Questions

B. It helps laboratories develop programs that promote highly ethical and lawful conduct, especially in terms of billing.

C. It prevents physicians from referring Medicare patients to self-owned laboratories.

D. It establishes that all clinical laboratories must be certified by the federal government with programs to ensure quality, appropriate personnel training, and regular proficiency assessment.

E. It directs how health care information is managed.

2. Which one of the following statements describes an Advance Beneficiary Notice of Noncoverage?

B. A legal notice provided to all Medicaid participants.

C. A legal notice provided to all uninsured patients receiving outpatient chemotherapy.

D. A legal notice provided to Medicare fee-for-service participants delineating services expected to not be covered under their Medicare insurance plan.

E. A legal notice to all insured patients delineating services routinely not covered by major insurance carriers.

3. Which one of the following is a mission of the Agency for Healthcare Research and Quality (AHRQ)?

B. To direct the Department of Health and Human Services (DHHS).

C. To oversee the National Institutes of Health (NIH) research programs.

D. To be the largest source of funding for biomedical research.

E. To provide health care to the elderly and indigent.

4. In method validation studies, Clinical Laboratory Improvement Amendments (CLIA) regulations state that a laboratory must test for analytical specificity. Which one of the following sets of experiments would satisfy this requirement?

B. Running samples without the analyte of interest (i.e., Matrix blanks), ensuring that a zero sample actually reads zero.

C. Running both positive and negative samples and determining the specificity by taking true negatives and dividing by true negatives plus false positives.

D. Running samples spiked with increasing concentrations of an analyte and determining the concentration of the analyte that most specifically discriminates diseased from healthy patients.

E. Running samples spiked with the highest measurable concentration of the analyte of interest followed by a Matrix blank.

5. Which one of the following provides the best definition for analytical sensitivity?

B. The value obtained when the number of true positives is divided by the sum of the true positives and the false negatives.

C. The lowest possible concentration of an analyte that is accurately and reproducibly measured by an assay.

D. The performance of the assay when measuring an analyte in the presence of an interfering substance.

E. The formula that relates instrument response to analyte concentration.

6. The Centers for Disease Control and Prevention (CDC) classifies laboratories by biosafety level. Which one of the following represents the best example of a level 3 laboratory?

B. A clinical chemistry laboratory.

C. A clinical hematology laboratory.

D. A laboratory working with highly infectious fungal pathogens.

E. A satellite clinical laboratory in an emergency department.

7. Which one of the following is the best definition of “calibration verification”?

B. The process of testing known concentrations of an analyte throughout the reportable range and confirming that the assay returns the appropriate value, within an established allowable error.

C. The process of comparing the slope and y-intercept of the current calibration curve with the previous curves.

D. The process of running previously assayed patient samples with a new lot of calibration material and comparing them with results obtained when the same samples were run using a previous lot of calibration material.

E. The process of running samples of known high and low analyte concentrations and plotting them on a Levey-Jennings chart.

8. You are the director of a large hospital laboratory that is accredited by the College of American Pathologists (CAP). Which one of the following indicates how often your laboratory will be subject to a routine inspection by CAP?

B. Once every year.

C. Once every 2 years.

D. Once every 3 years.

E. Once every 5 years.

9. A new lot of reagent arrives in the laboratory and after several days of concurrent analysis with the old lot of reagent, a significant positive shift in the value of the high quality control (QC) material using the new reagent lot relative to the same QC material using the old reagent lot is noted. The section supervisor thinks this is a differential matrix interaction of the new lot with the high control and that it will not affect patient results. Which one of the following is the best piece of experimental evidence to support this hypothesis?

B. Random patient samples are run using the old and new reagent lots and then compared. The correlation coefficient should be close to 1.

C. Calibration standards dissolved in methanol are run across the full analytical range of the instrument using the old and new reagent lots and are then compared. The correlation coefficient should be close to 1.

D. The analyte should be extracted from each level of control material using a solid-phase extraction procedure and then run using the old and new reagent lots. The correlation coefficient should be close to 1.

E. The assay should be recalibrated; the control material should then be run and compared between both reagent lots.

10. Your laboratory currently runs a full menu of moderate-complexity testing and is accredited by CLIA under a certificate of accreditation. A treating physician asks you to add a test that the Food and Drug Administration (FDA) has classified as a “waived” test. Which one of the following statements is the appropriate course of action with regard to regulatory compliance?

B. You must apply for a CLIA certificate of registration.

C. You must apply for a CLIA certificate of compliance.

D. No additional certificates are necessary.

E. You cannot run a waived test in a laboratory that performs predominantly moderate-complexity testing.

11. Laboratory testing in the United States is regulated through the CLIA program. The program is overseen by which one of the following regulatory entities?

B. The AABB.

C. The CAP.

D. The Joint Commission.

E. The Centers for Medicare and Medicaid Services (CMS).

12. At a minimum, before introducing a new FDA-approved assay into the laboratory, which one of the following groups of performance characteristics must be assayed during a method validation and compared with manufacturer claims, to be compliant with CLIA ’88 regulations?

B. Accuracy, analytical sensitivity and specificity, reportable range, and a full reference range study with a minimum of 120 patient samples.

C. Accuracy, clinical sensitivity and specificity, analytical specificity and sensitivity, full reference range study, and reportable range.

D. Extraction efficiency, reportable range, full reference range study, QC material stability, and analytical sensitivity and specificity.

E. Only accuracy and precision must be confirmed.

13. According to CLIA regulations, which one of the following best indicates how often laboratories must perform QC evaluation (i.e., assay QC samples) for most assays that are performed 24 hours a day?

B. Once every 24 hours.

C. Every time the assay is performed.

D. Once every 48 hours.

E. Once every week.

14. You are the director of a newly established laboratory that will perform a mix of waived and nonwaived, moderate-complexity testing. Which one of the following best describes when you can begin testing?

B. After you are inspected by your state Department of Health and have received your certificate of compliance.

C. After you have been inspected by an approved accreditation agency and have received your certificate of accreditation.

D. After your state Department of Health, or an approved accreditation agency, and CMS have both inspected your laboratory.

E. Once you have validated your assays to your satisfaction.

15. A laboratory medical director is overseeing the implementation of a new hematology analyzer and is in the process of setting up delta checks for several complete blood cell count parameters. Which one of the following best describes a delta check?

