INDIANA UNIVERSITY HEALTH
BLOOMINGTON
TITLE: Categories of Research
APPROVED: Kevin Rush
ORIGINATION: 09/26/2003
IRB – INSTITUTIONAL REVIEW BOARD
POLICY NUMBER: SC 502
PAGE 1 OF 8
REVIEW WITH REVISION: 07/13/2012
REVIEW ONLY:
1. POLICY
The categories of research defined in these policies involve either methodologies that might
require additional considerations or for which there are federally mandated determinations
that IRBs are required to make and document. These categories of research include, but are
not limited to:




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Clinical research involving devices
Genetic research
Medical records and chart review
Residual body fluids, tissues and recognizable body parts
Protocols lacking plans for human involvement
Specific Policies
1.1
Clinical Research Involving Devices
Medical Device: A medical device is defined, in part, as any healthcare product that
does not achieve its primary intended purposes by chemical action or by being
metabolized. Medical devices include, among other things, surgical lasers,
wheelchairs, sutures, pacemakers, vascular grafts, intraocular lenses, and orthopedic
pins. Medical devices also include diagnostic aids such as reagents and test kits for in
vitro diagnosis (IVD) of disease and other medical conditions such as pregnancy.
Investigational Device Exemption (IDE): An investigational device is a medical device
which is the subject of a clinical study designed to evaluate the effectiveness and/or
safety of the device. The investigations must be conducted according to the
requirements of the IDE regulations [21 CFR part 812]. Certain clinical investigations
of devices may be exempt from the IDE regulations [21 CFR 812.2(c)]. Unless exempt
from the IDE regulations, an investigational device must be categorized as either a
"significant risk" (SR) or "nonsignificant risk" (NSR) device. This determination is
initially made by the sponsor. The proposed study is then submitted either to the FDA
(SR studies) or to an IRB (NSR studies).
Classification of Devices: The class distinction is made primarily on the level of risk to
users/patients and therefore, the level of FDA oversight needed to ensure that the
device is safe and effective as labeled.

Class I/General Controls: Many devices need very little regulation to assure
that they are safe and effective. Basic controls such as those on
manufacturing and claims were expected to be sufficient. Examples: crutches,
band-aids, cast components, etc.
TITLE: Categories of Research
REVIEW WITH REVISION: 07/13/2012
POLICY NUMBER: SC 502
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
Class II/Special Controls: This is the largest device category and encompasses
those device types that could be considered to be safe and effective if they met
Class I restrictions and if there were some additional standards according to
the kind of device. Examples: wheelchairs, tampons, magnetic resonance
imager, etc.

Class III/Premarket Approval: These are devices about which there is
insufficient information to determine that they are safe and effective. Any
"new" devices (i.e., they are not substantially equivalent to any prior device)
about which there are few or no data are automatically Class III. Examples:
heart valves (known to present hazards requiring clinical demonstration of
safety and effectiveness) OR not enough known about safety or effectiveness
to assign to Class I or II.
Regulatory Guidance
SR device studies must be conducted in accordance with the full IDE requirements [21
CFR part 812], and may not commence until 30 days following the sponsor's submission
of an IDE application to FDA. Based upon the review of the information provided to the
FDA, they may impose restrictions on the study to balance risks/benefits to the subject.
The study may not begin until FDA has approved the IDE application and the IRB has
approved the study.
NSR device studies do not require submission of an IDE application to FDA. The
sponsor is required to conduct the study in accordance with the "abbreviated
requirements" of the IDE regulations [21 CFR 812.2(b)]. Unless otherwise notified by
the FDA, an NSR study is considered to have an approved IDE if the sponsor fulfills the
abbreviated requirements; which include, among other things, the requirements for IRB
approval and informed consent, record keeping, labeling, promotion and study
monitoring. NSR studies may begin immediately following IRB approval.
If the study is submitted to the IRB, the full board (or Chairperson, or designee, if the
review is expedited) will determine whether, in the context of the study or by the nature of
the investigational medical device (see significant risk devices list), the study presents a
significant risk (SR) or a non-significant risk (NSR) of harm to study subjects. This
assessment will be based on the information provided by the Investigator and/or the
Sponsor. The IRB’s device risk determination must be documented in the IRB meeting
minutes.
Making the SR/NSR Decision
Four elements are contained in the definition of a SR device. Each element is modified
by the phrase "and presents a potential for serious risk to the health, safety or welfare of
a subject". If it presents a serious risk of harm under any circumstance, it is a SR device;
that is, a SR device is one that presents a serious risk of harm.

