NIH Clinical Trials and Human Subjects

In 2018, NIH greatly expanded which studies meet the definition of a clinical trial. Complete the questionnaire below (or the online questionnaire) to determine if your study meets the definition of a clinical trial:

1. Does the study involve human participants?
2. Are the participants prospectively assigned to an intervention?
3. Is the study designed to evaluate the effect of the intervention on the participants?
4. Is the effect that will be evaluated a health-related biomedical or behavioral outcome?

If you answered YES to all questions, your study is a clinical trial (even if it has previously not been defined as a clinical trial).

Be sure to verify that the funding opportunity announcement to which you are applying allows clinical trials. 

Find Grant Funding 

If you are not sure if your research involves the use of human subjects or whether it is exempt from federal regulations, NIH has developed an Infopath Questionnaire to help you determine what type of study you are proposing: 

Decision Tool: Am I Doing Human Subjects Research?

Depending on the type of study you are proposing in your application, the links below will help guide you through the NIH application requirements for each type of study.

Type of StudyDescription

Non-Exempt Human Subjects

• Studies which propose human subjects that do not meet any of the exemption criteria and that DO NOT meet the definition of a Clinical Trial.

Exempt Human Subjects

• Research involving the collection or study of existing data and/or specimens if publicly available or information recorded such that subjects cannot be identified.

Delayed Onset Studies

• Studies for which there is no well-defined plan for human subject involvement at the time of submission.

Clinical Trials

• Studies that involve human participants prospectively assigned to an intervention where the study is designed to evaluate the effect of the intervention on the participants and whose effect is a health-related or behavioral outcome.

No Human Subjects

• Studies that involve the use of human data and/or specimens but that do not constitute the use of human subjects

A full menu of templates and guidelines for the PHS Human Subjects and Clinical Trials Information Form is below. To view templates and guidelines organized by type of study (non-exempt, exempt, delayed onset, clinical trial, no human subjects) click the "What Do I Need to Know?" tab.

• Conditions or Focus of the Study (text field)
• Eligibility Criteria (text field)
• Inclusion of Individuals Across the Lifespan (attachment)
• Inclusion of Women and Minorities (attachment)
• Recruitment and Retention Plan (attachment)
• Study Timeline (attachment)
• Protection of Human Subjects (attachment)
• Protection of Human Subjects (Exempt Studies Only) (attachment)
• Single IRB (sIRB) Plan (attachment)
• Data and Safety Monitoring Plan (attachment)
• Overall Structure of the Study Team (attachment)
  • For free, editable Study Team templates, contact gsu@mednet.ucla.edu
• Detailed Description (text field)
• Interventions (text field)
• Study Phase (drop-down)
• Outcomes and Measures (text field)
• Statistical Design and Power (attachment)
• FDA-regulated Interventions (attachment)
• Dissemination Plan (attachment)
• Delayed Onset Justification (attachment)
• No Human Subjects Justification (attachment)

For a general overview of the changes and its implications for NIH applications on or after January 25th, 2018, view our PowerPoint. 

GSU video NIH updates

In addition to resources provided by the UCLA CTSI, below are additional resources and helpful links that can help provide additional guidance on your NIH application and studies:

• UCLA IRB Office  
• NIH Inclusion Across the Lifespan Policy Information
• NIH Inclusion Across the Lifespan: Guidance for Applying the Policy (PDF)
• NIH PHS Human Subjects and Clinical Trials Information Form (PDF)
• NIH Interactive Questionnaire, “Does your human subjects research study meet the NIH definition of a clinical trial?”
• NIH Infopath Questionnaire
• NIH Definition of Clinical Trial Case Studies
• NIH Funding Opportunities
• ClinicalTrials.gov Protocol Registration Data Element Definitions
• Overview of New NIH Policies on Human Subjects Research (video)

Resources for applications on or after January 25th, 2023:

• New NIH FORMS-H Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2022
• NIH High-Level Grant Application Form Change Summary for FORMS-H
• NIH Annotated Form Set for FORMS-H 
• NIH SF424 FORMS-H

CTSI Grants Submission Unit (GSU)
Email: gsu@mednet.ucla.edu
GSU 

CTSI Biostat Support (for Non-Cancer studies) provided by the Biostatistical, Epidemiology and Research Design (BERD) program
Email: domstat@mednet.ucla.edu
BERD

CTSI ResearchGo (including Good Clinical Practice, Study Protocol templates, FDA guidance, etc)
Email: ResearchGo@mednet.ucla.edu
ResearchGo

Most NIH funding opportunity announcements (FOAs) state within the title whether clinical trials are allowed. There are four categories: 1) Clinical Trials Not Allowed, 2) Clinical Trials Optional, 3) Clinical Trials Required, and 4) Basic Experimental Studies involving Humans (BESH).

If these designations are not listed in the title of the FOA, check Section II. Award Information subsection titled “Clinical Trial?” which will list whether clinical trials are allowed, required, or optional.

