INTERNATIONAL ORGANIZATION FOR
STANDARDIZATION
ISO Background
Operating since 1947, the International Organization
for Standardization (ISO) is a nongovernmental
association consisting of representatives from over 150
countries, one member per country. There are
approximately 3,000 ISO technical committees and
working groups, with participation from about 50,000
experts, contributing to the development of ISO standards
that provide the framework for compatible technology
internationally. Efforts to achieve technical consensus for
each standard are coordinated by a central secretariat in
Geneva, Switzerland. As the world’s largest developer of
standards, the organization’s goal is to define quality
standards for organizations to facilitate and promote the
trade of products and services internationally. The
standards are also used by governments to establish
health, safety, and environmental laws.
While ISO certification is voluntary in the United States, it
serves as an attractive credential—especially for
companies that intend to reach an international market—
and demonstrates the intent to manage quality through
practices deemed acceptable by the ISO. Conformance
to standards inherently contributes to higher quality,
safety, reliability, and interchangeability of products and
services. This potentially increases a company’s
marketability, customer retention, and acquisition of new
customers.
Benefits of the ISO standards
An ISO certificate does not ensure a company’s product
or service quality; it attests that a company adheres to
documented processes and quality controls. Product
quality is achieved through adherence to defined
processes that are designed to deliver products and
services that meet the company’s predefined
requirements. The increased credibility associated with
ISO certification leads to the following advantages:
• Decreased operating expenses stemming from
scrap and rework
• Enhanced management control through
management review participation
• Reduced product liability risk due to a robust
quality- management system
• Increased customer satisfaction as a result of
customer- focused quality systems
• Increased marketability from the commitment to
meeting internationally accepted quality
standards
ISO 9000 Family
The quality standards in the ISO 9000 family focus on
quality management and include QMS requirements that
are general for the manufacturing and service industries.
Based on basic quality-management principles, ISO 9001
provides the criteria for a quality-management system.
The eight quality-management principles are:
• Leadership
• Customer focus
• Process approach
• System approach to management
• Involvement of people
• Factual approach to decision making
• Continual improvement
• Mutually beneficial supplier relationship
ISO 9001 first requires that an organization determine its
quality policy and related quality objectives. Quality
objectives must be measurable and include those needed
to meet the requirements of the product, for example, on-
time results or employment of assays with sufficient
specificity to meet medical needs. The organization must
also develop a quality manual (QM), which will include a
description of how the processes in the QMS interact,
either as a flow map, cross-references to the standard, or
a written description. The QM also contains information
on the six written procedures that ISO 9001 requires:
• Control of documents
• Control of records
• Internal audits
• Control of nonconforming product
• Corrective action
• Preventive action
ISO 15189
First published in 2003, ISO 15189 is based on ISO 9001
and a standard known as ISO/IEC 17025. It is an
international standard specifically developed for medical
laboratories, although it may be of relevance to such
disciplines as clinical physiology and medical imaging. It
is a much longer document than ISO 9001, and the
requirements are very detailed; to the QMS requirements
of ISO 9001 it adds the technical and competency factors
that are relevant to laboratories.
ISO Certification Process:
Although the ISO develops standards, it is not a certifying
body (or registrar); rather, assessment and certification to
an ISO standard are performed by external certification
bodies. The ISO’s Committee on Conformity Assessment
(CASCO) has developed and published standards related
to the certification process; the standards contain
assessment techniques, deemed good practices based
on an international consensus. Maintaining an ISO
certificate is an iterative process, as demonstrated by
requirements for annual surveillance and certification
renewal every three years.
MANAGEMENT OF POINT-OF-CARE TESTING
Point-of-care testing (POCT) presents some of the most
controversial and difficult laboratory management
challenges. There is a commonly held view among
laboratory workers that POCT represents a compromise
in test quality in the interest of speed to obtain results.
Many of the challenges presented by POCT are
substantially different from those of any aspect of
centralized laboratory testing. Common challenges
include crossing traditional physical and organizational
boundaries, performing tests at a large number of
locations, training a large number of personnel with
limited laboratory experience, using technologies or
devices that differ from those in central laboratories,
capturing test results and control values into information
systems, and difficulty in tracking costs and program
activity.
There is not complete agreement about the definition of
POCT, and a variety of other terms such as “near
patient,” “bedside,” or “alternative site” testing have
been used as approximate synonyms. POCT is also
defined as testing that is performed outside defined
laboratory facilities, including not only central laboratories
but also small satellite or special-function laboratories in
physician offices, intensive care units, and emergency
rooms.
A. Organizational Challenges
1. Political challenges - laboratory workers often were
highly antagonistic to the perceived competition and lower
analytical quality provided by POCT. Laboratory directors
and managers secured the four walls of the laboratory by
building a fortress of organizational boundaries,
regulations, and arguments to serve as moats and
barriers to prevent outsiders from intruding into the
domain of laboratory testing. This management strategy
sought the disappearance of POCT. Instead, POCT often
developed under separate management from the central
laboratory, and testing volume grew rapidly as testing
technologies advanced.
2. Setting goals for POCT management - One of the
key initial steps in the management of POCT is the
development of institutional goals. Common motivations
for hospital administration and nursing units to seek
additional management support for POCT are
deficiencies in accreditation surveys, difficulty in meeting
accreditation standards, problems with the quality of test
results of POCT, resulting in complaints or lawsuits, and
requests from nurses who feel the need for assistance to
address laboratory regulations. Developing a broader
vision of the goals of POCT and a commitment from
institutional leadership is important for moving beyond a
minimal standard of performance and generating a
positive sense of mission and purpose. More far-reaching
goals in management of POCT are to provide testing that
will improve patient care and to improve organizational
efficiency.
