Basic rules and review process of the Review Committee

Institutional (IRB)

Introduction
In this module, an overview of the basic rules is provided.
on the protection of human beings in research that govern the
participation of human subjects in research in the United States.
Learning objectives
At the end of this module, you will be able to:
Describe the function, authority, and composition of the review committee
Institutional (Institutional Review Board, IRB).
Indicate the IRB requirements for conducting research with
human subjects.
Describe the types of review by an IRB.
Describe the process of working with an IRB.
Identify other regulations and regulatory groups that require compliance
depending on the type of research being conducted.

Functoina,uthortiya,ndcompostoinoftheIRB

Function of the IRB

An IRB is a oversight committee established to help protect the
rights and the welfare of human research subjects. The standards
they require the review and approval of the IRB for the research in which
human subjects participate if they are conducted or are funded or regulated by
U.S. federal agencies and departments. The organizations of
research can choose to apply the requirements a all the
research, regardless of the source of funding. Although the
Federal regulations refer to the term IRB, it is possible that a
organization opts for a different name for this committee. To clarify
when an IRB review is required, in the following table there
they review some definitions of federal regulations and guidelines.

Definitions of federal regulations and guidelines

Term Definition
Research A systematic exploration, including research development,
the tests and the evaluations, which is designed to
"develop or contribute to generalizable knowledge" (Protection
of human subjects 2017). If researchers have doubts
Regarding whether a planned activity is research, it must
contact the office of your IRB.
This definition of research specifically excludes what
next:
Academic and journalistic activities (such as oral testimonies).
Public health surveillance activities.
Collection and analysis of information, biological samples or
records by a criminal justice agency or for it in
relationship with activities authorized by law or by court order
only for the purposes of criminal justice or criminal investigation.
Authorized operational activities (as determined by each)
 agency) in support of intelligence, national security, defense or
other national security missions (Protection of individuals
humans 2017).
Subject A living individual regarding whom a researcher (whether a
human professional or a student) who conducts research:
Obtains information or biological samples through the
intervention or interaction with the individual, and uses them, studies or
analysis.
Obtains, uses, studies, analyzes, or generates private information
identifiable or identifiable biological samples" (Protection of
human subjects 2017).
Note: Some state laws include deceased persons and
fetuses as "human subjects". Consult the local IRB
definition of human subject that applies in the state where it
the information will be carried out.
Information Information about behavior that takes place in a context
private in which the individual can reasonably expect that he is not
being observed or recorded, and information that the individual
provided for specific purposes and regarding which the individual
you can reasonably expect that it will not be made public
(for example, a medical record) (Protection of subjects
humans 2017).
Information Private information regarding which the researcher may or
private I could easily determine the identity of the subject or this.
identifiable could be associated with the information” (Protection of the subjects
humans 2017) .
Samples "A biological sample regarding which the researcher can"
biological or could easily determine the identity of the subject or this
identifiable could be associated with the biological sample" (Protection of the
human subjects 2017).
Information The guide from the Office for the Protection of Human Beings in
private or the Research (Office for Human Research Protections, OHRP)
samples (OHRP 2008) from the Department of Health and Human Services
biological the United States (Department of Health and Human Services,
encoded HHS) considers that private information or samples are
they can individually identify when they can link with
specific people directly or indirectly through
coding systems. The OHRP guide (2008) recommends
that only a person or entity with knowledge is authorized
to determine whether the data or the coded biological samples
are considered research. The OHRP recommends that they not be
grant the researchers the authority to determine from
independent form that a research involves
private information or coded samples do not involve subjects
humans.
Research Any experiment that involves a test article and one
clinic or more human subjects and that must meet the requirements
for the presentation prior to the Food Administration and
Medications... or those that do not need to meet the requirements for
the presentation prior to the Food Administration
Medications... but whose results aim to
to present later to the Food Administration and
Medicines, or to be kept for inspection by
this, as part of a research request or permission for
marketing" (Institutional review committees 2015).
Clinical trial "A research study in which one or more subjects
humans are prospectively assigned to one or more
interventions (which may include placebo or other control) for
evaluate the effects of interventions on outcomes
 biomedical or behavioral health (Protection of subjects
humans 2017).

Faculty of the IRB

Federal regulations stipulate that an IRB may:

approve a research study,

require modifications (to ensure approval)
disapprove a research, conduct continuous reviews of
compliance with federal requirements and institutional policy,
check that there have been no major changes since the last one
review
to observe, or to have a third party observe, the investigation and the process
to obtain consent,
suspend or reject approvals.
Federal regulations grant IRBs the authority to approve,
to require modifications or disapprove, including research activities
exemptions in which the limited review by an IRB is a condition of
exemption (Protection of human subjects 2017).

Composition of the IRB

Federal regulations state that the IRB membership shall include:

at least five members,

members from diverse backgrounds,
at least one member whose main interests focus on areas that do not
scientific
at least one member whose main interests focus on areas
scientific
at least one member who is not otherwise affiliated with the
organization (and that is not part of a person's immediate family)
that is affiliated with the institution).
The regulations also stipulate that the IRB membership will include
(Protection of Human Subjects 2017):

Reviewers sufficiently qualified through experience and

specialized knowledge (professional competence) in the areas of
research that is commonly reviewed.

