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GENERAL APPLICATION GUIDE FOR NIH AND OTHER PHS AGENCIES
SF424 (R&R) - Forms Version E
Released: September 25, 2017

G.500 - PHS Human Subjects and Clinical Trials Information

Complete the PHS Human Subjects and Clinical Trials Information form after you have completed the G.220 - R&R Other Project Information Form.

This form accommodates the full spectrum of all types of clinical trials, including, but not limited to, exploratory/development, mechanistic, pilot/feasibility, early phase, efficacy, effectiveness, group-randomized, and others.

Who should use the PHS Human Subjects and Clinical Trials Information form:

All applicants must use the PHS Human Subjects and Clinical Trials Information form regardless of your answer to the question "Are human subjects involved?" on the G.220 - R&R Other Project Information Form.

If you answered "Yes" to the question "Are human subjects involved?" on the G.220 - R&R Other Project Information Form, see the "If Yes to Human Subjects" section for instructions.

If you answered "No" to the question "Are human subjects involved?" on the G.220 - R&R Other Project Information Form, see the "If No to Human Subjects" section for instructions.

Additional Instructions for Training:

K12 and D43 applicants applying to FOAs that accept clinical trials (i.e., 'clinical trial required' or 'clinical trial optional'): Use the PHS Human Subjects and Clinical Trials Information form to submit delayed onset studies if you are proposing any human subject studies in your application. Do not fill in Study Records. Follow the instructions in your FOA.

All other Training applicants: This form is not applicable and will not be available to you.

Note for studies involving only the secondary use of identifiable biospecimens or data: For studies where the only involvement of human subjects is the use of identifiable biospecimens or data originally collected for another purpose, complete the PHS Human Subjects and Clinical Trials Information form with information specific to the current study and not the original collection unless the information associated with the original collection is pertinent to the proposed study. If information about the original collection is necessary, provide context and clearly distinguish between the current study and historical information.

Using the PHS Human Subjects and Clinical Trials Information form:

Follow instructions on the PHS Human Subjects and Clinical Trials Information form that are specific to your answer to the "Are Human Subjects Involved?" question on the G.220 - R&R Other Project Information Form. The PHS Human Subjects and Clinical Trials Information form allows you to add study record(s) and/or delayed onset study(ies), as applicable.

Within each Study Record: PHS Human Subjects and Clinical Trials Information, you will add detailed information at the study level. Add a separate study record for each protocol involving human subjects proposed in your application. Do not duplicate studies within your application. Each study within the application should be unique and should have a unique study title. Each study record is divided into numbered sections:

Note: The PHS Human Subjects and Clinical Trials Information form will capture detailed information at the study level. Although you are encouraged to refer to information in the PHS Human Subjects and Clinical Trials Information form in your discussion of the Research Strategy, do not duplicate information between the Research Strategy attachment and the PHS Human Subjects and Clinical Trials Information form.

The PHS Human Subjects and Clinical Trials Information form is dynamic and may eliminate sections that are not relevant to your application. The dynamic form behavior may not be enabled on all submission methods.

Additional Instructions for Career Development:

There are three primary situations by which K applicants can apply for human subjects and/or clinical trial research.

Career Development Award (CDA) applicants who are not proposing a clinical trial: Follow the standard instructions to complete the PHS Human Subjects and Clinical Trials Information form.

CDA applicants who are proposing an independent clinical trial: Follow the standard instructions to complete the PHS Human Subjects and Clinical Trials Information form. If you are proposing an independent clinical trial, make sure you are applying to a FOA that requires clinical trials.(Note that not every study record within your application has to be a clinical trial).

CDA applicants who are proposing to gain clinical trial research experience under a mentor's supervision (i.e., you will not be leading an independent clinical trial): You will generally follow the standard instructions to complete the PHS Human Subjects and Clinical Trials Information form, but follow relevant Career Development instructions where they are given. Make sure you are applying to a FOA that does NOT allow independent clinical trials, but does encourage a clinical trial research experience led by a mentor/co-mentor as part of your research career development. Additionally, the mentor or co-mentor is required to include a statement to document leadership of the clinical trial. The statement must include the following:

  • Source of funding;
  • ClinicalTrials.gov identifier (e.g., NCT87654321), if applicable; and
  • A description of how the mentor or co-mentor's expertise is appropriate to guide the applicant in any proposed clinical trials research experience.

This statement must be included in the "Plans and Statements of Mentor and Co-Mentor(s)" attachment in the G.410 - PHS 398 Career Development Award Supplemental Form.

For more information:

Additional Instructions for Fellowship:

Fellowship applicants are permitted to conduct research involving human subjects; however, they are NOT permitted to lead an independent clinical trial.

Fellowship applicants who are not proposing a clinical trial: Follow the standard instructions to complete the PHS Human Subjects and Clinical Trials Information form.

Fellowship applicants who are proposing to gain clinical trial research experience under a sponsor's supervision (i.e., you will not be leading an independent clinical trial): You will generally follow the standard instructions to complete the PHS Human Subjects and Clinical Trials Information form, but follow relevant Fellowship instructions where they are given. Make sure you are applying to a FOA that does NOT allow independent clinical trials, but that does encourage a clinical trial research experience led by a sponsor/co-sponsor (or another member of the mentoring team). Additionally, the sponsor or co-sponsor is required to include a statement to document leadership of the clinical trial. The statement must include the following:

  • Source of funding;
  • ClinicalTrials.gov identifier (e.g., NCT87654321), if applicable; and
  • A description of how the sponsor or co-sponsor's expertise is appropriate to guide the applicant in any proposed clinical trials research experience.

This statement must be included in the "Sponsor and Co-Sponsor Statements" attachment of the G.430 - PHS Fellowship Supplemental Form.

Additional Instructions for Multi-project:

For multi-project applications with studies that are self-contained within a single component:

Overall Component: Do not complete a study record.

Other Component: Complete a separate study record for each human subjects study that is self-contained within a single component.