3. Developing management Structures for POCT -
There are political issues that central administration and
depart- mental leaders need to sort out. These include
issues such as what department and who will direct
testing, institutional priorities for POCT, and how costs
and revenues will be assigned.
● Some POCT programs are organized as extensions of
the clinical laboratory, with all testing performed by
laboratory staff such as phlebotomists or medical
technologists.
● A more common organizational structure is that testing
is performed by nurses or other non-laboratory staff, but
these are organized under a single POCT management.
●A third organizational model, more common in the past,
is for POCT in each clinical department or nursing unit to
operate as a separate laboratory. This does simplify the
management of each unit.
4. Laboratory Licensure and Accreditation - The initial
question to address is how many and what types of
licenses to apply for. It is possible to perform POCT under
the same license as the central laboratory. However,
many laboratory directors have been reluctant to cover
POCT under their licenses due to concerns about
compliance of POCT with laboratory standards and lack
of direct control over how testing is performed. Also,
including POCT under the main laboratory license means
that the same accreditation standards must be applied for
POCT and central laboratory testing.
B. Operational Challenges:
1. Determining the Scope of POCT Services - One of
the most critical operational challenges is deciding what
sites will perform POCT and what menu of tests should
be offered. A starting point for this analysis is to inventory
the types and testing volumes of ongoing POCT.
Obtaining an accurate inventory of POCT can be difficult
due to the dispersed nature of testing, the lack of
information systems, and in some cases, the lack of
recognition of what represents a laboratory test.
Commonly overlooked POCT activities might include
occult blood testing, urine dipstick testing, physician-
performed microscopy, and whole blood coagulation
testing.
2. Analyzing Costs and Benefits - Although it would
seem that the cost of a test would be an objective quantity
that could be calculated precisely, the absolute and
relative costs of POCT and central laboratory testing are
some of the most controversial issues relating to POCT.
It turns out to be difficult to account for labor for POCT,
which involves small bits of time by a large number of
staff.
3. Clinical Impact - An important part of deciding whether
a point-of-care test should be adopted is assessing its
potential clinical impact. The general assumption is that
faster results make for better patient care and better
outcomes. However, POCT does not always offer optimal
results if proper protocols are not followed, and QC is not
performed. Even if the testing is conducted properly,
performance may be inferior to that of more robust
laboratory-based methods.
4. Resource utilization - It is a key consideration when
implementing point-of-care testing. In some cases, POCT
can be used to more efficiently allocate valuable supplies
such as blood products. In one prospective, randomized
trial POCT was used in coagulopathic cardiac surgery
patients to manage hemostatic therapy. In this study
patients were randomly assigned to either conventional
testing or a POCT group. The study found that on average
THE POCT group required fewer blood products (five
units conventional versus three units).
C. Quality Assurance Challenges
1. Staff training and competency - One of the greatest
challenges and a key to making POCT work is training
and assurance of the competency of staff. Even if test
devices are operating perfectly, accurate test results will
not be produced if staff personnel are not educated about
appropriate specimen collection and operation of test
devices. Considering that training is one of the most
important functions of the coordinators of POCT, teaching
skill should be one of the prime factors in the selection of
testing coordinators. It can be difficult to schedule enough
training sessions to accommodate a large number of staff,
so it may be helpful to have self- instruction videos or web-
based instruction as additional options.
2. Quality assurance - This can be a very demanding
activity due to the large number of analyzers that need to
be tracked. Most POCT devices require limited
maintenance such as cleaning and battery replacement,
but if this is neglected, devices may fail. Portable devices
may be dropped or exposed to vibration, water, extremes
of heat or cold, or other environmental challenges that
may lead to equipment failure. In part, this is a training
issue, but even with appropriate maintenance and use,
periodic device failures are likely. Lack of experience of
the testing staff with troubleshooting equipment or
reagent problems requires on-call support by POCT
coordinators or other experts.
D. Technological Challenges
1. Rapid changes of menu, devices and technology. -
Historically, POCT was severely limited by the small menu
of tests that could be performed and by the relatively poor
analytical quality of tests. However, advances in
technology and successful miniaturization of devices
have made it technically feasible to perform virtually any
test as POCT. Ongoing advances in the microfabrication
of devices and in nanotechnology provide the promise of
substantial future technological change and further
reduction in the size of POCT devices. Miniaturization of
testing devices alone is not sufficient to make a test
suitable for POCT. It is also important to reduce analysis
times, to simplify the operation of test devices, and to
minimize requirements for specimen preparation. To be
suitable for POCT, a test usually must accept an
unprocessed sample such as whole blood, and the
analysis times must be less than about 15 minutes.
2. Lack of Equivalence between POCT and Central
Laboratory Tests - In many cases, the specimen type or
fundamental measuring principles of POCT devices differ
from those used in the central laboratory, and these can
be confusing to clinicians who are trying to interpret test
results. Thus, it is important to perform careful
comparisons of POCT and central laboratory results.
Differences in whole blood specimens used for POCT
versus serum or plasma samples used for central
laboratory testing can lead to systematic differences in
results for tests.
PRINCIPLES OF PREANALYTIC AND
POSTANALYTIC TEST MANAGEMENT
The primary function of a clinical laboratory is to provide
accurate, clinically relevant data for the diagnosis of
medical conditions in patients. Once available, the data
can be used to provide the individual patient a
management plan to increase the probability of achieving
a desirable outcome. The production of laboratory data is
a culmination of sequential processes constituted of
preanalytic, analytic, and postanalytic laboratory activities
that begin with a clinician’s request for specific studies on
an individual patient. The level of quality of service
provided by a laboratory can affect patient care outcomes
considerably, either positively or negatively. To achieve
optimal patient outcomes, it is imperative to evaluate the
effect of preanalytic and postanalytic activities on the
clinical significance and medical impact of laboratory
tests.
