Human Subjects

Questions and Answers Table of Contents

How do I determine if I am conducting human subjects research?

Investigators conduct human subjects research if they obtain data by intervention or interaction with a living person or obtain individually identifiable private information about a living person. Click on the glossary links for definitions of these terms.

The Office for Human Research Protections decision tree Is an Activity Research Involving Human Subjects? is very helpful for figuring this out. Also see our tutorial page Are You Conducting Human Subjects Research? and Private Information or Biological Specimens in Human Subjects Research questions and answers.

For more help, see FAQs from Applicants Human Subjects Research and FAQs About Research Using Human Specimens, Cell Lines or Data on the Office of Extramural Research's Web site.

Who can help me determine if my study is considered to be human subjects research?

Take a look at Who determines if research that involves coded data or specimens is human subjects? and Can my institution provide guidance about whether my research is considered human subjects, or should I contact someone at NIAID? in our Private Information or Biological Specimens in Human Subjects Research questions and answers.

Will the scientific review officer and peer reviewers evaluate my application's human subjects determination?

Yes. See How Human Subjects Applications are Reviewed in NIAID's human subjects tutorial.

Does FDA's Interim Final Rule on Medical Devices; Exception From General Requirements for Informed Consent affect my human subjects determination?

See the following:

• Will the OHRP Guidance about research conducted under FDA Interim Final Rule 21CFR50.23(e) impact research funded by NIH? on NIH's Office of Extramural Research Web site.
• Medical Devices; Exception From General Requirements for Informed Consent in the Federal Register.

Is it common for NIAID research to be exempt from human subject requirements?

No. Since NIH clarified what it considers to be human subjects research, the six human subjects exemptions rarely apply to NIAID applicants. Most research at NIAID is now either "human subjects" or "not human subjects." For more details, see NIAID's Is Your Research Exempt? tutorial page.

To learn how NIH clarified its policy on human subjects research, see the December 30, 2004 Guide notice, which was based on OHRP's Guidance on Research Involving Coded Private Information or Biological Specimens.

How can I find out if my research is one of the rare studies at NIAID that may be exempt from human subject requirements?

Remember, exemptions usually won't apply to NIAID research. However, if you have used the Human Subject Regulations Decision Charts, reviewed both NIH and NIAID guidance, and still believe your study may be exempt:

1. Consult with your institution: It's up to institutions to create policies that will instruct applicants on how to follow the Office for Human Research Protections' Guidance on Research Involving Coded Private Information or Biological Specimens and obtain approval.
2. Contact your program or project officer for additional assistance.

For more information, read What is a human subjects exemption? in NIAID's Private Information or Biological Specimens in Human Subjects Research questions and answers.

Where can I find guidance on research involving coded private information or biological specimens?

See the December 30, 2004, Guide notice, which was based on OHRP Guidance on Research Involving Coded Private Information or Biological Specimens. Also, visit our Private Information or Biological Specimens in Human Subjects Research questions and answers.

Does NIAID have special procedures and instructions for human subjects applications?

Yes. All human subjects applications must also comply with the NIAID Clinical Terms of Award. Investigators should read this document to see what NIAID expects in the application and after award. These instructions are in addition to, not in lieu of, those in the PHS 398 or funding opportunity announcement.

Additionally, for research in China, follow the instructions in NIAID Clinical Terms of Award Restriction for China.

For further details, see the Human Subjects SOPs.

Also, in May 2005 NIAID launched a mandatory, two-step approach to funding investigator-initiated clinical trials: a Clinical Trial Planning Grant (R34) followed by a Clinical Trial Implementation Cooperative Agreement (U01). Only PIs who have completed the R34 can apply for a U01.

For more information, go to Investigator-Initiated Clinical Trial Planning and Implementation Grants.

Where do I find information and advice on preparing a human subjects application?

You must read and follow the instructions in either the funding opportunity announcement (for electronic applications) or the PHS 398 (for paper applications) and RFA, RFP, and PA notices, in addition to the NIAID Clinical Terms of Award.

For more help and advice, visit our How to Write a Human Subjects Application tutorial on our Human Subjects, Clinical Research page.

Is it necessary to list the name of the PI grantee on each of the grant's protocols?

No, it's not essential. If, for example, the grantee has subcontracted out their human subjects research, the project leader overseeing the work done at the subcontractor site might be the one listed on the related protocols, rather than the PI of the grant. The subcontracted project leader is not required to list the PI's name on the protocol.

When you submit the protocol for IRB or IEC review, it's more important for the subcontractor to provide other identifying information about the grant itself (i.e., title, grant number).

If the IRB approval document submitted to the grants management specialist does not reflect the PI's name, we will request written confirmation that the protocol's IRB approval belongs with the application to be funded. (This also applies to IACUC approvals.) So the name on the protocol can be different than the name listed on the grant. We will verify at the time of award that the approval covers the application being funded.

For fellowship and career awards, is it necessary to be covered by an IRB approval?

