QUICK GUIDE - Using Human Biological Specimens at UC Davis
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Brief Overview
Summary Tables: Common Types of Research Involving Specimens
Investigators Have No Subject Contact
Table 1: De-identified or coded specimens; no access to private information
Table 2: Specimens with limited private information, but the investigator does not
record the identifiable information or link it to the specimens
Table 3: Specimen with limited private information
Investigators Have Subject Contact
Table 4: Specimens obtained for research and/or banking using minimal risk procedures
Table 5: Specimens obtained for research and/or banking using procedures that pose a
greater than minimal risk
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Detailed Information and IRB Submission Requirements for Common Types of Research Involving
Specimens
 Specimens Without Identifiers – Minimal Risk – No Subject Contact
 De-identified vs. Identified vs. Coded Specimens
 IRB Submission Guidance
 Informed Consent Consideration
 Access to Identifiers, But Identifiers Are Not Recorded or Linked to Specimens –
Minimal Risk – No Subject Contact
 IRB Application Requirements
 Informed Consent
 Specimens With Limited Private Information – Minimal Risk – No Subject Contact
 IRB Application Requirements
 Informed Consent
 Research and/or Banking – Minimal Risk – Subject Contact
 IRB Application Requirements
 Informed Consent
 Research and/or Banking - Greater Than Minimal Risk – Subject Contact
 IRB Application Requirements
 Informed Consent
Consent Considerations
o Consent Topics Related to Specimen Collection for Research and/or Banking
o Submission to the NIH SWAS Data Repository
o Consent Requirements for Collecting Research Specimens from Minors
Resources
----------------------------------------------------------------------------------------------------------------------------------------Brief Overview: Research, Human Subjects and Biological Materials
Because the federal definition of human subjects extends to people who are sources of biological specimens
and identifiable private information, research with these materials often requires review and approval by UC
Davis Institutional Review Board (IRB) via Human Subjects Review Committees.
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The type of data considered to be Protected Health Information (PHI), along with a detailed
discussion of all HIPAA regulations (45 CFR 164.512), is provided on the UC Davis HIPAA
Guidance Website.
The UC Davis IRB is committed to supporting investigators in fulfilling all regulatory responsibilities to ensure
continued research with this valuable resource.
The level of IRB review and oversight is based on the level of risk the study poses. Specimen research risks
potentially include one or both of the following:
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Risk of harm from procedures used to obtain specimens, and/or
Risk associated with the loss of privacy and confidentiality due to personally identifiable
information that may be associated with specimens.
To help investigators find information pertinent to their study, some of the most common types of research
involving human specimens are summarized in the tables below. When needed, links also are provided to
more detailed information located in this document and elsewhere.
Select the link that best describes the proposed study to access a summary table that shows key study
features and discusses the level of IRB review that may be required.
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Table 1: De-identified or coded specimens – investigators have no access to private information
and no subject contact
Table 2: Specimens initially obtained with limited private information, but the investigators do
not record/keep this information; no subject contact
Note: Table 2 does not apply to research that involve access to and review of medical
records – see Table 3 for research involving medical records.
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Table 3: Specimens with limited private information; no subject contact
Table 4: Specimens obtained for research and/or banking through subject contact using
minimal risk procedures
Table 5: Specimens obtained for research and/or banking through subject contact using
procedures that pose greater than minimal risk
Note: Table 5 includes specimens collected as part of treatment studies (clinical trials) or
for banking and future use.
Summary Tables: common Types of Research Involving Human Specimens
TABLE 1: RESEARCH USING SPECIMENS WITHOUT IDENTIFIERS – MINIMAL RISK – NO SUBJECT
CONTACT
STUDY FEATURES
IRB REQUIREMENTS
INVESTIGATOR
 No subject/donor contact
 No access to identifying data
SPECIMENS
 Pre-existing, on-the-shelf
 Sources might include
o Specimen Banks
o Repositories
o Commercial Entities
 De-identified: Identifiers do not
Confirm that the project does
exist; or
NOT qualify as Human Subjects
 De-linked: Identifiers irreversibly
Research by viewing the Human
stripped: or
Subjects Decision Chart.