Pre-analytical Activities
The preanalytic phase refers to all steps taken before
actual testing is performed on a patient’s specimen. It
includes test selection, test ordering, patient/specimen
identification, specimen collection and transportation,
specimen processing and preparation, as well as
appropriate specimen storage prior to testing.
1. Test selection and Implementation
a. Test complexity - Waived tests are defined as
simple laboratory examinations and procedures that have
simple methodologies or pose no reasonable risk of harm
to the patient if performed incorrectly. Nonwaived tests
have more difficult methodologies and, with one
exception, more rigorous regulatory requirements. The
exception is the differing levels of training required for
personnel performing either moderate- or high-complexity
testing. When determining whether to add a specific test
to the menu, laboratories must decide into which of these
categories the test fits and whether or not the laboratory
meets the requirements to perform this level of testing.
b. Type of tests - Clinicians’ self-described
reasons for ordering tests are usually somewhat diverse,
in that tests are often ordered for establishing a baseline,
assessing prognosis, reassuring patients, and helping
with treatment decisions. Appropriateness of ordering and
effects of testing often go beyond diagnosis or immediate
treatment decisions in this setting. Thus, understanding
testing needs from the clinician’s point of view can help in
developing strategies to optimize patient care while at the
same time enhancing cost-effectiveness.
c. Test sensitivity, specificity and predictive
values - The sensitivity of a test is the percentage of
individuals who have the particular disease for which the
test is used and for whom positive test results are found.
Specificity shows the percentage of individuals who do
not have the particular disease being tested and for whom
negative test results are found. While sensitivity and
specificity do not change with various populations of
unwell or healthy people, predictive values can vary
considerably depending on the age, gender, or
geographic location of those tested. The positive
predictive value provides the probability that a positive
result indicates the presence of disease. Conversely, the
negative predictive value provides the probability that a
negative result indicates the absence of disease.
d. Available technology - Advancements in
science and technology have allowed and will continue to
allow laboratories the opportunity to increase and
enhance test menus to aid clinicians in their endeavors to
monitor and provide medical services to patients.
e. Cost studies - Cost-benefit analysis is a very
important step in the assessment for test implementation.
Several methods are available to assist with the cost
accounting process. Procedural analysis can also be
implemented using published CLSI guidelines. These
guidelines include methods for analysis that can justify the
addition of new procedures, assist in determining the
frequency of test runs, and supply information regarding
the performance of laboratory personnel or
instrumentation.
2. Appropriate Test Utilization
a. Test evaluation - It may appear difficult to
determine which tests should be evaluated. There are
many examples of tests for which monitoring of testing
practices is mandatory to determine appropriateness.
These examples may include, but are not limited to,
repetitive testing on the same specimen sites within short
time periods (e.g., 24 hours), excessive numbers of
cultures (e.g., more than two to four blood cultures per
episode, daily sputum cultures), cultures of superficial
sites (e.g., pressure ulcers), and cultures of inappropriate
specimens (nasal swabs for etiologies of pneumonia).
b. Utilization and appropriateness - Utilization
and appropriateness issues are related. While utilization
may have more to do with frequency of testing,
appropriateness is concerned with the use of tests for the
right patient in the correct setting for the proper monitoring
and for diagnostic or therapeutic reasons. Improving
utilization has the ability to reduce laboratory costs while
precluding several unpleasant alternatives such as
rationing laboratory tests or eliminating some altogether
c. Importance of communication - Consensus
between medical staff and laboratorians can help effect
positive change. This examination can lead to the
establishment of customized groupings of laboratory tests
for various specialties, which can provide quality results
for the lowest cost (e.g., hepatitis serology panel for acute
hepatitis and Epstein-Barr virus serology panel for acute
mononucleosis). Outdated tests may be eliminated, and
sequential protocol testing may be developed in line with
diagnostic algorithms.
3. Specimen Acquisition, Transport and Storage
a. Requisition information - One of the
laboratory’s primary responsibilities is to ensure that
adequate information is provided to the clinician-client to
make appropriate choices in specimen collection and test
ordering. The laboratory must establish and follow written
policies and procedures characterizing and describing
each of the following, when applicable:
• Patient preparation
• Specimen collection (routine vs. STAT)
• Specimen labeling, including patient name or unique
patient identifier and, when appropriate, specimen source
(some cases require more information; can be modified
as required)
• Specimen storage and preservation
• Conditions for specimen transportation
Specimen processing
• Specimen acceptability and rejection
• Specimen referral
• Specimen reporting timelines
4. Test Ordering
a. Electronic test request - Electronic requests
are frequently utilized in hospital settings where the
laboratory information system (LIS) is connected with
either handheld devices or stationary terminals that the
medical staff may use to order tests. Electronic test
ordering systems are becoming more common, even in
off-site locations and clinics, and in many instances can
be designed to help guide physician test order choices.
b. Test requisition - Typically, a written or
electronic requisition consists of a demographics section
and a test selection section. If the laboratory transcribes
or enters test requisition or authorization information into
a record system or a laboratory information system, the
laboratory must ensure that the information is transcribed
or entered accurately.
Post-analytical Activities
The post-analytic phase refers to all steps taken after
actual testing is performed on a patient’s specimen. It
includes the reporting of test results, report review, result
archiving, and specimen storage, as well as assessment
of all post-analytic activities.
1. The Report
a. Report turnaround time - It is the laboratory’s
responsibility not only to make available the TAT
information for all tests, but to periodically monitor TAT to
determine that reports are being sent without excessive
delay and that there are no problems in the process.
When excessive TAT is confirmed, corrective action (CA)
must be initiated, and all steps in the CA process must be
documented. If any delay occurs beyond the expected
TAT for any test, the laboratory must have a process in
place to notify the clinician of the status of the specimen.
b. Types of reports - The main means used for
reporting laboratory results are Electronic Medical Record
(EMR), Web-based reports, and standard paper reports.