For multi-project applications with studies that span components:

Overall Component: Complete one study record for each study if it spans multiple components. This study record must include sufficient information for all components that are involved in the particular study. This might occur when an application includes a data coordinating center or recruitment core, or when participant assessments for one study are conducted across multiple components (e.g., the study includes an imaging core and clinical site).

Applicants must follow all policies and requirements related to formatting, proprietary information, human subjects, and clinical trials. See the following pages for more information:

Note: There are no page limits for any attachments in the PHS Human Subjects and Clinical Trials Information form.

PHS Human Subjects and Clinical Trials Information

Applicants must complete the human subjects questions on the G.220 - R&R Other Project Information Form prior to completing this form.

Are Human Subjects Involved? Yes/No

This field is pre-populated from the G.220 - R&R Other Project Information Form. If the value in this field appears to be incorrect, you may correct it by adjusting it on the G.220 - R&R Other Project Information Form.

Is the Project Exempt from Federal regulations? Yes/No

This field is pre-populated from the G.220 - R&R Other Project Information Form. If the value in this field appears to be incorrect, you may correct it by adjusting it on the G.220 - R&R Other Project Information Form.

Exemption number: 1, 2, 3, 4, 5, 6, 7, 8

This field is pre-populated from the G.220 - R&R Other Project Information Form. If the value in this field appears to be incorrect, you may correct it by adjusting it on the G.220 - R&R Other Project Information Form. You should not have selected exemption 7 or 8, as these are not yet being used.

Note: If you change your answer to the "Are Human Subjects Involved" question on the G.220 - R&R Other Project Information Form after you have started entering information into the PHS Human Subjects and Clinical Trials Information form, your data in the PHS Human Subjects and Clinical Trials Information form may be lost.

If No to Human Subjects

If you answered "No" to the question "Are Human Subjects Involved?" on the G.220 - R&R Other Project Information Form, answer the following question(s) about the use of human specimens and/or human data.

Does the proposed research involve human specimens and/or data?

Select "Yes" or "No" to indicate whether the proposed research involves human specimens and/or data.

Applications involving the use of human specimens or data may not be considered to be research involving human subjects, depending on the details of the materials to be used. To help determine whether your research is classified as human subjects research, refer to the Research Involving Private Information or Biological Specimens flowchart.

Note: If you answered "No" to the "Does the proposed research involve human specimens and/or data?" question, skip the rest of the PHS Human Subjects and Clinical Trials Information form unless otherwise directed by your FOA.

If Yes, provide an explanation of why the application does not involve human subjects research.

If you answered "Yes" to the "Does the proposed research involve human specimens and/or data?" question, you must provide a justification for your claim that no human subjects are involved.

Attach the justification as a PDF file. See NIH's Format Attachments page.

This justification should include:

Note: Once you have attached the justification, skip the rest of the PHS Human Subjects and Clinical Trials Information form unless otherwise directed by your FOA.

If Yes to Human Subjects

If you answered "Yes" to the question "Are Human Subjects Involved?" on the G.220 - R&R Other Project Information Form, add a study record for each proposed study involving human subjects by selecting "Add New Study" or "Add New Delayed Onset Study," as appropriate.

Other Requested Information

Who may provide Other Requested Information:

Follow the instructions below and any instructions in your FOA to determine whether you are permitted to include the "Other Requested Information" attachment.

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Content:

Content is limited to what is described in your FOA or in these instructions. Do not use the "Other Requested Information" attachment to include any other information.

Renewal applications: When preparing a renewal (or resubmission of a renewal), you can provide a list of ongoing studies or ClinicalTrials.gov identifiers (e.g., NCT87654321).

Additional Instructions for Multi-project:

For multi-project applications with studies that span components:

Overall Component: For each study that spans components, describe the components involved with the study.

Other Components: Each component should include an attachment that indicates that the details of the study are included in the Overall component within this attachment.

Study Record(s)

Adding Study Record Attachment(s):

Add a study record for each proposed study involving human subjects. If your study is a delayed onset study, see the instructions for Delayed Onset Study(ies).

For all submission methods, the Study Record is used to collect human subjects study data. Note: The steps to add a Study Record attachment(s) may vary with the submission method. For example, from the ASSIST Human Subjects and Clinical Trials tab, use the 'Add New Study' button to access the data entry screens to enter study record information directly into ASSIST. With other submission methods, you may have to extract a blank copy of the Study Record, complete it offline, and then attach it to your application.

The PHS Human Subjects and Clinical Trials Information form accommodates up to 150 separate Study Records.

Format:

All attachments must be PDF files. The study records are already fillable PDFs when extracted. Do not alter the format of the study record file. Use unique file names for each human subject study record.

Content:

Follow the instructions in the "Study Record: PHS Human Subjects and Clinical Trials Information" section below.

Delayed Onset Study(ies)

Additional Instructions for Training:

K12 and D43 applicants applying to FOAs that accept clinical trials (i.e., 'clinical trial required' or 'clinical trial optional'): Use the PHS Human Subjects and Clinical Trials Information form to submit delayed onset studies if you are proposing any human subject studies in your application. Do not fill in Study Records. Follow the instructions in your FOA.

If any of your human subjects studies meet the agency definition of "delayed onset human subject study," enter the information as instructed below. For any study that you include as a delayed onset study in this section, do not fill out a full study record, as the delayed onset record is sufficient.

Notes on delayed onset studies:

Study Title

This field is required.

The Study Title can have a maximum of 600 characters.

Enter a brief, unique title that describes the study the participants will be involved in. Each study within your application must have a unique Study Title. The first 150 characters will display in the application image bookmarks.

Note on multiple delayed onset studies: If you are including multiple delayed onset studies in one delayed onset study entry, you may enter "Multiple Delayed Onset Studies" as the title of this record.

Anticipated Clinical Trial?

This field is required.

Check this box if you anticipate that this study will be a clinical trial. For help determining whether your study meets the definition of clinical trial, see the Clinical Trial Questionnaire below.

Read your FOA carefully to determine whether clinical trials are allowed in your application.