If you are involved in human subjects research with your sponsor, you must be covered by their IRB approval.

Do I need an institutional assurance to conduct human subjects research?

Yes. Visit the Human Subjects SOPs.

Do I need to replace my Single Project Assurance with a Federalwide Assurance?

On December 31, 2005, the Federalwide Assurance became the only valid human subjects assurance. However, if you obtained a Single Project Assurance before that date, it is effective until the end of your project.

Your institution will still need a Federalwide Assurance for new projects. See the Human Subjects SOPs for more information.

When should I start working on obtaining or renewing a Federalwide Assurance?

See Is it ok if I do not yet have my Federalwide Assurance number when I apply?

Can I obtain, update, and renew a Federalwide Assurance, IRB or IEC registration online?

Yes you can. The Office for Human Research Protections provides these features on its Electronic Submission System.

To register, go to Filing of a New FWA or Filing a New IORG-IRB/IEC(s) Registration.

To update, go to Update and Renewal of Domestic (U.S.) or International (non-U.S.) Federalwide Assurances or Update and Renewal of an IORG-IRB/IEC Registration. If you have any questions, email your regional or country coordinator listed on Contact Information/Staff Assignments.

Is it ok if I do not yet have my Federalwide Assurance number when I apply?

Yes, because it's not necessary for peer review; the official due date for your Federalwide assurance (FWA) is "just-in-time," which means just before NIAID is ready to issue an award. To make sure you can obtain it in time for award, keep this in mind: Typically, it takes the Office for Human Research Protections (OHRP) two weeks or less to approve your FWA application. However, if OHRP spots a problem with your FWA application, it will probably take longer. See OHRP for more information.

When should I start getting IRB or IEC approvals?

Though your certification of IRB or IEC approval is due "just-in-time," i.e., just before we are ready to issue an award, you should start the approval process well before the application's due date because revisions and final approval can take time. If the certification is ready, include it in the application. Read more in Plan for IRB or IEC Approval. Also see the Human Subjects Certifications: IRB or IEC SOP.

Do I need IRB approval for a clinical trial Web site?

Yes, if you're planning to use it to advertise for subjects. When a site goes beyond listing basic descriptive information, IRB approval is usually required. For details, read OHRP Guidance on Institutional Review Board Review of Clinical Trial Web sites.

Where can I find information about IRB and IEC requirements for foreign applications?

See IRB, IEC, and FWA Requirements for Foreign Countries. For more information, see the Human Subjects Certifications: IRB or IEC SOP. Also, see the Investigator Responsibilities section of Human Research Questions and Answers on the Office for Human Research Protections' Web site.

Where can I find information about research in foreign populations?

See Investigating Foreign Populations.

Do all investigators on a human subjects application have to show training in the protection of human subjects?

Yes. Your application must show mandatory training in the responsible conduct of research for all key personnel on the grant. Follow instructions in the September 5, 2001, Guide notice and consult NIH's Frequently Asked Questions.

Also see our Document Training in Research Conduct, Sample Letter to Document Training in the Protection of Human Subjects, and Human Subjects Certifications: Training SOP.

For more information, see the Investigator Responsibilities section of Human Research Questions and Answers on the Office for Human Research Protections' Web site.

Are human subjects applications reviewed differently?

Yes. In addition to the regular review criteria, reviewers use four other criteria to judge human subjects research applications. Read more in How Human Subjects Applications are Reviewed.

If my description of human subjects protection is inadequate, how will this affect the review of my application?

During peer review, the panel will discuss whether the human subjects protection described in your application is adequate. That information will be reflected in your summary statement and may affect the priority score, depending on the nature and severity of inadequacies, e.g., information missing from your application.

See After Peer Review questions and answers. In addition, your application will be coded to reflect the inadequacy, which must be addressed before an award is made.

Can a human subjects concern lead to a bar to award?

Yes. During peer review, the scientific review group will assess the human subjects section of your application. Based on the concerns expressed by the scientific review group, codes will be given to your application that may bar or restrict your award. A code 44 indicates a bar to award due to a human subjects issue. Codes typically appear with a brief explanation. Under normal circumstances, you will not be funded until you address the issues; contact your program officer for advice.

Can I get an award if I have a bar?

You may receive an award, but a restriction on the terms of the award prevents you from spending funds on the parts of your project that are barred. Check your Notice of Award for specifics, and see Read Your Notice of Award, Know Your Terms in the NIH Grant Cycle: Application to Renewal. Also see Human Subjects SOPs.

Can I begin accruing subjects before my start date?

No. Before you enroll any subjects, NIAID staff must approve your protocol and have your IRB approval and other documents on file. Read Before You Enroll Participants in our human subjects tutorial, and see Must I send NIAID the IRB-approved protocol before accruing patients or enrolling participants? on this page.

For more information, see the Investigator Responsibilities section of Human Research Questions and Answers on the Office for Human Research Protections' Web site.