Although somewhat infrequently used now, paper reports
will likely survive for a period of time as backup systems
in the event of electric or computer down- time. With the
EMR, laboratory data are transmitted to a hospital
information system (HIS) and are integrated with patient
demographic information, providing integrated reports for
in-house patients. When available, Web-based reports
have the advantage of multiple access points, and
clinicians can access them from any Internet connection.
c. Result format - The standard test report must
include the name and address of the laboratory at which
the test was performed, the test that was performed, the
test results (including the unit of measurement, if
applicable), any information regarding the condition and
disposition of specimens that do not meet the laboratory’s
criteria for acceptability, as well as the laboratory’s
reference or normal ranges for specific tests, if
applicable. The reports should be easy to read,
unambiguous, readily interpretable, and use standard
terminologies.
Storage and Retention
Regulatory constraints require that the laboratory have
processes and procedures for the retention and storage
of specimens and records. Storage regulations may differ
between various agencies.
1. Specimens - A procedure should be in place for their
retention based on the most stringent regulatory
requirements for the individual laboratory.
CAP - College of American Pathologists
CLIA - Clinical Laboratory Improvement Amendments
TJC -The Joint Commission Laboratory Accreditation
2. Records - Typically test requisitions and reports must
be stored in a retrievable fashion for a minimum of two
years. Some records, especially in areas of
immunohematology (5 years), histocompatibility (5
years), histology (10 years), cytology (10 years), bone
marrow (10 years), and cytogenetics (25 years), may
require longer retention periods.
SELECTION AND IMPLEMENTATION OF NEW
EQUIPMENT AND PROCEDURES
Introduction
The selection of new laboratory equipment or procedures
is complex and time-consuming. Faced with changing
clinical needs and limited financial resources,
laboratorians must make difficult choices about which
new equipment, technology, procedures and assays, or
combinations of these to acquire and implement and how
to incorporate them into their diagnostic laboratories. The
choice of which to buy may be further confused by
conflicting advice and persuasive salesmanship, as well
as the rapidly changing policy environment. The selection
process calls for a clear understanding of the principal
need for the acquisition of the new equipment, and the
selection process must be carried out in an objective
manner, taking into account the practicality, reliability, and
fitness for purpose with input from potential end users,
clinicians, and management teams.
A. Technical/ Performance Consideration
1. Specimen type - This factor is critical in terms of the
flexibility of various platforms or assays; a platform with
limited specimen flexibility will have limited flexibility in
routine laboratory operations.
2. Specimen volume - What are the minimum and
maximum volumes required to run the assay? This
volume should include the dead volume and can be an
issue particularly for pediatric specimens and short
collections. The sample volume requirement can also be
an issue for shared specimens or limited-volume
specimens such as CSF and pleural fluid.
3. Test menu - This is an important consideration given
the decreasing budgets of many modern laboratories; by
offering multiple assays on one platform the laboratory
can often increase efficiency and decrease reagent cost
due to volume- based purchasing of reagents.
4. Turnaround time/batch size - What is the total
elapsed time from sample loading to reporting results?
Are STAT results needed for some or all of the tests
offered on the platform? Are specimens tested in a batch
capacity, and if so, what are the batch sizes? Does the
platform offer truly random-access testing or partially
random-access testing? Some platforms claim a “random
access” feature, but there may be limitations such as the
inability to interrupt a batch run to perform a different test
type or run a different sample type. Are the results
continuously reported, or are results reported in a “batch”
format?
5. Operational throughput - What is the maximum
capacity of testing offered per shift or per day? The
throughput incorporates multiple variables including the
number of samples that can be loaded onto the platform
at one time and the total “onboard time” for any given
sample. Other variables that can influence throughput
include the “hands-on time” for sample preparation and
the time required to load the samples onto the platform.
6. Open or closed platform - Does your laboratory have
any plans for internal assay development? Some
platforms allow for laboratory test development, while
others only allow vendor-specific assays and reagents.
7. Available interface - The ability to directly transfer
results from the testing platform to the LIS and to avoid
manual data entry is a critical factor in terms of improving
patient safety through accurate result reporting.
8. Assay performance- These factors represent
objective measures of an instrument or assay, such as
precision, accuracy, linearity, sensitivity, and specificity.
During the evaluation period the laboratory must verify the
performance of these objective measures through the
validation process.
9. Regulatory clearance/ approval - Equipments must
have clearance or approval to accredited agencies or
institutions that indicates the performance characteristic.
10. Control availability - Many vendors sell controls,
and thus availability is not an issue; however, this is an
important factor to consider because for certain assays
controls are not available commercially, and thus issues
such as consistency and reliability can become limitations
to assay performance.
B. Physical/ Technology Requirements
1. Space requirement- What are the physical
specifications of the equipment, including size and
weight, and how will the instrument fit in the laboratory
and within any existing workstations if applicable?
Additionally, it is important to consider not just the
physical footprint of the instrument but also the space
needed for proper ventilation and access required for
routine maintenance and servicing of the instrument.
2. Power - Will the existing power supply in the laboratory
be sufficient to support the operation of the equipment?
Will additional dedicated or backup power be required?
Alterations to existing electrical supply can significantly
increase the overall cost of implementation.
3. Data - If the instrument will require a connection to the
Internet for cloud-based services or be interfaced with
other equipment or the laboratory information system, the
data line requirements must be carefully evaluated.
4. Plumbing/water - Some instruments require high-
quality water supplies or direct access to plumbing to
remove waste.
5. Temperature/ Humidity - Most equipment requires
specific environmental controls to operate optimally.
Consider not just the existing environmental conditions
but also the impact the addition of the new equipment will
have through heat production, etc. Ventilation and air
conditioning are critical factors for optimal instrument
performance.