B. It is a quality measure by which a patient’s previous result is compared with the current one.

C. It is a quality measure by which samples are visually checked for hemolysis.

D. It is a level of an analyte thought to be life-threatening to the patient, requiring verbal notification to the ordering provider.

E. It is a quality measure that occurs when results fall above the analytical limit of an assay.

16. Which one of the following statements best describes the benefit(s) that the Family and Medical Leave Act (FMLA) provides to eligible individuals?

B. The FMLA provides employees with up to 16 weeks of paid, job-protected leave for the birth or care of a newborn child.

C. The FMLA provides employees with up to 16 weeks of unpaid, job-protected leave for females and 12 weeks for males for the birth or care of a newborn child.

D. The FMLA provides employees with up to 12 weeks of unpaid, job-protected leave per year leave for qualifying reasons.

E. The FMLA provides employees with continuous health insurance coverage for up to 16 weeks.

17. In the United States, blood banks are regulated by which of the following entities?

B. The CAP.

C. The CMS.

D. The CDC.

E. The FDA.

18. Which one of the following statements best describes the role of the FDA in the regulation of laboratory-developed tests (LDTs)?

B. LDTs are considered medical devices, and each laboratory must receive FDA approval before implementing an LDT.

C. LDTs are considered medical devices, but the FDA has exercised enforcement discretion on LDTs.

D. LDTs are not considered medical devices, but the FDA regulates them.

E. LDTs may or may not be considered medical devices, and the FDA considers each assay on a case-by-case basis and decides whether to regulate.

19. During an interview with a potential laboratory technologist, which one of the following questions is appropriate to ask?

B. Were you born in the United States?

C. What is your native language?

D. How old are you?

E. Are you capable of performing all of the duties required by this position?

20. The International Organization for Standards (ISO) standard 15189:2007 deals with which one of the following?

B. Standards for pricing and reimbursement in medical laboratories.

C. Laboratory services that must be covered under universal health insurance plans.

D. Standard requirements for laboratory technologist school curricula.

E. Standard requirements for retirement benefit packages.

21. As the director of a laboratory performing high-complexity testing, you are required to ensure that your laboratory is appropriately staffed with all required levels of qualified personnel whose duties and qualifications are clearly defined by CLIA. The laboratory director can assume the responsibility of which one of the following required positions given appropriate training and background?

B. Clinical consultant.

C. General supervisor.

D. Testing personnel.

E. The laboratory director can assume any and all of these positions.

B. The assay is precise but not accurate.

C. The assay is neither precise nor accurate.

D. The assay is clinically useless.

E. The assay is precise and accurate.

B. Negative trending of QC results.

C. Result interference by an unknown substance.

D. The use of an inappropriately narrow reference range.

E. The need to change the technical range for the assay.

24. Which one of the following best describes how to plot a Levey-Jennings chart?

B. The x-axis as the “Gold standard method” and the y-axis as “Test method.”

C. The x-axis as “Calibrator level” and the y-axis as “% CV.”

D. The x-axis as “Run #” and the y-axis as “Concentration.”

E. The x-axis as “Instrument response” and the y-axis as “Expected concentration.”

25. In a method validation study, a sample at the proposed lower limit of quantification (LoQ) is run 20 times, 4 times daily for 5 days. Which one of the following answers best describes the performance parameters that can be determined from this experiment?

B. Validation of the LoQ, intraday and interday reproducibility, and accuracy at the LoQ.

C. Validation of the LoQ and establishment of accuracy at the LoQ.

D. Validation of the LoQ and establishment of the reportable range.

E. Establishment of reproducibility at the LoQ.

26. A laboratory director is designing a validation experiment for quantifying a drug metabolite in urine by gas chromatography–mass spectrometry. She asks her laboratory technologist to run a blank urine sample spiked with the lowest clinically relevant value of the metabolite 20 times and to average the signal/noise ratio of the analyte peak at this concentration. The laboratory director is trying to establish which one of the following analytical performance parameters?

B. Analytical sensitivity

C. Clinical specificity.

D. Clinical sensitivity.

E. The lower limit of linearity.

27. Which one of the following entities administers the Medicaid insurance program?

B. The FDA.

C. The American Medical Association.

D. Individual states.

E. Private insurance companies.

28. You are validating a high-complexity assay to measure analyte X. In a method comparison study, you choose 40 samples that span the analytical range of your method, analyze them by the new method, and compare your results with a reference, gold standard method at a reference laboratory. The resulting correlation analysis reveals a coefficient of determination (R²) of 0.99, an intercept of + 0.1, and a slope of 1.34 when the gold standard is plotted on the x-axis. Which one of the following statements best describes your assay?

B. Your assay correlates well with the reference method but has a positive proportional bias.

C. Your assay correlates well with the reference method but has a negative constant bias.

D. Your assay correlates well with the reference method. No other statements can be accurately made.

E. Your assay correlates poorly with the reference method and shows a positive proportional bias.

29. Which one of the following government agencies is responsible for developing standardized materials for calibration, weights, and measures?

B. The NIH.

C. The CMS.

D. The National Institute of Standards and Technology (NIST).

E. The DHHS.

30. Which one of the following statements best describes a requirement(s) expected of employers by the Occupational Health and Safety Administration (OSHA)?

B. Provide subsidized health insurance for all employees and offer at least two separate insurance plans.

C. Display an OSHA poster in the workplace informing employees about the Occupational Safety and Health Act.

D. Require that all employees receive an annual physical health exam with urine drug screening.

E. Receive state OSHA agency approval before increasing the number of employees.

31. Which one of the following is the best example of a postanalytical error?

B. The sample is drawn into an inappropriate tube.

C. The sample is run using a reagent lot that has expired.

D. The phlebotomist did not fill the tube completely on a sample sent for coagulation testing.

E. The autosampling pipette was jostled and is now drawing only 1.3 μL of sample instead of 1.5 μL of sample.

32. Which one of the following statements best describes proficiency testing?

B. A quality assessment tool that involves testing two levels of QC material before testing patient samples.

C. A quality assessment tool by which laboratories test samples with unknown results and compare their results.

D. A quality assessment tool that involves running calibrators every 6 months to ensure linear assay results.

E. A quality assessment test given to all newly hired technologists to ensure appropriate training and competency.

33. Your laboratory receives a proficiency testing (PT) specimen from an approved provider of PT material for a particular analyte. Which one of the following choices best describes how the sample should be handled?