In addition, many parent grants have been reissued as two separate FOAs to distinguish projects that will involve clinical trials and those that do not. For instance, the NIH Research Project Grant is now split into two funding opportunities: PA-20-185, NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) and PA-20-183, NIH Research Project Grant (Parent R01 Clinical Trial Required).

The NIH also recently created an additional option for R01 applications: Basic Experimental Studies involving Humans (BESH). According to the NIH, "These studies fall within the NIH definition of a clinical trial and also meet the definition of basic research. Types of studies that should submit under this FOA include those that prospectively assign human participants to conditions and that assess biomedical or behavioral outcomes in humans for the purpose of understanding the fundamental aspects of phenomena WITHOUT specific application towards processes or products in mind."

Please note that the requirements for applying for a BESH study will still be the same as those for applying for a CT.

Like parent announcements for clinical trials and non-clinical trials, there is a separate parent announcement for BESH opportunities.

For more information on this type of study, please see NOT-OD-18-212 or give us a call.

NIH has greatly expanded which studies meet the definition of a clinical trial. Many behavioral mechanistic studies now fall into the category of a clinical trial. To determine whether this might be the case for your proposal, complete the questionnaire to determine if your study meets the definition of a clinical trial.

If you are still unsure, NIH has clinical trial case studies designed to help you define your study:

NIH Definition of Clinical Trial Case Studies

NIH defines a study record as, “a set of data elements associated with a study involving human subjects. Each proposed protocol must have its own study record.” In terms of an NIH application involving human subjects, each proposed study within the application must have its own study record within the PHS Human Subjects and Clinical Trials Information Form, customized to the individual study.

NIH definition of study record

The NIH recommends that in many cases, applications only require a single study record. A study record can cover multiple hypotheses, aims, and/or processes. If your study records would duplicate much of the information input into study record fields on the PHS Human Subjects and Clinical Trials Information Form, you probably only need 1 study record.

If you anticipate that you will need multiple distinct protocols, then multiple study records may be preferable at the application phase. Two separate types of studies may also require separate study records (i.e., if your study is proposing 1 RCT and 1 delayed onset study). If you are unsure, it is better to consolidate than to create too many records. NIH has confirmed that they will not turn away applications if they do not contain enough study records, as long as enough information is provided to ensure a proper review. The structure of the study records can be adjusted later, if needed.

NIH instructions for study records

NIH provides rules for text fields. In short, each text field has a specific character limit that must be adhered to. Characters must be in plain text and cannot incorporate smart/curly quotes (“ ”), EM/Long dashes (—) or proprietary fonts or special characters. All formatting will be lost (including bolding, bullet points, subscripts, and superscripts). Tables, graphics, and figures are also not allowed.

NIH recommends that to format paragraph spaces, include a blank line between paragraphs. To format bullet lists (i.e., for Eligibility Criteria), use “list item” characters such as hyphen (-) or asterisk (*) followed by a space and then the item list.

Medical Subject Headings (MeSH) are NLM’s curated medical vocabulary of keywords for which studies and publications are organized. NLM has created a hierarchically organized terminology for indexing and cataloging biomedical information such as MEDLINE/PubMed and other NLM databases.

If you are unsure of the MeSh Terms for the particular condition or focus of your study, NLM provides an easy MeSH-on-Demand search function.

However, it should be noted that the “Condition or Focus of the Study” does not apply to all aspects of human subject recruitment. For instance, studies that will recruit healthy volunteers to compare against a specific disease would not need to include the MeSH term for healthy volunteers unless those health subjects were the focus of the study.

If your study, whether a clinical trial or not, involves more than 1 interaction point for participants (e.g., multiple visits, longitudinal follow-up, etc.), NIH requires that you provide a retention plan to mitigate potential loss/dropout rates, which decrease power for statistical analyses. This is particularly important if you anticipate that retention will be difficult.

If the participants will only be seen once, it is sufficient to simply acknowledge this in the Retention Plan component.

The Recruitment and Retention Plan replaces the “Recruitment and Informed Consent” section of the Protection of Human Subjects document. More information can be found in the Retention Plan Guidelines (Word document).

The NIH SF 424 Forms H Guidelines instructions for the study timelines state that you should “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.” However, investigators should consider that the study timeline is now part of the additional review criteria for applications involving clinical trials. Study timelines should therefore follow the NIH review criteria in addition to the instructions above. Reviews will evaluate your timeline on the following:

Study timeline is described in detail Study timeline takes into account start-up activities, anticipated rate of enrollment, and planned follow-up assessment Project timeline must be feasible and well justified Project should incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative databases, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate Study timeline should address potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)

3. https://grants.nih.gov/grants/how-to-apply-application-guide/forms-h/general/g.500-phs-human-subjects-and-clinical-trials-information.htm#2.7

Currently, the UCLA CTSI provides free statistical design, analyses and guidance on grant applications. They can help advise faculty on how best to approach the new Statistical Design and Power document as well as how to incorporate this information into the overall research strategy. Contact information is listed below:

CTSI Biostat Support
Email: domstat@mednet.ucla.edu
Website: https://ctsi.ucla.edu/about/programs/pages/bio_prog

Within the Resource Sharing Plan, NIH applications seeking $500,000 or more in direct costs in any 1 budget year are expected to address a Data Sharing Plan (or if required by the funding opportunity announcement). The Data Sharing Plan should cover how final research data will be shared. This typically includes publications, conferences, and allowing others protected access to the data generated via NIH funds.