If I'm conducting a clinical trial, does my Research Plan need to address expectations for the clinical intervention?

Yes, for phase III clinical trials. In addition to providing a Data and Safety Monitoring Plan, you should address whether you expect to find clinically important gender, race, or ethnicity differences in the intervention effect.

For more information, see "Question 5: Does your proposed research meet criteria for an NIH-Defined Phase III Clinical Trial?" in the PHS 398 or the instructions in the funding opportunity announcement (for grants that have moved to electronic application). Also, see Create a Data and Safety Monitoring Plan in our human subjects tutorial.

Are independent data and safety monitoring boards required for all clinical trials?

It depends on the type of clinical trial you're doing. Phase III clinical trials must be reviewed by an independent data and safety monitoring board (DSMB). Others may require DSMB oversight. For details, see NIAID Clinical Terms of Award, Create a Data and Safety Monitoring Plan, and Human Subjects Certifications: IRB or IEC SOP at NIAID Research Funding.

Am I responsible for acquiring informed consent?

See Plan for IRB or IEC Approval and We Must Have Approval from All IRBs or IECs in our human subjects tutorial. Also see the Informed Consent and Investigator Responsibilities sections of Human Research Questions and Answers on the Office for Human Research Protections' Web site.

What are informed consent requirements for research involving in vitro diagnostic devices?

Take a look at If I use leftover human specimens to conduct an in vitro diagnostic device study, do I need to get informed consent? in our Private Information or Biological Specimens in Human Subjects Research questions and answers.

For additional information, see the Informed Consent section of Human Research Questions and Answers on the Office for Human Research Protections' Web site.

If I want to submit my clinical study for publication, do I need to register early in the process?

Registering early with ClinicalTrials.gov may be necessary if you want your study to be considered for publication in a journal governed by the International Committee of Medical Journal Editors (ICMJE). For phase III clinical trials, ICMJE's publication policy requires registration before you enroll your first patient. This may also be required for other types of clinical trials. For details, read "Is This Clinical Trial Fully Registered?"

Could not registering affect my ability to publish?

Yes. If you want your study results to be published in a journal governed by the International Committee of Medical Journal Editors, make sure you understand its registration policy.

That policy may require that you register your clinical trial before you enroll your first patient. To see how it applies to your research, read "Is This Clinical Trial Fully Registered?"

Must I send NIAID the IRB-approved protocol before accruing patients or enrolling participants?

Yes. See NIAID Clinical Terms of Award, page 3. Also, see Can I begin accruing subjects before my start date? on this page.

Do T32 grants need IRB approval before an award is made?

No. T32 grants are one exception to the rule, though they still must show approval before you start the research that involves human subjects.

Do I have to inform my program or project officer of my reports to FDA?

Yes. See Ongoing Reporting Requirements in Guidance for Compliance with NIAID Clinical Terms of Award, page 5.

As an investigational new drug sponsor, must I notify FDA and NIAID about adverse events?

Yes. See Guidance for Compliance with NIAID Clinical Terms of Award, page 7. Also take a look at Report Adverse Events Promptly in our human subjects tutorial.

For a clinical trial, how often must I send an Inclusion Enrollment Report form?

Send an Inclusion Enrollment Report form annually. See Guidance for Compliance with NIAID Clinical Terms of Award, page 7. For more information, see Send the Inclusion Enrollment Form With Your Progress Report in our human subjects tutorial.

Can NIH help me protect the confidentiality of my research subjects?

Yes, with a certificate of confidentiality. See NIH's Certificates of Confidentiality Kiosk for details and follow instructions on applying for the certificate. Since the advent of the NIH site, NIAID no longer maintains an NIAID site for this topic.

Does NIH have requirements for HIPAA?

No. NIH doesn't ask applicants to address the Health Insurance Portability and Accountability Act because NIH is not a covered entity. You can read the HIPAA Privacy Rule to see if the requirements apply to you.

If I can't complete a clinical trial within the performance period of my current award, can I apply for an extension?

You may be able to apply for an extension. To learn more, read the NIAID Policy for Extension of Investigator-Initiated Clinical Trials Guide notice. Also see our Investigator-Initiated Clinical Trial Administrative Extensions SOP and Investigator-Initiated Clinical Trial Administrative Extensions questions and answers.

Do I need to register my clinical trial with ClinicalTrials.gov?

If you are conducting an applicable clinical trial, you must register with ClinicalTrials.gov. For more information, see Before You Enroll Participants.

If I have other questions about human subjects, is there another good source of information?

Yes. See Human Research Questions and Answers on the Office for Human Research Protections' Web site and the Frequently Asked Questions section of Research Involving Human Subjects on the Office of Extramural Research's Web site.

What if my question wasn't answered here, or I'd like to suggest a question?

Email deaweb@niaid.nih.gov with the title of this page or its URL and your question or comment. We answer questions by email and post them here. Thanks for helping us clarify and expand our knowledge base.