Note on multiple delayed onset studies: If you are including multiple delayed onset studies in one delayed onset study entry, and you anticipate that any of these studies will be a clinical trial, check the "Anticipated Clinical Trial?" checkbox.

Additional Instructions for Career Development:

CDA applicants who are proposing to gain clinical trial research experience under a mentor's supervision (i.e., you will not be leading an independent clinical trial): Do not check the "Anticipated Clinical Trial?" box.

Additional Instructions for Fellowship:

Do not check the "Anticipated Clinical Trial?" box. Fellowship FOAs do not allow independent clinical trials.

Justification Attachment

This attachment is required.

Attach the justification as a PDF file. See NIH's Format Attachments page.

Note on multiple delayed onset studies: If you are including more than one delayed onset study in any given delayed onset study entry, address all the included studies in a single justification attachment.

Study Record: PHS Human Subjects and Clinical Trials Information

Section 1 - Basic Information

Who must complete "Section 1 - Basic Information:"

"Section 1 - Basic Information" is required for all studies involving human subjects.

1.1 Study Title (each study title must be unique)

The "Study Title" field is required.

The Study Title can have a maximum of 600 characters.

Enter a brief title that describes the study the participants will be involved in. If there is more than one study (i.e., you are including more than one study record and/or delayed onset study in your application), each one must have a unique study title. The first 150 characters will display in the bookmarks of the application image.

Note: When registering a clinical trial in ClinicalTrials.gov, all study titles across your organization must be unique.

1.2 Is this Study Exempt from Federal Regulations?

An answer to the "Is this Study Exempt from Federal Regulations?" question is required.

Indicate whether the study is exempt from Federal regulations for the Protection of Human Subjects.

For more information, see the NIH's Exempt Human Subjects Research infographic.

1.3 Exemption Number

The "Exemption Number" field is required if you selected "Yes" to the "Is this Study Exempt from Federal Regulations?" question.

Select the appropriate exemption number(s) for this particular study. Multiple selections are permitted. Do not select exemption 7 or 8, as these are not yet being used. Regardless of whether these exemptions may apply to you in the future, you must fill out your application following the instructions below. The instructions do not take exemption 7 and 8 into account.

For more information:

The categories of research that qualify for exemption are defined in the Common Rule for the Protection of Human Subjects. These regulations can be found at 45 CFR 46.

Need help determining the appropriate exemption number?

The Office of Human Research Protections (OHRP) guidance states that appropriate use of exemptions described in 45 CFR 46 should be determined by an authority independent from the investigators (for more information, see OHRP's Frequently Asked Questions). Institutions often designate their Institutional Review Board (IRB) to make this determination. Because NIH does not require IRB approval at the time of application, the exemptions designated often represent the opinion of the PD/PI, and the justification provided for the exemption by the PD/PI is evaluated during peer review.

1.4 Clinical Trial Questionnaire

The Clinical Trial Questionnaire is required.

Note for mechanistic studies: Many mechanistic studies (i.e., those designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention) meet the NIH definition of a clinical trial.

Answer "Yes" or "No" to the following questions to determine whether this study involves a clinical trial. Answer the following questions based only on the study you are describing in this study record.

1.4.a. Does the study involve human participants? Yes/No
1.4.b. Are the participants prospectively assigned to an intervention? Yes/No
1.4.c. Is the study designed to evaluate the effect of the intervention on the participants? Yes/No
1.4.d. Is the effect that will be evaluated a health-related biomedical or behavioral outcome? Yes/No

If you answered "Yes" to all the questions in the Clinical Trial Questionnaire, this study meets the definition of a clinical trial.

Refer to the table below for information about what sections of this form are required, based on your answers to Question 1.4 "Clinical Trial Questionnaire."

Form Section If you answered "yes" to all the questions in the Clinical Trial Questionnaire If you answered "no" to any of the questions in the Clinical Trial Questionnaire
Section 2 - Study Population
Characteristics
Required Required
Section 3 - Protection and
Monitoring Plans
Required Required
Section 4 - Protocol Synopsis Required Do not complete
Section 5 - Other Clinical Trial-related Attachments Required if specified in the FOA Do not complete
Additional Instructions for Career Development:

CDA applicants who are proposing to gain clinical trial research experience under a mentor's supervision (i.e., you will not be leading an independent clinical trial): Even if you answered "Yes" to all the questions in the Clinical Trial Questionnaire, only certain fields of the PHS Human Subjects and Clinical Trials Information form are required (and other fields are not allowed) because the study is not an independent clinical trial. Do not provide information in "Section 4 - Protocol Synopsis" or in "Section 5 - Other Clinical Trial-related Attachments" of the study record. Inputting information into these sections will result in errors and will prevent your application from being accepted.

You will generally follow the standard instructions to complete the PHS Human Subjects and Clinical Trials Information form, but follow relevant Career Development instructions where they are given.

Additional Instructions for Fellowship:

Fellowship applicants who are proposing to gain clinical trial research experience under a sponsor's supervision (i.e., you will not be leading an independent clinical trial): Even if you answered "Yes" to all the questions in the Clinical Trial Questionnaire, only certain fields of the PHS Human Subjects and Clinical Trials Information form are required (and other fields are not allowed) because the study is not an independent clinical trial. Do not provide information in "Section 4 - Protocol Synopsis" or in "Section 5 - Other Clinical Trial-related Attachments" of the study record. Inputting information into these sections will result in errors and will prevent your application from being accepted.

You will generally follow the standard instructions to complete the PHS Human Subjects and Clinical Trials Information form, but follow relevant Fellowship instructions where they are given.

For more information:

1.5. Provide the ClinicalTrials.gov Identifier (e.g., NCT87654321) for this trial, if applicable

If a clinical trial has already been entered into ClinicalTrials.gov, enter the ClinicalTrials.gov identifier (e.g., NCT87654321) for this trial.

If you are building on an existing study (e.g., ancillary study), enter the ClinicalTrials.gov identifier only for the ancillary study, not the parent study.