B. The PT sample should be split; one aliquot should be run in your laboratory and the other aliquot should be sent to a reference laboratory to ensure concordant results.

C. The PT sample should be entered into your laboratory’s workflow and tested and resulted as with any other patient specimen.

D. The PT sample should be treated as any other patient sample. If send-out is required as a reflex for this analyte, your laboratory should send it out as per protocol.

E. The PT sample should be run multiple times during multiple days and the values averaged to minimize error.

34. Which one of the following is the best definition of “unsuccessful” participation or performance in PT?

B. Failure to submit the results of a testing event in the requisite amount of time.

C. A clerical error in reporting the results for a testing event.

D. Repeated unsatisfactory test scores for an analyte or for the entire testing event in a particular specialty or subspecialty on two consecutive PT events or two of three testing events.

E. This is not a term used in assessing performance in PT events.

35. The quality manager of your laboratory recommends that your laboratory register for a PT program for a test that the FDA has classified as “waived.” Which one of the following best describes how you should you respond to this recommendation?

B. You should agree. Although PT is not required for waived tests, if a valid PT program exists, participation will help ensure your laboratory’s accuracy in result reporting.

C. You should disagree. After looking through the CLIA regulations for PT, you notice the analyte you are measuring is not on the list of regulated analytes for which PT is required.

D. You should disagree. The FDA does not require PT for tests it deems waived.

E. You should disagree. PT will only highlight your laboratory’s inaccuracy.

36. Which one of the following is most characteristic of root cause analysis (RCA), regardless of the method that is used?

B. Favors the subjective opinion of experts.

C. Results in an executable and quantifiable solution(s).

D. Seeks to identify and blame the specific person or group responsible.

E. Uses the Ishikawa fishbone diagram.

37. Which one of the following is a specific management infrastructure required for Six Sigma certification?

B. Merger and acquisitions attorneys.

C. Only the chief executive officer commitment is required.

D. Six Sigma consultants.

E. Support of engineers.

38. Section 1877 of the Social Security Act (42 U.S.C. 1395) prohibits which one of the following?

B. Professional billing for laboratory tests without a physician-documented order that includes the physician’s signature.

C. Physician patient referral to an entity for a designated health service from which the physician will financially benefit.

D. Performing genetic tests without a signed consent form.

E. Performing HIV tests without a signed consent form.

39. A supervisor informs you that the QC values for an assay performed in your laboratory have triggered the 8_1.5s Westgard rule. Which one of the following types of type of analytical error does this most likely indicate?

B. User error.

C. Random error.

D. Imprecision.

E. A bias trend.

40. An area supervisor from your laboratory asks you to review your QC rules. She says that QC is failing too frequently using the 1_2S Westgard rule and troubleshooting reveals no errors in the method. This has been the case over multiple reagent lots. You would like to maintain the sensitivity of the rule with regard to error detection but would also like to decrease the false-alert rate. Which one of the following is the most logical step?

B. Change to using the 8_1s rule.

C. Adopt a hybrid rule combining the 1_3s and 2_2s rules in a multirule scheme.

D. Rules are not necessary, and each QC value should be judged individually.

E. Ask the supervisor to change lots of QC material; the failure rate is likely due to a faulty batch.

41. Which one of the following is the most common type of CLIA certificate issued?

B. Certificate for provider-performed microscopy procedures.

C. Certificate of registration.

D. Certificate of compliance.

E. Certificate of accreditation.

B. 2%.

C. 15%.

D. 10%.

E. 5%.

42b. Which one of the following statements best describes whether this amount of carryover acceptable?

B. This amount of carryover is acceptable because it is less than 10 mIU/mL.

C. This amount of carryover is acceptable because it is less than 15% of the original sample.

D. This amount of carryover is not acceptable because it is more than 5% of the original sample.

E. This amount of carryover is not acceptable because it is more than 0.2 mIU/mL.

43. According to CLIA regulations, laboratories that hold a certificate of waiver must comply with which one of the following?

B. Have a designated laboratory director who holds a medical degree.

C. Follow the test manufacturer’s instructions.

D. Engage in CLIA-directed PT.

E. Record all patient test results in an electronic format.

44. Laboratory testing in the United States is regulated through CLIA. The CLIA program is overseen by which one of the following regulatory entities?

B. The AABB.

C. The CAP.

D. The Joint Commission.

E. The CMS.

45. CLIA quality system regulations require verification of a manufacturer’s stated performance specifications for which one of the following categories of tests?

B. Provider-performed microscopy tests approved by the FDA.

C. Moderate-complexity tests approved by the FDA.

D. Waived, provider-performed microscopy, and moderate-complexity tests approved by the FDA.

E. All FDA-approved tests used for patient care.

46. Which one of the following is categorized as a waived test according to the CLIA classification?

B. Fecal occult blood examination.

C. Urine sediment examination.

D. Fecal leukocyte examination.

E. The fern test.

47. According to CLIA regulations, cytology slide preparations must be retained for which one of the following periods of time?

B. 2 years.

C. 5 years.

D. 10 years.

E. Indefinitely.

48. According to CLIA regulations, clinical pathology test records must be retained for at least which one of the following periods of time?

B. 2 years.

C. 5 years.

D. 10 years.

E. Indefinitely.

49. Which one of the following methods best helps ensure the accuracy of a test?

B. Analyze samples with no measurable analyte spiked with low concentrations of analyte.

C. Analyze samples with a high value followed by samples with a low value.

D. Analyze a sample 20 times and determine the mean and SD.

E. Compare samples between the test method and a reference method.

Major points of discussion

■ The physician self-referral ban, or Stark Act, prevents physicians from referring Medicare patients to self-owned laboratories.

■ HIPAA directs how health care information is managed.

■ The OIG compliance guidelines help laboratories develop programs that promote highly ethical and lawful conduct, especially in terms of billing. The OIG is responsible for identifying fraud and abuse in laboratory testing, as regulated by the CMS.