C. Human Resources
1. Staffing - Depending on the assay or instrument in
question, staffing requirements could go up or down. With
automation or platforms that require less hands-on time,
the new instrumentation could free up existing staff to
perform different laboratory tasks.
2. Workflow - Can the equipment or assay be run during
all shifts? What is the required hands-on time? How will
the addition of the new assay or platform impact existing
work practices? All aspects of testing need to be included
in the evaluation, not only direct testing but sample
preparation time, quality control practices, and
maintenance.
3. Ease of use - Do the technologists who will use the
instrument find it “user friendly”?
4. Training requirement - What types of training are
required prior to implementation, and are training
programs offered by the vendor? Is there an additional
cost associated with the required training?
D. Financing
1. Instrument cost - In addition to the actual cost of the
equipment, what are the available options for purchasing
or financing? Are there options for lease or reagent rental
agreements?
2. Cost of operation - What are the direct and indirect
costs over the lifetime of the instrument?
3. Cost per result - This number involves a variety of
factors including the cost of reagents, disposables,
calibrators, controls, labor, maintenance, repeats, etc.
Additionally, it is important to have a good idea of the
volume of samples you will be running, as the cost of
reagents is typically impacted by the volume of reagent
purchased from the vendor.
4. Warranty - Many instruments have a limited warranty.
5. Maintenance contract - The details of the annual
maintenance contract should be discussed up front, as
they can vary widely and significantly impact the cost to
operate the equipment. Details should include what is
covered by the annual contract as well as the cost of
additional requirements such as after-hours or holiday
repair calls and parts that need to be replaced on
maintenance schedules (e.g., bulbs, probes, etc.).
6. Consumable costs - What are the estimated reagent,
calibrator, and control costs given the laboratory’s
estimated test volume? Important factors to consider in
this analysis include the size of the reagent kits and their
shelf life once opened. If a vendor sells only large kits and
the shelf life of reagents is short, a laboratory may end up
paying for wasted reagents, increasing the cost
unnecessarily.
7. Software requirements - Are there up-front costs
associated with software purchases, and will there be
costs associated with software upgrades? Is there a cost
associated with the implementation of an LIS interface?
Who will actually be handling the upgrades, interface, etc.
(company or laboratory personnel)?
Confidentiality and Conflict of interest
Throughout the entire process of selection and decision
making, it is critical that all those involved in the process
remain independent, free of obligation or suspicion, and
completely fair and impartial. Maintaining the integrity,
credibility, and confidentiality of selection and acquisition
of equipment requires a clear set of guidelines, rules, and
responsibilities to govern the behavior of the decision
makers. Those involved in the selection process are not
permitted to communicate about or discuss the
procurement or evaluation process with any other
employee who is not involved in this process.
Furthermore, the employees and team members shall not
disclose the scoring outcomes or content of the
proposals.
Implementation and Product Placement
The implementation of a new procedure or instrument
requires coordination between the placement site and the
vendor. Typically, the vendor requires the placement site
to fill out questionnaires regarding the physical
characteristics of the space, and then the vendor will
inspect the site to clarify what, if any, physical changes
might be required prior to placement. The timing of the
purchase can be significantly impacted by any required
changes to the space such as electric, plumbing, data,
etc. If the purchase of an instrument is delayed, this can
impact the original quoted price, so laboratories need to
be diligent about planning and coordinating the entire
process.

CHARGES AND FEES FOR LABORATORY SERVICES
Introduction
The ultimate goal in the provision of laboratory services is
to make certain that information is delivered to ordering
healthcare providers in a timely manner that ensures that
quality is maintained, costs are minimized, and clinical
relevance is established. At the same time, it is paramount
to make sure that the laboratory does not lose money in
doing so. To make money in the laboratory business, it is
critical that one establish charges that at least cover total
costs and control expenditures such that low-paying fee
schedules do not put the laboratory at risk for significant
loss.
Setting Cost
The responsibility for cost analysis of individual laboratory
procedures rests primarily with the laboratorian. In
general, an “orderable and reportable test” will map to a
specific Current Procedural Terminology (CPT) code or
codes, as well as to the institutional charge code for
accounting purposes. The cost per reportable test is a
composite of all related costs. These include the obvious
costs such as average direct costs (e.g., reagents,
equipment), including labor, and indirect costs, including
overhead and support services (e.g., housekeeping,
couriers, billing, customer service, marketing), but they
also include hidden costs such as quality control,
calibration, repeats, dilutions, and wastage. The cost per
reportable test is considered to be a parameter that allows
“apples to apples” comparisons between methods
(interassay) and between laboratories (intra-assay).
In addition, the cost per reportable test is a useful tool for
setting charges such that the laboratory maintains an
appropriate profit margin. The break-even point is the
point at which net income equals total costs. Net income
takes into account actual payment for services and
deducts actual costs as well as “bad debt,” that is, the
amount that is not reimbursed by any potential payor.
Obviously, the goal is to do better than break even since
profits are essential to support business development. To
be profitable, one must have a clear understanding of both
total costs per reportable test as well as expected net
income.
Setting Charges
One must consider the actual total costs and the expected
reimbursement, so that one can exceed the break-even
point. In general, it is never good business to price any
service below cost, and in fact, this practice could be
viewed as an inducement for ordering providers to submit
federally reimbursed testing to a particular laboratory. On
the other hand, one
cannot charge federal payors “substantially in excess of
usual charges,” potentially leading to a conclusion that
these payors are being overcharged. At the same time,
one must review the market situation and ensure that
charges are comparable to those of competitors unless
the service offered has a quantifiable value- added
component. In some market settings, laboratories may
identify tests that are high volume and offer them at a
charge below cost (termed a “loss leader”). At the same
time, more esoteric, high-cost procedures with lower
utilization may be offered with a substantial profit margin
to make up the difference (termed “pull-through”). In
addition, the billing simplicity of a contractual arrangement
in which clients or patients are billed directly is considered
a justification for offering deep discounts since billing
costs are substantially lower and the percentage of
services paid for is significantly higher.