Section 2 - Study Population Characteristics

Who must complete "Section 2 - Study Population Characteristics:"

All of "Section 2 - Study Population Characteristics" is required for all human subjects studies unless either or both of the following apply to you:

2.1 Conditions or Focus of Study

At least 1 entry is required, and up to 20 entries are allowed. Each entry is limited to 255 characters.

Identify the name(s) of the disease(s) or condition(s) you are studying, or the focus of the study. If available, use appropriate descriptors from NLM's Medical Subject Headings (MeSH) so the application can be categorized. Include an entry for each condition.

2.2 Eligibility Criteria

List the study's inclusion and exclusion criteria. To provide a bulleted list, use a dash (or other character) followed by a space ("- ") at the start of each bullet. Be sure to check the formatting in the assembled application image. Further explanation or justification should be included in the Recruitment and Retention plan.

Your text entry is limited to 15,000 characters.

For more information about formatting text entry fields, see NIH's Rules for Text Fields page.

2.3 Age Limits

Minimum Age

Enter the numerical value for the minimum age a potential participant can be to be eligible for the study. Provide the relevant units of time (i.e., years, months, weeks, days, hours, or minutes). If there is no lower limit or no lower limit is known, enter "N/A (No Limit)" and do not enter a unit of time.

Maximum Age

Enter the numerical value for the maximum age a potential participant can be to be eligible for the study. Provide the relevant units of time (i.e., years, months, weeks, days, hours, or minutes). If there is no upper limit or no upper limit is known, enter "N/A (No Limit)" and do not enter a unit of time.

2.4 Inclusion of Women, Minorities, and Children

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Content:

Organize your attachment into two sections, following the headings and specified order below, and discuss each of the points listed below. Start each section with the appropriate section heading - "Inclusion of Women and Minorities" and "Inclusion of Children." Also include any additional information requested in the FOA.

You will also have to complete an Inclusion Enrollment Report (IER). Note that you may need to include multiple IERs for each study. Refer to the instructions for the IER below for more information.

1. Inclusion of Women and Minorities

Address the following points:

Existing Datasets or Resources. If you will use an existing dataset, resource, or samples that may have been collected as part of a different study, you must address inclusion, following the instructions above. Generally, you must provide details about the sex/gender, race, and ethnicity of the existing dataset/resource and justify the details as appropriate to the scientific goals of the proposed study.

For more information about what is considered an existing dataset or resource for inclusion policy, see the NIH FAQs on Monitoring Inclusion When Working with Existing Datasets and/or Resources.

NIH-Defined Phase III Clinical Trials. If the proposed research includes an NIH-Defined Phase III Clinical Trial, the "Inclusion of Women, Minorities, and Children" attachment MUST address plans for how sex/gender, race, and ethnicity will be taken into consideration in the design and valid analysis of the trial. See the instructions for "Valid Analysis" and "Plans to test for Differences in Effect among Sex/gender, Racial, and/or Ethnic Groups" below.

Additional information about valid analysis is available on the NIH Policy and Guidelines on The Inclusion of Women and Minorities as Subjects in Clinical Research page.

Valid Analysis (for NIH-Defined Phase III Clinical Trials only):

Address the following issues for ensuring valid analyses:

Plan to Test for Differences in Effect among Sex/gender, Racial, and/or Ethnic Groups (for NIH-Defined Phase III Clinical Trials only):

Applicants also should address whether they plan to test for differences in effect among sex/gender, racial, and/or ethnic groups and why such testing is or is not appropriate.

This plan must include selection and discussion of one of the following analysis plans:

2. Inclusion of Children

For the purposes of the Inclusion of Children, individuals under 18 are defined as a child; however, exclusion of any specific age or age range group (e.g., older adults) should be justified in this section. In addition, address the following points:

For more information, see:

2.5 Recruitment and Retention Plan

Who must complete the "Recruitment and Retention Plan" attachment:

The "Recruitment and Retention Plan" attachment is required unless either or both of the following apply to you:

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Content:

Describe how you will recruit and retain participants in your study. You should address both planned recruitment activities as well as proposed engagement strategies for retention.

2.6. Recruitment Status

Who must complete the "Recruitment Status" question:

The "Recruitment Status" question is required unless either or both of the following apply to you:

Content:

From the dropdown menu, select a single "Recruitment Status" that best describes the proposed study, based upon the status of the individual sites. If any facility in a multi-site study has an individual site status of "recruiting," then choose "recruiting" for this question. Only one selection is allowed. Choose from the following options:

2.7. Study Timeline

Who must complete the "Study Timeline" attachment:

The "Study Timeline" attachment is required unless either or both of the following apply to you:

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Content:

Provide a description or diagram describing the study timeline. The timeline should be general (e.g., "one year after notice of award"), and should not include specific dates.

Note: Additional milestones or timelines may be requested as just-in-time information or post-award.

2.8. Enrollment of First Subject

Who must complete the "Enrollment of First Subject" question:

The "Enrollment of First Subject" question is required unless either or both of the following apply to you:

Content:

Enter the date (MM/DD/YYYY) of the enrollment of the first subject into the study. From the dropdown menu, select whether this date is anticipated or actual.

Inclusion Enrollment Report(s)

Who must complete the Inclusion Enrollment Report(s):

An Inclusion Enrollment Report is required for all human subjects studies unless, on Question 1.3 "Exemption Number," you selected only Exemption 4 and no other exemptions.

Using the Inclusion Enrollment Report:

Each proposed study, unless it falls under Exemption 4, must contain at least one Inclusion Enrollment Report (IER). However, more than one IER per study is allowed.

Once you have added an IER for a given study, you may edit, remove, or view it.

Note: The IER format should NOT be used for collecting data from study participants.

Note: You can add a maximum of 20 IERs per study record. These can be a combination of planned and cumulative reports.