2. A. A legal notice provided to all uninsured patients before they receive any medical care.
B. A legal notice provided to all Medicaid participants.
C. A legal notice provided to all uninsured patients receiving outpatient chemotherapy.
D. A legal notice provided to Medicare fee-for-service participants delineating services expected to not be covered under their Medicare insurance plan.
Rationale: An Advance Beneficiary Notice of Noncoverage is a notice provided by independent laboratories, health care practitioners, and medical suppliers to Medicare participants for services when payment is expected to be denied if the patient receives the service/supply.
E. A legal notice to all insured patients delineating services routinely not covered by major insurance carriers.
Rationale for A, B, C, and E: An advance beneficiary notice is required for people who have Medicare insurance (not uninsured patients).

Major points of discussion

■ The Advance Beneficiary Notice of Noncoverage was formerly named the Advance Beneficiary Notice.

■ The law requires a provider to notify a beneficiary in advance if the service will likely be denied as “not reasonable and necessary.” If an Advance Beneficiary Notice of Noncoverage is not given, providers may not bill Medicare or the individual patient for these services.

■ Medicare is a health insurance program for people 65 years or older, people younger than 65 years with certain disabilities, and people of all ages with end-stage renal disease.

■ Its focus areas are the comparison of effectiveness of new treatments, quality improvement, patient safety, the use of health information technology in patient safety, and determining the cost effectiveness of health care.

■ AHRQ, like its sister agency the NIH, applies more than 80% of its budget for research. However, the NIH is the largest source of funding for biomedical research in the United States.

■ Possible interfering substances vary by analyte and analytical method but can include hemolysis, lipemia, icterus, hyperproteinemia, and prescription drug interferences.

■ It is generally impossible to test for all possible interferences; thus, the most commonly encountered interfering substances should be determined and assayed.

■ Analytical specificity is distinct from clinical specificity.

■ Clinical specificity, which is sometimes part of method validation, is determined by taking the number of true negatives identified by the assay and dividing by the sum of the true negatives and false positives.

5. A. The false-negative rate of the assay.
Rationale: This would be determined by the subtracting the clinical sensitivity from 1.
B. The value obtained when the number of true positives is divided by the sum of the true positives and the false negatives.
Rationale: This is the clinical sensitivity.
C. The lowest possible concentration of an analyte that is accurately and reproducibly measured by an assay.
Rationale: See Major Points of Discussion.
D. The performance of the assay when measuring an analyte in the presence of an interfering substance.
Rationale: This is the analytical specificity.
E. The formula that relates instrument response to analyte concentration.
Rationale: This is the calibration curve.

Major points of discussion

■ Analytical specificity is best defined as the performance of the assay when measuring an analyte in the presence of an interfering substance.

■ The calibration curve is best defined as the formula that best correlates instrument response to analyte concentration.

■ Clinical sensitivity is defined as the true-positive rate of an assay and is calculated as the ratio of true positives divided by the sum of true positives and false negatives.

■ Clinical specificity is defined as the true-negative rate of an assay and is calculated as the ratio of true negatives dividied by the sum of true negatives and false positives.

6. A. A training laboratory for students.
Rationale: A training laboratory for student education typically deals only with samples that are not usually infectious and is classified as a level 1 laboratory.
B. A clinical chemistry laboratory.
Rationale: A clinical chemistry laboratory is classified as a level 2 laboratory.
C. A clinical hematology laboratory.
Rationale: A clinical hematology laboratory is classified as a level 2 laboratory.
D. A laboratory working with highly infectious fungal pathogens.
Rationale: A biosafety level 3 laboratory works with microbiological agents that may cause fatal disease through inhalation. A laboratory that works with highly infectious fungal pathogens meets this definition.
E. A satellite clinical laboratory in an emergency department.
Rationale: A satellite clinical laboratory in an emergency department usually performs only routine tests, including chemistry and hematology assays; therefore, it is classified as a level 2 laboratory.

Major points of discussion

■ Biosafety level 2 laboratories are suitable for work involving agents of moderate potential hazard to personnel and the environment.

■ Biosafety level 3 laboratories are suitable for work with indigenous or exotic agents that may cause serious or potentially lethal disease after inhalation.

■ Biosafety level 4 laboratories are suitable for work with dangerous and exotic agents that pose a high individual risk of aerosol-transmitted laboratory infections. These include agents that cause severe to fatal disease in humans for which vaccines or other treatments are not available.

7. A. The process of testing and adjusting an assay so that the instrument measurements best correlate with the known analyte concentrations.
Rationale: This is the definition of “assay calibration.” This should be done more frequently than every 6 months.
B. The process of testing known concentrations of an analyte throughout the reportable range and confirming that the assay returns the appropriate value, within an established allowable error.
Rationale: This is the correct definition of “calibration verification.”
C. The process of comparing the slope and y-intercept of the current calibration curve with the previous curves.
Rationale: This is good practice. When recalibrating an assay, tracking the slope and intercept helps identify calibration shifts. However, this is not the definition of “calibration verification.”
D. The process of running previously assayed patient samples with a new lot of calibration material and comparing them with results obtained when the same samples were run using a previous lot of calibration material.
Rationale: This is good laboratory practice when changing lots of calibration reagent. The patient samples should be chosen to span the analytical range of the assay. However, this is not the definition of “calibration verification.”
E. The process of running samples of known high and low analyte concentrations and plotting them on a Levey-Jennings chart.
Rationale: This describes a quality control (QC) performance procedure and not calibration verification.

Major points of discussion

■ Calibration verification should also be performed after major servicing of the equipment, changing to a new lot of reagents, or when the performance of the assay is questionable.

■ The goal of calibration verification is to ensure that your assay maintains accuracy across its analytical range.

■ Calibration verification is a quality assurance measure.

■ Calibration of an assay is best defined as the process of adjusting an instrument response to maximize the correlation with analyte concentration. This is distinct from calibration verification.

■ A laboratory should establish, a priori, what tolerance limits it will allow for variation within calibration verification. These limits should be based on the clinical accuracy requirement of the assay.

■ A CLIA-accredited laboratory is one that is inspected by accrediting organizations that have been approved by the CMS.

■ An approved accrediting organization can inspect a laboratory in lieu of the CMS.

■ CMS has granted the CAP Laboratory Accreditation Program deeming authority.

■ Samples should be both QC material and real patient samples (in matrix) that span the analytical range of the assay to prove that the new reagent lot reacts the same as the old lot in matrix and in the “pseudo-matrix” in which many QC materials are prepared.

