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Does your research fall under human subjects regulations? How should you
prepare, submit, and manage a clinical award?
For
electronic submissions, read
Part II
Supplemental Instructions for Preparing the Human Subjects Section
of the Research Plan in the Grant Application Guide for your Grant
Application Package.
For paper submissions, read Part II
Supplemental Instructions for Preparing the Human Subjects Section
of the Research Plan in the PHS 398.
Then, look at the specific NIAID requirements
and highlights from the official NIH guides featured in this tutorial.
Table of Contents
- Are You Conducting Human Subjects Research?
- Stay in Contact With Your Program Officer
- Is Your Research Exempt?
- Key Points to Remember About Human Subjects Exemptions
- Planning and Writing Your Research Application
- Avoid Conflicts of Interest
- Know the Requirements for Investigator-Initiated Clinical Trials
- Plan
for Registering an IRB or IEC and Obtaining an FWA
- IRB,
IEC, and FWA Requirements for Foreign Countries
- Special Guidance for Domestic and Foreign Applicants
- Investigating Foreign Populations
- Develop Your Human Subjects Research Plan
- Create a Data and Safety Monitoring Plan
- How Human Subjects Applications are Reviewed
- What Happens If Reviewers Have Concerns?
- Before You Enroll Participants
- We Must Have Approvals from All IRBs or IECs
- We'll Discuss Data and Safety Monitoring With You
- Meet Requirements for IND or IDE
- Show Recombinant DNA Advisory Committee Approval
- Document Training in Research Conduct
- Include the Federalwide OHRP Assurance
- Resolve Peer Review Concerns
- Maintaining Your Award
- IRBs and IECs Have Ongoing Requirements
- Amendments, Suspensions, Terminations, and Extensions
- Report Data and Safety Monitoring Reviews
- Report Adverse Events Promptly
- Send the Inclusion Enrollment Form With Your Progress Report
- Other Reporting Requirements
- Know Which NIAID Staff Can Help You
- Clinical Terms of Award Checklist
- More Human Subjects Links
Are You Conducting Human Subjects Research?
To
determine if your proposed study will be considered human subjects research by NIH,
carefully read the following:
- Electronic applications. Section 2, Scenarios, under Part II, Supplemental Instructions for Preparing the Human Subjects Section of the Research Plan, in the Grant Application Guide for your Grant
Application Package.
- Paper applications. Section 2, Scenarios, under Part II, Supplemental Instructions for Preparing the Protection of Human Subjects Section of the Research Plan, in the PHS 398.
- Contracts. Read Sections L and M in the request for proposals.
Take note, the HHS regulations for Protection
of Human Subjects in 45 CFR Part
46 define
a human subject as a living person about whom
an investigator conducting research
obtains either: data through intervention or interaction with the
person, or identifiable private information.
Before deciding whether your research includes human subjects, make sure
you understand NIH's Guidance
on Research Involving Coded Private Information or Biological Specimens.
NIH clarified its definition of human subjects research in that policy,
which is now reflected in the PHS 398 and Grant
Application Packages.
A number of terms are key to understanding this
policy, including:
In general if you're using coded private information, data,
or specimens, NIH will consider your research to
involve human subjects
unless it meets both of the following conditions:
- You are not collecting samples by interacting or intervening with
living people.
- None of the investigators or
collaborators listed
in the application can identify
the subjects through coded private information
or specimens (e.g., an investigator's
access to identity is prohibited
by a written
agreement).
If
any investigator involved in the research can determine a subject's identity
or has access
to identifiers,
the
research
is considered to involve human subjects and human subjects requirements
apply.
An application is not considered
to be human subjects research if none of the personnel listed in
the application can identify the subject or
have access to the subject identifiers. If one person listed has access,
the application may be subject to human subjects requirements.
To see in which category your research falls, check out the HHS Human
Subject Regulations Decision Charts and NIH's decision chart
for Research
Involving Private Information or Biological Specimens.
If you still have questions about whether or
not your application has human subjects, it's a good idea to run
them by your institutional
review board or independent
ethics committee before you submit
your application.
Keep in mind, NIH recommends that investigators
are
not given the
independent authority to determine whether their research involves
human subjects. For details, read the HHS Office
for Human Research Protections' Guidance
on Research Involving Coded Private Information or Biological Specimens.
For more help, see the following on NIAID's Web site:
Most requirements for protecting
human subjects are codified in the law, 45 CFR Part
46.
Also, if you're submitting a multiproject application, follow human
subjects instructions and complete the requirements for each component
of the application.