Multi-site studies: Generally, if the application includes a study recruiting subjects at more than one site/location, investigators may create one IER or separate, multiple IERs to enable reporting by study or by site, depending on the scientific goals of the study and whether monitoring of inclusion enrollment would benefit from being combined or separated. At a minimum, participants enrolled at non-U.S. sites must be reported separately from participants enrolled at U.S. sites, even if they are part of the same study. Please review the FOA to determine whether there are any other specific requirements about how to complete the IER.

Duplicative Inclusion Reports: It is important that the IER for a given study be associated with only one application and be provided only once in a given application (e.g., do not submit the same IER on both the data coordinating center and the research site). If submitting individual application(s) as part of a network or set of linked applications, please provide the IER with the individual site applications unless otherwise directed by the FOA.

Renewal applications: When preparing a renewal (or resubmission of a renewal), investigators should provide a narrative description regarding the cumulative enrollment from the previous funding period(s) as part of the progress report section of the research strategy attachment in the application. The IER should NOT be used for this purpose. If a given study will continue with the same enrollment or additional enrollment, or if new studies are proposed, provide a new IER for each as described in the instructions below.

Resubmission applications: If IERs were provided in the initial submission application, and if those studies will be part of the resubmission application, complete the IER and submit again with the resubmission application, regardless of whether the enrollment has changed or not. Also, provide any new (additional) IERs.

Revision applications: Provide an IER if new studies are planned as part of the Revision and they meet the NIH definition for clinical research.

Additional Instructions for Multi-project:

For multi-project applications with studies that are self-contained within a single component:

Other Component: Include the IER(s) with the component(s) that involves the study(s), unless otherwise directed by the FOA.

For multi-project applications with studies that span components:

Overall Component: Should the study span more than one component, include the IER with the study record in the Overall Component and insert a comment in the comment field of the IER to indicate what other components it is associated with.

For more information:

Refer to the Inclusion of Women and Minorities as Participants in Research Involving Human Subjects - Policy Implementation Page.

1. Using an Existing Dataset or Resource?

The "Using an Existing Dataset or Resource" question is required.

Indicate whether this study involves the use of an existing dataset or resource.

For additional guidance on what is considered an existing dataset, refer to the NIH FAQs on Monitoring Inclusion When Working with Existing Datasets and/or Resources.

2. Enrollment Location Type (Domestic/Foreign)

The "Enrollment Location Type" field is required.

Select whether the participants described in the IER are based at a U.S. (Domestic) or at a non-U.S. (Foreign) site. At a minimum, participants at U.S. and non-U.S. sites must be reported separately (i.e., on separate IERs), even if it is for the same study.

For additional guidance on how to complete the IER if you will be working with non-U.S. populations, refer to these FAQs on Monitoring Inclusion in Non-US Research Participants.

3. Enrollment Country(ies)

The "Enrollment Country(ies)" field is optional.

Indicate the enrollment country or countries for the participants. Multiple U.S. sites can be reported together in one IER. Foreign countries can be reported together in one IER. However, you must use separate IERs for U.S. and non-U.S. sites. You can add up to 200 countries per IER.

4. Enrollment Location(s)

The "Enrollment Location(s)" field is optional.

Indicate the type of enrollment location (e.g., hospital, university, or research center), not the name of the enrollment location.

Enrollment locations are typically where the research is conducted, and can be different from the recruitment site.

5. Comments

Your comments are limited to 500 characters.

Enter information you wish to provide about this IER. This includes, but is not limited to, addressing information about distinctive subpopulations if relevant to the scientific hypotheses being studied. If inclusion monitoring is conducted on another study or NIH grant (e.g., data coordinating center or research site), please indicate here.

Revision applications: If there are no updates to the IER(s) in your original grant application, do not include an IER in your Revision application. Instead, provide a comment in this field to the effect that previous IER(s) are still applicable. If you are revising the IER(s) in your original grant application, provide a comment here to that effect.

Additional Instructions for Multi-project:

For multi-project applications with studies that span components:

Overall Component: Should the study span more than one component, include the IER with the study record in the Overall Component and insert a comment here in the comment field to indicate what other components it is associated with.

Planned

Who must complete planned enrollment tables:

You must enter planned enrollment counts if your proposed study will not use an existing dataset or resource. Planned enrollment generally means that individuals will be recruited into the study and/or that individuals have already been recruited and continue to be part of the study.

For more information about what is considered an existing dataset or resource for inclusion policy, see the NIH FAQs on Monitoring Inclusion When Working with Existing Datasets and/or Resources.

For more information on racial categories, see the NIH Glossary definition of Racial Categories.

For more information on ethnic categories, see the NIH Glossary definition of Ethnic Categories.

Racial Categories

American Indian/Alaska Native:

These fields are required.

Enter the expected number of females and males (in the respective fields) who are both American Indian/Alaska Native and Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who are both American Indian/Alaska Native and Hispanic or Latino.

Asian:

These fields are required.

Enter the expected number of females and males (in the respective fields) who are both Asian and Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who are both Asian and Hispanic or Latino.

Native Hawaiian or Other Pacific Islander:

These fields are required.

Enter the expected number of females and males (in the respective fields) who are both Native Hawaiian or Other Pacific Islander and Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who are both Native Hawaiian or Other Pacific Islander and Hispanic or Latino.

Black or African American:

These fields are required.

Enter the expected number of females and males (in the respective fields) who are both Black or African American and Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who are both Black or African American and Hispanic or Latino.

White:

These fields are required.

Enter the expected number of females and males (in the respective fields) who are both White and Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who are both White and Hispanic or Latino.

More than One Race:

These fields are required.

Enter the expected number of females and males (in the respective fields) who both identify with more than one racial category and are Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who both identify with more than one racial category and are Hispanic or Latino.

Total:

The total fields at the bottom will be automatically calculated and reflect the totals of all racial categories for females, males, and individuals of unknown/not reported sex/gender who are Not Hispanic or Latino and of all racial categories for females, males, and individuals of unknown/not reported sex/gender who are Hispanic or Latino. The "Total" fields in the right column will be automatically calculated to total all individuals.

Cumulative (Actual)

Who must complete cumulative (actual) enrollment tables:

You must enter cumulative enrollment counts if your proposed study will use an existing dataset or resource.

