Regulations chapter 2 Flashcards
- According to CLIA and CAP regulations,
which one of the following individuals is
considered to be a director of a clinical molecular
laboratory?
A. Dr. A, a member of the corresponding
academic society
B. Dr. B, appointed by the institute as the
director laboratory
C. Dr. C, board certified in the corresponding
specialty
D. Dr. D, listed on the laboratory’s CAP and
CLIA certificate as the lab director
E. All of the above
F. None of the above
D. Dr. D, listed on the laboratory’s CAP and
CLIA certificate as the lab director
- A scientist plans to develop a Sanger
sequencingbased test for the FAS (TNFRSF6)
gene to assist diagnosis of autoimmune
lymphoproliferative syndrome in a clinical
molecular laboratory. There are no commercially
available FDA-cleared/approved assays for it.
According to the Clinical Laboratory
Improvement Amendments (CLIA) regulations,which one of the following descriptions most
appropriately describes this test?
A. Waived test
B. Nonwaived test
C. Moderate-complexity test
D. High-complexity test
E. None of the above
D. The laboratory-developed Sanger sequencing
assay for the FAS gene is a high-complexity test
system.
- A scientist plans to develop a quantitative
PCRbased test for pathogenic variants in the
NPM1 gene to assist in the diagnosis of acute
myeloid leukemia (AML) in a clinical molecular
laboratory. There are no commercially available
FDA-cleared/approved assays for it. According to
the Clinical Laboratory Improvement
Amendments (CLIA) program, which one of the
following descriptions most appropriately
describes this test?
A. Waived test
B. Nonwaived test
C. Moderate-complexity test
D. High-complexity test
E. None of the above
D. The laboratory-developed quantitative PCR
assay for the NPM1 gene is a high-complexity test
system.
- A scientist plans to validate a quantitative HIV-1
RNA assay for viral load assessment with the
Bayer VERSANT HIV-1 RNA 3.0 Assay (bDNA), a
FDA-approved commercially available assay, in a
clinical molecular laboratory. According to the
Clinical Laboratory Improvement Amendments
(CLIA) program, which one of the following
descriptions most appropriately describes this test?
A. Waived test
B. Nonwaived test
C. Moderate-complexity test
D. High-complexity test
E. None of the above
D. HIV-1 RNA quantitative PCR assay is a highcomplexity
test system.
- A scientist developed a quantitative PCR-based
test for pathogenic variants in the NPM1 gene to
assist in the diagnosis of acute myeloid leukemia
(AML) in a clinical molecular laboratory. He used
the data published in a peer-reviewed article,
since there were no commercially available FDAcleared/
approved assays for it. The validation
was done as planned, and the summary was
written. Who has the authority to review and
approve the validation, according to the College
of American Pathologist (CAP)’s regulations, if
applicable?
A. Clinical Laboratory Improvement
Amendments (CLIA)
B. College of American Pathologist (CAP)
C. The chair of the department
D. The laboratory director
E. The supervisor of the laboratory
F. All of the above
G. None of the above
D. According to the College of American
Pathology (CAP) All Common Checklist dated
July 28, 2015, COM.40000, “There is a summary
statement, signed by the laboratory director (or
designee who meets CAP director qualifications) prior
to use in patient testing, that includes the
A scientist planned to validate the bioMe´rieux
THxID BRAF assay, an FDA-approved
commercially available assay, to detect
somatic mutations in order to guide the
therapy of metastatic melanoma in a clinical
molecular laboratory. The protocol received
from bioMe´rieux was for 20-μL total volume for
each reaction. To save money, the scientist
decided to use 10 μL for each reaction. Which
validation stringency should he follow for the
validation, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
A. Follow the validation procedure for FDAapproved
assay.
B. Follow the validation procedure for FDAapproved
assay, and add analytical sensitivity
and specificity.
C. Follow the validation procedure for FDAapproved
assay with both 20-μL and 10-μL
reactions.
D. Follow the validation procedure for a
laboratory-developed assay.
E. None of the above.
D. Follow the validation procedure for a
laboratory-developed assay.“If an FDA-cleared/
approved test is modified to meet the needs of the user or
if the test is developed by the laboratory (LDT), both
analytical and clinical performance parameters need to
be established.
A scientist reviewed last month’s data in a
clinical molecular laboratory and found that the
failure rate of the KRAS test was 10% higher
than that for the previous 6 months and for the
same month last year. Which one of the
following is the most appropriate term used to
define the nature of this monthly review of
failure rate, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
A. Quality assurance
B. Quality control
C. Quality improvement
D. Quality planning
E. All of the above
F. None of the above
A. Quality assurance (QA) is a way of preventing
mistakes or defects in the process of testing clinical
samples and avoiding problems when delivering the
results to customers, which is the part of quality
management focused on providing confidence that
quality requirements will be fulfilled.
A scientist reviewed last month’s quality control
data in a clinical molecular laboratory and
found that the failure rate of the KRAS test was
10% higher than that for the previous 6 months
and for the same month last year. Which one of
following actions should he take to resolve the
problem, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
A. Quality assurance
B. Quality control
C. Quality improvement
D. Quality planning
E. All of the above
F. None of the above
C. Quality improvement (QI) is a formal approach
to the analysis of performance and systematic
efforts to improve it. This question is a good
example. The initial finding was the high failure
rate based on the data gathered through the
quality assurance program. Further investigation
found that the reaction volume at the end of
procedure became very low (from 20 μL to 5 μL).
So the laboratory worked on two plans to solve
the problem. This troubleshooting process is
called quality improvement (QI).
A clinical molecular genetic scientist has been
working in a start-up company for 2 months. He
has been purchasing reagents and writing policies
and procedures for this new laboratory. Which
one of the following should be included in his
quality management plan for the clinical
laboratory, according to the College of American
Pathologist (CAP)’s regulations, if applicable?
