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1 I am an Investigator

Those in the process of applying for a grant, cooperative agreement or R&D contract. This includes those submitting an SBIR/STTR application. Those who have submitted an application. Those who have been funded. 

3 Investigator Pre-Submission

Human subjects research is research involving: 

  • A living individual
  • About whom an investigator (whether professional or student) conducting research obtains
    • Data through intervention or interaction with the individual, or
    • Identifiable private information

Non-Exempt Human Subjects Research

Research that meets the definition of research involving human subjects and must remain compliant with the Federal regulations, 45 CFR 46. To be compliant the award institution must:

  • Maintain a valid Federal-wide Assurance (FWA) with the Office of Human Research Protections
  • Review and approve the study protocol annual through the Institutional Review Board (IRB).

NIH requirements:

Exempt Human Subjects Research

Research that is considered exempt from the federal regulations on the protection of human subjects does not need an FWA or annual IRB approval. Exempt human subjects research meets the definition of human subjects research but meets the criteria of one of the six exempt study designs:

  • Exemption 1 - Research conducted in an educational setting involving normal educational practice.
  • Exemption 2 - Research using educational tests, survey procedures; interviews; or observations of public behavior, unless subjects are identifiable and disclosure could place them at risk. This exemption for parts involving educational tests is applicable to children. However, this exemption for parts involving survey or interview procedures or observations of public behavior does not apply to research involving children, except for research involving observation of public behavior when the investigator(s) do not participate in the activities being observed.
  • Exemption 3 - Research using educational tests, survey procedures; interviews; or observations of public behavior, if the subjects are public officials or candidates for public office or federal law requires that confidentiality be maintained. Not typically used in NIH research projects.
  • Exemption 4 - Research involving the collection or study of existing data, documents, records, pathological or diagnostic specimens; if these sources are publicly available or if the information is recorded in such a manner that subjects cannot be identified. Since 2008 guidance from OHRP, E4 is seldom applicable; most research with existing data or specimens is either non-exempt human subjects research (code 30) or not human subjects research (code 10).
  • Exemption 5 - Research and demonstration projects that evaluate public benefit or service programs. Not typically applicable to NIH research projects.
  • Exemption 6 - Research that evaluates taste and food quality; or consumer acceptance of foods. Not typically applicable to NIH research projects.

NIH specific considerations:

  • Exemptions that are used for NIH research typically include Exemptions 1, 2 and 4.
  • Investigators involved in research considered exempt must still meet the Human Subjects education requirement.

For applications that propose the use of human specimens or data but are not considered human subjects research: Check “No” to Human Subjects. You should upload a Protection of Human Subjects section that clearly discusses the source of all human specimens and data and state whether or not anyone on the research team has the ability to link the specimens or data to subjects’ identifiable information.

For applications that propose research involving human subjects that meets one of the six exemptions: Check “Yes” to Human Subjects. Check “Yes” to Exempt from Federal regulations. Check the appropriate exemption number(s). You will need to provide a detailed justification in the Protection of Human Subjects section that explains why your study is considered to be exempt from Federal regulations.

For applications that propose non-exempt research involving human subjects: Check “Yes” to Human Subjects. Check “No” to Exempt from Federal regulations. You must submit a complete Protection of Human Subjects section.

  • If your study involves a clinical trial you must include a Data and Safety Monitoring Plan (DSMP) commensurate with the risk of your study.
  • If your study involves an NIH-defined Phase III or multisite Clinical Trial your DSMP must include a Data and Safety Monitoring Board.
  • If approved, you will need:
    • certification of approval from your Institutional Review Board (IRB)
    • to provided your institution’s Federalwide Assurance (FWA) number
    • and, certification that all key personnel have received human subjects education.

For more help preparing your Protection of Human Subjects section (complete instructions), see Preparing the Human Subjects section

Once your application has been received by the NIH it will:

  • Be assigned to a Scientific Review Officer who will coordinate the peer review panel;
  • Be assigned to a Program Officer, whom you can contact if you have additional questions; and
  • Undergo peer review.

