The Principles of Clinical Cytogenetics - Extra Materials - Springer

108 Michael Watson and Steven Gersen
with the karyotypes, to determine whether or not they can identify the abnormality (a biased process,
because these individuals obviously must know that something is wrong), and soliciting their opinions
as “expert witnesses” concerning whether or not the laboratory should have caught the abnormality
or whether it was too subtle to detect. Regardless of the nature of the error that is detected, it
is important to determine the cause of the problem and to put into place the necessary changes to
minimize recurrence.
THE LABORATORY QUALITY ASSURANCE PROGRAM
In order to realize the benefits of having tracked the function of the laboratory and monitored its
performance and problems, an organized process of review, communication, and staff education is
required. This could involve subsets of the laboratory personnel but at certain times, it is part of the
ongoing training and continuing education program that should be available to the entire staff.
Oversight
In addition to the numerous steps already described, cytogenetics labs, like all other clinical laboratories,
are subject to many external guidelines, inspections, and tests that ensure and improve quality.
These vary from country to country and even from state to state in the United States. Oversight of
clinical laboratories is in two main forms. The Food and Drug Administration (FDA) regulates manufacturers
of devices, some reagents, some software, and testing kits sold to laboratories. Though the
FDA has suggested that the regulation of laboratories is within the purview of its federal mandate
because the laboratories make some of their own reagents, there is no precedent for their involvement
at this level. The majority of direct laboratory oversight is focused on laboratory practices, including
personnel requirements, general quality control and assurance, and quality control and assurance
specific to the area of practice. Clinical cytogenetics is among the areas of CLIA ’88 regulation with
specialty specific requirements (CFR§493.1276).
United States
ACCREDITATION, INSPECTIONS AND EXTERNAL PROFICIENCY TESTING
Under the Clinical Laboratory Improvement Amendment of 1988 (CLIA ’88), every laboratory
performing moderate- to high-complexity testing (i.e., every cytogenetics laboratory) must enroll in
Health and Human Services approved external inspection and testing programs. In fact, virtually all
clinical laboratories in the United States do so under the auspices of the CLIA-deemed program of
the College of American Pathologists (CAP). This accrediting organization inspects laboratories and
provides the American College of Medical Genetics (ACMG)/CAP proficiency testing survey program,
according to CLIA requirements, several times a year. A lab’s ability to perform and be reimbursed
for testing depends on successful participation in each aspect of this process, as repeated
failure can lead to loss of accreditation. As of this time, no areas of genetic testing have mandated
performance requirements for their proficiency testing programs.
The College of American Pathologists sends a team, typically from another laboratory, to inspect
each facility every other year; during off-years, the laboratory must conduct and report the results of
a self-inspection. Proficiency testing and interlaboratory comparison programs vary according to
specialty; in cytogenetics, the proficiency tests generally consist of four unknowns in the form of
banded metaphase preparations plus sufficient clinical information for the lab to make a diagnosis. A
fifth unknown, in the form of a peripheral blood sample, is also frequently submitted, but the reader
will appreciate the logistical and medical challenges of this procedure; there are enough cytogenetics
laboratories in the United States that care must be taken not to exsanguinate the individual (typically
a carrier of some rearrangement) who has volunteered to be the test subject!
State requirements can be quite variable. Several require participation in the CAP programs. However,
this is often difficult for private-sector laboratories. One of the more rigorous programs is admin-