A. Calibrating the pipette at least once a year
B. Checking the quality of new lots and new
shipments of reagents against old ones
C. Having a written quality management plan
D. Maintaining discontinued procedures for at
least 2 years
E. Participating in the CAP Proficiency Test (PT)
F. All of the above
G. None of the above
F. All of the above
A courier picked up a peripheral-blood sample
(lavender) from an outreach draw station for
BCR-ABL1 quantitative testing at the main
hospital. He checked the identifiers of the sample
on the requisition form and the tube to make sure
the identity of the sample matched. At a
minimum, how many identifiers have to be on
the tube for a collected peripheral-blood sample,
according to the College of American Pathologist
(CAP)’s regulations, if applicable?
A. At least one
B. At least two
C. At least three
D. At least four
E. None of above
B. According to the College of American
Pathology (CAP) Laboratory General Checklist
dated July 28, 2015, GEN.4049, “All primary
specimen containers are labeled with at least two
patient-specific identifiers.” And according to the
CAP All Common Checklist dated July 28, 2015,
COM.06100, “All primary specimen containers
are labeled with at least two patient-specific
identifiers.”
Therefore, at least 2 identifiers have to be on
the tube for a collected peripheral blood sample
according to the College of American Pathologist
(CAP)’s regulation.
A courier picked up a peripheral-blood sample
(lavender) from a local obstetrician/gynecologist
(Ob/Gyn) practice for cystic fibrosis testing in the
main hospital. He noticed the patient’s name was
donor BJ. And the only usable identifier on the
requisition form and the tube was patient’s
medical record number. Which type of deficiency
would an on-site College of American Pathologist
(CAP) inspector find it to be, according to the
College of American Pathologist (CAP)’s
regulations, if applicable?
A. Phase 0
B. Phase I
C. Phase II
D. Phase III
E. None of above
E. This is not a deficiency. According to the College
of American Pathologists (CAP) All Common
Checklist dated July 28, 2015, COM.06100, “All
primary specimen containers are labeled with at
least two patient-specific identifiers.” However, it
also states “In limited situations, a single
identifier may be used if it can uniquely identify
the specimen.
A scientist just finished validation of a HER2
FISH assay with archived formalin-fixed,
paraffin-embedded (FFPE) tissue samples in a
clinical molecular laboratory at a hospital.
According to procedure, he sends samples to the
cytology laboratory in the same hospital for
hybridization, then takes the slides back for analysis. How should the clinical molecular
laboratory perform proficiency test on this HER2
FISH assay, according to the College of American
Pathologist (CAP)’s regulations, if applicable?1
A. Enroll in the College of American Pathologist
(CAP) HER2 immunohistochemistry (IHC)
proficiency test.
B. Enroll in the College of American Pathologist
(CAP) HER2 FISH proficiency test.
C. Perform an alternative HER2 FISH proficiency
test.
D. All of the above.
E. None of the above.
C. According to the College of American
Pathologists (CAP) All Common Checklist dated
July 28, 2015, COM.01300, “Proficiency testing
for HER2 (ERBB2) is method specific. If the
laboratory performs HER2 (ERBB2) testing by
multiple methods, the laboratory must
participate in PT for each method. . . If the
laboratory sends its FISH (or ISH) slides for
hybridization to another facility, the laboratory
must perform an alternative assessment of the test
twice annually and may not participate in formal
(external) PT.”
A scientist in a clinical molecular laboratory of a
hospital just finished validation of a HER2 FISH
assay with archived formalin-fixed, paraffinembedded
(FFPE) tissue samples. According to
procedure, she sends samples to the cytology
laboratory in the same hospital for hybridization,
then takes the slides back for analysis. Therefore,
the clinical molecular laboratory must perform an
alternative assessment of the HER2 FISH assay
instead of the CAP formal proficiency test. At a
minimum, how frequently should the laboratory
perform the alternative assessment of the HER2
FISH assay, according to the College of American
Pathologist (CAP)’s regulations, if applicable?
A. Every quarter
B. Semiannually
C. Annually
D. Biennially
E. None of the above
B. According to the College of American
Pathologists (CAP) All Common Checklist dated
July 28, 2015, COM.01300, “Proficiency testing for
HER2 (ERBB2) is method specific. If the
laboratory performs HER2 (ERBB2) testing by
multiple methods, the laboratory must participate
in PT for each method. . . If the laboratory sends
its FISH (or ISH) slides for hybridization to
another facility, the laboratory must perform an
alternative assessment of the test twice annually
and may not participate in formal (external) PT.”
A clinical molecular laboratory in a hospital
received specimens for proficiency test of a BRAF
assay from the College of American Pathologist
(CAP) last week. The specimens were treated as
regular clinical samples, and were signed out in
the electronic reporting system in the laboratory.
Who should sign the Proficiency Test (PT)
Attestation Statement according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
a. The laboratory director or designee
b. All individuals involved in the testing process
c. All staff in this laboratory
d. The quality control office of the hospital
A. a, b, and d
B. a, c, and d
C. a and b
D. a and c
E. a, b, c, and d
C. The laboratory director or designee
and all individuals involved in the testing process
should sign the Proficiency Test (PT) Attestation
Statement according to CAP’s regulation.
A clinical molecular laboratory in a hospital
received specimens for a proficiency test of a
BRAF assay from the College of American
Pathologist (CAP) last week, which was 3 months after test was launched. The specimens were
treated as regular clinical samples and were
signed out in the electronic reporting system in
the laboratory. At a minimum, how frequently
should proficiency tests (PT) of this assay be done
according to the Clinical Laboratory Improvement
Amendments (CLIAs) 1988?
A. Annually
B. Biennially
C. Twice a year
D. Three times a year
E. None of above
C. According to the College of American
Pathology (CAP) All Common Checklist dated
July 28, 2015, COM.01500, “For test for which
CAP does not require PT, the laboratory at least
semi-annually exercises an alternative performance
assessment system for
A director of a CAP/CLIA-certified clinical
molecular laboratory received specimens for a
proficiency test (PT) of a BRAF assay from the
College of American Pathologist (CAP). One of
the samples showed unacceptable results. Which
type of deficiency would this discrepancy be,
according to the College of American Pathologist
(CAP)’s regulations, if applicable?