For additional information regarding the Post-Submission process please see our Post-Submission page.

Human Subjects Infographic

List of Common SRG Concerns:

  • Human Subjects section is missing or incomplete
  • Data and Safety Monitoring Plan is missing or incomplete
  • Source of data or specimens is missing or inadequately discussed
  • Risks: inadequate discussion of physical or clinical risks
  • Risks: Inadequate discussion of protections Risks: inadequate discussion of psychological or suicidality
  • Risks: discussion of incidental findings or referrals is missing or inadequate
  • Confidentiality is inadequately discussed
  • Informed consent is inadequately discussed
  • Recruitment is inadequately discussed

Common SRG Concerns separated by applications that are funded versus unfunded.

3 Investigator Post-Submission

The HHS regulations require the NIH to evaluate all applications and proposals involving human subjects (45 CFR part 46.120). This independent evaluation is conducted at the NIH through the peer review system and NIH staff review, and, as required, will take into consideration the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. On the basis of this evaluation, the NIH may approve or disapprove the application or proposal, or enter into negotiations to develop an approvable one.

  • The first level of review is carried out by a Scientific Review Group (SRG) composed primarily of non-federal scientists who have expertise in relevant scientific disciplines and current research areas.
  • The human subjects plan in the application is reviewed for both scientific merit and ethical consideration. The human subjects plan is given an overall rating of “acceptable” or “unacceptable” if there are concerns or incomplete information. While the human subjects plan is rated separately, it can impact the overall application score.
  • The second level of review is performed by Institute and Center (IC) National Advisory Councils or Boards.
  • Councils are composed of both scientific and public representatives chosen for their expertise, interest, or activity in matters related to health and disease.
  • Only applications that are recommended for approval by both the SRG and the Advisory Council may be recommended for funding.
  • Final funding decisions are made by the IC Directors.

For more information on the Peer Review process click here.

The summary statement is a combination of the reviewers' written comments and the Scientific Review Officer’s summary of the members' discussion during the study section meeting. It includes the recommendations of the study section, a recommended budget, and administrative notes of special considerations.

The summary statement should be available through your eRA Commons account within 30 days of peer review. After reading the summary statement, you may want to discuss the critiques and your options with the Program Officer (PO) assigned to your application. If there are human subjects concerns, you will need to work with your PO to resolve the SRG concerns. See “Unacceptable Human Subjects” section above for more information.

Example of the first page of a Summary Statement. Study involves non-exempt human subjects research and was given a Human Subjects code of 30. Had there been concerns about the human subjects involvement this application would have been coded 44 for Human Subjects. (Special thanks to Dr. Joseph McCune and NIAID.)

Example of the Summary Statement Resume. For this study the Protection of Human Subjects was deemed Acceptable. Had there been SRG concerns they would have been noted here. (Special thanks to Dr. Joseph McCune and NIAID.)

 

The request for Just-in-Time information is a standard notice and request for information from all principal investigators with grant applications receiving an impact score at or below the NIH’s payline. If a decision is made to fund this application, the assigned IC will need the following information PRIOR to making an award. Applicants must submit their information at least 60 days before the proposed project period start date. However, you should contact the IC for specific guidance. All of the information must be submitted electronically using the Just-In-Time feature of the eRA Commons found in the Commons Status section. For information on the Commons see: https://commons.era.nih.gov/commons/index.jsp. For studies involving non-exempt human subjects you must submit certification of:

  • Your Institution’s FWA Number: The Federalwide Assurance (FWA) is the only type of assurance currently accepted and approved by the Office of Human Research Protections (OHRP). Through the FWA, an institution commits to HHS that it will comply with the requirements in the HHS Protection of Human Subjects regulations at 45 CFR part 46.
  • IRB Approval: the certification date of IRB review and approval must be submitted. Pending or out-of-date approvals are not acceptable.
  • Human Subjects Education: certification that any person identified as senior/key personnel involved in human subjects research has completed an education program in the protection of human subjects must be submitted. **Studies involving exempt human subjects research must also provide certification of HS education.