Even if only one of the components includes human
subjects, you are considered to be applying for a human subjects research
grant. Go to our Instructions for Preparing a Multiproject Grant Application.
To indicate you are applying for human subjects research you must
check "yes" for "human
subjects.
Additional Resources
Stay in Contact With Your Program Officer
If you're planning an application for human subjects research and need to
contact a program officer,
go to the Contact Staff for Help contact list.
After review, stay in close contact with the
assigned program officer who's listed on your summary statement, or your just-in-time or Notice of Grant Award mailer.
Additional Resources
Is Your Research Exempt?
We
expect few exemptions for human subjects at NIAID, so
how can you decide if one applies to you?
Since the Office for Human Research Protections clarified what it considers to be human subjects research,
the six human subjects exemptions rarely
apply to NIAID.
Almost all research at NIAID is either "human
subjects" or "not human subjects."
What is human
subjects research? You are conducting
human subjects research if you obtain data by intervening or interacting with
a living person or if you obtain individually identifiable private
information about a living person. Click on the glossary links in
blue for definitions.
If your research is not considered
to be human subjects, you
won't need to address human
subjects reporting requirements.
If you've looked through NIH and
NIAID guidance and still think your research may be exempt, contact
your program or project officer.
To learn more about exemptions, read
the following:
- Electronic applications. Section 2, Scenario C, under Part II, Supplemental
Instructions for Preparing the Human Subjects Section of the Research
Plan, in the Grant Application Guide for your Grant
Application Package.
- Paper applications. Section 2, Scenario C, under Part II, Supplemental
Instructions for Preparing the Protection of Human Subjects Section of the Research
Plan, in the PHS 398.
For additional information about
human subjects research and exemptions, see NIAID's:
Key Points to Remember About Human Subjects Exemptions
Remember,
most NIAID-funded research is either "human subjects" or "not
human subjects" and is usually not exempt.
To help determine which your research is,
see the Office for Human Research Protections' decision
chart Is
an Activity Research Involving
Human Subjects? For more details, visit Is
Your Research Exempt?
If you still think your research
may be exempt, talk
to your program or project officer. If
he or she agrees that an exemption applies, you must:
To learn more about Research Plan requirements, see the following:
For exemptions other than exemption 4:
To learn about the different exemptions, visit
Part III, Policies, Assurances, Definitions, and Other Information in the PHS 398 and scroll down to section 3, Definitions. Or see Part III, Policies, Assurances, Definitions, and Other Information, in the Grant Application Guide for your Grant
Application Package, and scroll down to section 3, Definitions.
Additional Resources
Planning and Writing Your Research Application: Avoid Conflicts of Interest
NIH takes financial conflicts of interest very seriously.
By law, institutions must manage, reduce, or eliminate financial conflicts of interests (FCOI) for any person -- including subawardees and collaborators -- responsible for the design, conduct, or reporting of funded research.
As you plan your project, avoid conflicts of interest stemming from a financial relationship (including the appearance of a conflict) that can negatively affect the rights and welfare of your subjects.
As an investigator, you must give your institutional official a list of your significant financial interests as well as those of your spouse and dependents. The list should include any financial opportunities you expect to be affected by the proposed research. Read more in the Financial Conflicts of Interest for Awardees SOP.
Your IRB or IEC, institutional business official, and you should also read the Federal Register notice, Financial
Relationships and Interests in Research Involving Human Subjects.
If you think you may have or could appear to have a financial conflict of interest, you must inform NIAID before spending any new NIH funds. Read our Financial Conflict of Interest for Awardees SOP.
Know the Requirements for Investigator-Initiated Clinical Trials
NIAID
uses a two-step approach to funding investigator-initiated clinical trials: a Clinical Trial Planning Grant (R34) followed by a Clinical Trial Implementation Cooperative Agreement (U01).
R34s provide funding for the preparation of 1)
materials NIAID staff need to determine a project's feasibility and
2) documentation necessary
for
implementing
the clinical
trial
in the U01.
This two-step process does not apply to applications responding to requests for applications (RFA). If
you're applying for a clinical trial through an RFA, make sure you
follow
instructions in the RFA.
If you plan to apply for an investigator-initiated clinical trial,
you'll need to consider many details in addition to the information
we highlight on this tutorial page.
For more information, go to Investigator-Initiated Clinical Trial Planning and
Implementation Grants. Also, follow NIAID
Clinical Terms of Award instructions, and visit Investigator-Initiated
Clinical Trial Planning and Implementation Grants questions and answers.
