statistical analysis boundaries. 

All other aspects of the NOFO remain the same. 

Inquiries

Please direct all inquiries to:

Beda Jean-Francois, Ph.D.  
National Center for Complementary & Integrative Health (NCCIH) 
Phone: 202-313-2144 
Email: [email protected]