Diversity in its integration, which includes race, gender, and background

cultural issues and sensitivity regarding certain matters such as being
community attitudes.
Knowledge of organizational committees (including policies and
resources) and the regulations, applicable laws, and codes of conduct and
professional practice.
Note: If an IRB reviews research involving populations that
they could be vulnerable to coercion or undue influence (for example,
 children, people in prison, people with reduced capacity to make
decisions or economically or educationally disadvantaged people), the IRB
should consider the inclusion of a person with experience and
knowledge about these categories of subjects (Protection of subjects)
humans 2017). It is possible that regulations may also require the inclusion
from a voting member of the IRB who has specialized knowledge about
the relevant research (for example, research in which
people in prison participate). The IRBs may have the support of
experts for problematic reviews, but those people cannot
vote on the disposition of the request. If a member of the IRB has a
conflict of interest, that member cannot be present for the review of
this project (except to provide information to the IRB as requested) and not
You can vote on that project.

Requirements of the IRB for research involving human subjects

IRB Requirements
There may be differences in the practices of organizations and IRBs.
that guarantee compliance with federal regulations and in the details
from the applicable regulations. The following are the minimum federal requirements.
Organizations or the IRB can add protections or procedures.
additional to these minimum requirements.
Minimum information in a request to the IRB for evaluation by an IRB
Analysis of Identification and assessment of risks and benefits
risks/benefits anticipated.
anticipated Determination that risks have been minimized.
Determination that the risks are reasonable in
relationship with the possible benefits.
Consent Process and documentation to obtain consent
informed informed.
Assent The affirmative agreement of a minor or a person who
she cannot make decisions for herself to participate
in the research.
Process and documentation to obtain consent.
Selection of subjects Equitable selection in relation to gender, race, and the
ethnic origin.
Impartial distribution of benefits among the
populations of the community.
Provision of additional guarantees for the populations
vulnerable individuals susceptible to pressure to achieve their
participation.
Guarantees It is guaranteed that the recruitment of subjects does not invade the
individual privacy and that there are procedures for
ensure that the confidentiality of the is supervised
information collected during the investigation.
Plan of the Clinical research studies often
research for the they include safety and data monitoring plans or
collection security and data monitoring committees
storage and the Data Safety Monitoring Boards/Committees,
data analysis DSMB/DSMC); the IRB will review the plans for
ensure that they are suitable to protect the
human subjects.
Researchers are qualified to collect,
manage and analyze data responsibly and
 they have a plan to analyze the data in a way
significant.
Design/methods of the They are appropriate and scientifically valid and, therefore,
research they justify the exposure of individuals to the risks of the
research.
Additional information About the identification, recruitment and
guarantees if the research involves populations
specials.
Issues Principal investigator ratings
additional ones that the investigator, PI) and the scientific collaborators.
IRB must review Complete description of the proposed research.
Provisions for the adequate protection of the
rights and the well-being of individuals.
Compliance with federal laws/regulations and
relevant state and organizational policies.
Funding proposals from HHS (other agencies of
financing may also have requirements/expectations
similar ones).
Researcher's manual/researcher protocols (for
the research regulated by the Administration of
Food and Drug
Administration, FDA] of the U.S.

Responsibilties of principal investigators and staf

research
The principal investigators and research staff have
specific responsibilities. They must take care of the following:

Protect the rights and welfare of human subjects that

they participate in a research.
Understanding the ethical standards and regulatory requirements that govern the
research activities involving human subjects.
Conduct or supervise the research personally.
Ensure that all staff, collaborators, and the
colleagues who participate in the realization of the study about the study, the
regulations governing research and organizational policies.
Ensure that all research activities have the
Approval of the IRB and other approvals required by the organization
before involving human subjects.
Implement the research activity as approved by the IRB.
Obtain informed consent from the subjects before
participate in the research and document consent according to the
IRB approval.
Keep written records of the IRB's reviews and decisions, and
obtain and maintain documented evidence of informed consent
of the subjects (or of their legal representatives [legally authorized
representatives, LAR]).
Obtain IRB approval for any proposed changes to the plan
of research before its implementation.
Comply with IRB requirements for timely submission of
reports on unforeseen problems that involve risks for the
subjects or other people, including adverse events, the reports of
 security received from the sponsor or the summarized reports of
security and data oversight.
Obtain approval for the continuation of the IRB on the schedule
stipulated by the IRB.
Adopt provisions for the guaranteed retention of records
completed research and all research materials.
Ensure the confidentiality and security of all information
obtained from human subjects and about them.
Verify that approval has been obtained from the IRB for all
organizations that engage in collaborative activities with others
organizations.
Notify the IRB about the emergency use of a drug or
device in research phase within five working days (or
before if required by the IRB policies) of the administration of the article
test.
Notify the IRB about any new relevant information that
it may affect the health or privacy security of the subjects.

Possible consequences when following the IRB regulations

Suspension of the research project.

Suspension of all research projects of a researcher
principal.
Inability to use the data or publish the results.
Notification regarding non-compliance to sponsors, agencies
regulatory bodies and funding agencies.
Disqualification by the FDA to use products in phase
research.
Inability to receive funds from federal grants.
Additional supervision and monitoring by the IRB or oversight by
third party participation in research activities.
Termination of employment.

Loss of licenses.
Immediate suspension of all investigations in an organization.
These are not theoretical consequences. All or some of these consequences
they have been applied in centers where research with human subjects is
was carried out inadequately or without IRB approval.