Additional Resources
Plan
for Registering an IRB or IEC and Obtaining an FWA
IRB
or IEC approval. Before NIAID can issue a human subjects award, your
organization must comply with the following:
Your certification
of IRB or IEC approval
is due "just-in-time," i.e., just before
we are ready to issue an award. Nevertheless, we recommend that you
start the approval process early -- well before the application's
due date -- because revisions and final approval can take time. If
the certification of IRB or IEC approval is
ready, include it in the application.
Your organization's IRB or IEC
performs many functions. It reviews research to make sure human subjects
are protected, may
require
modifications
or disapprove the research, looks at privacy issues, and determines
the need for informed consent.
If you need
informed consent, the IRB or IEC must approve the informed consent
form, unless the IRB or IEC waives appropriately
the requirements for documenting informed consent.
For details about informed consent, read 45
CFR 46.116, 45
CFR 46.117, and 45
CFR 46.115. Also visit the Informed
Consent section of Human
Research Questions and Answers on the Office
for Human Research Protections' Web site.
Before you enroll subjects, your
organization must certify to
NIAID that an IRB or IEC designated under your organization's
FWA has reviewed and approved your research project. There
are two types of review: full board and expedited.
For more information,
see 46.107, 46.110,
and 46.111 of 45 CFR Part 46, the Research on
Human Specimens NIH brochure, and NIAID's Human
Subjects Certifications: IRB or IEC SOP.
Grants supporting human subjects research usually
require you to obtain IRB or IEC approval before award.
Certain
grant mechanisms, such as training grants (T32), do not require
IRB or IEC approval before an award is made but do require a grantee
to submit certification of IRB or IEC approval before beginning any
nonexempt human subjects research.
For other grant types,
contact your SRO or program officer to find out if IRB or IEC approval is required.
To register an IRB or IEC for the first time
or to update or renew
an existing IRB or IEC registration online, go to Electronic
Submission System for Federalwide Assurances and IRB/IEC Registrations.
Also, if you're planning to use a clinical trials Web site to advertise for clinical trial subjects, you may need IRB
or IEC approval.
Under certain circumstances, when a site goes beyond listing basic
descriptive information, approval is required. For details, read "OHRP's
guidance on Institutional Review Board (IRB) Review of Clinical Trial
Websites."
If you're performing clinical
research at a foreign or domestic site,
your organization will
need to
obtain a Federalwide
Assurance before
your work can be funded. For information about
obtaining an assurance, see the following:
In very limited circumstances, some collaborators
may not be required to obtain their own FWA, including a collaborating
individual investigator who operates under
another institution's FWA. See Guidance
on Extension of an FWA to Cover Collaborating Individual Investigators
and Introduction of the Individual Investigator Agreement.
If you're applying from a foreign
country or plan to include a foreign research site in your domestic
application, you should also read IRB,
IEC, and FWA Requirements for Foreign Countries in this tutorial.
For
additional information, see IRBs and IECs
Have Ongoing Requirements.
Additional Resources
IRB,
IEC, and FWA Requirements for Foreign Countries
If you're applying from a foreign
country, make sure you read Plan
for Registering an IRB or IEC and Obtaining an FWA in
our tutorial for information about submitting certification of institutional review board (IRB)
or independent ethics committee (IEC)
approval.
- The just-in-time submission policy
described on the tutorial page applies to you.
- However, you should start the process as
early as possible since approvals for foreign applications may
take a
long
time.
Also, if you're applying from a country that has a national IRB or
IEC, its approval process may be in addition to, or in lieu of, local IRB or IEC approval.
To prevent delays in your research, find out early on if IRB or IEC approval is required for each country associated with your proposed study, and if so, what's required for clearance. These rules and regulations are determined within each country.
Clear communication with all involved IRBs and IECs can facilitate the clearance process.
It may also benefit you to appear before each IRB or IEC in person to discuss issues and points of collaboration. If there are multiple levels of IRB or IEC review, you must send NIAID the full documentation from all the IRBs or IECs. Check with your program officer for advice.
If you have a domestic or foreign grant with
foreign research sites, take
note of the following:
On rare
occasions, some collaborators may not be required
to obtain their own FWA. To learn more about
these special circumstances,
see the following:
For information about training requirements and foreign translations
see Document Training
in Research Conduct and Human
Subjects Certifications: Training SOP.
Additional Resources
Special Guidance for Domestic and Foreign Applicants
If
you're proposing a new clinical research study, you must provide information
about the participants you plan to include
in a Targeted/Planned Enrollment Table,
and submit that table with your application.
