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Case Report Example
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During the course
of normal sign-out, Dr. Smith notices that patient Jones has an unusual
variant of renal cell carcinoma that has features noteworthy enough to
warrant writing up and submitting as a case report. She remarks on this
to the resident, who is interested in collaborating in this project.
Two facts govern the
type of approval necessary for this case. The first is that it is not
possible to anonymize an individual case, so that it is not possible to
obtain an OHSR exemption for this research. The second fact is the protocol
status of the patient and whether the case report relates to the protocol.
Variation 1:
The patient is enrolled in an NIH protocol studying renal cell carcinoma.
Follow Approval Path D.
Variation 2:
The patient is enrolled in an NIH protocol for diabetes and the renal
cell carcinoma was identified incidentally and removed without a new protocol
consent (such as the UOB tissue procurement protocol). Follow Approval
Path E.
Variation 3:
The case was received as a consultation case from a pathologist outside
the NIH. The patient is not enrolled on any protocol. Follow Approval
Path F.
Basic Science Investigation Example
Dr. Nobel, a Ph.D.
molecular biologist in the NCI, has discovered a new gene that she feels
is linked to breast cancer. She would like to investigate its expression
in human tissue to describe its expression in normal breast and breast
cancer and to relate expression to prognosis. The factors which govern
her use of the tissues mainly revolve around whether or not she is using
anonymized tissue samples.
Variation 1:
At the start of her study she obtained 20 coded specimens of tissue from
a publicly available tissue bank. The tissue bank strips all identifiers
from the tissue prior to sending them to Dr. Nobel. Follow Approval
Path C.
Variation 2:
She contacts the Post-mortem section to obtain autopsy tissues from multiple
organs to look at the distribution of gene expression. Follow Approval
Path B.
Variation 3:
She sets up a collaboration with Dr. Rutger, an oncologist, who has a
protocol written to include the search for new oncomarkers in breast cancer.
She would like to obtain tissues from his patients. Follow Approval
Path D.
Obtaining Fresh Tissue from Living Patients
Dr. Xerxes would like
to create tumor cDNA libraries from patients with colon carcinoma. For
a variety of reasons he would like to get this tissue from patients undergoing
surgery at the Clinical Center. He is aware that Dr. Coldnife, a surgeon,
has a tissue procurement protocol written for patients he operates on.
Variation 1: Because the tissue must be obtained as fresh as possible,
it is not practical to try to anonymize the tissue collection. Therefore,
and OHSR exemption from IRB review is not appropriate. In order to get
the fresh tissue, Dr. Xerxes must do the following:
1. Contact
Dr. Coldnife in order to arrange a collaboration. If Dr. Coldnife's
protocol is yet to be written, Dr. Xerxes might be able to participate
as an associate investigator. If the protocol is already in place, it
would have to be written to include the construction of cDNA libraries.
If the protocol does not include this permission, he would have to follow
Approval Path E to get the IRB's permission
to proceed.
2. Each time tissue was collected, a "Tissue Procurement
and Transfer Form" would have to be filled out and signed by a
PI or AI on the protocol. If Dr. Xerxes was one of the AI's, he could
sign for himself.
Variation 2:
Dr. Xerxes and Dr. Coldnife set up a mechanism to anonymize samples via
a third party not involved in the research. The third party delivers tumor
samples to Dr. Xerxes' lab stripped of any information that would allow
him to identify the patient. Dr. Xerxes would follow Approval
Path C to get permission for his project, but
would have to explain the anonymization process in detail on the OHSR
form.
Protocol Case Review example
Dr. Hamm is asked
to review a series of cases by Dr. Owens, an NIH PI, so that pathology
data from the cases is contributed by a single pathologist.
Variation 1. The case
evaluation involves review of previously prepared slides with or without
additional tests already covered by the protocol. Dr. Hamm follows Approval
Path D.
Variation 2. Dr. Owens
and Dr. Hamm decide that it would add much to the study to look at non-lesional
tissue for germline mutations, an experiment that is not covered already
in the protocol. They now need to follow Approval Path
E, and would probably have to amend the protocol and re-consent
patients in this particular instance.
Reference Pathologist/Basic Scientist example
Dr. Alphabeta is named
as the reference pathologist for a large multicenter trial. She will be
receiving slides from a central data center that have been coded, but
which are ultimately still linked to the original patient information.
Variation 1.
NIH is participating in the multicenter trial, and an NIH IRB has approved
the study. Dr. Alphabeta is an associate investigator on the NIH protocol.
Follow Approval Path C.
Variation 2.
NIH is not participating in the trial. Dr. Alphabeta would still be able
to use Approval Path C, but would need to provide
OHSR with documentation of IRB approvals from the participating centers.
Variation 3.
Dr. Alphabeta is a molecular biologist receiving tissue samples from the
multicenter trial, and her part of the project is covered under the protocol.
She would still Follow Approval Path C, as above.
Use of tissue for test development example
Dr. Britainnica, and
his technician, Ms. Americana, are evaluating a new antibody for use in
the clinical diagnostic lab. They would like a collection of tumors and
normal tissues for titration and validation. There is no intention to
publish the information.
Variation 1.
This is part of clinical service and a necessary part of bringing a new
test into the diagnostic service. There is no ethical approval required.
(Approval Path A). Tissues for this purpose need
to be chosen according to the tissue use guidelines. (See below)
Variation 2.