For more information about what is considered an existing dataset or resource for inclusion policy, see the NIH FAQs on Monitoring Inclusion When Working with Existing Datasets and/or Resources.

For more information on racial categories, see the NIH Glossary definition of Racial Categories.

For more information on ethnic categories, see the NIH Glossary definition of Ethnic Categories.

Racial Categories

American Indian/Alaska Native:

These fields are required.

Enter the number of females and males (in the respective fields) who are both American Indian/Alaska Native and Not Hispanic or Latino. Enter the number of females and males (in the respective fields) who are both American Indian/Alaska Native and Hispanic or Latino. Use the "Unknown/Not Reported" fields as needed (i.e., race and/or ethnicity is unknown).

Asian:

These fields are required.

Enter the number of females and males (in the respective fields) who are both Asian and Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who are both Asian and Hispanic or Latino. Use the "Unknown/Not Reported" fields as needed (i.e., race and/or ethnicity is unknown).

Native Hawaiian or Other Pacific Islander:

These fields are required.

Enter the number of females and males (in the respective fields) who are both Native Hawaiian or Other Pacific Islander and Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who are both Native Hawaiian or Other Pacific Islander and Hispanic or Latino. Use the "Unknown/Not Reported" fields as needed (i.e., race and/or ethnicity is unknown).

Black or African American:

These fields are required.

Enter the number of females and males (in the respective fields) who are both Black or African American and Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who are both Black or African American and Hispanic or Latino. Use the "Unknown/Not Reported" fields as needed (i.e., race and/or ethnicity is unknown).

White:

These fields are required.

Enter the number of females and males (in the respective fields) who are both White and Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who are both White and Hispanic or Latino. Use the "Unknown/Not Reported" fields as needed (i.e., race and/or ethnicity is unknown).

More than One Race:

These fields are required.

Enter the number of females and males (in the respective fields) who both identify with more than one racial category and are Not Hispanic or Latino. Enter the expected number of females and males (in the respective fields) who both identify with more than one racial category and are Hispanic or Latino. Use the "Unknown/Not Reported" fields as needed (i.e., race and/or ethnicity is unknown).

Unknown or Not Reported:

These fields are required.

Enter the number of females, males, and individuals of unknown/not reported sex/gender (in the respective fields) whose race is unknown/not reported and who are Not Hispanic or Latino. Enter the number of females, males, and individuals of unknown/not reported sex/gender (in the respective fields) whose race is unknown/not reported and who are Hispanic or Latino. Enter the number of females, males, and individuals of unknown/not reported sex/gender (in the respective fields) who are both of unknown/not reported race and of unknown/not reported ethnicity. Use the "Unknown/Not Reported" fields as needed (i.e., race and/or ethnicity is unknown).

Total:

The total fields at the bottom will be automatically calculated and reflect the totals of all racial categories for females, males, and individuals of unknown/not reported sex/gender who are Not Hispanic or Latino and of all racial categories for females, males, and individuals of unknown/not reported sex/gender who are Hispanic or Latino. Use the "Unknown/Not Reported" fields as needed (i.e., race and/or ethnicity is unknown). The "Total" fields in the right column will be automatically calculated to total all individuals.

Section 3 - Protection and Monitoring Plans

Who must complete "Section 3 - Protection and Monitoring Plans:"

All of "Section 3 - Protection and Monitoring Plans" is required for all studies involving human subjects, unless otherwise noted.

3.1 Protection of Human Subjects

The "Protection of Human Subjects" attachment is required.

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Do not use the "Protection of Human Subjects" attachment to circumvent the page limits of the Research Strategy.

For Human Subjects Research Claiming Exemptions: If you are claiming that your human subjects research falls under any exemptions, justify why the research meets the criteria for the exemption(s) that you have claimed. This justification should explain how the proposed research meets the criteria for the exemption claimed. Do not merely repeat the criteria or definitions themselves.

For Studies that involve Non-Exempt Human Subjects Research: For any proposed non-exempt study involving human subjects, NIH requires a Protection of Human Subjects attachment that is commensurate with the risks of the study, its size, and its complexity. Organize your attachment into four sections, following the headings and specified order below, and discuss each of the points listed below. Start each section with the appropriate section heading - Risks to Human Subjects, Adequacy of Protection Against Risks, Potential Benefits of the Proposed Research to Research Participants and Others, and Importance of the Knowledge to be Gained. Also include any additional information requested in the FOA.

1. Risks to Human Subjects

a. Human Subjects Involvement, Characteristics, and Design

b. Study Procedures, Materials, and Potential Risks

2. Adequacy of Protection Against Risks

a. Informed Consent and Assent

b. Protections Against Risk

c. Vulnerable Subjects, if relevant to your study

Explain the rationale for the involvement of special vulnerable populations, such as fetuses, neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations. 'Prisoners' includes all subjects involuntarily incarcerated (for example, in detention centers).

Pregnant Women, Fetuses, and Neonates or Children

If the study involves vulnerable subjects subject to additional protections under Subparts B and D (pregnant women, fetuses, and neonates or children), provide a clear description of the risk level and additional protections necessary to meet the HHS regulatory requirements.

Prisoners

If the study involves vulnerable subjects subject to additional protections under Subpart C (prisoners), describe how proposed research meets the additional regulatory requirements, protections, and plans to obtain OHRP certification for the involvement of prisoners in research.

Refer to HHS regulations, and OHRP guidance:

3. Potential Benefits of the Proposed Research to Research Participants and Others
4. Importance of the Knowledge to be Gained

For more information:

Refer to the NIH's Research Involving Human Subjects site.

3.2 Is this a multi-site study that will use the same protocol to conduct non-exempt human subjects research at more than one domestic site?

Select "Yes" or "No" to indicate whether this is a multi-site study that will use the same protocol to conduct non-exempt human subjects research at more than one domestic site.