A. Phase 0
B. Phase I
C. Phase II
D. Phase III
E. None of above
E. This is not a deficiency according to the College
of American Pathologist (CAP)’s regulations.
However, the laboratory must have written
procedures for the proper handling, analysis,
review, and reporting of proficiency testing
materials.
A CAP inspection team comes to the molecular
pathology laboratory in the department of
pathology of a hospital for an on-site inspection.
The team member for the molecular laboratory
finds that the CYP2C19 test is on the test menu of
the laboratory, but not on the current College of
American Pathologist (CAP) activity menu. The
director explains that the test was developed 6
months ago, and he has not had a chance to add
it to the CAP activity menu. Which type of
deficiency would this discrepancy be, according
to the College of American Pathologist (CAP)’s
regulations, if applicable?
A. Phase 0
B. Phase I
C. Phase II
D. Phase III
E. None of above
B. This is a Phase I deficiency according to the
College of American Pathologist (CAP)’s
regulations. In the College of American Pathology
(CAP) All Common Checklist dated July 28, 2015,
COM.01200, it states “The laboratory’s current
CAP Activity Menu accurately reflects the testing
performed.” If the laboratory failed to inform
CAP the change of the test menu, it would be a
phase I deficiency. In the situation described in
the question, “the inspector should contact the
CAP (800-323-4040) for instructions and record on
the appropriate section page in the Inspector’s
Summation Report (ISR) whether those tests were
inspected or not inspected.”
A clinical molecular scientist reviewed last
month’s quality control data in the laboratory,
and found that the detection rate of the KRAS test
was 50% lower than it had been in the previous 6
months and in the same month last year. He
started to investigate the reason while sending the
samples to a reference laboratory. During
investigation, the laboratory received CAP
proficiency test (PT) specimens for this test. One
of the ideas was to send the specimens to the
reference laboratory as clinical samples. Which
type of deficiency would it be if the laboratory sent the CAP specimens to a reference laboratory,
according to the College of American Pathologist
(CAP)’s regulations, if applicable?
A. Phase 0
B. Phase I
C. Phase II
D. Phase III
E. None of above
C. Under CLIA’88 regulations, there is a strict
prohibition against referring proficiency testing
(PT) specimens to another laboratory with a
different CLIA number, even if the second
laboratory is in the same health care system. If a
laboratory refers College of American Pathology
(CAP) PT specimens to another laboratory in any
circumstances, it is a Phase II deficiency.
A clinical molecular laboratory in a hospital
received specimens for proficiency test (PT) of a
BRAF assay from the College of American
Pathologist (CAP) last week, which was 3 months
after test was launched. The specimens were
treated as regular clinical samples and were
signed out in the electronic reporting system in
the laboratory. How long should the primary
records of the proficiency test (PT) be retained,
according to the Clinical Laboratory Improvement
Amendments (CLIA) 1988?
A. At least 1 year
B. At least 2 years
C. At least 3 years
D. At least 4 years
E. At least 5 years
F. At least 10 years
B. According to the College of American
Pathology (CAP) All Common Checklist dated
April 21, 2014, COM.01700, “Primary records
related to PT and alternative assessment testing
are retained for two years (unless a longer
retention period is required elsewhere in this
checklist for specific analytes or disciplines).
These include all instrument tapes, work cards,
computer printouts, evaluation reports, evidence
of review, and documentation of follow-up/
corrective action.”
A start-up clinical molecular genetics laboratory
in the state of Arizona welcomed its first on-site
inspector on a Monday morning. There were only
two tests in this laboratory—factor V Leiden and
factor II. The director shared with the inspector
that he used an alternative approach for the
proficiency test (PT) in order to save money.
Which type of deficiency would it be, according
to the College of American Pathologist (CAP)’s
regulations, if applicable?
A. Phase 0
B. Phase I
C. Phase II
D. Phase III
E. None of above
C. This is a Phase II deficiency according to the
College of American Pathologist (CAP)’s
regulations. According to the CAP All Common
Checklist dated July 28, 2015, COM.01300, “The
laboratory participates in the appropriate
required proficiency testing (PT)/external
quality assessment (EQA) program accepted by
CAP for the patient testing performed.”
A start-up clinical molecular genetics laboratory
in the state of Arizona welcomed its first on-site
inspector on a Monday morning. There were only
two tests in this laboratory—BRAF and EGFR.
The director shared with the inspector that he
used an alternative approach for the proficiency
test (PT) in order to save money. Which type of
deficiency would it be, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
A. Phase 0
B. Phase I
C. Phase II
D. Phase III
E. None of above
E. This is not a deficiency according to the College
of American Pathologist (CAP)’s , “For tests for which CAP does not
require PT, the laboratory at least semi-annually
exercises an alternative performance assessment
system for determining the reliability of analytic
testing.”
BRAF and EGFR molecular assays fall into this
category, which requires alternative assessment.
According to COM.01500, “Appropriate
alternative performance assessment procedures
include participation in an external PT program
not required by CAP;
According to the Centers for Disease Control and
Prevention (CDC) classification of biohazardous
waste, the risk group 1 agents are:
A. Agents that are not associated with disease in
healthy adult humans.
B. Agents that are associated with serious or
lethal human disease for which preventive or
therapeutic interventions may be available
(high individual risk but low community risk).
C. Agents that are associated with human disease
that is rarely serious and for which preventive
or therapeutic interventions are often available.
D. Agents that are likely to cause serious or lethal
human disease for which preventive or
therapeutic interventions are not usually
available (high individual risk and high
community risk).
A. In a research laboratory, this would include
solid waste generated from any work with human
or nonhuman primate blood, tissue, or cells and
microbiological agents that may cause human
illness. The Basis for the Classification of
Biohazardous Agents by Risk Group (RG) is as
follows:
* Risk Group 1 (RG1): Agents that are not associated
with disease in healthy adult humans.
According to the Centers for Disease Control and
Prevention (CDC) classification of biohazardous
waste, the Risk Group 4 agents are:
A. Agents that are not associated with disease in
healthy adult humans.