Types of review by an IRB

Contact the IRB office for the guidelines for the
presentation of a study for review by the IRB. According to the
federal regulations, there are three possible review procedures
part of an IRB:

1. Review by a convened committee/in full

2. Expedited review
3. Review to obtain exemption status
 Review by a convened committee in full
The review by a full committee or the review by the IRB
convened is the type of standard review described in the regulations
federal. It should be used for the initial review of all studies that do not
meet the requirements for an expedited review or to obtain status of
exemption. The procedures and conditions for the review by a
the full committee demands the following:

The review must be conducted at a convened IRB meeting. In the

the meeting must be attended by a majority of the IRB members
quorum.
At least one member whose interests must be present at the meeting.
mainly focus on non-scientific areas (furthermore, the policy of the
FDA recommends that a doctor be present.
In order to approve a research study, the IRB must determine that it
meet all the requirements specified in section 46.111 of the title
45 of the Code of Federal Regulations
CFR) (y, if applicable, section 56.111 of title 21 of the CFR). Please consult
“Frequently Asked Questions About Human Research
frequent questions about research involving human subjects”
yInformation Sheet Guidance for Institutional Review Boards (IRBs)
Clinical Investigators, and Sponsors (Information guide for
institutional review boards (IRB), clinical researchers and
sponsorsfor more information.
The majority of the members present at the meeting must approve the
research.
Members of the IRB who have a conflict of interest in a project
Research can provide information to the IRB, but they cannot
participate in the review of the plan nor be present to vote. The
members who have a conflict do not count towards the quorum for the
review of that study.
The IRB must notify (in writing) the researchers and the organization
about your decision to approve, modify, or disapprove the investigation.
IRBs must maintain detailed documentation of their activities.
the meeting, this includes attendance, voting on the measures, the
basis of the measures and a written summary of the analysis by
an IRB of the controversial issues and their resolution.
Although it is not specifically addressed in the regulations, IRBs may
use a 'main reviewer system'. In this system, all members
from the IRB they receive basic information about the research proposal, but
a "main reviewer" with experience or knowledge is assigned
specialized in the field of study to conduct a thorough review
from the request to the IRB and any attached documentation (for example, a
Investigator's manual or funding requests). The lead reviewer
He will then report his findings to analyze them in a committee meeting.
called/in full. In some organizations, reviewers may be able to
in contact with the researcher if you have questions or suggestions before the
meeting. Additionally, the IRB in some organizations may request that the
Researchers should attend the IRB meeting or be available by phone.
to answer any questions that may arise in the meeting.
 Expeditious review
Federal regulations establish categories that IRBs can use.
to invoke the expedited review process. The president of an IRB or other
IRB member designated by the president can carry out the review.
expeditious. IRB members who have a conflict of interest cannot
designated as reviewers responsible for the expedited review. The reviewers
those in charge of expedited reviews can:

approve a research study

require modifications (to ensure approval),
postpone the meeting with the convened IRB.
The reviewers responsible for expedited reviews cannot disapprove.
a research study. Each IRB that uses an expedited review must have a
method to keep all IRB members informed about the
investigations approved under the expeditious review.

Research categories that meet the requirements for expedited review

The HHS Secretary will provide a list of the categories of
research that meets the requirements for rapid review in
the Federal Register, at least, every eight years. Organizations can
adopt all or some of the categories when determining if a
research activity can be properly reviewed through a
expedited review process. An IRB can use an expedited review to
the categories published in section 46.110 of title 45 of the CFR and also
for minor changes in previously approved research during
the period for which approval is granted (for example, a
amendment). Categories 1 to 7 apply to initial and ongoing reviews.
by an IRB. Categories 8 and 9 apply only to the
continuous reviews. Federal regulations establish two criteria.
principles for an expedited review.

The research must not involve a 'risk greater than the minimum.'
Minimum risk means that 'the probability and magnitude of damage or the
anticipated discomfort related to the research should not exceed
those that are usually found in daily life or during the
development of routine physical or psychological exams or tests
(Protection of human subjects 2017; Institutional review boards
2015).
The entire research project must be in line with one or
more than the categories defined at the federal level (OHRP 2003).
Some organizations/IRBs have additional requirements. Consult the office.
of the IRB to know how the IRB in your organization manages the
expedited reviews.

Category1
Clinical studies on drugs or medical devices regarding which
a new drug application in the research phase is not required
(investigational new drug, IND) or exemption for devices in phase of
investigation (investigational device exemption, IDE). Similarly, a
study with an approved/authorized medical device that is used for
compliance with its approved/authorized label.More details.

Category 2
Blood sample collection through finger prick, puncture in
the heel, ear puncture or venipuncture.More details.
Category 3
Potential collection of biological samples for research purposes
non-invasive ways.More details.
Category 4
Data collection through non-invasive procedures used
routinely in clinical practice, as long as the conditions are met
following conditions:
The non-invasive procedure should not include general anesthesia or
sedation that is routinely used in practice or the
clinical procedures that involve the use of X-rays or microwaves.
When it use devices doctors must to be
approved/authorized for marketing. (Generally, the studies
which aim to evaluate the safety and efficacy of the device
doctor do not meet the requirements for the expedited review, including the
studies of medical devices authorized for new indications.
Examples of non-invasive procedures

Physical sensors that are applied to the surface of the body or to a

distance, and that do not involve the application of significant amounts of
energy in the subject nor an invasion of the subject's privacy.
Measurement or assessment of sensory acuity.
Magnetic resonance imaging.
Electrocardiography, electroencephalography, thermography, detection of
naturally occurring radioactivity, electroretinography, ultrasounds,
infrared imaging diagnosis, Doppler blood flow and
echocardiography.
Moderate exercise, muscle strength tests, evaluation of the
body composition and flexibility tests when applicable according to
the age, weight, and health of the person.