Select "N/A" only if any of the following apply (do not select "N/A" if none of the following apply):

Applicants who check "Yes" are expected to use a single Institutional Review Board (sIRB) to conduct the ethical review required by HHS regulations for the Protections of Human Subjects Research.

Note: The NIH sIRB policy applies to participating domestic sites. Foreign sites participating in NIH-funded, multi-site studies are not expected to follow this policy.

Additional Instructions for Career Development:

Check "N/A," as the sIRB policy does not apply to career development awards.

Additional Instructions for Training:

Check "N/A," as the sIRB policy does not apply to training awards.

Additional Instructions for Fellowship:

Check "N/A," as the sIRB policy does not apply to fellowship awards.

For more information:

If yes, describe the single IRB plan

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Although one sIRB attachment per application is sufficient, you must include a file for each study within your application. All file names within your application must be unique. You may either attach the same sIRB plan (with different file names) to different studies or attach a file that refers to the sIRB plan in another study within your application. For example, you may attach a file that says "See sIRB plan in the 'My Unique Study Name' study."

Content:

The sIRB plan should include the following elements:

For Studies with Legal-, Regulatory-, or Policy-based Claims for Exception as described by the sIRB Policy: Indicate that review by an sIRB will not be possible for all or some sites (specify which sites) because local IRB review is required by an existing federal/state/tribal law or policy. Include a specific citation to the relevant law, policy, or regulation.

For sites requesting an exception based on compelling justification: Indicate which site(s) is requesting an exception to the use of the sIRB and provide compelling justification based on ethical or human subjects protection issues or other well-justified reasons. NIH will determine whether to grant an exception following an assessment of the need. Note: If you intend to request an exception to the sIRB policy based on compelling justification, do not account for this exception in your proposed budget. The proposed budget must reflect any necessary sIRB costs without an exception (i.e., applicants should not assume that an exception will be granted when considering what sIRB costs to include in the budget).

For more information:

3.3 Data and Safety Monitoring Plan

A "Data and Safety Monitoring Plan" attachment is required if you answered "Yes" to all the questions in the "Clinical Trial Questionnaire." The "Data and Safety Monitoring Plan" attachment is optional for all other human subjects research.

For human subjects research that does not involve a clinical trial: Your study, although it is not a clinical trial, may have significant risks to participants, and it may be appropriate to include a data and safety monitoring plan. If you choose to include a data and safety monitoring plan, you may follow the content criteria listed below, as appropriate.

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Content:

Additional Instructions for Career Development:

CDA applicants who are proposing to gain clinical trial research experience under a mentor's supervision (i.e., you will not be leading an independent clinical trial): Include only the following information in your data and safety monitoring plan (i.e., do not follow the standard instructions for the data and safety monitoring plan):

  • The names of the individual(s) or group that will be responsible for trial monitoring (i.e., the lead investigator of the clinical trial)
  • If applicable, the name of an independent safety monitor or a data and safety monitoring board
Additional Instructions for Fellowship:

Fellowship applicants who are proposing to gain clinical trial research experience under a sponsor's supervision (i.e., you will not be leading an independent clinical trial): Include only the following information in your data and safety monitoring plan (i.e., do not follow the standard instructions for the data and safety monitoring plan):

  • The names of the individual(s) or group that will be responsible for trial monitoring (i.e., the lead investigator of clinical trial)
  • If applicable, the name of an independent safety monitor or a data and safety monitoring board

For any proposed clinical trial, NIH requires a data and safety monitoring plan (DSMP) that is commensurate with the risks of the trial, its size, and its complexity. Provide a description of the DSMP, including:

For more information:

3.4 Will a Data and Safety Monitoring Board be appointed for this study?

The "Data Safety and Monitoring Board" question is required if you answered "Yes" to all the questions in the "Clinical Trial Questionnaire." This question is optional for all other human subjects research.

Check the appropriate box to indicate whether a Data Safety and Monitoring Board (DSMB) will be appointed for this study.

3.5 Overall Structure of the Study Team

The "Overall Structure of the Study Team" attachment is required if you answered "Yes" to all the questions in the "Clinical Trial Questionnaire." This question is optional for all other human subjects research.

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Content:

Provide a brief overview of the organizational structure of the study team, particularly the administrative sites, data coordinating sites, enrollment/participating sites, and any separate laboratory or testing centers.

Note: Do not include study team members' individual professional experiences (i.e., biosketch information).

Section 4 - Protocol Synopsis

Who must complete "Section 4 - Protocol Synopsis:"

If you answered "Yes" to all the questions in the "Clinical Trial Questionnaire:" All the questions in the "Protocol Synopsis" section are required.

If you answered "No" to any question in the "Clinical Trial Questionnaire:" Do not provide information in this section. Inputting information in this section will result in errors and will prevent your application from being accepted.

Additional Instructions for Career Development:

CDA applicants who are proposing to gain clinical trial research experience under a mentor's supervision (i.e., you will not be leading an independent clinical trial): Do not provide information in "Section 4 - Protocol Synopsis." Inputting information in this section will result in errors and will prevent your application from being accepted.

Additional Instructions for Fellowship:

Do not provide information in "Section 4 - Protocol Synopsis." Inputting information in this section will result in errors and will prevent your application from being accepted.

4.1 Brief Summary

Enter a brief description of objectives of the protocol, including the primary and secondary endpoints. The Brief Summary is limited to 5,000 characters.

For more information about formatting text entry fields, see NIH's Rules for Text Fields page.

4.2. Study Design

4.2.a. Narrative Study Description

Enter a narrative description of the protocol. Studies differ considerably in the methods used to assign participants and deliver interventions. Describe your plans for assignment of participants and delivery of interventions. You will also need to show that your methods for sample size and data analysis are appropriate given those plans. For trials that randomize groups or deliver interventions to groups, special methods are required; additional information is available at the Research Methods Resources webpage.

The narrative description is limited to 32,000 characters.

For more information about formatting text entry fields, see NIH's Rules for Text Fields page.