B. Agents that are associated with serious or
lethal human disease for which preventive or
therapeutic interventions may be available
(high individual risk but low community risk).
C. Agents that are associated with human disease
that is rarely serious and for which preventive
or therapeutic interventions are often available.
D. Agents that are likely to cause serious or lethal
human disease for which preventive or
therapeutic interventions are not usually
available (high individual risk and high
community risk).
D. In a research laboratory, this would include
solid waste generated from any work with human
or nonhuman primate blood, tissue, or cells and
microbiological agents that may cause human
illness. The Basis for the Classification of
Biohazardous Agents by Risk Group (RG) is as
follows:
* Risk Group 4 (RG4): Agents that are likely to cause
serious or lethal human disease for which preventive
or therapeutic interventions are not usually
available (high individual risk and high community
risk)
According to the Centers for Disease Control and
Prevention (CDC) classification of biohazardous
waste, the Risk Group 2 agents are:
A. Agents that are not associated with disease in
healthy adult humans.
B. Agents that are associated with serious or
lethal human disease for which preventive or
therapeutic interventions may be available
(high individual risk but low community risk).
C. Agents that are associated with human
disease that is rarely serious and for which
preventive or therapeutic interventions are
often available
D. Agents that are likely to cause serious or lethal
human disease for which preventive or
therapeutic interventions are not usually
available (high individual risk and high
community risk).
B. In a research laboratory, this would include
solid waste generated from any work with human
or nonhuman primate blood, tissue, or cells and
microbiological agents that may cause human
illness. The Basis for the Classification of
Biohazardous Agents by Risk Group (RG) is as
follows:
* Risk Group 2 (RG2): Agents that are associated
with human disease that is rarely serious and for
which preventive or therapeutic interventions are
often available.
According to the Disease Control and Prevention
(CDC) classification of biohazardous waste, the
risk group 3 agents are:
A. Agents that are not associated with disease in
healthy adult humans.
B. Agents that are associated with serious or
lethal human disease for which preventive or
therapeutic interventions may be available
(high individual risk but low community risk).
C. Agents that are associated with human disease
that is rarely serious and for which preventive
or therapeutic interventions are often available.
D. Agents that are likely to cause serious or lethal
human disease for which preventive or
therapeutic interventions are not usually
available (high individual risk and high
community risk).
C. In a research laboratory, this would include
solid waste generated from any work with human
or nonhuman primate blood, tissue, or cells and
microbiological agents that may cause human
illness. The Basis for the Classification of
Biohazardous Agents by Risk Group (RG) is as
follows:
* Risk Group 3 (RG3): Agents that are associated with
serious or lethal human disease for which preventive
or therapeutic interventions may be available (high
individual risk but low community risk).
Human immunodeficiency virus (HIV) spreads
through certain body fluids and attacks a person’s
immune system by destroying CD4-positive T
cells. This makes it harder and harder for the body
to fight infections and other diseases. Currently, no
effective cure exists for HIV. But with proper
medical care, HIV can be controlled. According to
the Centers for Disease Control and Prevention
(CDC) classification of biohazardous waste, to
which risk group does the HIV-1 virus belong?
A. Risk Group 1
B. Risk Group 2
C. Risk Group 3
D. Risk Group 4
E. Risk Group 5
C. HIV-1 and 2 viruses are in the risk group 3
The Ebola virus causes an acute and serious
illness that is often fatal if left untreated. Ebola
virus disease (EVD) first appeared in 1976 in two
simultaneous outbreaks, one in what is now,
Nzara, South Sudan, and the other in Yambuku,
Democratic Republic of Congo. The latter
occurred in a village near the Ebola River, from
which the disease takes its name. According to
the Centers for Disease Control and Prevention
(CDC) classification of biohazardous waste, to
which risk group does the Ebola virus belong?
A. Risk Group 1
B. Risk Group 2
C. Risk Group 3
D. Risk Group 4
E. Risk Group 5
D. Ebola virus is in the Risk Group 4
According to the Centers for Disease Control and
Prevention (CDC) classification of biohazardous
waste, to which risk group do hepatitis B,
cytomegalovirus (CMV), EpsteinBarr virus (EBV),
and herpes simplex types 1 and 2 viruses belong?
A. Risk Group 1
B. Risk Group 2
C. Risk Group 3
D. Risk Group 4
E. Risk Group 5
B. Hepatitis B, cytomegalovirus [CMV, EpsteinBarr
virus (EBV)], and herpes simplex types 1 and 2
viruses are in risk group 2
Rabies virus has a nonsegmented and negativestranded
RNA genome. Rabies disease is most
often transmitted through the bite of a rabid
animal such as raccoons, skunks, bats, and foxes.
According to the Centers for Disease Control and
Prevention (CDC) classification of biohazardous
waste, to which risk group does rabies virus belong?
A. Risk Group 1
B. Risk Group 2
C. Risk Group 3
D. Risk Group 4
E. Risk Group 5
B. Rabies virus is in risk group 2
An ACMG board-certified molecular geneticist
started a job as a director in a commercial
laboratory. He planned to review all the
procedures and policies in the laboratory in the
first 2 months. He found that one of the procedures
stated that a designee of the director would review
and assess instrument and equipment maintenance
and function-check records semiannually. He felt it
was wrong. How frequently should he or his
designee review and assess instrument and
equipment maintenance and function check
records, according to the College of American
Pathologist (CAP)’s regulations, if applicable?
A. At least monthly
B. At least quarterly
C. At least twice a year
D. At least annually
E. At least biennially
A. According to the College of American
Pathology (CAP) All Common Checklist dated
July 28, 2015, COM.04200, “Instrument and
equipment maintenance and function check
records are reviewed and assessed at least monthly
by the laboratory director or designee.”
An ACMG board-certified molecular geneticist
started a job as a director in a commercial
laboratory. He planned to review all the
procedures and policies in the laboratory in 2
months. He found that one of the procedures
stated that a designee of the director would check
the 20 thermal cyclers against each other once a
year. He noticed that 10 of the thermal cyclers
were from Applied Biosystems (ABI), 5 were
from Eppendorf, and the remaining 5 were from
Thermo Fisher Scientific. Which one of the
following statements is correct, according to the
College of American Pathologist (CAP)’s
regulations, if applicable?