"Significant risk device" means an investigational device that:
1. Is intended as an implant and present a potential for serious risk to the
health, safety, or welfare of a subject;
TITLE: Categories of Research
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POLICY NUMBER: SC 502
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2. Is purported or represented to be for use in supporting or sustaining human
life and presents a potential for serious risk to the health, safety, or welfare
of a subject;
3. Is for a use of substantial importance in diagnosing, curing, mitigating, or
treating disease, or otherwise preventing impairment of human health and
presents a potential for serious risk to the health, safety, or welfare of a
subject; or
4. Otherwise presents a potential for serious risk to the health, safety, or
welfare of a subject…"
The first step in making the decision as to whether a device should be declared SR or
NSR is to understand all of the possible harms in terms of their potential frequency, their
severity, and their permanence. Theoretical risks should be included.
The second step is to examine the source of each potential harm. Is it due to the
underlying disease, the baseline patient care, procedures required by the protocol to
evaluate the effects of the device, the device itself or the modification made that makes
it investigational.
With this information, the IRB must use its judgment as to whether the device constitutes
a significant or non-significant risk to the subject. The FDA guidance alters the language
in an important manner when it refers to a "significant risk device study". This refers to
the decision made by the IRB and how it should take in account all of the risks presented
by the protocol: risks from the investigational form of the device; risk of the entire device;
risks from tests done to evaluate research results; risks of the treatment of the patient;
and the underlying disease. This could result in a SR decision for a study of a non-risky
device within the context of a very risky study.
The Decision to Approve or Disapprove
Once the decision has been reached as to whether the device is a significant or
nonsignificant risk device, the IRB should decide whether to approve the project or not.
The criteria for deciding if SR and NSR studies should be approved are the same as for
any other FDA regulated study [21 CFR 56.111]. The IRB should use the same criteria it
would use in considering approval of any research involving a FDA regulated product [21
CFR 56.111]. Some NSR studies may also qualify as "minimal risk" studies and thus may
be reviewed through an expedited review procedure [21 CFR 56.110]. FDA considers all
SR studies to present more than minimal risk, and thus, to be reviewed by a full Board. In
making its determination on approval, the IRB should consider the risks and benefits of
the medical device compared to the risks and benefits of alternative devices or
procedures. The IRB should assure that risks to subjects are minimized and are
reasonable in relation to anticipated benefits and knowledge to be gained, subject
selection is equitable, informed consent materials and procedures are adequate, and
provisions for monitoring the study and protecting the privacy of subjects are acceptable.
TITLE: Categories of Research
REVIEW WITH REVISION: 07/13/2012
POLICY NUMBER: SC 502
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Minutes of IRB meetings must document the rationale of SR/NSR and subsequent
approval or disapproval decisions for the clinical investigation.
IRB reporting requirements about an NSR study?
 There is no requirement to report to FDA when an NSR study starts. The requirements
for IRB review, informed consent, adverse event reporting and labeling still apply. In
addition, the sponsor should understand that proceeding with an NSR study is at their
risk and they may voluntarily seek advice or inform FDA about the decision without
filing an IDE with FDA.