4.2.b. Primary Purpose

Enter or select from the dropdown menu a single "Primary Purpose" that best describes the clinical trial. Choose from the following options:

4.2.c. Interventions

Complete the "Interventions" fields for each intervention to be used in your proposed protocol. If an arm of the study to which subjects will be assigned (as discussed in 4.2.a. Narrative Study Description) includes more than one intervention (e.g., drug plus educational intervention), complete this section for each intervention. You can add up to 20 interventions.

Intervention Type: Enter or select from the dropdown menu the intervention type the clinical trial will administer during the proposed award. Choose from the following options:

Name: Enter the name of the intervention. The name must be unique within each study record. The name is limited to 200 characters.

Description: Enter a description of the intervention. The description is limited to 1,000 characters.

4.2.d. Study Phase

Enter or select from the dropdown menu a "Study Phase" that best describes the clinical trial. If your study involves a device, choose "Other."

Choose from the following options:

Is this an NIH-defined Phase III clinical trial? Yes/No

Select "Yes" or "No" to indicate whether the study includes an NIH-defined Phase III clinical trial.

4.2.e. Intervention Model

Enter or select from the dropdown menu a single "Intervention Model" that best describes the clinical trial. If you select "Other," provide a description in the space provided. Choose from the following options:

4.2.f. Masking

Select "Yes" or "No" to indicate whether the protocol uses masking. Note that masking is also referred to as "blinding."

If you answered "Yes" to the "Masking" question, select one or more types of masking that best describes the protocol. Choose from the following options:

4.2.g. Allocation

Enter or select from the dropdown menu a single "Allocation" that best describes how subjects will be assigned in your protocol. If allocation is not applicable to your clinical trial, select "N/A" (e.g., for a single-arm trial). Choose from the following options:

4.3. Outcome Measures

Complete the "Outcome Measures" fields for each primary, secondary, and other important measures to be collected during your proposed clinical trial. You may have more than one primary outcome measure, and you can add up to 50 outcome measures.

Name: Enter the name of the individual outcome measure. The outcome measure must be unique within each study record.

Type: Enter or select from the dropdown menu the type of the outcome measure. Choose from the following options:

Time Frame: Indicate when a measure will be collected for analysis (e.g., baseline, post-treatment).

Brief Description: Describe the metric used to characterize the outcome measure if the metric is not already included in the outcome measure name. Your description is limited to 999 characters.

4.4. Statistical Design and Power

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Content:

Specify the number of subjects you expect to enroll, the expected effect size, the power, and the statistical methods you will use with respect to each outcome measure you listed in 4.3 Outcome Measures.

You will need to show that your methods for sample size and data analysis are appropriate given your plans for assignment of participants and delivery of interventions. For trials that randomize groups or deliver interventions to groups, special methods are required; additional information is available at the Research Methods Resources webpage.

4.5 Subject Participation Duration

Enter the time (e.g., in months) it will take for each individual participant to complete all study visits. If the participation duration is unknown or not applicable, write "unknown" or "not applicable." The subject participation duration is limited to 255 characters.

4.6 Will the study use an FDA-regulated intervention?

Select "Yes" or "No" to indicate whether the study will use an FDA-regulated intervention (see the definition of "FDA Regulated Intervention" under the Oversight section of the ClinicalTrials.gov Protocol Registration Data Element Definitions for Interventional and Observational Studies page).

4.6.a. If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status:

This attachment is required if you answered "Yes" to the "Will the study use an FDA-regulated intervention?" question.

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Content:

Describe the availability of study agents and support for the acquisition and administration of the study agent(s). Please indicate the IND/IDE status of the study agent, if applicable, and whether the investigators have had any interactions with the FDA. If the study agent currently has an IND/IDE number, provide that information. Note: The awarding component may request consultation with the FDA and the IND/IDE sponsor about the proposed clinical trial after peer review and prior to award.

4.7 Dissemination Plan

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

Although one Dissemination Plan per application is sufficient, you must include a file for each study within your application. All file names within your application must be unique. You may either attach the same Dissemination Plan to different studies or attach a file that refers to the Dissemination Plan in another study within your application. For example, you may attach a file that says "See Dissemination Plan in the 'My Unique Study Name' study."

Content:

Explain briefly your plan for the dissemination of NIH-funded clinical trial information and address how the expectations of the policy will be met. The plan must contain sufficient information to assure the following:

Note: Do not include informed consent documents in your application.

Note: If your human subjects study meets the definition of "Delayed Onset," include the dissemination plan in the delayed onset study justification.

For more information:

See the NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information.

Section 5 - Other Clinical Trial-related Attachments

Who must complete "Section 5 - Other Clinical Trial-related Attachments:"

If you answered "Yes" to all the questions in the "Clinical Trial Questionnaire:" Include an attachment only if your FOA specifies that an attachment(s) is required or permitted; otherwise, do not include any Other Clinical Trial-related attachments.

If you answered "No" to any question in the "Clinical Trial Questionnaire:" Do not provide information in this section. Inputting information in this section will result in errors and will prevent your application from being accepted.

Additional Instructions for Career Development:

CDA applicants who are proposing to gain clinical trial research experience under a mentor's supervision (i.e., you will not be leading an independent clinical trial): Do not provide information in "Section 5 - Other Clinical Trial-related Attachments." Inputting information in this section will result in errors and will prevent your application from being accepted.

Additional Instructions for Fellowship:

Fellowship applicants proposing to gain clinical trial research experience under a sponsor's supervision (i.e., you will not be leading an independent clinical trial: Do not provide information in "Section 5 - Other Clinical Trial-related Attachments." Inputting information in this section will result in errors and will prevent your application from being accepted.

5.1 Other Clinical Trial-related Attachments

Format:

Attach this information as a PDF file. See NIH's Format Attachments page.

A maximum of 10 PDF attachments is allowed in the "Other Clinical Trial-related Attachments" section.

Content:

Provide additional trial-related information only if your FOA specifically requests it. Include only attachments requested in the FOA, and use requested file names. If a specific file name is not given in the FOA, use a meaningful file name since it will become a bookmark in the assembled application image.