 Coded: Identifiers firewallIf the study qualifies as human
protected
subjects research, submit an
CONSENT
 Study adheres to the scope of
Exempt Certification OR
research allowed by the original
Expedited Review.
consent (if applicable)
RISK
 Minimal
 Private data nonexistent or
securely protected
More Details
Specimens Without Identifiers – Minimal Risk – No Subject Contact
It’s fairly common for researchers to receive specimens from banks and repositories that are either deidentified or coded. Studying human specimens without identifiers protects the identity of the subject/donor
without compromising the goals of meaningful research. Each is described below:
 De-identified Specimens: Investigators need to be aware of the type of specimen-associated data
that is considered de-identified (also termed de-linked or anonymous) versus information that is
personally identifiable. The table below shows examples of each.
Type of Information
De-identified
Examples
Demographics (Race, Gender, Age)
Diagnosis
Histopathology
Specimen Descriptors (Type, Condition, Amount)
Identified
Patient Identifiers (Name, Medical Record Number)
Family History (Pedigree)
Treatment and Outcome Data*
*Patient identifiers may be needed to access long-term follow up information
 Coded Specimens: Coded biological specimens means that:
o Identifying information (such as name, social security number, medical record number)
is replaced with a code comprised of numbers, letters, or a combination thereof ; and
o A key to decipher the code exists, enabling linkage of the identifying information with
the specimens.
IRB Requirements for Research Involving De-identified or Coded Specimens:
According to guidance from the Office on Human Research Protections (OHRP), the human subject definition
does not apply to research involving de-identified or coded specimens, under specific conditions. Therefore,
IRB review is not required.
To guide PIs in making this determination (whether human subjects are involved or not), the NIH published
the diagram “Research Involving Private Information or Biological Specimens”.
Both the following conditions must be met in order for the human subjects definition to not apply to
the research:
1. The research is not regulated by the Food and Drug Administration (FDA), AND
2. One or more of the following apply:
 The key to decipher the code is destroyed before researcher begins, or
 PI and holder of the key enter into an agreement prohibiting the release of the
key under any circumstances, or
 There are IRB-approved written policies for the repository or data management
that prohibit the release of the key, or
 There are other legal requirements prohibiting the release of the key under any
circumstances.
IMPORTANT NOTE: If these conditions are not applicable, the coded data or specimens are considered
human subjects.
Informed Consent Consideration: The recipient of specimens should ask the source for assurance that
the specimens were obtained with a valid informed consent under an IRB-approved protocol. The
specimens should be used within the scope of research described in the original consent.
TABLE 2: RESEARCH USING HUMAN SPECIMENS: ACCESS TO IDENTIFIERS, BUT IDENTIFIERS ARE NOT
RECORDED OR LINKED TO SPECIMENS - MINIMAL RISK – NO SUBJECT CONTACT
STUDY FEATURES
IRB REQUIREMENTS
INVESTIGATOR
 No subject contact
 Access to limited identifiers
SPECIMENS
 Pre-existing, on-the-shelf
 Collected for a purpose other than
Exempt Certification (Category 4,
the proposed research
No Subject Contact)
 Researcher can have access to
associated identifiers (minimum
Important note: Research that
necessary to meet study goals),
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CONSENT
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RISK
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but is not allowed to record
identifiers or link them to the
specimens
Medical record review is not
allowed
Study adheres to the scope of
research allowed by the original
consent
Request a waiver of
consent/authorization for this
project
Minimal, provided investigator
securely protects private data
More Details
involves access to and review of
medical records does not qualify
for exemption.
IRB Requirements for Exempt Category #4 Specimen Research: At times, investigators may receive specimen
that have identifiable information associated with them, but the investigator does not need to keep the
identifiers linked to the specimens. If the investigator does not record the identifiers or link them to the
specimens, the research may be eligible for review under the exempt category.
