What must I include in "Protection of Human Subjects"?
When preparing your application, you should know that in
addition to the regular review criteria for scientific merit,
reviewers use four other criteria to judge human subjects
- Risks to subjects.
- Adequacy of protection against risks.
- Potential benefits to the subjects and others.
- Importance of the knowledge to be gained.
Part II: Supplemental
Instructions for Preparing the Protection of Human Subjects Section of
the Research Plan is found in the PHS 398 and the SF424and
can be helpful when writing this section.
It is important that you complete and submit the Targeted/Planned Enrollment Table with your application which indicates the proposed ethnic, racial and gender compositions of your study population.
Reviewers will also evaluate your plans for recruiting and
retaining subjects. Trial recruitment that is slower than
expected can result in prolonged trial durations, increased
costs, uneven workload, and morale problems, both for trial
participants and clinical research team members. Furthermore, when recruitment
is so poor that it needs to be curtailed before the trial's
target sample size is reached, study power is reduced and
there may be a need to revise study endpoints.
The Office of Research on Women's Health provides pertinent information on the recruitment and retention of women and minorities in clinical research and may be useful as you consider your plans for recruiting these special populations.
It is good to demonstrate that you have access to the population
under study and to provide realistic estimates of how many
in the population will meet your inclusion/exclusion criteria. If
you have done preliminary work with this same population,
you may wish to describe successful strategies previously
used. You will need to describe which strategies you
plan to use for identifying and enrolling participants
Once enrolled into the study it is important that you have
strategies outlined for retaining patients. A brief
statement as to how you plan to keep patients in the study
Women and Minorities
NIH requires that women and minorities be included in all
research studies unless the nature of the research makes
it inappropriate to do so. You will need to provide
justifications for inclusion or exclusion of these populations. NIH
provides guidance on Inclusion
of Women and Minorities as Subjects in Clinical Research. NHLBI
clarifies what proportion of women and minorities is appropriate
to include in your study, in a document called Questions
and Answers on Inclusion of Minorities and Women in Study
The Office of Research on Women's Health provides a brief history, policy documents and outreach information on inclusion, recruitment and retention of women, men and minorities in clinical research.
NIH policy mandates that children must be included in all
human subjects research conducted or supported by the NIH
unless there are scientific and/or ethical reasons not
to include them. NIH has developed Inclusion
of Children Policy Implementation for further reference. You
may also find additional information from OHRP on Special
Protections for Children as Research Subjects.
The Office for Human Research Protections ( OHRP ) provides
guidance on International
Human Subjects Research Protections to help those involved
in research familiarize themselves with the laws, regulations,
and guidelines of particular countries where the research
will be conducted. You may go to page 5 of the document
and click on a country of interest.
Data and Safety Monitoring Plans ( DSMP )
NIH policy established a requirement for Data and Safety
Monitoring Plans (DSMPs) as a means of ensuring that all
clinical research have a level of monitoring commensurate
with scope and risk, and that this monitoring be an integral
part of the research plan. The purpose of the DSMP
is to delineate how participant safety and data integrity
will be monitored. Monitoring the ongoing study plays
an essential role in protecting the safety of participants
and assuring the integrity of research; hence developing
an effective monitoring plan is of paramount importance.
A DSMP is required for every grant application or contract
proposal submitted to NHLBI that includes a clinical study. Grants
that include multiple clinical research protocols addressing
separate research questions in different groups of subjects
must have a DSMP for each protocol.
Peer reviewers will gauge the adequacy of your plans to
protect subjects from research risk and to include required
populations. 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 fund . If
a grant will be funded by NHLBI, a detailed DSMP must be
included as part of the formal protocol that is submitted
to NHLBI Program Staff and the applicant’s IRB for
approval before accrual of human subjects begins.
All clinical research that entails greater than "minimal
risk" requires independent monitoring. "Minimal
risk" is defined in 45 CFR 46, Section 102 (i) as: a
risk where the probability and magnitude of harm or discomfort
anticipated in the proposed research are not greater, in
and of themselves, than those ordinarily encountered in daily
life or during the performance of routine physical or psychological
examinations or tests. For example, the risk of drawing a
small amount of blood from a healthy individual for research
purposes is no greater than doing so as part of a routine
In the Human Subjects section of the grant application,
there should be a separate subsection entitled, "Data
and Safety Monitoring Plan (DSMP)". The DSMP should
provide a general description of the overall framework for
data and safety monitoring. It should address the following
- What will be monitored
- How often data and safety will be monitored
- Who will monitor
- Where monitoring will occur
- How the clinical study sites, research pharmacy (ies),
and core laboratory(ies) will be monitored.
- How adverse events will be assessed and reported.
Monitoring requirements may differ depending on the type,
complexity and phase of your clinical study. A plan
may include the following types of monitoring:
- Principal Investigator and IRB -- may be appropriate for
a blood sample study.
- 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
- Independent Monitoring Committee or Safety Monitoring
Committee -- a small group of independent investigators
and biostatisticians who review data.
You will work with NHLBI to make the final decision about safety monitoring before you begin your study. Please 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 for more information.
Information about sharing your data can be found at the NIH Data Sharing Policy Site. NHLBI requires that limited
access data sets be prepared for selected clinical trials
and epidemiology studies. In general these may include
cooperative agreements, some ancillary studies or trials/studies
requesting greater than $500,000 direct costs in one year. It
is important that you read this guidance to determine if
your application might fall into one of these categories
and the budgetary implications of data dissemination.
Be certain that your budget is realistic and appropriate
for your project’s aims and methods. Investigators
salaries must be less than or equal to the current
government cap. Modular budgets are applicable
to certain research grant applications requesting $250,000
or less per year in direct costs. Consortium/contractual
F&A costs are not factored into the direct cost limit. Modular
budgets are simplified and detailed categorical information
should not be submitted with the application.Follow
the instructions for the modular
budget format in the PHS
398 form when preparing a
modular budget. More information on NIH
Modular Research Grant Applications is provided by
The instructions for a non-modular budget can be found in
the SF424 or
PHS 398 or in the instructions in the RFA to which you are
responding. Non-modular budgets require much
more detail about salaries, travel, equipment, patient care
costs and budget justification information, among other things.
Human Subjects Application and Grant Handbook is an excellent tutorial presented
by National Institute of Allergy and Infectious Diseases (NIAID).
to Investigators Submitting Clinical Research Applications sponsored
by the Center for Scientific Review. This site gives
additional information to assist investigators in writing
and submitting applications.
Page Last Updated: February 2011
Content Manager: ClinicalResearchPolicyManager@nhlbi.nih.gov