A. He should check the thermal cyclers from the
same manufacturer against each other at least
once a year.
B. He should check all 20 thermal cyclers against
each other at least once a year.
C. He should check the thermal cyclers from the
same manufacturer against each other at least
twice a year.
D. He should check all 20 thermal cyclers against
each other at least twice a year.
E. None of the above.
D. According to the College of American
Pathology (CAP) All Common Checklist dated
July 28, 2015, COM.04250, “If the laboratory uses
more than one nonwaived instrument/method to
test for a given analyte, the instruments/methods
are checked against each other at least twice a year
for comparability of results.” It also states, “This
requirement applies to tests performed on the
same or different instrument makes/models or by
different methods.” Please also be aware that “This
comparison is required only for nonwaived
instruments/methods accredited under a single
CAP number.”
An ACMG board-certified molecular geneticist
started a job as a director in a commercial
laboratory. He planned to review all the
procedures and policies in the laboratory in the
first month. He found that one of the
procedures stated that a designee of the director
would check the 20 thermal cyclers against each
other once a year. He noticed that 10 of the
thermal cyclers were from Applied Biosystems
(ABI) and the rest were from Eppendorf or
Thermo Fisher Scientific. How frequently should
he or a designee check the thermal cyclers
against each other for comparability of results in
the laboratory, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
A. At least monthly
B. At least quarterly
C. At least twice a year
D. At least annually
E. At least biennially
C. According to the College of American
Pathology (CAP) All Common Checklist dated
July 28, 2015, COM.04250, “If the laboratory uses
more than one nonwaived instrument/method to
test for a given analyte, the instruments/methods
are checked against each other at least twice a year
for comparability of results.”
A newly ACMG board-certified molecular
geneticist started a job as a director in a
commercial laboratory 2 months ago. While he
reviewed the procedures and policies, he found
that the laboratory used a triplet primer PCR
assay without methylation-sensitive
confirmation for the fragile X test. Before taking
any action on it, the laboratory received
specimens from the College of American
Pathologist (CAP) for proficiency testing on
fragile X. One of the specimens was homozygous
for allele 30. Since the gender of the specimen
was unknown, the director was concerned about
whether there was a gross deletion or a
mutation in the primer region leading to allelic
drop. He called a director at another institute to
discuss the result before finalizing it. Which type
of deficiency would it be if they discussed the
results, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
A. Phase 0
B. Phase I
C. Phase II
D. Phase III
E. None of above
C. It would be a Phase II deficiency. According to
the College of American Pathology (CAP) All
Common Checklist dated July 28, 2015,
COM.01800, “Results must be reported by
personnel within the laboratory. There is a strict
prohibition against interlaboratory
communications about proficiency testing
samples or results until after the deadline for
submission
Dr. A, a newly board-certified molecular
geneticist, started to work for a hospital 10 days
ago. He planned to review all the procedures
and policies in the laboratory in the first 2
months. He found that some of the procedures
had not been reviewed for more than 5 years.
How frequently should the technical policies and
procedures be reviewed by the current laboratory director or designee in a clinical
molecular genetics laboratory, according to the
College of American Pathology (CAP)
regulations, if applicable?
A. At least monthly
B. At least quarterly
C. At least twice a year
D. At least annually
E. At least biennially
F. At least once in 5 years
E. According to the College of American
Pathology (CAP) All Common Checklist dated
July 28, 2015, COM.10100 “There is
documentation of review of all technical policies
and procedures by the current laboratory director
or designee at least every two years.”
Dr. A, a newly board-certified molecular
geneticist, started to work for a hospital 10 days
ago. He planned to review all the procedures and
policies in the laboratory in the first 2 months. He
found that some of the procedures had not been
reviewed for more than 5 years. Which type of
deficiency would it be, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
A. Phase 0
B. Phase I
C. Phase II
D. Phase III
E. None of above
C. It would be a Phase II deficiency.
Dr. B, a director of a clinical molecular genetics
laboratory in an academic center, validated a
clinical next-generation sequencing (NGS) panel
for somatic mutations in solid tumors. When
should the procedure for this new test be
reviewed and approved, according to the College
of American Pathologist (CAP)’s regulations, if
applicable?
A. It should be reviewed and approved 30 days
before implementation.
B. It should be reviewed and approved 15 days
before implementation.
C. It should be reviewed and approved before
implementation.
D. It should be reviewed and approved within 1
month after implementation.
E. None of above.
C. According to the College of American
Pathology (CAP) All Common Checklist dated
July 28, 2015, COM.10200, “The laboratory
director reviews and approves all new technical
policies and procedures, as well as substantial
changes to existing documents, before
implementation. This review may not be delegated
to designees in laboratories subject to the CLIA
regulations. Paper/electronic signature review is
required. A secure electronic signature is
desirable, but not required.”
Dr. B, the only director of a clinical molecular
genetics laboratory in an academic center,
validated a clinical next-generation sequencing
(NGS) panel for somatic pathogenic variants
in solid tumors. By whom should this procedure
for the new test be reviewed and
approved, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
A. BJ, the supervisor of the laboratory
B. Dr. B
C. Dr. C, the chair of the department
D. Dr. D, the chief medical officer of the hospital
E. College of American Pathologist (CAP)
F. All of the above
G. None of above
B. Dr. B
JJ, a technologist in a clinical molecular genetics
laboratory, came to Dr. E, the director, to
complain about the speed of the computer. The
laboratory support team assessed the situation
and suggested the purchase of a new remote
drive or the deletion some files in the current
hard drive to free some space. Dr. E decided to
delete some of the discontinued procedures.