Specifically, exempt category #4 applies to research that involves the collection or study of existing* data,
documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available**
or if the information is recorded by the investigator in such a manner that subjects cannot be identified
directly or through identifiers linked to the subjects.
IMPORTANT NOTE: Research that involves access to and review of medical records
does not qualify for exemption.
*Existing means collected (i.e. on the shelf) prior to the research for a purpose other than the proposed
research. It includes data and specimens collected in research and non-research activities.
**Publicly available means available to the general public. Note; while there are groups that make specimens
accessible to the research community, these specimens generally are not available to the general public and
usually are not considered to be “publicly available”.
Consent Issues
 Study adheres to the scope of research allowed by the original consent
 May need waiver of consent/authorization depending on associated identifiers
TABLE 3: RESEARCH USING HUMAN SPECIMENS: ACCESS TO AND RECORDING OF IDENTIFIERS MINIMAL RISK – NO SUBJECT CONTACT
STUDY FEATURES
IRB REQUIREMENTS
INVESTIGATOR
 No subject contact
 May have access to and record
limited identifiers
SPECIMENS
 Collected for non-research
purposes or for research purposes
under certain circumstances (see
expedited review category 5)
 Associated identifiers, if any, are
minimum necessary to meet study
goals
Expedited Review
(No Subject Contact)
CONSENT
 Study adheres to the scope of
research allowed by the original
consent
 Request a waiver of
consent/authorization for this
project
RISK
 Minimal, provided investigator
securely protects private data
More Details
Research involving previously collected specimens that have identifiers associated most likely qualifies for
expedited review category 5 with no subject contact.
IRB Requirements for Expedited Review, Category 5, No Subject Contact: The investigator cannot interact
with subjects, and although access to private information is allowed, use of specimen-associated identifiers is
restricted and privacy protection measure must be in place.
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The private information requested is the minimum necessary to meet research goals, and
Private information will not be reused or inappropriately disclosed
Data are secured by appropriate methods including:
o The key to coded data is kept separately and securely
o Data are kept in a locked file cabinet, office, or suite
o Electronic data are password-protected or stored on a secure network
Informed Consent: It usually is not necessary to obtain additional consent from donors of previously collected
specimens, provided that the study meets the criteria for waving consent in minimal risk research required by
OHRP (45 CFR 46) and by HIPAA (45 CFR 164.512):
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There are minimal risks for the subjects
It would not be practicable to obtain consent
The subjects’ rights and welfare would not be adversely affected, and
It would not be appropriate to inform subjects about the study
IMPORTANT NOTE: If the proposed research falls outside the uses specified in the original consent form, the
investigator will need to consent donors. The study should be identified as “Subject Contact,” and the IRB
must review and approve all materials used for re-consenting. The IRB strongly encourages subject contact to
be made by letter, not by phone, and preferably by someone known to the donor who was involved in the
original specimen collection. Please discuss with the UC Davis IRB if questions.
TABLE 4: RESEARCH AND/OR BIOBANKING INVOLVING HUMAN SPECIMENS: MINIMAL RISK –
SUBJECT CONTACT
STUDY FEATURES
IRB REQUIREMENTS
INVESTIGATOR
 Subject contact through
interaction and/or intervention
using minimal risk procedures
 Access to identifiers
SPECIMENS
 Collected prospectively
 Collected specifically for the
research project by the
investigator or collaborators using
minimal risk procedures and/or
 Surgical or diagnostic specimens
that would be otherwise thrown
away
 Associated identifiers, if any, are
minimum necessary to meet study
Expedited Review
goals
(Subject Contact)
 Possibly retained for future use
CONSENT
 Consent required
 HIPAA authorization or waiver
may be required if identifiers are
used
RISK
 Specimens obtained using
procedures posing no more than
minimal risk
 Private data secured and disclosed
only to those specified in IRBapproved protocol
More Details
IRB Requirements: Research using human specimens qualifies for expedited review by the IRB if the study
procedures pose no more than a minimal risk to participants. Protocols may include provisions for specimen
banking for future research.