Category5
Investigations involving data, documents, records, or samples that:

have been obtained, or

will be obtained solely for purposes unrelated to research
(for example, medical diagnosis or treatment).
Note: Some research in this category may be exempt.
from the HHS regulations indicated in section 46.101(b)(4) of title 45
of the CFR. This list refers only to the investigations that do not
are exempt.
Category 6
Data collection from voice, video, digital, or recordings.
images created for research purposes.
 Category 7
Research on individual or group characteristics or behaviors.More
details.

Category 8
Continuous review of previously approved research by an IRB
called/fully with respect to which:
The investigation is permanently closed for the
registration of new subjects; all subjects have completed all
the interventions related to research and investigation
remain active only for long-term follow-up of subjects.
No subjects have been registered nor have additional risks been identified.
The remaining research activities are limited to data analysis.

Category9
Continuous review of research that has not been conducted under an IND request or
IDE, and when categories 2 to 8 do not apply, but the IRB has determined and
documented in a meeting of the convened committee/in full that the investigation does not entail
a risk greater than the minimum and no additional risks have been identified.

Expedited review process

Upon conducting the review, the reviewer in charge of the expeditious review must
determine that the research meets the conditions for the
expedited review procedures.

To approve a research activity, the reviewer must determine that it

they meet all the requirements specified in the federal regulations
(section 46.111 of title 45 of the CFR and section 56.111 of title 21 of the CFR).
The reviewers can approve the research, require modifications (to
ensure approval) or refer the investigation to an IRB meeting
called/in full for a review to be carried out in accordance with the
procedures for a 'full committee review' described above
and stipulated in section 46.108(b) of title 45 of the CFR and section
56.108(c) of Title 21 of the CFR.

Expedited procedures can also be used for review.

minor modifications of previously approved research.

Review to obtain exemption status

Federal regulations specifically define six categories of
research with human subjects that are exempt from the others
regulatory provisions. The OHRP guide (2016) states that the
Determinations of exemption status must be handled by individuals.
independent of the research and who know well the interpretation of the
regulations governing the conduct of research with human subjects
Many organizations grant the authority to make determinations about
exemption status to the IRB. Consult the IRB office to find out to whom
has been granted the authority to make the determination of exemption.Note:The
determination must be made before the start of the investigation or of the
activity; it cannot be taken retroactively.

Exempt investigations
The regulations of section 46 of title 45 of the CFR (Protection of the
human subjects 2017) have determined that the following eight categories of
research meets the requirements to obtain the exemption status.

Category1
Investigations carried out in established or commonly educational environments
accepted that specifically involve normal educational practices, that
it is unlikely that they will diminish the opportunity that students have to
learn the required educational content or the assessment of educators
that provide instructions. This includes research on strategies
regular and special instructional and educational programs, and research on the
effectiveness of instructional techniques, curricula or management methods
classes or the comparison between these.

Category2
Investigations that only include interactions that involve tests
educational (cognitive, diagnostic, aptitude, achievement), procedures
of surveys, interview procedures, or the observation of behavior
public (including visual or audio recordings) if they comply with, when
less, one of the following criteria:

The information obtained is recorded in such a way that it does not

can easily determine the identity of human subjects,
directly or through identifiers linked to the subjects.
The disclosure of the responses of the human subject outside of the
research should not reasonably generate a risk of facing
a criminal or civil responsibility on the part of the subject nor harm his
economic situation, the possibility of finding employment, nor its reputation.
The researcher records the information obtained in such a way that
the identity of human subjects can be determined easily,
directly or through identifiers linked to the subjects, and a
IRB conducts a limited review to make the determination required by the
section 46.111(a)(7).
Note: Federal regulations specify that the first two options of
this exemption (46.104[d][2][i] and 46.104[d][2][ii]) involving educational tests
or the observation of public behavior can only be applied to the
research with children when the researcher does not participate in the activities
that are observed.

Category3
Research involving benign behavioral interventions along with the
collection of information from an adult subject through oral responses or
in writing (including data entry) or audiovisual recordings if the
subject prospectively accepts the intervention and the collection of information,
and it complies with at least one of the following criteria:

The researcher records the information obtained in such a way that

it is not easy to determine the identity of human subjects,
directly or through identifiers linked to the subjects.
The disclosure of the human subject's responses outside of the
research should not reasonably generate a risk of facing
a criminal or civil liability on the part of the subject nor harm his
economic situation, the possibility of finding employment, progress
educational nor its reputation.
The researcher records the information obtained in such a way that
the identity of human subjects can be easily determined,
directly or through identifiers linked to the subjects, and a
IRB conducts a limited review to make the determination required by the
section 46.111(a)(7).
For the purposes of this provision, benign behavioral interventions are
understand those interventions with a brief duration, harmless, that do not
they produce pain, non-invasive from a physical perspective, with few
probabilities of producing significant and long-lasting adverse effects on the
subjects and regarding which the researcher has no reason to think
that the subjects will consider them offensive or embarrassing. As long as
all of those criteria are met, among the examples of interventions
benign behavioral patterns include the following:

Make the subjects play online.

Make the subjects solve puzzles under different conditions
of noise.
Make the subjects decide how to distribute a modest amount of
cash received between them and other people.
If the research involves deceiving subjects about the nature or the
research purposes, this exemption does not apply unless the subject
authorize the deception through a prospective agreement to participate in a
investigation under circumstances in which the subject is informed that they do not
will know neither the nature nor the purposes of the research, or will have
misleading information about it.