- For electronic applications, use the Targeted/Planned
Enrollment Table in your Grant
Application Package.
- For paper applications, use the Targeted/Planned Enrollment Table
in the PHS 398.
Later, when you're required to
submit a progress report, you'll need to provide updated information
about your data in an Inclusion Enrollment Report
Table.
For more information, read Send
the Inclusion Enrollment Form With Your Progress Report in this
tutorial.
To learn more about enrollment
tables and special instructions for renewal (competing
continuation) and revision (competing
supplement) applications, look at the following:
- Electronic applications. Read section 4.3, Instructions for Completing the Targeted/Planned
Enrollment Tables for Reporting Race and Ethnicity Data for Subjects
in Clinical Research, under Part II, Supplemental Instructions for Preparing the Human Subjects Section of the Research Plan, in the Grant Application Guide for your
Grant
Application Package.
- Paper applications. Read section 4.3, Instructions
for Completing the Targeted/Planned Enrollment Tables for Reporting
Race and Ethnicity Data for Subjects in Clinical Research, under Part II, Supplemental Instructions for Preparing the Protection of Human Subjects Section of the Research Plan, in the PHS 398.
For additional information, see Investigating
Foreign Populations and Develop
Your Human Subjects Research Plan in this tutorial.
For human subjects research, you must include justification for inclusion
or exclusion of children. Find more information in OHRP's guidance on Special Protections
for Children as Research Subjects.
You may need to file an incident report with OHRP if an incident occurs during your research; for example, you're not in compliance with human subjects regulations or IRB or IEC requirements, or you've discovered unanticipated risks to human subjects.
Read the Guidance on Reporting Incidents to OHRP for details on whether to report an incident, information to include, timelines, and other important items.
Take a look at the OHRP
Web site for additional guidance on human subjects.
Investigating Foreign Populations
For
foreign awards, the NIH policy on inclusion of women and minority groups
in research is the same as that for research conducted in the U.S.
For both foreign awards and
domestic awards with foreign components, report on study populations
using the Targeted/Planned Enrollment Tables.
These tables are based on the U.S. definitions of
minority populations. See the following for definitions and information about
the tables:
- Electronic applications.
- Read section 5.8, the NIH
Policy on Reporting Race and Ethnicity Data: Subjects
in Clinical Research, under Part II, Supplemental Instructions for Preparing the Human Subjects Section of the Research Plan, in the Grant Application Guide for your Grant
Application Package.
- Use the Targeted/Planned Enrollment Table in
your Grant
Application Package.
- Paper applications.
- Read
section 5.8, the NIH
Policy on Reporting Race and Ethnicity Data: Subjects in Clinical
Research, under Part II, Supplemental Instructions for Preparing the Protection of Human Subjects Section of the Research Plan, in the PHS
398.
- Use the Targeted/Planned Enrollment Table in
the PHS
398.
If there is scientific rationale
for examining subpopulation group differences within a foreign
population, you should consider designing your study to accommodate
those differences and discuss these inclusions in your application.
For more details, see NIH
Policy and Guidelines on the Inclusion of Women and Minorities as Subjects
in Clinical Research.
Additional Resources
Develop Your Human Subjects Research Plan
As
you develop your Research Plan, remember that principal
investigators should have a culturally sensitive outreach
plan involving relevant people and organizations,
e.g., family, religious organizations,
and community leaders, with a goal of building trust through communication
and cooperation.
In some cases, conducting a community consultation may
benefit potential participants and your study. Although a community
consultation is not required, NIH supports and encourages it in many
areas of research. To learn more, read Points
to Consider When Planning a Genetic Study That Involves Members of
Named Populations.
Some NIAID divisions require
your protocol in the application. To
find out if this is the case, and see other instructions, read the RFA to which you're responding. If
you still have questions, contact the program officer in the relevant program.
For contact information, see Stay
in Contact With Your Program Officer.
Additional Resources
Create a Data and Safety Monitoring Plan
Whatever the structure of the monitoring plan, the PI and IRB or IEC are responsible for oversight of safety monitoring along with one of the following:
- independent safety monitor
- independent monitoring committee
- DSMB.
See We'll Discuss Data and Safety Monitoring With You for additional information.
In your monitoring plans, include a description of the mechanisms you will use to report adverse events to the IRB or IEC, FDA, and NIH.
A peer review group will review your plan, and its comments or concerns will appear in your summary statement.