How long should the discontinued procedures
be maintained in a clinical molecular genetics
laboratory, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
A. At least 1 year
B. At least 2 years
C. At least 5 years
D. At least 7 years
E. At least 16 years
F. At least 23 years
G. Forever
B. At least 2 years
Dr. J, a clinical molecular geneticist, called Dr. G,
an oncologist in the same hospital, about a
patient’s abnormal PML/RARA quantitative
results. What information should be recorded in
the patient’s record for this communication,
according to the College of American Pathologist
(CAP)’s regulations, if applicable?
a. Patient ID
b. Date of the phone call
c. Time of the phone call
d. Laboratory individual responsible for the
phone call
e. Person notified in the physician office (first
and last name)
f. Test results
g. Recommendations
h. “Read-back” of the results
A. a, b, d, e, and h
B. a, b, d, e, f, and h
C. a, b, c, d, e, f, and h
D. a, b, d, e, f, and h
E. a, b, c, d, e, f, g, and h
F. None of above
C. a, b, c, d, e, f, and h
recommendation is not necessary for preliminary
results.
Dr. D, a director of a clinical laboratory in
Wisconsin, found that a lot of restriction
enzymes in the laboratory had passed the
expiration date. It would be a huge waste to
throw them away, so he tested the enzymes with
positive controls, negative controls, and 10
previous patient samples. All the results were
correct, so he decided to keep using those
enzymes clinically. Which type of deficiency
would this decision be, according to the College of American Pathologist (CAP)’s regulations, if
applicable?
A. Phase 0
B. Phase I
C. Phase II
D. Phase III
E. None of above
C. This is a Phase II deficiency
Dr. A, an ACMG board-certified molecular
geneticist, started a job as a senior director in a
commercial laboratory 2 months ago. When
reviewing the procedures and policies in the
laboratory, he found that the laboratory only
checked new reagent lots against old reagent lots,
but not against new reagent shipments in the
same lot. The manager explained that it was done
that way in order to save money. Dr. A changed
the procedure to check new reagent lots and new
shipments against old reagent lots and old
shipments. Why did Dr. A make the change,
according to the College of American Pathologist
(CAP)’s regulations, if applicable?
A. Because it is a Phase 0 deficiency if the
laboratory doesn’t check new shipments in the
same lot.
B. Because it is a Phase I deficiency if the
laboratory doesn’t check new shipments in the
same lot.
C. Because it is a Phase II deficiency if the
laboratory doesn’t check new shipments in the
same lot.
D. Because it is a Phase III deficiency if the
laboratory doesn’t check new shipments in the
same lot.
E. Because it makes Dr. A feel more
comfortable to have both new lots and new
shipments checked.
F. None of above.
C. It would be a Phase II deficiency if the
laboratory does not check new shipments
Dr. A, an ACMG board-certified molecular
geneticist, started a job as a senior director in a
commercial laboratory 2 months ago. He
observed the staff performing each test. When he
was observing JJ, a technologist, setting up a
quantitative PCR reaction for BCR-ABL1, JJ
found that the reagents in the kit were not
enough for this run. JJ took out another kit with
a different lot number from the freezer. The new
lot was checked and verified. JJ pipetted the
remaining reagents from the old kit to the new
kit and explained to Dr. A that this was a new
policy in the laboratory to save money. Dr. A
stopped JJ and changed the procedure
immediately. Why did Dr. A stop JJ and make
the change to the procedure, according to the
College of American Pathologist (CAP)’s
regulations, if applicable?
A. Because it is a Phase 0 deficiency to mix kit
components from different lots.
B. Because it is a Phase I deficiency to mix kit
components from different lots.
C. Because it is a Phase II deficiency to mix kit
components from different lots.
D. Because it is a Phase III deficiency to mix kit
components from different lots.
E. Because Dr. G did not feel that it was right to
mix kit components from different lots.
F. None of above.
C. It would be a Phase II deficiency if JJ used
reagents from kits within different kit lots,
according to the College of American Pathologist
(CAP)’s regulations. According to the CAP All
Common Checklist dated July 28, 2015,
COM.30500, “If there are multiple components of
a reagent kit, the laboratory uses components of
reagent kits only within the kit lot unless
otherwise specified by the manufacturer.” And
laboratories should have “Written policy defining
allowable exceptions for mixing kit components
from different lots.”
Dr. G, an ACMG board-certified molecular
geneticist, started a job as a senior director of a
clinical molecular pathology laboratory in a
hospital 2 months ago. He started to observe the
staff to performing each test. When he was
observing BJ, a technologist, as he set up a
quantitative PCR reaction for BCR-ABL1, a man
put an Eppendorf thermal cycler on the bench,
and told BJ it was fixed. BJ explained to Dr. G
that the Eppendorf thermal cycler had had a
problem and that a clinical engineer took it a few
days ago. While they were talking, Emily, another
technologist, walked in with her PCR plate. Emily
started to set up her PCR in the newly fixed
thermal cycler. Dr. G suggested that Emily use
other thermal cyclers in the laboratory. Why did
Dr. G suggest the use of other thermal cyclers in
the laboratory, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?1
A. It is a Phase 0 deficiency to use newly fixed
instruments/equipment before performance
verification.
B. It is a Phase I deficiency to use newly fixed
instruments/equipment before performance
verification.
C. It is a Phase II deficiency to use newly fixed
instruments/equipment before performance
verification.
D. It is a Phase III deficiency to use newly fixed
instruments/equipment before performance
verification.
E. Dr. G felt that using newly fixed instruments/
equipment before performance verification did
not feel right.
F. None of above.
C. It would be a Phase II deficiency if Emily uses
the newly fixed thermal cycler before
performance verification, according to the College
of American Pathologist (CAP)’s regulations.
According to the CAP All Common Checklist
dated July 28, 2015, COM.30550, “The
performance of all instruments and equipment is
verified upon installation and after major
maintenance or service to ensure that they run
according to expectations.” It also states,
“Performance verification is necessary after
repairs or replacement of critical components of
an instrument or item of equipment.”1
A start-up CAP/CLIA-certified clinical
molecular genetics laboratory has only two
technologists, one part-time on-site supervisor,
and one part-time off-site director. The
technologists validated a BRAF assay with
formalin-fixed and paraffin-embedded (FFPE)
tissue samples. The supervisor approved the
validation summary and sent it to the director. Before the director replied, the husband of the
supervisor, a physician in the same hospital, sent
a FFPE sample for the BRAF test. How should the
laboratory treat this sample, according to the
College of American Pathologist (CAP)’s
regulations, if applicable?1
A. Set up the sample for the BRAF test while
waiting for the director to approve the
validation for the final report.