Category 4
Secondary research for which consent is not required:
Uses of identifiable private information or identifiable biological samples
for secondary research if it meets at least one of the
following criteria:

Identifiable private information or biological samples

identifiable information is available to the public.
The researcher records the information, which may include information
about biological samples, in such a way that it cannot be determined with
facilitates the identity of human subjects directly or through
identifiers linked to the subjects, the researcher does not communicate
with the subjects and the researcher does not re-identify the subjects.
 The research involves only the collection of information and the
analysis on the use of identifiable health information by
researcher when such use is regulated by section 160 of the title
45 of the CFR, as well as by subparts A and E of section 164,
the purposes of "health care activities" or "research" according to the
definition of these terms in section 164.501 or for 'activities and
"public health purposes," as described in section 164.512(b).
A department or federal agency conducts the investigation, or
well this is done in their name, and in the research it is used the
information generated by the government or that it collected for activities
different from the research, if the research generates private information
identifiable that is maintained or will be maintained in technologies of
information subject to section 208(b) of the E-Government Act
(E-Government Act) of 2002, note of section 3501 of title 44 of
USC. and in compliance with said sections, if all the information
identifiable private data that is collected, used, or generated as part of the
activity will be maintained in record systems subject to the Law of
Privacy Act of 1974, section 552(a) of title 5 of the USC and, if
corresponds, the information used in the research was collected from
compliance with the Paperwork Reduction Act
Act of 1995, section 3501 et seq. of title 44 of the USC.

Category 5
Research and demonstration projects carried out or funded by a
department or a federal agency or, otherwise, subject to approval
from the heads of a department or an agency (or to the approval of the heads
of offices or other agencies subordinate to those to whom the authority was delegated
to carry out research and demonstration projects) and designed to
study, evaluate, improve or otherwise examine the programs of
benefits or public services, including the procedures to obtain them
benefits or services under such programs, possible changes or the
alternatives to said programs or procedures or the possible changes in the
methods or levels of payment of benefits or services under said
programs. Among these projects are included, by way of example, the
internal studies conducted by federal employees and studies by virtue of
contracts or consulting agreements, cooperation agreements or grants. The
exempt projects also include the exemption from other requirements, for
other mandatory sections through the application of laws, for example, the sections
1115 and 1115A of the Social Security Act and its
modifications.

Each department or federal agency that carries out or funds the

research and demonstration projects must be established at a site
publicly accessible federal web or in any other way that the chief
of the department or agency may determine a list of the
research and demonstration projects that the department or the
federal agencies carry out or finance under this provision. It must
publish the research or demonstration project on this list beforehand
that the research with human subjects begins.

Category6
Assessment of food quality and flavors, and acceptance studies by
part of the consumers.

If healthy foods are consumed without additives.

If a food containing an ingredient is consumed at a level equal to or
lower than what is determined to be safe for its use or with an agrochemical or
environmental pollutant at a level equal to or less than that determined
safe under the FDA, or approved by the Environmental Protection Agency
Environmental or the Inspection and Food Safety Service of
U.S. Department of Agriculture

Category7
Storage or maintenance for secondary research regarding
of which broad consent is required:

Storage or maintenance of identifiable private information or

identifiable biological samples for potential secondary research
if an IRB conducts a limited review and makes the determinations required by the
section 46.111(a)(8).

Category8
Secondary research for which consent is required
broad: Research involving the use of identifiable private information or
identifiable biological samples for secondary research if
meet the following criteria:

Obtaining broad consent for storage,

maintenance and the use of private information or biological samples
identifiable for secondary research in accordance with the
section 46.116(a)(1) to (4), (a)(6) and (d).
Obtaining the documentation of informed consent or of the
exemptions related to the documentation of consent
compliance with section 46.117.
An IRB conducts a limited review and makes the determination that is required.
section 46.111(a)(7) and decides that the investigation to be conducted is
finds within the scope of the broad consent to which it is made
reference in paragraph (d)(8)(i) of this section.
The researcher does not include the disclosure of individual results of the
investigation of the subjects as part of the study plan. This
the provision does not prevent researchers from complying with any requirement
law that requires them to disclose individual results of the
research.

When is the appropriate time for a review to obtain this exemption status?
In accordance with section 46 of title 45 of the CFR (Protection of the
human subjects 2017), are not suitable for exemption from research
that involve the following:
 People in prison (except for investigations that are intended
to encompass a broader population of subjects than just in a manner
incidental, includes people in prison).
Surveys and interviews with children.
Observations of children's public behavior when the researcher
participate in the activities that are observed.

Special considerations
Researchers and IRB reviewers should be aware that there may be
special considerations for the different types of research. For example,
Some policies may limit the IRB's ability to waive the requirements.
for obtaining informed consent, or research that normally
may be considered exempt will require review by an IRB.
For example, the policy for the transmission of genomic data (Genomic Data
Sharing Policy, GDSP) of the National Institutes of Health
Health, NIH) for data on human subjects and non-human subjects has
implications for researchers if they want to access the data from this database
data or if they want to provide data to this database and are funded by the
NIH. Under this policy, the IRB must review the research if the investigator
It will provide data to the database of genotypes and phenotypes.
Genotypes and Phenotypes, dbGaP) and the research is funded by the NIH.
Normally, review by the IRB would not be required according to the
regulations because research is generally considered research
with non-human subjects (NIH 2014).
If the principal investigator receives funding from the NIH and needs access to the database
of data, the determination of non-human subjects cannot be used. The IRB
you must review the investigation to ensure that there were adequate provisions
to obtain consent for the collection of biological samples.