Investigators will need to provide detailed information regarding:
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Privacy Protection: The use of specimen-associated identifiers is restricted and privacy protection
measures must be in place.
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o The private information requested is the minimum necessary to meet research goals, and
o Private information will not be reused or inappropriately disclosed.
Data Security: Private information associated with human specimens must be secured by appropriate
methods. Some acceptable data security methods include:
o Keeping the key to coded data separately and securely; and/or
o Securing data in a locked file cabinet, an office, or suite
o Password-protecting electronic data storing on a secured network
Specimen Collection for Future Research and/or Specimen Repository/Bank Administration:
o Investigators will be asked to provide information on what types of specimens will be collected,
where the specimens will be stored, with whom the specimens will be shared, and how the
specimens will be kept confidential.
Informed Consent and HIPAA Authorization: Investigators conducting minimal risk research involving contact
with participants must use IRB-approved consent materials.
Some important consent topics pertaining to specimen collection for research and/or banking are explained in
the guidance below.
For additional information on the following topics, refer to the UC Davis IRB website:
o Recruitment and consent information
o A sample consent form for obtaining specimens
o HIPAA guidance
TABLE 5: RESEARCH AND/OR BIOBANKING INVOLVING HUMAN SPECIMENS: PROCEDURES POSE
GREATER THAN MINIMAL RISK
STUDY FEATURES
IRB REQUIREMENTS
INVESTIGATOR
 Subject contact through
interaction and/or intervention
 Access to identifiers
SPECIMENS
 Obtained prospectively
 Obtained using procedures that
pose greater than minimal risk,
including collection that is :
o Part of a larger trials, or
o Solely for banking, or
o Retained for future use
Full Committee Review
 Associated identifiers are
Application
minimum necessary to meet study
goals
CONSENT
 Consent required
 HIPAA authorization required
RISK
 Specimens obtained using
procedures posing greater than
minimal risk
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Private data secured and disclosed
only to those specified in IRBapproved protocol
More Details
A study proposing to collect specimens using procedures that pose greater than minimal risk to participants
must undergo full committee review by the UC Davis IRB. Protocols vary widely and may include specimen
banking for future research. For example,
o Specimens will be collected using procedures posing greater than minimal risk or as part
of a larger protocol such as a clinical trial or intervention study.
o Greater than minimal risk procedures will be used to obtain additional specimens
and/or materials in excess of that required for diagnosis or treatment.
Some of the key IRB application requirements and conditions for informed consent/HIPAA authorization are
discussed below.
IRB Application Requirements: Investigators involved with treatment studies or with the collection of
specimens for banking and/or future research using procedures that pose greater than minimal risk are
required to submit a Fill Committee Review that includes information on the specimen collection, consent
forms, and plans to obtain HIPAA authorization. The type of specimen-related information required in the
application includes:
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Privacy Protection: The use of specimen-associated identifiers is restricted and privacy protection
measures must be in place.
o The private information requested is the minimum necessary to meet research goals, and
o Private information will not be reused or inappropriately disclosed.
Data Security: Private information associated with human specimens must be secured by appropriate
methods. Some acceptable data security methods include:
o Keeping the key to coded data separately and securely; and/or
o Securing data in a locked file cabinet, an office, or suite
o Password-protecting electronic data storing on a secured network
Specimen Collection for Future Research and/or Specimen Repository/Bank Administration:
o Investigators will be asked to provide information on what types of specimens will be collected,
where the specimens will be stored, with whom the specimens will be shared, and how the
specimens will be kept confidential.