B. Set up the sample for the BRAF test,
giving the preliminary results to the
ordering physician while waiting for the
director to approve the validation for the final
report.
C. Set up the sample for the BRAF test, reporting
it out before the director approves the
validation.
D. Hold the sample while waiting for the director
to approve the validation.
E. Explain to the ordering physician that the
method for the BRAF test has not been
validated in this laboratory.
F. None of above.
E. The lab staff should explain to the ordering
physician that the method for the BRAF test has
not been validated in this laboratory, and the lab
could not accept clinical specimens for this test
yet. According to the College of American
Pathologist (CAP) All Common Checklist dated
July 28, 2015, COM.40000, “There is a summary
statement, signed by the laboratory director (or
designee who meets CAP director qualifications) prior
to use in patient testing, that includes the
evaluation of validation/verification studies and
approval of each test for clinical use.
Dr. Z has been validating the FDA-cleared/
approved quantitative COBAS AmpliPrep/
COBAS TaqMan CMV test from Roche Molecular
Systems for cytomegalovirus (CMV) in a clinical
molecular pathology laboratory in Florida. He
gathered all the data to write the validation
summary. What components should he include in
the validation summary, according to the College
of American Pathologist (CAP)’s regulations, if
applicable?
a. Analytical accuracy
b. Analytical precision
c. Analytical sensitivity
d. Analytical specificity
e. Cross-contamination
f. Interferences
g. Reportable range
A. a, b, c, and d
B. a, b, and g
C. a, b, f, and g
D. c, d, f, and g
E. a, b, c, d, e, f, and g
F. None of the above
C. The College of American Pathologist (CAP)
has clearly different validation requirements for
FDA-cleared/approved and non-FDA-cleared/
approved tests. Non-FDA-cleared/approved tests
include laboratory-developed tests (LTDs) and
modified FDA-cleared/approved tests. According
to the CAP All Common Checklist dated July 28,
2015, COM.40000, “For an FDA-cleared/approved
test, a summary of the verification data must
address analytical performance specifications,
including analytical accuracy, precision, interferences,
and reportable range, as applicable.” It also states
that the summary statement must include a
written assessment of the validation/verification
study, including the acceptability of the data. The
summary must also include a statement
approving the test for clinical use with an
approval signature such as, “This validation
study has been reviewed, and the performance of
the method is considered acceptable for patient
testing.”
Dr. Y has been validating the FDA-cleared/
approved quantitative COBAS AmpliPrep/
COBAS TaqMan CMV test from Roche Molecular
Systems for cytomegalovirus (CMV) in a clinical
molecular pathology laboratory in Florida. And
he planned to use the assay on cerebrospinal fluid
(CSF) specimens, too, which was not been
approved or cleared by the FDA. He gathered all
the data to write the validation summary. What components should he include in the
validation summary according to the College of
American Pathologist (CAP) regulations, if
applicable?
a. Analytical accuracy
b. Analytical precision
c. Analytical sensitivity
d. Analytical specificity
e. Cross-contamination
f. Interferences
g. Reportable range
A. a, b, c, and d
B. a, b, and g
C. a, b, f, and g
D. c, d, e, f, and g
E. a, b, c, d, e, f, and g
F. None of the above
E. The College of American Pathologist (CAP) has
clearly different validation requirements to FDAcleared/
approved and non-FDA-cleared/
approved tests. No-FDA-cleared/approved tests
include laboratory-developed tests (LTDs) and
modified FDA-cleared/approved tests. According
to the CAP All Common Checklist dated July 28,
2015, COM.40000, “for modified FDA-cleared/approved tests or LDTs, the summary must
address analytical sensitivity, analytical specificity,
and any other parameter that is considered
important, to assure that the analytical
performance of a test (e.g., specimen stability,
reagent stability, linearity, carryover, and crosscontamination,
etc.), as appropriate and
applicable.”
A clinical molecular pathology laboratory
decides to discontinue its CYP2C19 test used to
predict therapeutic response to clopidogrel
(commonly known as Plavix) as an antiplatelet
agent for cardiovascular disorders, because it is
an extremely low volume test. How long should
the laboratory keep the procedure for the
CYP2C19 test after discontinuation, according to
the College of American Pathologist (CAP)’s
regulations, if applicable?
A. At least 1 year
B. At least 2 years
C. At least 5 years
D. At least 7 years
E. At least 16 years
F. At least 23 years
G. Forever
F. According to the College of American Pathology
(CAP) All Common Checklist dated July 28, 2015,
COM.10500, “When a procedure is discontinued, a
paper or electronic copy is maintained for at least
2 years, recording initial date of use, and
retirement date. For genetic testing, in order to
meet the requirements of some states relating to
the testing of minors (under the age of 21), it is
recommended that laboratories retain procedures
(paper or electronic) for at least 23 years (to cover
the interval from fetal period to age 21).”
Therefore, the laboratory should keep the
procedure for the CYP2C19 test for at least 23
years after discontinuation.