Each NIAID division has a system to oversee and monitor conduct of clinical trials to ensure participants' safety and the validity and integrity of data. That oversight is separate from the data and safety monitoring implemented in your study. For more information see the NIH Policy for Data and Safety Monitoring and Further Guidance on a Data and Safety Monitoring for Phase I and Phase II Trials.
Phase I and II
For phase I and II clinical trials, you must include a general description of your data and safety monitoring plan in your research application.
After award but before you begin a clinical trial, you'll need to submit a detailed monitoring plan as part of your protocol, first to your IRB or IEC and then to NIAID for review
and approval.
Since the degree of monitoring should correspond with level of risk,
phase I and II clinical trials may have more leeway in the type of monitoring
used. However, if you're planning a clinical trial that
involves potentially high risks or special populations, you must
consider additional monitoring safeguards, which could include a
DSMB.
Phase III
For phase III clinical trials, you'll need to submit an even more detailed monitoring plan in your
initial application and include plans for using a data and safety
monitoring board (DSMB).
All phase III clinical trials must use a DSMB. All multisite clinical trials
involving interventions that entail potential risk to participants
must also use a DSMB.
Multisite
If you're planning multisite phase I or II clinical trials, you'll need to organize one of the above monitoring options to prepare timely summary reports of adverse
events and distribute them to all sites and IRBs or IECs. The frequency of the summary reports will depend on the nature of the clinical trials. For additional guidance on reporting adverse events for multisite clinical trials with a DSMB,
see the June 11,
1999, Guide notice.
Additional Resources
How Human Subjects Applications are Reviewed
When preparing your application, you should consider how it will be read by reviewers. In addition to the regular review criteria for scientific merit, reviewers use four other criteria to judge human subjects research applications. Keep them in mind when planning your project and application:
- Risks to subjects.
- Adequacy of protection against risks.
- Potential benefits to the subjects and others.
- Importance of the knowledge to be gained.
You also need to provide justifications for inclusion or exclusion
of populations (gender, minorities, and children). To learn more,
read the following:
- Electronic applications. Under Part II, Supplemental Instructions for Preparing the Human Subjects Section of the Research Plan, see the following:
- Paper applications. Under Part II, Supplemental Instructions for Preparing the Protection of Human Subjects Section of the Research Plan, see the following:
- 5.6 NIH Policy on the Inclusion of Women and Minorities
in Clinical Research.
- 5.7 NIH
Policy on Inclusion of Children,
in the PHS
398 for more information.
Peer reviewers will gauge the adequacy of your plans to protect
subjects from research risk and to include required populations, an assessment independent of your IRB's or IEC's. If your description is inadequate or your application does not comply with requirements, your priority score may suffer and your application may get a bar to award.
Read our human subjects warning, and see NIAID Decision Trees for Human Subjects Requirements to learn how reviewers determine whether you meet requirements.
Inadequately addressing any required item may negatively affect
your score. In
rare circumstances, if you fail to address any required item, your
application may not get a review or receive a score. To
cut your risks, leave no questions about what you propose to do.
Clearly
state
how you
will include diverse groups and protect subjects from study-related risks,
and describe the benefits of your research to patients and public
health.
Although your institution determines whether
your research is considered human subjects, the scientific
review officer works with peer reviewers
to confirm or amend this determination to comply with NIH's Implementation
of Office for Human Research Protections (OHRP) Guidance on Research
Involving Coded Private Information or Biological
Specimens.
If they
conclude that the human subjects determination is insufficient,
the scientific review officer will note this by placing
a human subjects code on
your summary
statement. See What
Happens if Reviewers Have Concerns? for more
details.
For additional information,
see Are
You Conducting Human Subjects Research? in
this tutorial.
What Happens If Reviewers Have Concerns?
To
avoid reviewers raising concerns, make
it obvious that you've thought through every issue, and show explicitly
how you
will comply with all human subjects requirements.
Whether you're applying for a grant or contract, reviewers and NIAID staff examine your application carefully. Reviewers assess how well your application meets each requirement, judging its comprehensiveness and whether your plans to include special populations and protect subjects are acceptable.
Any problems, such as inadequate protection
of human subjects or inclusion of special populations, may
negatively affect your priority
score, causing reviewers to designate
a human subjects concern. This
creates a bar to award until you resolve
it to the satisfaction of the NIH Office of Extramural Research.
A human
subjects involvement code or a human
subjects inclusion code on the summary statement may indicate
that
NIAID
is barred from issuing the award.
When risks are serious and protections unacceptable, reviewers may propose
the application be "Not Recommended for Further Consideration." Reviewers
may also suggest changes, such as limiting the scope of the work.