Determining Payment Amounts
The amount of payment made for laboratory services may
be based on one of two general categories. A fee
schedule represents one category, although payment
amounts typically vary based on payor. Actual provider
charges may apply to some payors, while payor-defined
fee schedules may be the basis for others. In capitated
payment agreements, the payment takes the form of a
negotiated agreement for a specified level or category of
service, often based on diagnosis or clinical condition.
1. Fee schedules - Counter to attempts to develop
rational charges based on real costs and net income is
the concept of payor-established fee schedules. Many
payors will arbitrarily establish a fee schedule for defined
services, and it is the laboratory’s responsibility to
determine whether to do business with that particular
payor. Fee schedules are generally loosely based on
charges although usually set at a percentage substantially
lower than actual charges.
2. Capitated Payments - Capitated contracts for
laboratory services are somewhat uncommon in
outpatient arenas, but they may play a major role in the
provision of laboratory services in extremely cost-
constrained markets. In health maintenance
organizations (HMOs), laboratories may also be asked to
develop a capitated payment scheme. In laboratories, a
common payment mechanism is a per-member-per-
month basis for provision of the most common laboratory
services, with a separate fee schedule often appended for
high-cost, esoteric services carved out of the capitated
contract. Inpatient service reimbursement may also be
considered a type of capitated payment. Medicare and
most other payors generally reimburse for inpatient stays
as a specified amount based on either a diagnosis-related
group or a per diem amount.
Keys to Success in Reimbursement
Regardless of the type of payment situation, there are a
few key actions that can help guarantee that a laboratory
will be able to attain a reasonable profit or, at the least,
avoid any significant losses in fulfilling its mission to
provide high-quality, clinically relevant information at a
reasonable cost. Integral to this process is a firm
understanding of costs for procedures as well as correct
coding for procedures performed and complete
knowledge of all billing rules promulgated by a given
payor.
Retrospective Payment
The primary key to success in a retrospective (fee-for-
service) payment situation is to obtain payment for all
services that a physician orders and that you perform and
for which you report the result. Therefore, you should
code correctly and completely for all that you do and bill
for all that you code for. In any situation in which more
than one code applies, or if a procedure is added on by
request or as a reflex, the associated codes should be
added to the bill.
Prospective Payment
The primary key to success with prospective (capitated)
payment is also correct and complete coding. To
determine if a proposed payment amount is acceptable,
you must know (or project) the utilization rates for
services, including rates of use of add-on and reflex tests.
If certain esoteric tests are extremely high cost, you may
wish to carve out those services and amend the
agreement with a separate fee schedule for specific
services. As for retrospective payment situations, if the
proposed terms of the agreement are not financially
favorable, you can decline to provide service.
CURRENT TRENDS IN LABORATORY MANAGEMENT
Advances in Technology
Technological advances created revolutionary changes
in the way medicine and laboratory medicine are
practiced. The application of molecular biology, using
analysis of nucleic acids and proteins to diagnose
disease, assess prognosis, and tailor therapy, has had a
profound impact on the laboratory, as well as patient care,
globally. For example, using nucleic acid testing (NAT)
for the detection of transmissible pathogens allows earlier
diagnosis and treatment. The use of molecular
diagnostics to not only enhance diagnosis, but guide
treatment, has exploded. For example, in the field of
pharmacogenomics, testing can be used before instituting
therapy to determine if a certain medication will be
effective. Along with this cutting-edge technology comes
the need to understand the costs and unique logistics
associated with the rapidly changing landscape
of laboratory testing. Cellular-based therapies, from the
use of human stem cells to adipose tissue, are making
their way into the marketplace and are the basis of a new
industry that impacts laboratory practice. Quality and
regulatory agencies are looking for ways to ensure a safe
efficacious product.
The Electronic Medical Record
The motivation to use computerized information
systems in healthcare is driven by expectations that such
systems will improve the quality of care, increase patient
safety, and lower medical costs. Yet there are many other
factors to consider about the use of an electronic medical
record (EMR). The EMR can undoubtedly improve the
legibility of entries and can positively influence the
organization of the information in the record, making
retrieval of data more efficient. However, the EMR has
been blamed for interfering with the patient-physician
relationship. Patients report feeling like doctors are
so busy entering information into the computer that they
hardly have time to discuss the patients’ concerns and
plan of care. Many physicians do not possess the
computer skills to become proficient at data entry and
retrieval in the EMR. This maybe a cause of errors such
as documenting on the incorrect patient or choosing an
incorrect drug from a drop-down list. EMR software
developers continue to look for ways to reduce these
common human errors through the use of templates and
alerts to providers. Through improved functionality and Microelectronics, microfabrication, and micro
interoperability, the sharing of information to all providers computerization have revolutionized the way that
of care for the patient will be improved, thereby facilitating laboratory tests are performed. These technologies allow
patient care and safety. test results to be obtained in a matter of minutes or even
seconds. POCT, or near-patient testing, has long been
he electronic medical record versus the paper record touted as the technology that would change patient
Electronic record Paper record management in the world of managed care. The most
Improved legibility Often not readable obvious benefit of POCT is decreased turnaround
time (TAT). The premise that near-patient testing would
Patients feel the provider is Patient and provider can
radically change patient management under managed
ignoring them relate can discuss the plan of
care has not been substantiated. Bickford’s research
care
concluded that POCT had no significant impact on
Easier to locate information- Difficult to locate information hospital length of stay. Receiving rapid results
not reliant on memory reflects patient status at a given time and improves
Maybe slow providers may Faster especially for pharmacological management. However, for physicians
have a slow learning curve physicians not raised in to act, they must still wait for a complete manifest of
technology era results. As new technologies for POCT evolve, laboratory
Allows easy synthesis of Information is often disparate medicine professionals will continue to question the
information and difficult to locate accuracy and reliability of the instruments and the
Allows for easier, faster Paper must be results.