A clinical molecular pathology laboratory in
Florida has been offering a quantitative
cytomegalovirus (CMV) test with the FDAcleared/
approved COBAS AmpliPrep/COBAS
TaqMan CMV assay from Roche Molecular
Systems for more than 2 years. Last month the
laboratory moved from the main hospital to a
remote facility with the rest of the department of
pathology. Which of the following parameters
should be included in the verification after the
move, according to the College of American
Pathologist (CAP)’s regulations, if applicable?
a. Analytical accuracy
b. Analytical precision
c. Analytical sensitivity
d. Analytical specificity
e. Cross-contamination
f. Interferences
g. Reportable range
A. a, b, c, and d
B. a, b, and g
C. a, b, f, and g
D. c, d, e, f, and g
E. a, b, c, d, e, f, and g
F. None of the above
B. In the College of American Pathologist (CAP)
All Common Checklist dated July 28, 2015, there
is chapter dedicated to “Method Performance
Specifications,” which clearly states, “The method
performance specifications must be validated or
verified in the location in which patient testing
will be performed. If an instrument is moved, the
laboratory must verify the method performance
specifications (i.e., accuracy, precision,
reportable range) after the move to ensure that the
test system was not affected by the relocation
process or any changes due to the new
environment (e.g., temperature, humidity, reagent
storage conditions, etc.). The laboratory must
follow manufacturer’s instructions for instrument
set up, maintenance, and system verification.”
A clinical molecular pathology laboratory used a
CYP2C19 assay to predict therapeutic response
to clopidogrel (commonly known as Plavix) as
an antiplatelet agent for cardiovascular
disorders. Two years ago, the laboratory
discontinued the test because of low volume.
Recently, the data from the send-outs indicated
the increase of volume for CYP2C19. The
laboratory is considering bringing the assay
back. Which one of the following requirements
must be met in order to put the test back into
production, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?
A. PT or alternative assessment performed within
30 days prior to restarting patient testing
B. Method of performance specifications verified,
as applicable, within 30 days prior to
restarting patient testing
C. Competency assessed for analysts within 12
months prior to restarting patient testing
D. All of the above
E. None of the above
D. According to the College of American
Pathologist (CAP) All Common Checklist dated
July 28, 2015, COM.40100, “When a test is put
back into production, the following requirements
must be met:
* PT or alternative assessment performed within 30
days prior to restarting patient testing.
* Method performance specifications verified, as
applicable, within 30 days prior to restarting
patient testing.
* Competency assessed for analysts within 12 months
prior to restarting patient testing.”
Also, a “test is considered to be taken out of
production when (1) patient testing is not offered
AND (2) PT or alternative assessment, as
applicable, is suspended. It does not apply to
situations where a proficiency testing challenge is
not performed due to a temporary, short-term
situation, such as a reagent back order or an
instrument breakdown. In those situations, the
laboratory must perform alternative assessment
for that testing event.”
Therefore, all the choices listed in the question
are the requirements, which must be met in order
to put the test back into production.
A clinical molecular pathology laboratory has
been offering an FDA-approved quantitative
HIV-1 RNA test for 1 year. However, the test has
been suspended for a month, and the laboratory
cannot participate in the most recent CAP
proficiency test (PT) because of an instrument
breakdown. Which one of the following
requirements must be met in order to put the
test back into production, according to the
College of American Pathologist (CAP)’s
regulations, if applicable?
A. PT or alternative assessment performed within
30 days prior to restarting patient testing
B. Method of performance specifications verified,
as applicable, within 30 days prior to
restarting patient testing
C. Competency assessed for analysts within 12
months prior to restarting patient testing
D. Perform alternative proficiency test (PT)
assessment
E. All of the above
F. None of the above
D. According to the College of American Pathologist (CAP) All Common Checklist dated
July 28, 2015, COM.40100, intermittent testing
“does not apply to situations where a proficiency
testing challenge is not performed due to a
temporary, short-term situation, such as a reagent
back order or an instrument breakdown. In those
situations, the laboratory must perform alternative
assessment for that testing event.” The quantitative
HIV-1 RNA test is one of the PT required tests.
The laboratory should perform alternative
assessment for the test.
Therefore, alternative proficiency test (PT)
assessment must be performed in order to put the
test back into production.
Dr. Z, a director of a clinical molecular pathology
laboratory, wants to validate the FDA-cleared/
approved Cystic Fibrosis 139-Variant Assay.
However, the laboratory has Illumina MiSeq
instead of Illumina MiSeqDx. Dr. Z decides to
validate the assay with Illumina MiSeq (MiSeqDX is the instrument for the FDA-cleared/approved
Cystic Fibrosis 139-Variant Assay). Which of the
following parameters should Dr. Z include in the
verification, according to the College of
American Pathologist (CAP)’s regulations, if
applicable?1
a. Analytical accuracy
b. Analytical precision
c. Analytical sensitivity
d. Analytical specificity
e. Cross-contamination
f. Interferences
g. Reportable range
A. a, b, c, and d
B. a, b, and g
C. a, b, f, and g
D. c, d, e, f, and g
E. a, b, c, d, e, f, and g
F. None of the above
E. The College of American Pathologist (CAP) has
clearly different validation requirements for FDAcleared/
approved and non-FDA-cleared/
approved tests. Non-FDA-cleared/approved tests
include laboratory-developed tests (LTDs) and
modified FDA-cleared/approved tests. According
to the CAP All Common Checklist dated July 28,
2015, COM.40000, “for modified FDA-cleared/
approved tests or LDTs, the summary must
address analytical sensitivity, analytical
specificity, and any other parameter that is
considered important, to assure that the analytical
performance of a test (e.g., specimen stability,
reagent stability, linearity, carryover, and crosscontamination,
etc.), as appropriate and
applicable.”
Which one of the following efforts is used to
verify or establish analytical accuracy, according
to the College of American Pathologist (CAP)’s
regulations?1
A. Using reference materials or other materials
with known concentrations or activities
B. Comparing results to an established
comparative method
C. Repeating measurement of samples at varying
concentrations or activities within-run and
between-run over a period of time
D. Testing the lower detection limit of an assay
E. A and B
F. A, B, and C
G. C and D
H. None of the above
E. According to the College of American
Pathologist (CAP) All Common Checklist dated
July 28, 2015, COM.40300, “Where current
technology permits, accuracy is established by
comparing results to a definitive or reference method,
or may be verified by comparing results to an
established comparative method. Use of reference
materials or other materials with known
concentrations or activities is suggested in
establishing or verifying accuracy.” And
“Precision is established by repeat measurement
of samples at varying concentrations or activities
within-run and between-run over a period of
time.” A lower detection limit establishes the
analytical sensitivity of a test.