■ Differences in QC values using two different lots of reagent may be due to different reactions between the new lot and the pseudo-matrix of the QC material. This difference in reaction may extend to patient samples and should be excluded by running patient samples across the analytical range using both lots.

■ New reagent lots should be “verified” in the above manner well before the old lot expires or runs out. This requires good inventory control.

■ It is ultimately the responsibility of the laboratory director to ensure that good QC practices are followed in the laboratory.

■ A priori, the laboratory should establish allowable differences in patient sample values between lots. These tolerance limits should be established based on the clinical accuracy needs of the assay.

10. A. You must apply for a CLIA certificate of waiver.
Rationale: This is issued to a laboratory that performs only waived testing. This certificate is not needed if the laboratory already operates under a certificate that allows for higher complexity testing.
B. You must apply for a CLIA certificate of registration.
Rationale: This certificate is issued to a laboratory to allow it to conduct nonwaived (i.e., moderate- and/or high-complexity) testing until the laboratory is surveyed (by the state Department of Health or an accreditation agency) to determine its compliance with CLIA regulations. Only laboratories that apply for a certificate of compliance or a certificate of accreditation will receive a certificate of registration. This is not needed for waived testing.
C. You must apply for a CLIA certificate of compliance.
Rationale: This certificate is issued to a laboratory once the state Department of Health conducts an inspection and determines that the laboratory is compliant with all applicable CLIA requirements. This type of certificate is issued to a laboratory that performs nonwaived testing and is not needed to add a waived test.
D. No additional certificates are necessary.
E. You cannot run a waived test in a laboratory that performs predominantly moderate-complexity testing.
Rationale: You can perform a waived test under either a certificate of compliance or a certificate of accreditation, both of which allow the laboratory to conduct moderate- or high-complexity tests.

Major points of discussion

■ There are six CMS-approved accreditation agencies:

• American Osteopathic Association

• American Society for Histocompatibility and Immunogenetics

• COLA

• CAP

■ The CLIA program is designed to ensure quality laboratory testing.

■ The CMS oversees the operation of the CLIA program.

■ The CMS recognizes additional accrediting agencies and will issue a certificate of accreditation to laboratories that receive accreditation from the AABB, American Osteopathic Association, American Society for Histocompatibility and Immunogenetics, COLA, CAP, and The Joint Commission.

■ Accuracy, reproducibility, reportable range, and reference range are the four performance characteristics of an FDA-approved, moderate-complexity assay that must, at a minimum, be confirmed.

■ Laboratory-developed tests are considered high-complexity tests and are held to a different standard of validation by CLIA regulations. Additional performance parameters must be assessed.

■ The purpose of a method validation is to assess the degree of uncertainty in the measurements made by the assay and to point out assay weaknesses and potential for error.

■ Accuracy is usually validated by running standards of known concentrations and comparing the measured concentration as a percentage of the expected concentration.

■ Precision or reproducibility (inter-run) is generally assessed by running at least two levels of an analyte in quadruplicate over 5 days. Precision is expressed as a % CV ([mean/SD] × 100%).

■ The reportable range is established by running increasing concentrations of the analyte and choosing the range of concentrations in which instrument response increases linearly with analyte concentration. A linear regression procedure is usually used.

13. A. Once every 12 hours.
B. Once every 24 hours.
Rationale: QC samples must be assayed once every 24 hours, or more frequently if recommended by the manufacturer.
C. Every time the assay is performed.
Rationale for A and C: These are too frequent.
D. Once every 48 hours.
Rationale: QC must be run more often than every 48 hours if the test is offered continuously (i.e., 24 hours a day).
E. Once every week.
Rationale: QC samples must be assayed more often than once a week for tests that are offered 24 hours day.

Major points of discussion

■ Laboratories can assay QC samples more frequently if deemed necessary to ensure accurate results.

■ QC samples should be assayed after calibration or maintenance of an analyzer to verify correct method performance.

■ Blood gas measurements have separate, stricter QC requirements. CLIA requires at least one QC level to be assayed every 8 hours for blood gas measurements.

■ A certificate of registration is issued to a laboratory to allow it to conduct nonwaived (moderate- and/or high-complexity) testing until the laboratory is surveyed (inspected) to determine its compliance with CLIA regulations. Only laboratories that apply for a certificate of compliance or a certificate of accreditation will receive a certificate of registration.

■ A certificate of provider-performed microscopy (PPM) is issued to a laboratory in which a physician, midlevel practitioner, or dentist performs specific microscopy procedures during the course of a patient’s visit. A limited list of microscopy procedures is included under this certificate type; these are categorized as moderate-complexity.

■ There are six CMS-approved accreditation organizations:

• American Osteopathic Association

• American Society for Histocompatibility and Immunogenetics

• COLA

• College of American Pathologists

• The Joint Commission

■ Delta checks are intended to detect either preanalytic or analytic errors in testing, such as specimen mix-up errors, diluted samples, or analyzer malfunction.

■ Laboratories individually determine (1) which assays will have delta checks and (2) the acceptable thresholds for intraindividual variation.

■ An example of an assay that commonly has a delta check is the mean corpuscular red blood cell volume.

■ Qualifying reasons include the birth of a newborn child; placement of a child for adoption or foster care; care for an immediate family member with a serious health condition; or employee medical leave if unable to work because of a serious health condition.

■ The FMLA applies to all public agencies, elementary and secondary schools, and companies with 50 or more employees.

■ The FMLA is enforced by the U.S. Department of Labor’s Employment Standards Administration, Wage and Hour Division.

■ The FMLA requires health insurance to be maintained during the leave if insurance was provided before the leave was taken.

■ The FDA conducts unannounced inspections of all blood banks on a periodic basis.

■ The FDA promulgates criteria for blood donor eligibility.

■ The CMS oversees the CLIA regulatory program.

■ The AABB, CAP, and The Joint Commission have accreditation standards for blood banks and will conduct inspections.