However, within the PHS Human Subjects and Clinical Trials Information Form, a dissemination plan is required if your study is a clinical trial in order to describe the plan for the dissemination of NIH-funded clinical trial information and address how you will meet NIH’s policy on the dissemination of NIH-funded clinical trial information. This does NOT include data dissemination but should cover the following 3 points: 1) ensuring that clinical trials are registered and results submitted to ClinicalTrials.gov, 2) clarifying that any informed consent documents will include specific statements relating to the posting of all relevant information to ClinicalTrials.gov, and 3) stating that your institution has an internal policy in place to ensure that clinical trials registration and results reporting occur in compliance with policy requirements.

For applications that include more than one clinical trial, you only need 1 dissemination plan that covers all proposed trials. See the Dissemination Plan Guidance (Word Doc) for additional guidance on how to draft this document. Contact ctsiora@mednet.ucla.edu for additional guidance, if needed.

UCLA, along with all CTSA sites and hundreds of other research institutions, are signatories to the SMART IRB agreement. Under SMART IRB, signatory institutions can enter into a single IRB arrangement for any study without negotiating a separate agreement. This is the preferred arrangement for UCLA, whenever possible. See the Single IRB (sIRB) Plan (Word Doc) for additional guidance and specific NIH requirements.

If you are preparing a domestic multi-site proposal, it is also recommended that you contact irbreliance@research.ucla.edu for guidance specific to your study before completing the sIRB Plan.

All subaward sites involved in your application must agree to the proposed Single IRB Plan included in the application.

For applications on or after January 25, 2019, all exempt and non-exempt human subjects research must submit a plan for including individuals across the lifespan or, if excluding based on age, provide a rationale and justification for the chosen age range.

In light of additional changes the NIH made for applications due on or after May 25, 2020 (Forms-G), you should now have two inclusion documents: Inclusion of Individuals Across the Lifespan, and Inclusion of Women and Minorities. Guidance can be found in Inclusion of Individuals Across theLifespan Guidelines (WORD) and Inclusion of Women and Minorities Guidelines (WORD).

NIH provides guidance on acceptable justifications for exclusion here:

• NIH Inclusion Across the Lifespan Policy Information
• NIH Inclusion Across the Lifespan: Guidance on Applying the Policy (PDF)

The SF 424 FORMS H states that the “Research Strategy attachment should be used to discuss the overall strategy, methodology, and analyses of the proposed research, but applicants should not duplicate information collected in the new PHS Human Subjects and Clinical Trials Information form.”

Similar to how biosketch information is traditionally not repeated within the research strategy, the full details of human subjects and clinical trials research should not simply be copied/pasted into the research strategy or vice versa.

This includes not duplicating information found on documents such as Statistical Design and Power (for clinical trials), Study Timelines (for research involving human subjects), and Protocol Overviews (in the Narrative Study Description for clinical trials).

Guidance thus far has been that the research strategy should provide high-level overviews for overall methodology and analysis but applicants should refer reviewers to detailed information in the correct components (e.g., “See Statistical Design and Power for more details”), where more detail and depth of analysis and power design will be described.

For some researchers, this may open up additional space within the research strategy in which newer components such as Rigor and Transparency can more thoroughly be addressed.

For applications involving clinical trials that do not have an existing external DSMB oversight mechanism, a DSMB should be composed of multidisciplinary members who are knowledgeable in the conduct of research, and should include those with backgrounds in biostatistics, experimental design, bioethics, and experts in the medical field of concern. UCLA offers two resources for establishing a DSMB:

For cancer-related clinical trials, applicants should consult JCCC’s Clinical Research Unit. For non-cancer studies, a DSMB is offered through CTSI’s Office of Regulatory Affairs.

For either DSMB, the appropriate offices should be approached during the application phase to ensure appropriate budgetary components are in place and to obtain descriptions of the DSMB’s roles and expertise for inclusion in the Data and Safety Monitoring Plan.

The “Detailed Description” (formerly called the "Narrative Study Description") is limited to 32,000 characters and should contain a detailed description of the protocol. This should NOT include the entire protocol or duplicate information found elsewhere (e.g., eligibility criteria, outcomes). The Detailed Description should also describe plans for delivery of interventions and plans for assignment of participants. You should also 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. 

All NIH clinical trial applications must select a study phase. Applicants should select “Other” for trials that do not have phases, including behavioral interventions and devices. 

If you select “Other” as the study phase on the PHS Human Subjects and Clinical Trials Information Form, you will be required to provide a brief explanation.