After validating the new test, Dr. Britainnica realized that they have
discovered new things about the antibody worthy of publication. They would
like to summarize their findings and publish them. If they used anonymous
tissue to begin with, they need to follow Approval Path
C to get permission to write the paper. If non-anonymized tissues
were used, they would need to follow Approval Path F.
Tissue Use Guidelines
In order to protect
prospectively collected protocol biopsies from being used for non-protocol
purposes, we have formal guidelines for selection of tissues for non-protocol
related research. In all cases, sufficient tissue should remain in the
slide files/archive for the patient's future diagnostic needs.
1. Tissues
collected as part of a specific protocol will be flagged as such by
the ordering physician, and the protocol number will be recorded in
the LIS as part of the specimen registration procedure. (We are working
on the information systems issues now.)
2. If the tissues collected as part of a specific protocol are
"limited" (defined below), then they may not be used as test
controls or as part of research studies without the permission of the
PI.
3. Limited specimens are defined as single block specimens. Larger,
multi-block specimens may be made available for non-protocol, anonymized
studies so long as at least one block is retained for the purposes of
the protocol. If there is doubt about what may be released from a large
case, then an impartial judgment should be sought from pathology attending
staff uninvolved in the research.
4. Specimens obtained off-protocol (for diagnosis only), may
be used for anonymized research or as controls.
5. In all situations, the patient's needs should come first,
then the protocol's, and any other use of the tissue last.
Approval
Pathways
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| Plan
of Research |
Non-research
use of tissue
• Tissue
for titering probes, controls
• Educational
use
• Validation
of clinical test (no intention to publish)
• Clinical
review
• Uses
for laboratory QA/QC
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Tissues are
all from deceased patients
• Autopsy
tissue
• Surgical/cytology
tissue from patients with known death dates
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Tissues are
irreversibly anonymized (stripped of any link to the original
patient)
• Samples
from the archive recoded by the archivist)
• Samples
anonymized by a tissue repository
• Samples
anonymized according to an IRB-approved protocol
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| Ethical
Approval Step |
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None required |
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None required |
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Apply to OHSR for exemption from IRB review |
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IF YOUR STUDY DOES NOT INVOLVE THE TISSUE ARCHIVEOR LABORATORY
OF PATHOLOGY TECHNICAL RESOURCES,STOP HERE, YOU ARE DONE
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TRC
Approval Step
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None required, fill out form for archivist to retrieve samples |
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Submit information below with TRC form, check "autopsy/ deceased
patient" box |
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Submit information below with TRC form |
| Additional
Information Needed |
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List of materials to be pulled, delivered to archivist |
• Autopsy
case numbersand/or
• Death
dates of patients
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• If
tissues are from NIH archive, search criteria for possible cases
• Copy
of OHSR exemption approval
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| What
Happens Next |
•
Archivist pulls materials |
• TRC
form is reviewed and approved
• Archivist
pulls materials
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• TRC
form is reviewed and approved
• Databases
queries are performed if necessary
• Archivist
pulls materials
• Recuts,
etc. are anonymized by archivist or other third party
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Approval
Path D |
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| Research
Type |
Identifiable
tissues obtained for research outlined in an NIH or non-NIH IRB
approved protocol with appropriate patient consent
• Protocol
driven case review
• Case
report or series on NIH patients for protocol-related pathology
• Molecular
or biochemical analysis on NIH patient material
• Evaluation
of samples from another institution obtained under protocol
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Identifiable
tissues obtained via an NIH or non-NIH IRB approved protocol to
be used in research not outlined in original protocol
• Research
to examine tissues using probes/techniques not envisioned at the
time of protocol approval
• Germline
research on tissues obtained under a non-germline protocol
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Identifiable
tissues not obtained as part of an IRB-approved protocol
• Case
report or series on non-NIH patients using tissue obtained through
routine care
• Molecular
or biochemical investigation of non-NIH tissues not obtained on
a specific research protocol
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| Ethical
Approval Step |
• NIH
protocol: review proposed research with PI to make sure that the
research is covered under original protocol. Work must done as
collaboration.
• Non
NIH protocol: Apply to OHSR for exemption from NIH IRB review,
will need copy of IRB approval from outside institutions
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Apply to IRB for waiver of consent
or
• Write
amendment to protocol to include new research. (Required for germline
example).
IRB may decide
not to waive consent. If the waiver is denied, a standard protocol
or amendment will have to be written and informed consent (re)obtained.
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Apply to IRB for waiver of consent. If the waiver is denied, a standard
protocol will have to be written and informed consent obtained |
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IF
YOUR STUDY DOES NOT INVOLVE THE TISSUE ARCHIVEOR LABORATORY OF
PATHOLOGY TECHNICAL RESOURCES,STOP HERE, YOU ARE DONE.
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| TRC
Approval Step |
• Submit
information below with TRC form
• PI/AI
signature required
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• Submit
information below with TRC form
• PI/AI
signature required for amended protocols
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Submit information below with TRC form |
| Additional
Information Needed |
• Case
list
• Protocol
number
• Copy
of OHSR exemption (if obtained)
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• Case
list
• Protocol
number
• Copy
of IRB waiver
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• Case
list
• Copy
of IRB waiver or new protocol number
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| What
Happens Next |
• TRC
form is reviewed and approved
• Queries
are run against the database if necessary
• Archivist
pulls materials
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• TRC
form is reviewed and approved
• Queries
are run against the database if necessary
• Archivist
pulls materials
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• TRC
form is reviewed and approved
• Queries
are run against the database if necessary
• Archivist
pulls materials
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Last Updated 1/12/2009 3:42:52 PM
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