AdditionalHIPAArequirementsthatindirectlyafectthereviewfor
obtain exemption status
The privacy rule is a federal regulation under the Law of
Portability and Responsibility of Health Insurance
and Accountability Act, HIPAA) of 1996 (sections 160 and 164 of title 45 of
CFR). If an IRB has been granted the responsibility to consider
issues related to HIPAA in research and whether the research
potentially falls under the HIPAA regulations, the IRB will not only apply
the exemption categories of section 46 of title 45 of the CFR but
it will also determine whether HIPAA applies. In some cases, the requirements of
the applicability of HIPAA is stricter than the exemption requirements
the HHS and, in other cases, less strict. A research project that
is exempt from IRB requirements for research involving subjects
humans cannot be exempt from the provisions of HIPAA. Likewise,
a project that is not exempt from review by an IRB could be
exempt from HIPAA. ConsultGuidance on Research Involving Coded
Private Information or Biological Specimens(Guide on the research
that involve private information or coded biological samples from the
OHRP and the NIH guide on theInstitutional review committees and the
HIPAA Privacy Rule.

Work process with an IRB

 Criteria for the approval of an IRB
The federal regulations of section 46 of title 45 of the CFR (Protection
of human subjects 2017) and of section 56 of title 21 (Committees of
institutional review 2015) lists the basic criteria that the IRB must
apply when reviewing research involving human subjects.
To approve a research project, the IRB must determine the following:

The risks that subjects may face are minimal.

The risks are reasonable in relation to the expected benefits.
for the subject, and for the advancement of knowledge.
The selection of subjects is equitable.
Informed consent will be obtained.
The informed consent will be properly documented or exempted.
If applicable, the research plan includes provisions
suitable for monitoring the collected data, in order to ensure
the safety of the subjects.
There are adequate provisions to protect the privacy of the
subjects and to maintain the confidentiality of the data.
When individuals are likely to be vulnerable to coercion or
undue influence, additional protective measures have been included in
the study to protect the subjects.
In addition, there are specific requirements regarding the process for
obtain informed consent. These will be detailed in the
informed consent module of the CITI program.
The IRB must determine that these conditions exist at the time of the
initial review and in each subsequent review conducted by the IRB.

Types of presentations to the IRB

Types of submissions to the IRB
Request for The first request for the approval of a specific project
initial review It is the request for the initial review.
Request of The IRB must review studies that involve a risk again.
review superior to the minimum and with a frequency of no less than once per
continue Year. An IRB may require a review more frequently.
according to the evaluation by the IRB of the relationship
risk/benefit of the study. The review may be a review
expeditious or complete. Unless an IRB determines otherwise and
document your justification, no review is required for the
research that involves minimal risk (research
that met the requirements for the expedited initial review) or
the research that is in data analysis or in
follow-up of subjects only (clinical data from
of clinical care procedures) (Protection of subjects
humans 2017).
Amendments or It is not possible to make changes to the approved studies, including
modifications the informed consent document, without prior review
and IRB approval. The review can be complete or
expeditious, according to the magnitude of the change and the effect of the change
about the risk/benefit relationship.
Reports to the IRB The
IRB may require reports for the following:
of problems adverse events or unforeseen problems that involve risks
unexpected events for subjects or other people
 ntos breach incidents
adverse deviations from an approved study plan and violations of
compliance the approval conditions,
summary reports on security supervision and data.

Initial review request

The initial review may consist of a committee convened/in full or a
expeditious review according to the type of study, the subjects, and the level of risk.

Continuous review request

The IRB must conduct a substantive continuous review and consider the same.
issues that were taken into account during the initial review.
Specifically, the following:

When a continuation review is conducted, the IRB uses the

procedures for a review by a convened committee
full.
To approve a research study, the IRB must determine that the following are being followed
fulfilling all the requirements for initial approval (specified
in section 46.111 of title 45 of the CFR and section 56.111 of title 21
of the CFR).
The IRB must review, at a minimum, the research plan and any
amendment, as well as the report on the status, including the following:
o the number of subjects gathered,
o a description of adverse events, the problems
unexpected events, the withdrawal of subjects, complaints, and the summary of information
new relevant,
o a copy of the current informed consent document.
Check the most recent information about continuous review requests in
theGuide on the continuous review of research by a
IRBfrom the OHRP.

The continuous review must be done at least once a year (within

the 365 days) from the previous approval. The conduct of reviews
Most frequent is left to the discretion of the IRB, and may be the result of the
consideration of the risks related to the study or the population
proposal. A researcher is responsible for knowing when it will expire the
approval of an IRB. However, most organizations/IRBs,
as a courtesy to its researchers, sends reminders to
to communicate that the IRB approval is about to expire. At some
moment before the approval deadline of the IRB, the researchers
You will receive a request to complete a progress report for review.
continues by the IRB. A researcher is responsible for completing the
request for continuous review and to send it again to the IRB before
the current approval period of the IRB has ended.

If the approval of a research plan expires before the IRB

Upon completing the review, the investigator must interrupt all procedures.
of the research. When the interruption of the research could put at
risk to subjects, the researcher must contact the IRB
immediately to obtain approval to continue treating the subjects
in that study.

Amendments and modifications

All amendments and modifications to a study require approval by
part of an IRB before it is implemented. If the researcher wants
change something in the research that would affect the subjects (for example, the
procedures for recruitment, key personnel, the criteria for
inclusion/exclusion the procedures of the research the
informed consent process/document, or the elements of the data
obtained), the researcher must obtain review and approval from the IRB beforehand.
from the implementation of the changes. The only exceptions are the changes
necessary to immediately protect the safety of the subjects, as applicable
indicated in sections 56.108(a)(4) and 56.115(a)(1) of title 21 of the CFR. If the
Researchers are unsure about the notification to the IRB regarding the
Changes must be communicated to the IRB office and guidance requested.
The IRB office can also provide researchers with instructions.
for the submission of a request to modify an approved research
by the IRB.