During peer review, if the SRG has concerns or find the human subjects information incomplete, the application will be rated as “Unacceptable” for human subjects and be given a Code 44. If your application is at or below the NIH payline, you may receive a Request for Just-in-Time Information. At this time you should work with your Program Officer to resolve the human subjects concerns. You must submit to your IC a written resolution to the SRG concerns. The IC will work with the Office of Extramural Programs to resolve the SRG concerns and any other identified concerns.

Resolving the Unacceptable Human Subjects Code

Your written response to SRG concerns should address the concern(s) noted in the Resume. The Resume is a summary of the outcome of the Peer Review discussions that highlights certain aspects of the application. It is located at the end of the Summary Statement after all of the individual critiques. Additionally, it is advised to respond to the concerns identified in individual critiques if they differ from the Resume. Resolution of the concern(s) depends on the complexity of the concern and the human subjects involvement. For many applications, a simple statement of clarification will suffice, while for more complex studies, you may want to consider revising your Protection of Human Subjects section. The response to the SRG concern should fully address the concern with a clear discussion of the plan to resolve all issues.

3 Investigator Post-Award

By accepting a grant award, grantees agree to comply with the requirements in the NIH Grants Policy Statement, unless the notice of award states otherwise. Terms and conditions related to human subjects research can be found here

Studies involving human subjects must have:

  • A current Federalwide Assurance (FWA) filed with OHRP.
  • Annual IRB approval.
  • All key personnel, including new personnel, involved in the human subjects component of the research must have human subjects education. The NIH offers Protecting Human Research Participants as a free and acceptable training option.

Adverse Events

An adverse event is defined as any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the involvement in a clinical research study. Adverse events can include serious and non-serious adverse events and unanticipated problems. An investigator is responsible for knowing the policies of the local IRB, adhering to these policies, and maintaining a copy of the policies in the study file. An investigator is also responsible for the accurate documentation, investigation and follow-up of all possible study-related adverse events. All adverse events must be reported to the IRB and, if appropriate, the DSMB and the NIH. All unanticipated problems must then be reported to the Office of Human Research Protections (OHRP) by the IRB. The timeline for reporting adverse events is commensurate with the severity of the event.

Clinical Trial

For studies that involve a clinical trial monitoring of the clinical trial should be conducted as described in the Data and Safety Monitoring Plan.

If you have any questions regarding the monitoring of your study contact your Program Officer.

Information about the ClinicalTrials.gov requirements can be found here.

If your study did not originally include human subjects. If you would like to add a human subjects component to your existing NIH-funded award you will need to discuss this potential award modification with your Program Officer. You cannot initiate human subjects research without first getting prior approval from your Program Officer. Additionally, before you can start any non-exempt human subjects research you must submit to your IC: a complete Protection of Human Subjects section, your institution’s Federalwide Assurance (FWA) number, an unconditional IRB approval, and certification that all the key personnel involved in the human subjects component of your study have received human subjects education.

If you would like to change the approved human subjects component of your study. Please discuss any considered changes to your approved protocol with your Program Officer. Changes that increase the risks to subjects, will now include a vulnerable population, such as children, or change from an exempt study to non-exempt (for example, a study that involves surveying adults about internet use (Exemption 2) will now include children) must receive NIH approval before the changes can be made. These changes may also require IRB notification and approval.

If the human subjects component of your study has been completed. The human subjects determination reflects the view of the peer review group regarding the involvement of human subjects for the duration of an award period. In exceptional cases where all aspects of human subjects research are completed before the end of the project period, a restriction will be placed on your Notice of Award that allows non-human subjects research to be conducted. This would not require on-going IRB approval. However, if you are conducting analysis of study data and can still link specimens or data to identifiers, on-going IRB approval continues to be required.

All studies involving clinical research must be monitored for inclusion tracking of women, minorities and children. With few exceptions, inclusion is tracked for all studies coded as non-exempt and exempt human subjects research, except Exemption 4. For information and questions regarding inclusion monitoring and tracking please refer to the NIH Inclusion Policies and Procedures pages:

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