SR device studies are governed by the IDE regulations [21 CFR part 812]. NSR device
studies have fewer regulatory controls and are governed by the abbreviated
requirements [21 CFR 812.2(b)].
Major differences between SR and NSR studies are in the approval process and in the
record keeping and reporting requirements.
1. NSR studies: The IRB acts as a surrogate to the FDA with respect to review and
approval of NSR studies. FDA is usually not apprised of the existence of approved
NSR studies because sponsors and IRB's are not required to report NSR device
study approvals to the FDA.
2. If the IRB believes that a device study is SR when it has been presented as a NSR,
the investigation may not begin until both the IRB and the FDA approve the
investigation. The sponsor should provide the IRB with a risk assessment and the
rationale used in making its risk determination [21 CFR 812.150(b)(10)]. If it is
still determined that it is a SR device, the sponsor must submit an IDE to the FDA,
or, if electing not to proceed with the study, notify FDA of the SR determination.
Study may not begin until the FDA approves the IDE and the IRB approves the
study. Sponsor and investigator(s) must comply with IDE regulations [21 CFR part
812], as well as informed consent and IRB regulations [21 CFR parts 50 and 56].
3. If a sponsor decides that the device is a NSR, they must provide the IRB with an
explanation of its decision and any other information that may assist the IRB in
evaluating the risk of the study; description of the device, reports of prior
investigations with the device, the proposed investigational plan, a description of
patient selection criteria and monitoring procedures as well as any other
information that the IRB deems necessary to make its decision. The sponsor
should inform the IRB if other IRB's have reviewed the proposed study and what
determination was made. The IRB may also consult with FDA for its opinion.
FDA Examples of Nonsignificant and Significant Risk Devices: see list attached.
1.2
Genetic Research
Genetic research may require special considerations.
1.4.1 Subjects of Genetic Research:
TITLE: Categories of Research
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POLICY NUMBER: SC 502
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At first consideration, much genetic research may appear to meet the criteria
for expedited review. These include:
• Pedigree studies, which look for a pattern of inheritance of a gene;
• Positional cloning studies, which are conducted to identify particular genes;
• Diagnostic studies, which gather samples to develop techniques to
determine the presence of specific DNA mutations.
However, these studies may create a vulnerable population in that subjects' autonomy
may be compromised. Therefore the full IRB must review these studies to answer the
following questions: Will the samples be made anonymous to maintain
confidentiality? If not, to what extent will the results remain confidential; and who will
have access to them? Will the samples be used for any additional studies not made
explicit at the time of donation, or will the samples be destroyed after specified, onetime use? Will the donor be informed of any and all results obtained from his or her
DNA? Will the donor be informed of the results of the entire study? Will family
members be implicated in the studies without consent?
Gene therapy research (administration of recombinant vectors), which is carried out to
develop treatments for genetic diseases at the DNA level, presents obvious and not so
obvious questions, including – considerations of delivery methods, target population,
required follow-up. Such protocols require use of external consultants to provide
independent guidance to the IRB. If the project involves gene therapy to human
subjects for other than clinical purposes, the study must be reviewed and approved by
the National Institutes of Health Recombinant DNA Advisory Committee prior to IRB
approval. Monitoring must be adequate, and a DSMB will be required.
Because there is still little regulatory guidance and relatively few ethical precedents,
genetic research will require close scrutiny, and the input of experts in this area.
1.3
Medical Records and Chart Review
Studies involving the use of existing public or privately held records only may qualify
for exempt status or expedited review. However, if the nature of the research could
put subjects' confidentiality at risk, the study will be reviewed by the full IRB. Studies
that involve only chart and record review can sometimes pose significant risk to
patients.
The most common breach of confidentiality is exposure of possible embarrassing
information without the knowledge or consent of the patient. Such studies may also
lead to recruitment of patients into future non-therapeutic studies in a manner, which
may provoke the patient to ask how his/her record was revealed to someone not part
of his/her therapeutic team. The present policy is to require IRB review of studies
involving chart review or data collection and analysis.
If identifiers were to be recorded, the research would require IRB review to ensure
that, among other things, procedures for protecting privacy and confidentiality are
adequate. Furthermore, the Investigator studying cancer risk factors may propose to
TITLE: Categories of Research
REVIEW WITH REVISION: 07/13/2012
POLICY NUMBER: SC 502
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go on to contact the subjects (if still living) or family members (if the subject is
deceased) to gather additional information, which may or may not be subject to the
federal regulations.
1.4
Residual Body Fluids, Tissues and Recognizable Body Parts
Body Fluids & Tissues: Research on existing specimens ("on the shelf" or frozen)
without identifying information (e.g., no names, initials, hospital number, etc.) may be
submitted to the IRB for expedited review, to include a short description of the
research and where the tissue is coming from.
1.5
Protocols Lacking Definite Plans for Human Involvement
Certain types of activities are planned and written with the knowledge that human
subjects may be involved, but without definite plans for such involvement. Examples
of such proposed activities are:

Training programs in which individual training projects remain to be
selected or designed.

Research, pilot or developmental studies in which the involvement of
human subjects depends on such things as the completion of survey
instruments or prior animal studies.