Reports on unforeseen problems/adverse events/breach

The federal reporting requirements for IRBs,
Researchers and funding sponsors can be confusing. Like
consequence, the IRBs tend to develop their own requirements for
presentation of idiosyncratic reports, based on your interpretation of
the FDA and OHRP guide. This presents some difficulties for the
Researchers given that, if the project is funded, the sponsor could
have reporting requirements that differ from the policies and the
IRB procedures.

At a minimum, to ensure compliance, the researcher is responsible.

the following:

Determine the IRB reporting requirements for submission with

regarding what must be reported, when it must be reported and the
procedure to submit the report.
Establish systems to ensure that the events that should
to inform themselves, identify and present themselves to the IRB in a timely manner.
Examples of events that must be reported

An unforeseen problem, which can be defined as any event

unexpected that affects the rights, security, or well-being of the
subjects. The event could be physical (for example, an adverse experience
to a drug or an adverse effect of a device) or imply certain harm
(for example, violation of confidentiality or damage to reputation of
a subject).
A serious adverse event, which can be defined as a death, a
adverse experience with a drug or potentially with a device
 mortal, a hospitalization or extension of an ongoing hospitalization,
a persistent disability/incapacity or a congenital anomaly or
birth defect.
An exception to the research plan, which can be defined as the
enrollment of a research subject that does not meet the criteria
inclusion/exclusion of the research plan.
A deviation from the research plan, which can be defined as
a deviation from the research plan according to the
IRB approval for a single subject.
Security supervision plan and summary reports of
committee.
Complaints about the rights of the subjects presented by the
subjects or by the parties involved, the relatives or the staff of the
study.
The IRB will use the reports to assess whether the risk/benefit relationship is still
reasonable, if it is necessary to make changes to the consent document
informed about the study procedures and if it is necessary to obtain the
consent. The IRB reporting requirements vary
regarding what should be reported, when should the reports be submitted
and what format they should have. Consult the IRB to determine its requirements.
specific.

Requirements for presenting additional reports

The principal investigator is responsible for reporting to a variety of others.
entities, in addition to the IRB. The following table summarizes the requirements of
minimum report presentation for each entity.
Entity Researcher reporting requirements
principal
Subject of the Although it may not be considered a reporting presentation in the
In the strictest sense, the process of informed consent is
a report for the potential subject regarding the research,
both before the investigation begins and in a manner
continues throughout the study.
Similarly, if there is new information during the investigation
available that could affect the subject's willingness to
to participate, a researcher has the obligation to provide you with that
information to the subject. This information must also be informed.
the IRB. The IRB office can provide guidelines on how to
You must provide the additional information.
The Most organizations have hierarchical structures.
organization established, so that the researcher prepares the reports
for the IRB, and the IRB must keep the organization informed.
However, consult the corresponding IRB to ensure that
that the researcher does not have the direct responsibility to report
the incidents to the organization.
Sponsor Adverse events must be reported immediately to
sponsor. Researchers must also control the
proposed changes by the sponsor that could be made to
study, based on the adverse event that occurred or the findings
preliminaries. The sponsor should also be informed about
serious or constant non-compliances in a study.
FDA Adverse events/unforeseen problems must be reported
directly to the FDA if the investigation is initiated by the
principal investigator (without external sponsorship) and falls under the
 FDA jurisdiction. Other requirements may apply.
presentation of reports related to research
regulated by the FDA.
DSMB/DSMC If the project has a DSMB/DSMC, consult the plan of
DSMB/DSMC for reporting requirements.

Records maintenance
The signed informed consent document is one of the records of
the most fundamental research that the researcher must obtain and
to preserve. It represents the verification that the subject was explained the
research and that the subject understood and willingly agreed to participate in
the research study. Researchers are responsible for preserving
the signed consent documents, the IRB correspondence and the
research records for at least three years after the
conclusion of the research activity (Protection of human subjects)
2017). However, local organizational policy or the requirements of
sponsors may determine that records be kept for longer
time. Consult the sponsor and the IRB office to ensure that
the retention requirement for at least three years complies with its
needs.

FDA regulations specify document retention requirements.

unique for studies regulated by the FDA (see section 312.62 [c])
from title 21 of the CFR). These requirements must be met for the studies
regulated by the FDA.

