The Application Guide has been updated to clarify instructions of the SF424, update program specific instructions and announce new policies. The new policies have been identified below. The updated Application Guide can be found here: https://grants.nih.gov/grants/how-to-apply-application-guide.html
This document will be sequentially numbered from Chapter I-XII and all references throughout have been modified to reflect this change. Part I of the document covers NSF's proposal preparation and submission guidelines, and Part II covers NSF's award, administration and monitoring guidelines.
Editorial changes have been made to either clarify or enhance the intended meaning of a sentence or section or ensure consistency with data contained in NSF systems or other NSF policy documents. Throughout the PAPPG, website references and Division or Office names have been updated to reflect current information.
The Department of Health and Human Services has issued a new regulation and the National Institutes of Health (NIH) has issued a new policy to increase the availability of information about clinical trials via ClinicalTrials.gov, a publicly accessible database operated by the National Library of Medicine (NLM), part of the NIH. The Final Rule, promulgated in accordance with section 402(j) of the Public Service Health Act, describes requirements for registering and submitting summary results information for certain clinical trials to ClinicalTrials.gov. The Final Rule will be codified at 42 CFR part 11. A complementary NIH policy applies to all clinical trials funded by NIH, regardless of whether they are subject to the Final Rule.
The Final Rule specifies requirements for registering certain clinical trials and submitting summary results information to ClinicalTrials.gov. The new rule expands the legal requirements for submitting registration and results information for clinical trials involving U.S. Food and Drug Administration-regulated drug, biological and device products.
The Final Rule applies to "responsible parties" for "applicable clinical trials." A responsible party is the sponsor of the clinical trial or a designated principal investigator. The responsible party could be an organization (such as a drug or device manufacturer, a university or academic medical center, or a government research organization such as the NIH), or an individual. The Final Rule specifies the approach for determining who is the sponsor of a clinical trial and explains how a sponsor can designate a principal investigator as the responsible party [see 42 CFR § 11.4(c)].
The Final Rule applies to trials that meet the legal definition of an "applicable clinical trial" and certain other clinical trials for which information is voluntarily submitted. Applicable clinical trials include certain interventional studies of drug, biological, and device products that are regulated by the FDA. Phase 1 trials of drug and biological products and feasibility studies of device products are excluded from the definition of an applicable clinical trial. A pediatric post-market surveillance study of a device product required by the FDA is also subject to the regulation.
In general, to be considered an applicable clinical trial, one or more of the following criteria also must be met:
The Final Rule requires that a responsible party register an applicable clinical trial at ClinicalTrials.gov no later than 21 days after enrolling the first participant (see § 11.24). Registration consists of submitting four categories of data elements: 1) descriptive information, 2) recruitment information, 3) location and contact information, and 4) administrative information.
If a drug or biological product studied in an applicable clinical trial is available under expanded access, the Final Rule requires the responsible party, if both the manufacturer of the drug product or biological product and the sponsor of the clinical trial, to also submit a separate expanded access record (or link to an existing expanded access record) containing certain details about how patients may obtain access to the investigational product. Expanded access is the use outside of a clinical trial of an investigational product (i.e., one that has not been approved by FDA). FDA's statute and regulations provide various mechanisms under which patients may be able to access investigational products outside of a clinical trial.
The Final Rule requires a responsible party to submit summary results information to ClinicalTrials.gov for any applicable clinical trial that is required to be registered, regardless of whether the drug, biological, or device products under study have been approved, licensed, or cleared for marketing by the FDA (see § 11.42). This represents an expansion of the statutory requirement, which requires the submission of summary results information only for applicable clinical trials of drug, biological, or device products that have been approved, licensed, or cleared by the FDA. The clinical trial results information submission requirements in the Final Rule apply to an applicable clinical trial with a primary completion date on or after the effective date of the Final Rule.
In general, results information must be submitted no later than one year after the primary completion date of the applicable clinical trial. Primary completion date is the date that the final subject was examined or received an intervention for the purpose of collecting the data for the primary outcome measure. Results information submission may be delayed for as long as two additional years if the responsible party submits a certification to ClinicalTrials.gov that either: 1) a drug, biological, or device product studied in the clinical trial is not yet approved, licensed, or cleared for marketing by the FDA AND is still under development by the manufacturer; OR 2) that the manufacturer is the sponsor of the clinical trial and has sought or will seek approval, licensure, or clearance for a new use of a product studied in the trial within one year. The Final Rule also permits responsible parties to request extensions to the results information submission deadline for "good cause" (See § 11.44).
The final NIH Policy complements the Final Rule in that the NIH Policy applies to all clinical trials funded in whole or in part by NIH, regardless of study phase, type of intervention, or whether they are subject to the Final Rule.
The NIH Policy applies to clinical trials which are defined as "a research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes."
In addition to the types of trials covered by the Final Rule, the NIH Policy applies to all other trials funded by NIH, including phase 1 trials of drug and biological products, small feasibility studies of device products, and clinical trials of behavioral, surgical, and other types of health and medical interventions. Clinical trials that use NIH-supported infrastructure, but receive no other NIH funds for the conduct of a specific clinical trial are not subject to the NIH Policy.
Applicants for NIH funding are required to submit a plan outlining how they will comply with the clinical trial information dissemination expectations of the policy. Consistent with the terms and conditions of their NIH funding, awardees undertaking clinical trials covered by the NIH Policy must ensure the submission and updating of the same type of registration and results information, and in the same timeframes, as responsible parties whose trials are subject to the Final Rule. An NIH-funded clinical trial that is also subject to the Final Rule should only have one entry in ClinicalTrials.gov containing its registration and results information. The policy takes effect on the effective date of the final rule, and applies to applications and proposals received and intramural clinical trials submitted for Institutional Review Board review on or after that date.
The Final Rule has a compliance date of 90 days after January 18, 2017, meaning that a responsible party has until April 18th to come into compliance with the requirements of the Rule.
The FDA has the authority to issue a Notice of Noncompliance to a responsible party who has failed to comply with the requirements for registering and submitting results information for an applicable clinical trial. The FDA may also impose civil monetary penalties for such violations. Additionally, a responsible party who commits a prohibited act(s) may be the subject of an injunction action or criminal prosecution brought by the Department of Justice.
Compliance with the NIH policy will be via the terms and conditions of the NIH award. Failure to comply with the terms and conditions of an NIH funding award could lead to grants enforcement actions, including termination of funding.
For more information:
Sharon Levine-Sealy, Director of Pre-Award Operations
Charlene Butcher, Executive Assistant
Ethan Denny, Contract Manager
Melissa Emanus, Assistant Director
Margaret Briggs, Sponsored Programs Associate
Laurian Bradford, Sponsored Programs Associate
TBH, Sponsored Programs Associate