If you're submitting a clinical research application, make sure you read Create a Data and Safety Monitoring Plan in this tutorial, so you can steer clear of the problems mentioned above.
Before You Enroll Participants
Documentation. Before issuing your Notice of Award,
NIAID may require that you submit additional documents just-in-time.
For details, see You Will Send Some Materials Just-in-Time.
If you have a bar from peer reviewers, work with
your program officer to
resolve it and submit a
revised plan. See the Bars to Grant Awards SOP
for details.
NIAID's grants management specialists will also check to see whether your organization has the following in place:
You can begin to enroll participants once program and grants staff
have received, reviewed, and approved all amended or missing documentation.
Registration. By law, you must register applicable clinical trials on ClinicalTrials.gov. However, NIH urges you to register all clinical trials on ClinicalTrials.gov even when registration is not required. See Section 801 of Public Law 110-85 and the November 16, 2007, Guide notice.
To determine when you must register, read When Must I Register My Trial in the November 16, 2007, Guide notice.
Submit the information to ClinicalTrials.gov. For registration information, see ClinicalTrials.gov Protocol Registration System.
Contact your program officer for assistance and to learn more about the registration process.
For additional information, see Clinical Trials.gov’s Protocol Registration System PRS and U.S. Public Law 110-85 and NIH's Fact Sheet -- Registration at ClinicalTrials.gov: As required by Public Law 110-85, Title VIII.
Also see Section 113 of Public Law 105-115 and Guidance for Industry Information Program on Clinical Trials for Serious or Life-Threatening Diseases and Conditions.
Make sure you understand the International Committee
of Medical Journal Editors' (ICMJE)
registration policy if you want your study published by a journal using ICMJE's standards.
Depending on the type of trial, ICMJE's publication policy may require that you register
before you enroll your first patient. To
see how this applies to your study, read "Is
This Clinical Trial Fully Registered?".
Additional Resources
We Must Have Approvals from All IRBs or IECs
If several institutions are involved, submit written documentation that each institution's IRB or IEC approved the protocol and informed consent document. You must show the version number or date approved, and dates for which these documents are valid.
Additional Resources
We'll Discuss Data and Safety Monitoring With You
Though your monitoring plans go through peer review, you will work with NIAID to make the final decision about safety monitoring before you
begin the study. You should discuss this topic with your program officer early on.
Remember that monitoring requirements may vary depending
on the nature, size, and complexity of the clinical trial. For
example, data and safety monitoring boards (DSMB) are required for multisite
clinical
trials involving high-risk
interventions, all phase III clinical
trials, and occasionally other types of trials.
For more details, see Create a Data and Safety Monitoring Plan.
One of the following will conduct the monitoring:
- Independent Safety Monitor -- a physician or other expert who is independent of the study and available to review and recommend actions regarding adverse events and other safety issues.
- Independent Monitoring Committee or Safety Monitoring Committee -- a small group of independent investigators and biostatisticians who review data.
- DSMB -- an independent committee that reviews interim safety and efficacy data and provides advice on continuing, modifying, or terminating the study.
We may require you to use an established NIAID DSMB if your proposed study poses sufficient risk to subjects. To inquire about this, contact your program officer.
Meet Requirements for IND or IDE
If your research involves a new medical intervention, you'll need to obtain an investigational new drug (IND) or investigational device exemption (IDE) from FDA, unless FDA exempts your research.
This requirement applies to therapeutics, vaccines, and other medical interventions as well as licensed products and devices used for a new purpose. If you have any questions, contact your program officer early in
the process.
Before
award, provide your program officer with the name and institution of the IND or IDE sponsor, the date you filed with FDA, IND or IDE number, written comments from FDA, and written responses to
those comments. You should also include risk information from the investigator's brochure, a review of the published
literature, or other credible source.
You must notify NIAID if the FDA puts your study on clinical hold, and send in copies of all correspondence with FDA, including documentation that the hold has been lifted.
For intervention studies, you must obtain regulatory oversight by either FDA (under an IND or IDE) or the regulatory body of the country where the research is to be conducted. In the case of a foreign regulatory body, send NIAID written documentation from the regulatory body showing you are in compliance with local laws.
Additional Resources
Show Recombinant DNA Advisory Committee Approval
If your application transfers recombinant
DNA, or DNA or RNA derived from recombinant DNA, into research participants, you'll need
additional approvals.
The NIH Recombinant DNA Advisory Committee must review your application before review by your institutional biosafety committee, FDA, and your IRB or IEC. Send NIAID written documentation, including comments, of those reviews and approvals.