Other regulations and regulatory groups

Regulatory and funding agencies

Depending on the nature of the research and the funding agency, there are
other regulations, policies, and procedures that may be necessary
consider. Below is a brief description of some
regulations, regulatory bodies and funding agencies that can
supervise the research. Funding agencies or local offices
the IRB can also provide guidelines on the possible application of
additional requirements in a research activity.
Agencies General regulations
regulatory/from
financing
HHS The HHS is responsible for a group of federal regulations
about human subjects. Section 46 of Title 45 of the CFR
(Protection of Human Subjects 2017) applies to all the
research with human subjects presented or funded
by the HHS. The subparts include the following:
Subpart A: Basic policy of HHS for the protection of the
human subjects.
Subpart B: Additional protections for women
pregnant women, human fetuses, and newborns that participate in
investigations.
Subpart C: Additional protections related to the
biomedical and behavioral research involving
 people in prison.
Subpart D: Additional protections for children participating
in investigations.
Subpart E: Registration of institutional review committees.
NIH The NIH includes funding agencies that provide
federal funds for biomedical research.
The NIH has firmly established the expectation that it should
they will use single Institutional Review Boards (sIRB) from
registration for the review of multicenter studies. In
onfinal policyon this subject, in force since January 25
In 2018, the NIH explained that the proposals of
investigations with national, multicenter human subjects
and non-exempt must include plans for the use of a sIRB.
The NIH requires that beneficiaries who carry out certain
types of clinical research studies have plans for
security and data monitoring or DSMB/DSMC. In general, the
NIH policy requires the establishment of a DSMB/DSMC.
for all phase III randomized clinical trials.
NIH Policy for thesecurity and data oversight
Policy for theNational Cancer Institute for the
security and data supervisionof clinical trials
Essential elements of a supervision plan
security and datafor clinical trials funded by the
National Cancer Institute
Moreguidelines on security and data supervisionfor
phase I and phase II clinical trials
Final policy of the NIH on the use of a single committee for
institutional review in the case of research
multicentric
ClinRegsit is an online database of information
regulations for clinical research specific to the country.
OHRP The OHRP is the oversight body of the HHS that
provides guidelines to IRBs and researchers conducting
research with human subjects. The OHRP policy and
the guidelines on guarantees, the regulations, the ethical principles,
the IRB guidebook, the reports from the OHRP/Office for the
Protection against Research Risks (Office for
Protection from Research Risks, OPRR), the questions
frequent and other relevant materials for protection of
the human subjects participating in research are
available at www.hhs.gov/ohrp. The OHRP publishes
on their website thecompilation of rules
internationalmore up-to-date.
FDA The FDA oversees the use of all medications.
devices, biological products, etc., including their use in the
research with human subjects. The FDA has several
regulations that directly affect consent
informed.
I TheInternational Council for Harmonisation
Council for Harmonisation, ICHoffersguidelines of the
Good Clinical Practice (GCP)It is
possible that research with human subjects that
conducted in international environments have requirements
additional requirements that must be met.
Department It is possible that the research funded by
of Education theDepartment of Educationfrom the US have
(Department of additional requirements that must be met.
Education
Department Research involving human subjects
of Affairs of recruited at a facility of theVAor carried out in this
Veterans they must also comply with the requirements as stipulated
(Department of VA. TheOffice of Research Oversight of
Veterans VAprovides several posts related to
Affairs, VA investigations on your website.
Other agencies It is possible that other federal agencies have policies,
federals additional procedures or requirements that must be applied to
the research involving human subjects.
Some examples are theDepartment of Defense
Department of Defense, theDepartment of Energy
Department of Energy, and theNational Foundation for the
Science (National Science Foundation).

Requirements for guarantees

The regulations and policies on the protection of human subjects of the HHS
require that any organization thatparticipatein research with subjects
humans not exempt or funded by HHS must send a guarantee of
written compliance to the OHRP. The Federalwide Guarantee
Assurance, FWA) is the only type of new guarantee accepted and approved by
the OHRP. The FWAs are also approved by the OHRP for use at the level
federal, which means that other departments and federal agencies that have
adopted the federal policy for the protection of human subjects (also
known as the Common Rule) can be covered under the FWA for the
research that they conduct or finance. The organizations that participate in
research conducted or funded by departments or agencies
federal entities that do not belong to HHS must consult the department
sponsoring organization to obtain guidelines on whether the FWA is appropriate
for the research in question.

A performance guarantee is a written document presented by a

organization (not an IRB) that participates in research with human subjects
no exemptions made or financed by the HHS. Through the guarantee, a
the organization commits to HHS to comply with the requirements
stipulated in the regulations for the protection of human subjects
(section 46 of title 45 of the CFR).

Registration of the IRB

Both the FDA and HHS require the registration of the IRB. Each IRB that is
designated by an organization under a performance guarantee
approved for federal use by the OHRP in accordance with
thesection 46.103(a) of title 45 of the CFRand that I review research in the
that involve human subjects conducted or financed by HHS must be
registered with the HHS. Additionally, any IRB in the U.S. that reviews
FDA-regulated research must be registered. All
IRB registrations are done through the OHRP website.

More reasons to contact the office of an IRB

Ensure that the organization is registered with the OHRP (if the
research is funded by federal dollars) or the FDA (if the
research involves products regulated by the FDA.
 Obtain the FWA number. Alternatively, this information can
find on the OHRP website.
Determine the FWA requirements for the activities of
multicenter research if federal dollars will be transferred to the
subcontractors.

Research cooperation and review by a single IRB (sIRB)

Cooperation research projects are research studies
that involve more than one organization. In accordance with the section
46.114 of Title 45 of the CFR (effective from January 20, 2020),
any institution located in the U.S. that participates in research
cooperation must depend on the approval of a single IRB for this
part of the research conducted in the United States" (Protection of
the human subjects 2017). This is reflected in the NIH's final policy "Use
of a single institutional review committee in the case of research
"multicentric," which established the expectation that a sIRB will be designated for
that conducts the ethical review of all national centers participating in
any multicenter study funded by the NIH (in effect since the 25th of
January 2018). There are exceptions to both HHS regulations and the
NIH policy, however, most of the research
multicentric will use the sIRB review. The aim is to reduce the burden.
administrative of the repetitive reviews and increase the effectiveness. The
HHS regulations also require a delegation agreement between the
organizations that delegate and those that serve as sIRB to include
the responsibilities that each one will assume.

Researchers can submit their studies to their local IRB or to a sIRB.

external for your review. Researchers must be aware of the different
IRB reporting requirements and specific policies of
any IRB that reviews your research.

Summary
The IRB has many functions and responsibilities in its mission to protect
human subjects participating in research. It is important that the
Researchers understand the IRB in order to work together with it.