information sharing copied and mailed or faxed
Difficult for others to follow Easier for others to read and Advances in Genetic Testing and Molecular
follow Pathology

The Human Genome Project

Advances in Diagnostic Testing Over the past 15 years, the Human Genome Project
New disease patterns, changing demographics, the aging (HGP), a joint program funded by the Department of
population, emerging diseases, and the threat of terrorism Energy (DOE) and the National Institutes of Health (NIH),
require innovative testing methods. Nucleic acid testing, has completed the sequencing of the total human
for example, has truly revolutionized the way medicine is genome. This project yielded genetic maps and new
practiced. Instead of waiting days or weeks to detect techniques to further genetic research and clinical testing.
certain viruses in culture, amplifying small amounts of The HGP’s significance is vast and has far-reaching
genetic material in a specimen makes it possible to detect implications:
a pathogen within hours. Looking at changes in the
genetic material of a tumor may improve the diagnosis of Pharmacogenetics Designing drugs specifically
certain malignancies. There is also hope that identifying modified to a person’s genetic make-up will be important
disease that is not yet macroscopically evident at the in the treatment of many genetic diseases.
genetic level will lead to earlier treatment. Nucleic acid
amplification testing has been introduced into blood donor Agricultural genetics Engineering genetically
screening over the last decade. The use of NAT has modified foods to be larger, more nutritious, and pest-
increased the sensitivity of pathogen detection and allows free.
for the earlier detection of transfusion-transmitted
pathogens than standard serologic tests allow. Forensic genetics DNA-based human identity
testing can be used to convict or acquit an individual
Due to changes and reductions in the laboratory work accused of a crime.
force, trying to do more with less is a dominant theme
in laboratory medicine. Automation will continue to Evolutional and anthropological
reduce personnel and laboratory costs. The use genetics Genetics is a major source of information about
of robotics can reduce the number of tasks that are the similarities and differences between humans and
currently done manually and thereby reduce the impact of other species.
human error. Track systems can help automate the
process of testing a single sample for multiple analytes, Microarray technology Research during the HGP has
thereby improving efficiency, and reducing personnel produced one technology, the microarray, with the
needs. By using a system of barcodes that identify greatest potential for disease detection
patients and samples throughout the process, the risk of and characterization.
misidentified patient samples has been reduced and may
become a thing of the past. This form of process control Emerging technological advances in clinical and
may have the ability to greatly reduce medical anatomic pathology
errors. Robotics is used for the delivery of supplies, A key component in the practice of anatomic and clinical
samples, and blood products in some hospitals. pathology in the future will be molecular
pathology. Practice protocols may rely on molecular
Point-of-care testing (POCT) testing for diagnosis of disease as well as the prognosis
and treatment in the laboratory disciplines such as Laboratory Paradigms
hematology, microbiology, histocompatibility, Before describing specific consultative roles, it is useful
cytogenetics, and surgical pathology. to discuss the new interactive laboratory and compare it
to the old, or traditional, laboratory.
Applications of genetic and molecular pathology
Use of molecular diagnostics and genetic testing is The Old Laboratory
increasing from 6 to 25% annually (57). These two fields Today, many clinical laboratories still operate
generate unique problems for the laboratory information according to the traditional laboratory model, which is
system (LIS). The IT needs include special nomenclature, a linear, unidirectional flow process of one activity
the ability to import/export images, and a database to preceding the next activity. The major concern in this
search karyotypes and to perform sequencing and model is the quality of the test performance and the
fragment analysis and place pressure on LIS systems to production features and internal organization of the
adapt. Common techniques used in molecular diagnostic laboratory (analytical phase). In the traditional model, the
testing include laser capture microdissection, DNA focus is on the science and technology and quality of test
sequencing, PCR, fluorescent in situ hybridization, micro- performance, and communication is almost nonexistent
and macro-array technology, and proteomics with mass prior to the test request or after the result is released. In
spectrometry. this model, the clinical laboratory is not concerned with
clinical appropriateness or interpretation of test results.
A New Workforce
The emergence of clinical scientists as consultants
represents a natural evolutionary growth in the role of the
clinical laboratory profession as it adapts to a changing
environment. This emerging role is being fostered not only
by the need to improve laboratory test utilization but also
by the extraordinary growth of decentralized testing. In
addition, the vast growth of molecular testing, not only for
familiar analytes or organisms, but for specific new and
esoteric disease markers, has created a need to improve
communications between clinical scientists and
healthcare providers. The increasing complexity of the The New Laboratory
clinical laboratory sciences is causing many physicians to The new laboratory model is an interactive process, and
seek information and to use interpretive guidelines, such the scope of laboratory services is broader. In this model,
as disease-specific care maps, necessary to make the focus is not only on the quality of test data generated
optimal and cost-effective use of the laboratory. These (process/analytical) but also on the clinical
guidelines were first evidenced following the diagnosis- appropriateness of test requests (input/pre analytical) and
related group initiatives as a means to reduce costs and the correct interpretation of and response to laboratory
provide more consistent patient care. information (output/postanalytical). The involvement of
the laboratory in the entire total testing process will have
It is important to recognize that clinical scientist a positive impact on patient outcomes, improve the
knowledge workers do both knowledge work and “manual clinical relevance and value of the laboratory’s service,
work”. Performance of a laboratory procedure constitutes and greatly enhance the cost-effectiveness of
manual work. Knowledge work related to the laboratory the laboratory operation.
procedure begins with data analysis and the use of
personal intellectual capital (experience). Knowledge
work also includes consultation with other clinical service
providers (pooled intellectual capital) and electronically
available intellectual capital. This new workforce of clinical
scientist knowledge workers has some unique
characteristics, which managers will need to recognize
and support.