For more information, go to the NIH Office of Biotechnology Activities Web site and the NIH Guidelines for Research Involving Recombinant DNA Molecules.
Additional Resources
Document Training in Research Conduct
Your application must document mandatory training for
investigators and key staff in the responsible conduct of clinical research.
When you're being considered for an award, you must submit documentation that the investigators involved in the human subjects research have completed research conduct training.
You can wait and send this information just-in-time when we request
it. However, if you have the information ready when you're submitting
your application it's okay to send it then. Include a list of key personnel, the title, and a
one-sentence description of the training. See our sample letter and visit
the Just-in-Time questions and answers.
Check with your institution to see
if it provides training in research conduct.
Alternatively, key
personnel
may
take the Protecting Human Research Participants course from the NIH's Office of Extramural Research. To learn more, read our Human
Subjects Certifications: Training SOP.
For investigators who speak other
languages,
see below for translations of approved training.
Additional Resources
Include the Federalwide OHRP Assurance
Before
we can issue an award, your institution must file a human subjects assurance online with the Office
for Human Research
Protections (OHRP).
If you already have an assurance,
include the number when you submit your application.
If you don't
have your assurance number at the time of application or if it
has changed since your last submission, you must provide it after
you
receive a just-in-time notification.
Just-in-time refers to information that we ask you to
send us after your application goes through initial peer review and
is
being considered
for an
award. For submission information,
see How do I submit JIT information? in
our Just-in-Time questions and
answers.
To learn more about assurances, see the bullets
below.
- Electronic
applications. See section 2, Assurances and Certifications, under Part III, Policies, Assurances, Definitions, and Other Information, in the Grant Application Guide for your Grant
Application Package.
- Paper applications. See section 2, Assurances and Certifications, under Part III, Policies, Assurances, Definitions, and Other Information, in the PHS 398.
Every institution doing human subjects research requires
its own Federalwide Assurance. Even if you're
not studying human subjects, but your collaborators are, you'll still
need to make sure that Federalwide
Assurances (FWA) with the Office for Human Research Protections are
in place. If you're applying for a multiproject application, reviewers
evaluate each project individually for compliance.
Go to Electronic
Submission System for Federalwide Assurances and IRB/IEC Registrations to
register, update, or renew a Federalwide Assurance. Also see the
FWA terms for domestic and international institutions.
Additional Resources
Resolve Peer Review Concerns
Before you start enrolling participants, you must resolve any concerns raised during the review of your application. If your protocol changes, you must receive IRB or IEC approval for these changes. Work with your program officer throughout this process to make sure you've taken all
necessary steps.
Additional Resources
Maintaining Your Award
Throughout
the award, you must comply with the reporting requirements below:
Always
promptly inform your program or project officer of major
changes to the protocol and any reports to FDA, including:
- Protocol amendments.
- Protocol termination.
- Temporary suspension of the protocol.
- Change in informed consent or IRB or IEC approval status.
- Temporary suspension or permanent termination of patient accrual.
- Other problems or issues that could affect study participants.
- FDA communications.
Additional Resources
IRBs and IECs Have Ongoing Requirements
All
relevant IRBs and IECs must review the protocol and analysis plans at intervals appropriate
to the degree of risk, at least once a year and whenever
changes occur in your procedures.
In
addition, report any changes in informed
consent or IRB or IEC approval status to NIAID.
For this reporting, send your program officer a copy of the following:
- IRB or IEC letter of renewal.
- Latest IRB- or IEC-approved protocol identified by version number or date.
- Latest IRB- or IEC-approved informed consent document identified by version number or date and dates it is valid.
To learn more about requirements for continuing
IRB and IEC review,
see the following:
Additional Resources
Amendments, Suspensions, Terminations, and Extensions
For
interim changes to the trial, you'll need to send your program officer certain
documentation. For example:
- Amendments or changes to the protocol, identified by version number or date. Except in the case of imminent danger to participants, your IRB or IEC must approve changes before they are implemented.
- Changes in informed consent documents, identified by version number or date. The IRB or IEC must approve changes before they are implemented.
- Temporary suspension or permanent termination of patient accrual.
- Temporary suspension or termination of the protocol.
- Change in IRB or IEC approval status.
- Other problems or issues that could affect participants.
Talk to your program officer to confirm what documentation is required.
Notify your program officer by fax or email within three working days of these events; then follow up with a detailed letter signed by you and your institutional business official, and include copies of relevant communications with the IRB or IEC.
