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Resources for NIH's Human Subjects and Clinical Trials Updates

The UCLA Clinical and Translational Science Institute (CTSI) Grants Submission Unit (GSU) has put together a number of tools and resources to clarify the new requirements for NIH applications regarding human subjects and clinical trial policies—and subsequent changes to the SF424 (Forms Version E or FORMS-E)—for applications on or after January 25, 2018. The resources are meant to help guide you through the requirements, based on the type of studies you are proposing within your application.

New Definition of Clinical Trials

NIH has greatly expanded which studies meet the definition of a clinical trial. Complete the questionnaire below (or online here) 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. 

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

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, available here.

A full menu of templates and guidelines for 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.

For a general overview of the changes and its implications for NIH applications on or after January 25th, 2018, our PowerPoint is available here. YouTube link to the recorded presentation (link coming soon).

Guidelines and Templates Menu

Contacts for Additional Support

NIH Human Subjects and Clinical Trials FAQs

Identifying the Correct Funding Opportunity

Does my FOA allow clinical trials?

Most NIH funding opportunity announcements (FOAs) state within the title whether clinical trials are allowed. There are three categories: 1) Clinical Trials Not Allowed, 2) Clinical Trials Optional, and 3) Clinical Trials Required.

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-18-484, NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) and PA-18-345, NIH Research Project Grant (Parent R01 Clinical Trial Required).

Does my study meet the definition of a clinical trial?

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 here: https://ctsi.ucla.edu/pages/HSapps.

If you are still unsure, NIH has clinical trial case studies designed to help you define your study that can be found here: https://grants.nih.gov/policy/clinical-trials/case-studies.htm.

Study Records

What is a study record?

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.”1 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.

1. https://grants.nih.gov/grants/glossary.htm#StudyRecord

How many study records do I need?

The NIH recommends that in many cases, applications only require a single study record2. 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.

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

Completing the PHS Human Subjects and Clinical Trials Information Form

The PHS Human Subjects and Clinical Trials Information Form includes many text boxes, sometimes with large character limits. How do I format the text fields properly?

NIH provides rules for text fields here: https://grants.nih.gov/grants/how-to-apply-application-guide/format-and-write/rules-for-text-fields.htm. 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. Guidelines and templates for individual text fields can be found here: https://ctsi.ucla.edu/pages/HSapps.

In “Conditions or Focus of the Study,” we are required to use appropriate descriptors from NLM’s Medical Subject Headings (MeSH). What is a MeSH heading and how do I find one for my study’s focus?

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: https://meshb.nlm.nih.gov/MeSHonDemand.

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.

What is the retention component of the Recruitment and Retention Plan?

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 here (Word document).

What is required for the study timeline?

The NIH SF 424 Forms E Guidelines instructions3 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-e/general/g.500-phs-human-subjects-and-clinical-trials-information.htm#2.7

Who can provide additional guidance on statistical design and power at UCLA?

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

How is the “Dissemination Plan” on the PHS Human Subjects and Clinical Trials Information Form different from the data sharing requirements on the “Resource Sharing Plan”?

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.

How do I write a single IRB plan?

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.

How do I ensure that I am not duplicating information in the research strategy and the content from the Human Subjects and Clinical Trials Information Form?

The SF 424 FORMS E 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.

Clinical Trials

My application needs a Data and Safety Monitoring Board (DSMB). How do I get a DSMB at UCLA?

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 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.

What is the difference between the “Brief Summary” and “Narrative Study Description”?

The “Brief Summary” requirement for NIH clinical trial applications is limited to 5,000 characters and should include a brief description of objectives of the protocol, including the primary and secondary endpoints. Clinicaltrials.gov also clarifies that the Brief Summary should include a concise summary of the study hypothesis, summarized for the lay public4.

In contrast, the “Narrative Study Description” is limited to 32,000 characters and should contain a narrative study description of the protocol, including more technical information than the Brief Summary. This should NOT include the entire protocol or duplicate information found elsewhere (e.g., eligibility criteria, outcomes). Narrative Study 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. Further guidance is available here: https://researchmethodsresources.nih.gov/.

4. https://prsinfo.clinicaltrials.gov/definitions.html

Which study phase do I choose for a behavioral outcomes study?

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. Additional definitions of study phase are available here: https://ctsi.ucla.edu/pages/HSapps.

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.