18. A. LDTs are not medical devices and therefore do not fall under the FDA’s jurisdiction.
Rationale: The FDA considers laboratory assays to be medical devices.
B. LDTs are considered medical devices, and each laboratory must receive FDA approval before implementing an LDT.
Rationale: Although LDTs are considered medical devices, the FDA exercises enforcement discretion on this issue to encourage rapid implementation of the newest, most-effective diagnostics into laboratories to improve public health.
C. LDTs are considered medical devices, but the FDA has exercised enforcement discretion on LDTs.
Rationale: Although LDTs are, indeed, laboratory devices, the FDA exercises enforcement discretion on this issue allowing laboratories to implement their assays after an in-house, CLIA-appropriate validation.
D. LDTs are not considered medical devices, but the FDA regulates them.
Rationale: The FDA does not regulate LDTs.
E. LDTs may or may not be considered medical devices, and the FDA considers each assay on a case-by-case basis and decides whether to regulate.
Rationale: The FDA is clear on its stance on the status of LDTs as medical devices over which it could exercise regulatory control, but chooses not to, in the interest of enhancing public health.

Major points of discussion

■ The definition of an LDT is a test designed in a laboratory for specific use only in that laboratory.

■ The FDA exercises enforcement discretion with regard to LDTs to enable implementation of the newest diagnostics in clinical laboratories in a meaningful time period.

■ The FDA’s proposed jurisdiction over LDTs is the subject of debate, particularly from the CMS, which considers LDTs a service offered by the laboratory to ordering physicians without any reagents or devices crossing state borders. Therefore, they argue that the FDA has no authority in regulating LDTs.

■ Although LDTs are not actively regulated by the FDA, CLIA has a strict set of performance criteria that must be established in method validation before releasing patient results. These include, but are not limited to, linearity, reproducibility, analytical sensitivity/specificity, reference range, and recovery/accuracy.

• A person may be disabled if he or she has a history of a disability (such as cancer that is in remission).

• A person may be disabled if he or she is believed to have a physical or mental impairment that is not transitory (lasting or expected to last 6 months or less) and minor (even if he or she does not have such an impairment).

■ The Age Discrimination in Employment Act of 1967 protects people who are age 40 years or older from discrimination because of age. The law also makes it illegal to retaliate against a person because the person complained about discrimination, filed a charge of discrimination, or participated in an employment discrimination investigation or lawsuit.

■ Title VII of the Civil Rights Law of 1964 makes it illegal to retaliate against a person because the person complained about discrimination, filed a charge of discrimination, or participated in an employment discrimination investigation or lawsuit. The law also requires that employers reasonably accommodate applicants’ and employees’ sincerely held religious practices, unless doing so would impose an undue hardship on the operation of the employer’s business.

■ Title I of the Americans with Disabilities Act of 1990 makes it illegal to discriminate against a qualified person with a disability, in the private sector or in state and local governments. The law also makes it illegal to retaliate against a person because the person complained about discrimination, filed a charge of discrimination, or participated in an employment discrimination investigation or lawsuit. The law also requires that employers reasonably accommodate the known physical or mental limitations of an otherwise qualified individual with a disability who is an applicant or employee, unless doing so would impose an undue hardship on the operation of the employer’s business.

■ The Genetic Information Nondiscrimination Act of 2009 makes it illegal to discriminate against employees or applicants because of genetic information. Genetic information includes information about an individual’s genetic tests and the genetic tests of an individual’s family members, as well as information about any disease, disorder, or condition of an individual’s family members (i.e., an individual’s family medical history). The law also makes it illegal to retaliate against a person because the person complained about discrimination, filed a charge of discrimination, or participated in an employment discrimination investigation or lawsuit.

20. A. Standards for quality and competence in medical laboratories.
Rationale: ISO 15189:2007 is the “Medical laboratories—Particular requirements for quality and competence” standards.
B. Standards for pricing and reimbursement in medical laboratories.
Rationale: ISO 15189:2007 does not regulate laboratory test pricing.
C. Laboratory services that must be covered under universal health insurance plans.
Rationale: ISO 15189:2007 does not regulate health insurance.
D. Standard requirements for laboratory technologist school curricula.
Rationale: ISO 15189:2007 does not regulate laboratory technologist training.
E. Standard requirements for retirement benefit packages.
Rationale: ISO 15189:2007 does not regulate employee work benefits.

Major points of discussion

■ ISO is a network of the national standards institutes of 163 countries.

■ International Standards for technical regulations on products, production methods, and services help ensure a certain level of performance and safety worldwide.

■ Adherence to ISO standards is voluntary. ISO has no legal authority to enforce its standards unless countries have incorporated them into their national laws.

■ If the laboratory performs a mix of moderate- and high-complexity testing, only those employees working on high-complexity testing must meet the above requirements.

■ These four positions can be filled by one person (i.e., the laboratory director) as long and he or she meets the qualifications and is able to meet the established responsibilities defined in Subpart M of CLIA.

■ It is the laboratory director’s responsibility to ensure that appropriate personnel work in the laboratory.

■ The personnel requirements for a laboratory are determined by the level of complexity of the assays run in the laboratory.

22. A. The assay is accurate but not precise.
Rationale: Accuracy refers to how closely an assay result value matches the true value of the analyte. This chart would show scatter around the expected value.
B. The assay is precise but not accurate.
Rationale: Precision refers to the reproducibility of the results.
C. The assay is neither precise nor accurate.
Rationale: The QC results are scattered, representing a large SD, and there is a bias trend away from the expected mean value. This suggests imprecision and inaccuracy.
D. The assay is clinically useless.
Rationale: Levey-Jennings control charts do not assess the clinical utility of laboratory tests but, rather, assess if the assay is performing as expected.
E. The assay is precise and accurate.
Rationale: A precise and accurate assay would have an observed mean value close to the expected mean value and a small SD.

Major points of discussion

■ Acceptable limits for the deviation of the QC results from the expected value are determined by the laboratory.

■ This is often achieved through the use of the Westgard rules, which are QC interpretive rules for statistical monitoring of assay accuracy and precision.

■ Accuracy can be assessed by measuring an analyte in reference material and comparing the result with the known certified concentration.

■ For all tests classified as CLIA nonwaived tests, a minimum of two levels of controls must be run on each day that patient testing is performed.

■ Levey-Jennings charts show QC results over time and plot how far each point lies from the mean expected value.

■ Just by chance, QC values should fall outside 2 SDs from the mean 5% of the time.