Institutional Support Programs where the selection of the project is the
responsibility of the institution or program administrator. When supporting
agencies requires review and certification for such programs, protocols are
to be submitted to the IRB with as much information as is available. The
protocols must include assurances that additional information will be
submitted when developed and, in the case of training grants, that all
trainees will submit individual protocols if human subjects are to be used.
The IRB can give "General Expedited Approval" to programs like those mentioned
above with the understanding that the specific research protocol will be submitted to
them once it has been developed. "General Expedited Approval" is not appropriate for
individual projects or to meet grant deadlines.
2. SCOPE
These policies and procedures apply to all research submitted to the IRB.
3. RESPONSIBILITY
IRB Manager (or equivalent) is responsible for maintaining up-to-date review tools for review
of research pertaining to these categories based on new and evolving applicable regulations
and guidelines.
IRB Chairperson (or designee) is responsible for ensuring the IRB members are well versed in
new and evolving regulations and guidelines pertaining to these categories, for selecting
primary reviewers with appropriate expertise to conduct the reviews of such research, and for
securing appropriate consulting expertise as needed for selected reviews.
TITLE: Categories of Research
REVIEW WITH REVISION: 07/13/2012
POLICY NUMBER: SC 502
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IRB Reviewer is responsible for conducting appropriate review of research planned for these
categories in consultation with any appropriate experts and resources.
4. APPLICABLE REGULATIONS AND GUIDELINES
21 CFR 812.66
21 CFR 50.24
21 CFR 56.104
45 CFR 46.101, 46.103, 46.118, 46.119
5. REFERENCES TO OTHER APPLICABLE SOPs
This SOP affects all other SOPs.
6. ATTACHMENTS
Two Sample Consent/Notification Document for Use of an HUD
SC 502-A
Risk Determination - Devices
SC 502-E
Waiver of Informed Consent for Access to Medical Records for
Research
7. PROCESS OVERVIEW
Present requirements concerning review of specific types of research that may require
additional considerations by the IRB.
8. PROCEDURES EMPLOYED TO IMPLEMENT THIS POLICY
Who
Task
IRB Coordinator
IRB Member
(Reviewer)
IRB Manager, or
designee
IRB Members
Include the checklist in the primary reviewer's
packet when a medical device is the study
article.
Perform the device risk determination to verify
that the Sponsor’s determination is accepted.
Notify the appropriate entities if the IRB rejects
the Sponsor’s NSR device determination.
Conduct review of NSR device or await Sponsor’s
submission of an IDE for SR devices before
proceeding with device study review.
Tool
Risk Determination Devices
Refer to SOP CO 602
B. Genetic Research
Who
Task
IRB Manager,
Chairperson, or
designee
Identify and invite appropriate consultant(s) who
may assist the IRB in its deliberations.
Tool
TITLE: Categories of Research
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POLICY NUMBER: SC 502
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Ascertain deliberations of other relevant research
review groups (e.g., NIH RAC, Institutional
Biosafety Committee).
C. Prospective Research in Emergency Settings – See SOP 503
D. Emergency Use of Investigational Articles (Retrospective Review) – See SOP 503
E. Medical Records and Chart Review
Who
Task
Tool
IRB Manager,
Chairperson or
designee
Determine whether the research is exempt from
IRB review, eligible for expedited review, or
subject to full IRB review.
Refer to SOP FO 302
and RR 401
IRB Coordinator
If subject to full or expedited IRB review, include
the Checklist in the primary reviewer's packet.
Waiver of Informed
Consent for Access to
Medical Records for
Research
F. Residual Body Fluids, Tissues and Recognizable Body Parts
Who
Task
Tool
IRB Manager,
Chairperson, or
designee
IRB Coordinator
Determine whether the research is exempt from
IRB review, eligible for expedited review, or
subject to full IRB review.
Refer to SOP FO 302
and RR 401
If subject to full or expedited IRB review, include
the Checklist in the primary reviewer's packet.
G. Protocols Lacking Definite Plans for Human Involvement
Who
Task
Tool
IRB Manager, or
designee
Determine whether the research is exempt from
IRB review, eligible for expedited review, or
subject to full IRB review.
If subject to full or expedited IRB review, include
the Checklist in the primary reviewer's packet.
Refer to SOP FO 302
and RR 401
IRB Coordinator