Consent Considerations: Consent Topics Pertaining to Specimen collection for Research and/or Banking
Consent forms used for studies proposing to collect specimens for research purposes should include the
following topics, as applicable:
o Types of specimens that will be kept and the name of the institution, department or
laboratory where specimens will be housed (a basic description of the repository)
o General descriptions of the types of research the specimens can be used for (e.g. cancer,
diabetes, cardiovascular research)
o The duration of specimen retention
o Types of data or medical information that will be collected with the specimens and how
long the information will be collected
o Who will have access to specimens and data (e.g. UC Davis researchers only, other
academic collaborators, industry sponsor)
o A description of the procedures for protecting the privacy of subjects and maintaining
the confidentiality of data
o Statement that specimens may be used in the development of tests, products, or
discoveries that may have potential commercial value and that subjects will not be paid
or receive money
o Instructions for donors to request destruction of remaining samples in the future
o If genetic testing will be performed, include information about the consequences of
DNA typing
Submission to the NIH GWAS Data Repository: Investigators who plan to submit data and/or specimens to
the NIH database of Genotypes and Phenotypes (dbGaP) for inclusion in the NIH GWAS data repository should
review guidance on the genome-wide association studies (GWAS). The NIH has strict standards for the data
that it will accept for inclusion in the repository. The UC Davis IRB must certify that studies with plans to
submit datasets to NIH GWAS repository received appropriate IRB review and approval. The IRB also must
certify that the informed consent document used to obtain consent form subjects whose data will be shared
includes specific NIH-required language. The guidance page explains the requirements in details.
Consent Requirements for Collecting Research Specimens from Minors: For detailed information on obtaining
informed consent/assent for minors, refer to the IRB guidelines “Minors in Research”. The requirements for
minors are age-dependent as shown in the table below:
Table of IRB Consent Guidelines for Minors by Age Group
Written Assent Form Required
Separate Parental Consent Form
Required
Infant – 7 years old
No
Yes
7-12 years old
Yes
Yes
13-17 years old (Option A)
Yes
No (add line to adolescent assent
form for parents to sign)
13-17 years old (Option B)
Yes
Yes
Age of Minor Participant
IMPORTANT NOTE: If there is continued interaction with subjects who reach the age of majority (18 years of
age in California), it would be appropriate to discuss in the consent form the continued storage and analysis of
biological materials previously collected.
EXPEDITED REVIEW: Categories of Research May Be Reviewed by the Institutional Review Board (IRB) through
an Expedited Review Procedure. An expedited review procedure consists of a review of research involving
human subjects by the IRB chairperson or by one or more experienced reviewers designated by the chairperson
from among members of the IRB in accordance with the requirements set forth in 45 CFR 46.110.
EXEMPT REVIEW: An Exemption, as it pertains to research involving human subjects is defined in 46.101(b) –
in order for proposed research to be exempt from the requirement of continuing IRB review and approval
under Exemption 4, investigators must propose the use of data or samples that are either :
existing and publicly available;
OR
existing and unidentifiable to the research team
What are the requirements for Exemption 4 (E4)?: HHS regulations state: Research involving the collection or
study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources
are publicly available or if the information is recorded by the investigator in such a manner that subjects
cannot be identified, directly or through identifiers linked to the subjects 46.101(b)(2).
If you receive or have access to existing individually identifiable private information or identifiable specimens
from living individuals (e.g., pathology or medical records), you are conducting human subjects research. If you
as the investigator or your collaborator record the information in such a manner that you cannot subsequently
access or obtain direct or indirect identifiers that are linked to the subjects, research activities that involve
data recorded in this manner meets the requirements of Exemption 4. If you will retain or can access any
identifiers, the research project is not exempt under Exemption 4.
Is research that meets the criteria for Exemption 4 considered human subjects research? Yes. Research that
meets the criteria for Exemption 4 is Human Subjects Research.
Exemption 4 includes research involving the collection or study of existing data, documents, records,
pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is
recorded by the investigator in such a manner that subjects cannot be identified, directly or through
identifiers linked to the subjects.
Please note: human subjects research that meets the criteria for Exemption 4 is not considered “clinical
research” as defined by NIH; therefore, the NIH policies for addressing inclusion of women, minorities and
children do not apply to research that is determined to meet the criteria for Exemption 4.
Resources:
UC Davis IRB Investigator Manual
UC Davis Guide for the Research Use of Human Biological Specimens
NIH Human Subjects Decision Tree