■ There are many Levey-Jennings rules that are used to flag a QC violation. For example, if a QC value falls 2 SDs beyond the mean, then it would be denoted a 1_2 s violation. If it falls 3 SDs beyond the mean, it is denoted 1_3 s.

■ The graphic representation allows for quick trend spotting and identification of rule violations.

■ The typical Levey-Jennings chart has the QC Run # on the x-axis and the QC result on the y-axis.

■ At least two levels of QC are typically run on an assay, and different levels should be graphed on separate Levey-Jennings chart.

■ It is often useful to denote the expected/average value of the QC material and then ± 2 SDs on the Levey-Jennings chart to help spot rule violations.

25. A. Validation of LoQ.
Rationale: If the reproducibility (CV < 15%) and accuracy (> 80%) meet a prespecified value, the LoQ is validated. However, there is additional information available from these experiments.
B. Validation of the LoQ, intraday and interday reproducibility, and accuracy at the LoQ.
Rationale: The within-day and between-day reproducibility are determined by running the same sample multiple times per day for multiple days. The values of these 20 runs can then be averaged to obtain a value for the sample that can be compared with the “known” value of the sample to establish accuracy at the LoQ. As long as these two measures fall within preestablished criteria, the proposed LoQ has been verified.
C. Validation of the LoQ and establishment of accuracy at the LoQ.
Rationale: The intraday and interday reproducibility is also determined by this experiment.
D. Validation of the LoQ and establishment of the reportable range.
Rationale: The reportable range is generally established by running samples across the hypothesized range and assessing linearity, usually by linear regression methods.
E. Establishment of reproducibility at the LoQ.
Rationale: Reproducibility is established at the LoQ, but additional information is also available.

Major points of discussion

■ By FDA method validation guidelines, the CV at the LoQ should be less than 15%.

■ By FDA method validation guidelines, the accuracy at the LoQ should be greater than 80%.

■ An appropriate LoQ is a value below the lowest, clinically relevant value of the analyte.

■ If no proposed LoQ is provided in the literature or from experience, the LoQ of the assay can be determined by either:

■ There are several ways to determine this value. One way is to average the ratio of analyte signal to background noise. For the limit of quantification, the signal/noise ratio is typically more than 10. For lower limits of detection, the signal/noise ratio is typically more than 3.

■ Another approach to establish a lower limit of quantification is by running a matrix sample without analyte (i.e., matrix blank) 20 times. To the average concentration of the blank, 4 to 5 times the SD of the multiple runs is added. This sum is now the lower limit of quantification.

■ Clinical sensitivity is the true-positive rate of an assay, which differs from analytical sensitivity.

■ To participate in Medicaid, states are required to offer the health insurance coverage to certain population groups.

■ States can expand the health insurance coverage to additional population groups if they deem this appropriate.

■ Classically, the reference method is plotted on the x-axis and your laboratory’s method on the y-axis.

■ If the plot is classically drawn, a slope greater than 1 implies a positive and proportional bias of your method relative to the reference method.

■ If plotted classically, a y-intercept term greater than 0 implies a constant positive bias.

■ Both constant and proportional biases may coexist in a method comparison study.

■ An R² value approaching 1 indicates that the linear regression line drawn between the two methods is an excellent fit. However, high coefficient of determination does not rule out bias in your method.

29. A. The FDA.
Rationale: The FDA is a part of the DHHS and regulates the manufacture of biologics, medical devices, and test kits.
B. The NIH.
Rationale: The NIH is an agency of the DHHS, the main aim of which is the performance and funding of biomedical research.
C. The CMS.
Rationale: CMS sets quality standards and reimbursement rates that apply to laboratories. These rates are often then adopted by other third-party payers.
D. The National Institute of Standards and Technology (NIST).
Rationale: The NIST is a branch of the U.S. Department of Commerce. Among other things, the NIST develops and distributes standardized calibration materials for a finite list of analytes.
E. The DHHS.
Rationale: This federal agency oversees the CMS, FDA, and OIG. It is not involved in developing standards for calibration.

Major point of discussion

30. A. Apply for state certification every 2 years and pay the annual membership fee.
Rationale: There is no application process for OSHA.
B. Provide subsidized health insurance for all employees and offer at least two separate insurance plans.
Rationale: OSHA does not mandate that employees provide health insurance.
C. Display an OSHA poster in the workplace informing employees about the Occupational Safety and Health Act.
Rationale: Employers are required to display a poster prepared by the Department of Labor containing this information.
D. Require that all employees receive an annual physical health exam with urine drug screening.
Rationale: OSHA does not mandate health exams or drug testing.
E. Receive state OSHA agency approval before increasing the number of employees.
Rationale: OSHA does not regulate staffing numbers.

Major points of discussion

■ The OSHA, which enforces the Occupational Safety and Health Act, is part of the U.S. Department of Labor.

■ OSHA standards are rules that employers must follow to protect employees from hazards.

■ These standards limit hazardous chemical exposure, require certain safety practices and equipment, require monitoring hazards, and require keeping records of workplace injuries.

■ All employers are required to display a poster prepared by the Department of Labor informing employees of their protections under the Occupational Safety and Health Act.

■ The analytical phase of testing is defined by those procedures dealing with sample manipulation, reagent preparation, calibration, measurement, and instrument readout.

■ The postanalytical phase involves recording test results, interpretation of results, and transmission of reports.

■ Errors can occur in any and all phases of the total testing process.

■ Proficiency samples should be tested in the same manner as patient samples.

■ Proficiency samples cannot be sent to reference laboratories for result correlation.

■ Laboratories should not discuss test results with other laboratories prior to the deadline for submission.

■ PT ensures accuracy and reliability of laboratory testing.

■ Delta checks compare current result values with previous result values for a given patient and flag samples that have exceeded predefined acceptable limits for variation.

■ The purpose of PT is to ensure the accuracy and reliability of your laboratory with regard to other laboratories performing the same or comparable assays.

■ To maintain a CLIA certificate, a laboratory must participate in a CLIA-approved PT program for all regulated moderate- and high-complexity tests performed under the CLIA certificate.

■ An unsatisfactory performance in PT means failure to attain the minimum satisfactory score for an analyte, test, subspecialty, or specialty for a testing event.

■ Clerical errors in entering PT results are counted as incorrect results and, therefore, as unsatisfactory performance for the analyte in question.