If a delay occurs due to circumstances beyond your control, you may be eligible for an administrative extension. See our Investigator-Initiated Clinical Trial Administrative Extensions SOP and Investigator-Initiated Clinical Trial Administrative Extensions questions and answers.
Additional Resources
Report Data and Safety Monitoring Reviews
You'll
need to send your program officer written summaries of the monitoring group's reviews
within 30 days of its meetings. If reviews happen frequently, send the summaries
semiannually or quarterly.
Additional Resources
Report Adverse Events Promptly
If your research is done under an IND or IDE, you must notify NIAID in writing if the FDA places your study on clinical hold. If it's not done under an IND or IDE, you and NIAID jointly determine safety reporting requirements.
IND and IDE sponsors must notify FDA about serious adverse events through safety
reports and provide copies to the NIAID program or project officer within
24 hours of FDA notification. These include:
Report other adverse events you document during the trial in the annual IND or IDE report.
If we have an issue, your program or
project officer will let you know within ten working days by email
or fax, followed in 30 days by an official letter.
For more information, read the Guidance
on Reviewing and Reporting Unanticipated Problems Involving Risks to
Subjects or
Others and Adverse Events issued by the Office
for Human Research Protections.
Additional Resources
Send the Inclusion Enrollment Form With Your Progress Report
NIH
requires you to send an Inclusion Enrollment Report form as part of your reporting requirement. It shows
the cumulative accrual and demographic information of participants
enrolled in your study.
If you're going to include foreign participants, you must clearly
document this in your inclusion enrollment tables.
Keep in mind that NIH's policy on including women and minority groups
is the same both inside and outside the U.S.
Read the following to determine 1) your requirements for
collecting data and 2) which Inclusion Enrollment Report form
to use to report your data:
- Electronic applications. See Part
II, Supplemental Instructions for Preparing the Human Subjects Section of the Research Plan, in the Grant Application Guide for the Grant
Application Package.
- Paper applications. See Part
II, Supplemental Instructions for Preparing the Protection of Human Subjects Section of the Research Plan, in the PHS
398 (PDF).
If you're conducting a clinical trial, send in the Inclusion Enrollment Report
semiannually. For other clinical studies, send it with your progress report.
When conducting an NIH-defined phase III clinical trial,
you have additional requirements:
- Report annual cumulative enrollment, as described above, and indicate
if data analysis has begun for the trial. If it has, report progress made in conducting valid analyses for gender, ethnic, and racial differences.
- When you have completed the trial,
you'll also need to use the Inclusion Enrollment Report form to provide
analyses
showing the
intervention differences among those groups.
Other Reporting Requirements
Recombinant DNA Advisory Committee Reports -- Send your NIAID program officer a copy of the adverse event and annual reports required by NIH's Office of Biotechnology Activities.
Research Conduct Training -- If you hire new staff, include documentation in your annual progress report that they were trained in the protection of human subjects. See our sample letter.
Additional Resources
Know Which NIAID Staff Can Help You
NIH
staff play different roles at each step of the way. If you
have questions about meeting human subjects requirements before
you send in your application, talk
to program staff.
After submitting your application,
or anytime before it's reviewed, talk to peer review staff, either
in our Scientific Review Program or in NIH's Center for Scientific Review, depending
where the application is being reviewed.
For more information about peer review staff, read their section of Contact Staff for Help.
After peer review, your program officer serves as your main contact for all issues related to
human subjects. He or she confirms the involvement of human subjects
and looks at potential risks and proposed protection measures.
If
the review group has identified a human subjects concern, contact
your program officer to see what should be done. He or she will
advise you what documentation is needed for NIH approval.
Before issuing a grant, NIAID's grants management staff make sure that your institution has filed an OHRP assurance and that we've received IRB certification and other required documentation. Call grants management staff for any business-type questions about your grant before or after you get your award. To find contact information for program and grants management staff, see Stay in Contact With Your Program Officer.
Our Web site's staff contact list has contact information for review, grants, contracts, and program staff, as well as a general discussion of roles; see Contact Staff for Help and When to Contact an NIAID Program Officer.
Clinical Terms of Award Checklist
The Clinical Terms of Award Checklist is at the end of the Guidance for
Compliance with NIAID Clinical Terms of Award. Scroll to the bottom of that document to see the checklist. It serves as a reminder of all the different
information that must be submitted to NIAID. You can complete the checklist and
send it to your program or project
officer with any other submissions you need to make.
Additional Resources
More Human Subjects Links
In
addition to visiting the Grant Application Guide and Grant
Application Package for electronic submissions, or PHS 398 for
paper submissions, see
these sites for more information:
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