- Knowledge workers are specialized
- They are able to acquire and supply theoretical
and analytical knowledge
- They are learning-based, prepared
CLINICAL AND EVIDENCE-BASED RESEARCH IN
through formal education
THE CLINICAL LABORATORY
- They exhibit the habit of lifelong learning
- They are effective in teams Introduction
- They seek meaning in their work
and advancement opportunities Laboratory interventions are becoming more data drive,
- They reach decisions by consensus, not outcome oriented and evidence based. As such,
command laboratory professionals need more background in
experimental study design and biostatistical methods, so
that laboratory data can be used to generate outcomes
data from quality improvement (QI) activities and
comparative analytics of new testing methods. In vitro
diagnostic clinical research studies that utilize human
tissues or fluids, which cannot be linked long-term to a
living individual, are common in many clinical laboratories
that perform research. This type of clinical research differs
from what is defined as patient-oriented research (POR),
which is commonly interventional, may occur in
collaboration with clinical laboratories, and is defined as
“research conducted with human subjects” (or on material
of human origin such as tissues, specimens, and
cognitive phenomena) for which an investigator (or
colleague) directly interacts with human subjects,
consented for the purpose of the study.
Types of Studies
1. Observational studies are those involving humans
(cohort or epidemiological studies) but not specifically
categorized as POR; rather, they involve recruitment of
patients (human subjects) and are often critical to
hypothesis generation and for subsequent interventional
studies. Observations generally relate to a public health
concern or biological principle. Observational studies are
primarily descriptive in nature and often lead to the
determination of data associations.
2. Mechanistic studies are useful to determine causality.
Such studies are hypothesis driven, and formulation of the
hypothesis is the critical element for the success of the
study. These studies are commonly smaller than
observational studies and are designed to determine
disease physiology or mechanism. They define detailed
endpoints which are assessed in response to a relevant
intervention or a disruption of biological function.
3. Therapeutic studies determine the efficacy of a
medicine or a treatment which is designed to improve a
condition or disease. These studies are often smaller,
more preliminary, and less generalizable than clinical
trials, but involve some of the same design issues.
4. Large-scale clinical trials - Randomized clinical trials
may take a long time to complete and are costly but are
necessary to definitively prove new treatment strategies,
to define new interventional approaches, and to confirm
the proof for existing approaches in clinical medicine.
Most large-scale clinical trials are randomized, and
placebo controlled to minimize confounding. Clinical trials
are always hypothesis driven and need to be adequately
powered, i.e., large enough to ensure that a negative
result is not the result of insufficient samples or patients,
but rather is the result of a true biological result or
diagnostic condition.
5. Meta analysis - is the process by which the results of
multiple individual studies are statistically combined. A
meta-analysis is the formal evaluation of the evidence
from two or more trials focused on answering the same
question. Meta-analysis commonly involves the statistical
combination of summary statistics from the various
studies, but the term is sometimes also used to refer to
the combination of their raw data.
Translational Research
Translational research can be described as the
transitioning of basic research practices and findings to
day-to-day use in a clinical setting, such as the clinical
laboratory. Although the phrase “bench to bedside” is a
colloquial description of this process, translational
research is not unidirectional. Once a biological premise
or tool is adapted to a medical setting, clinical data derived
from patients may inform both patient-oriented and basic
investigation. A second, important translational step is the
translation of research findings from POR and clinical
trials into daily clinical practice. Thus, POR plays an
important role in the translation of basic research findings
and clinical trial data to improve medical practice and
patient care.
The sequence of POR involves observation, generation of
a testable hypothesis, the design of a study that will test
this hypothesis, the performance of the study (hypothesis
testing), the collection of data from the study, data
analysis, interpretation of the data, and formulation of
conclusions.
Biostatistics
Descriptive statistics
Critical biostatistical analysis and assessment are critical
for interpretation of literature, for mindful participation in
clinical trials, translational research, or basic research, for
publication of your data, for intelligent conversation with
your statistician, and for documentation of evidence-
based improvements due to laboratory interventions. The
following test attributes are often described using
descriptive statistics with confidence intervals; however,
comparative statistics can also be used and are often
warranted:
• Accuracy
• Precision
• Analytical sensitivity
• Analytical specificity
• Analytical measurement range (limit of quantitation,
linearity)
• Reportable range
• Normal values
Inferential statistics: General Issues for Medical
Devices
Statistical issues in medical device studies include almost
all those confronted by clinical trials for pharmaceuticals.
Examples of statistical challenges posed by medical
devices include considerations of sample size and power,
handling of missing data, survival analysis, analysis of
quality-of-life variables, interim analysis, adjustments for
multiplicity of primary and/or secondary endpoints or of
hypotheses, sample size re-estimation, and meta-
analysis.

Evidence-Based Laboratory Medicine

Clinical laboratory scientists have been leaders in quality

assurance practice for decades but have not always
placed their results in the peer-reviewed literature. The
laboratory intervention approach to research aligns with
evidence-based medicine (EBM), a practice that refers to
the application of existing data to answer questions and
solve problems through systematic synthesis and
appraisal of data.

In the EBM process, standardized data acquisition and

analysis are used so that the data derived from the
process will add to the evidence-based body of
knowledge. The underlying premise of an evidence-based
approach is that healthcare decisions are guided by the
synthesis and appraisal of evidence from well-designed
studies, balanced with clinical expertise and individual
patient preferences. Challenges to practicing EBM in
clinical laboratories include the lack of research time
allocated to the clinical laboratory; lack of experimental
design and advanced biostatistical training in medical
laboratory science programs and fellowships; lack of
institutional support for mentoring and implementing an
evidence-based approach; and the lack of evidence from
well-designed diagnostic studies.