■ Failure to report the results of PT within the allotted time frame will cause the laboratory to receive a score of 0 for that event.

■ FDA-waived tests need not participate in PT programs.

■ The purpose of PT programs is to ensure quality, accuracy, and reliability of your laboratory results.

■ CMS provides a list of approved PT programs in which your laboratory can enroll to meet PT regulatory criteria.

■ PT participation is required for each CLIA certificate, not for each test site. Therefore, if you have multiple testing locations under one CLIA certificate, you need to register only for one PT program for any one regulated analyte.

■ An RCA assumes that errors are best reduced by identifying and preventing the root cause(s) of an error.

■ There are many methods and tools used in performing an RCA:

• Tools: Ishikawa fishbone diagram, change analysis, Pareto analysis, etc

■ All methods for performing RCAs have limitations. For example, a Pareto analysis requires data to be collected to track the frequency of certain errors. If the database is inaccurate or incomplete, the RCA will not result in an appropriate solution.

■ All RCAs share common characteristics regardless of the method or tools that are used:

2. No blame is placed on a single individual or group because adverse events are usually due to a chain of errors.

3. Specific causes and effects are identified; typically it identifies a system of errors rather than a single cause.

4. These causes and effects are supported by evidence.

5. Results in a clearly defined, executable, quantifiable solution(s) that can be monitored quantitatively.

37. A. Master “Black Belts” and “Green Belts.”
Rationale: Master “Black Belts” and “Green Belts” champion Six Sigma initiatives.
B. Merger and acquisitions attorneys.
Rationale: Attorneys may be needed for certain projects but are not required for implementation of Six Sigma.
C. Only the chief executive officer commitment is required.
Rationale: A commitment from all employees in the organization is required for Six Sigma to be effective.
D. Six Sigma consultants.
Rationale: Six Sigma consultants may be useful in initiatives but are not required.
E. Support of engineers.
Rationale: All employees of an organization must commit to Six Sigma, but not all organizations have engineers.

Major points of discussion

■ Six Sigma seeks to minimize the number of defects by eliminating the cause(s) of the defects.

■ This management style requires the full commitment of upper management, as well as all employees involved in the manufacturing process.

■ Six Sigma is characterized by champions called “Black Belts” and “Green Belts,” who lead initiatives to identify errors and develop executable solutions.

■ The following are considered designated health services: clinical laboratory services, physical and occupational therapy services, outpatient speech-language pathology services, radiology services, radiation therapy services, durable medical equipment and supplies, parenteral/enteral nutrients and supplies, orthotics and prosthetic devices and supplies, home health services, outpatient prescription drugs, and inpatient and outpatient hospital services.

■ There are three CLIA test categories: waived, moderate-complexity, and high-complexity testing.

■ The most commonly issued CLIA certificate is a waived certificate.

■ Common causes for a bias trend in QC results include a need for recalibration of the analyzer or an error in reconstituting the QC material.

■ A wide scatter of QC values suggests imprecision or poor reproducibility of results.

■ Westgard rules are QC interpretive rules used by laboratories for statistical monitoring of the accuracy and precision of their assays.

■ Westgard developed power functions in 1979 to express the probability that a particular QC interpretive rule would detect systemic error biases at a variety of magnitudes.

■ A 1_2s rule (i.e., one value > 2 SDs above or below the mean), although very sensitive for detecting systematic error biases, even small ones, also has a fairly high false-alert rate.

■ To improve the efficiency of QC interpretative rules, a combination of rules applied simultaneously may be considered (i.e., multirules).

■ The number of laboratories issued a certificate of waiver has grown to more than 50% of the approximate 225,000 laboratories enrolled as of 2011.

■ CLIA is user-fee funded; the biennial certificate fee is based on the type of certificate and the test volume of the performing entity.

■ Provider-performed microscopy procedures are considered moderately complex.

■ Carryover of an analyte could potentially cause a false elevation in patient results and, therefore, should be assessed when validating a new test system, if applicable to the methodology.

■ Accuracy can be assessed by measuring an analyte in reference material with a known concentration and comparing the result with the certified value.

■ Precision is the agreement between result values obtained by repeat measurements of a quantity.

■ The available CLIA certificates are the certificate of waiver, certificate for provider-performed microscopy procedures, certificate of registration, certificate of compliance, and certificate of accreditation.

■ The CMS-approved laboratory accreditation organizations include the AABB, COLA, American Society for Histocompatibility and Immunogenetics, CAP, and The Joint Commission.

■ Waived tests are defined as “simple laboratory examinations and procedures that have an insignificant risk of an erroneous result.”

■ The CLIA program is designed to ensure laboratory testing quality.

■ The CMS oversees the operation of the CLIA program.

■ The CMS recognizes additional accrediting agencies and will issue a certificate of accreditation to laboratories that receive accreditation from the AABB, American Osteopathic Association, American Society for Histocompatibility and Immunogenetics, COLA, CAP, and/or The Joint Commission.

■ Measuring accuracy determines whether the test results are correct. This can be tested by analyzing samples with known concentrations.

■ Precision ensures that comparable results are obtained when the same sample is tested repeatedly.

■ The reportable range of a test is the result range that is accurate. Values above or below this range should not be reported.

■ The FDA determines the classification category for all CLIA-regulated tests.

■ CLIA-regulated tests fall into one of three categories: waived, moderate complexity, or high complexity.

■ Provider-performed microscopy procedures are considered moderate-complexity tests and include vaginal, cervical, or skin wet mounts; potassium hydroxide preparations; pinworm examinations; fern tests; postcoital qualitative examinations of vaginal or cervical mucus; microscopic urinalysis; fecal leukocyte examination; semen analysis for presence and/or motility of sperm; and nasal smears for eosinophils.

■ Histopathology slide preparations must be retained for 10 years after the date of examination.

■ The CAP requires blood bank QC records be kept for a minimum of 5 years.

■ The CAP requires retention of QC records for the general laboratory for 2 years.

■ The CAP requires all peripheral blood smears/body fluid smears to be retained for 7 days.

■ Accuracy can also be assessed by comparing the test results from one method with the results from a reference method, using the same samples.

■ The analytical range of an assay refers to the interval between the highest and lowest concentrations of the analyte in which precision, accuracy, and linearity have been demonstrated to be acceptable.