Laboratory Information

This section gives information about maintaining a safe clinical laboratory environment. It offers lab safety tips, a discussion of quality control and quality assurance, details about reporting IVD problems, and resources for additional information.

• Current Lab Safety Tips:
  • Home Pregnancy Tests – How to Use a Popular Test Wisely
  • Practice Caution in Using Bio-Rad Platelia™ Aspergillus EIA
  • Use of Backup Testing for Negative Rapid Group A Strep Tests
  • Follow Good Laboratory Practices with Waived Laboratory Tests
  • Performance and Cautions in Using Rapid Influenza Virus Diagnostic Tests
  • Built-in Controls for Single Use Disposable Tests
  • Common Problems with the Use of Glucose Meters
  • Make Sure Glucose Meters Used in Testing Neonates are FDA Cleared for Testing in Neonates
  • Useful Tips to Increase Accuracy and Reduce Errors in Test Results from Glucose Meters
• Lab Safety Tip Archive
• Reporting Problems with Laboratory Tests and Equipment
• Patient Safety News
• Lab Tests Online

Home Pregnancy Tests – How to Use a Popular Test Wisely

(posted 4/2/04)

The first home pregnancy tests were marketed in the mid 1970’s. These tests are one of the most popular products for home diagnostic testing. It is estimated that about 33% of women have used these tests. The tests are popular because they allow women rapid access to highly sensitive and personal information. These tests can lead to earlier diagnosis and can provide pregnant women an opportunity to seek earlier health care intervention.

FDA is involved in the premarket review of these tests. Since the 1976 Medical Device Amendment, FDA assures that new pregnancy tests perform as well as those tests on the market since 1976. Premarket compares test performance between a new test and an established test. In these kinds of pregnancy devices the new test is compared to varying levels of the hormone human chorionic gonadotropin (hCG) that is the marker for pregnancy.

Recent investigators point out that the FDA review of analytical performance does not always mean a woman is pregnant. This discrepancy is because different tests have different abilities to detect low levels of hCG. Also hCG levels differ between pregnant women depending on the timing of the onset of pregnancy with regard to a menstrual period and depending on each woman’s unique biology.

The result is that pregnancy tests may be labeled up to 99% accurate when compared to other hCG tests, not to pregnancy. This may be true based on information submitted to the FDA. Therefore, labeling of these tests should clearly indicate that there is a possibility for both false positive tests and false negative tests, so patients should contact their health care provider to discuss any result.

Patients may frequently recognize incorrect results with the passage of time. False negatives may be detected by ongoing failure to have a period or the development of other obvious signs of pregnancy. False positives may be demonstrated by the unexpected onset of menses (regular vaginal bleeding associated with “periods”.) Repeat testing and/or other investigations such as ultrasound may provide corrected results.

If a patient has a negative result, it is always wise to consider this a tentative finding. Women should not use medications and should consider avoiding potentially harmful behaviors, such as smoking or drinking alcohol, until they have greater certainty that they are not pregnant.

Since September of 2003, studies for pregnancy tests have been posted on the Office of In Vitro Diagnostic Web Page (www.fda.gov/cdrh/oivd/) under new 510(k)s – decision summaries. FDA is considering what educational or regulatory tools might be available to help clarify the status, use, and interpretation of these tests.

Practice Caution in Using Bio-Rad Platelia™ Aspergillus EIA

FDA has cleared for marketing, the Platelia™ Aspergillus EIA, manufactured in France by Bio-Rad, Marnes-la-Coquette and distributed by Bio-Rad Laboratories, Redmond, WA, which detects Aspergillus galactomannan antigen in serum samples, and is an aid in the diagnosis of Invasive Aspergillus infection. Invasive Aspergillosis is a life-threatening invasive fungal infection that often occurs in leukemia patients, organ and bone marrow transplant patients, and patients whose immune systems are compromised by illness or chemotherapy.

There have been reports in the literature, in the U.S. and from Europe, of potential drug and device interaction that may occur when using the Platelia™ Aspergillus EIA galactomannan antigen assay to test sera from patients who are receiving piperacillin/tazobactam (Zosyn®), an injectable antibacterial combination product from Wyeth Pharmaceuticals, Inc. Recent reports 1,2 have indicated that positive galactomannan antigen tests results may occur in serum samples from patients treated with Zosyn®, but without Invasive Aspergillosis. Additional studies have also demonstrated positive galactomannan antigen test results in certain batches of Zosyn®. These results are highly suggestive of reactivity of the Platelia™ Aspergillus EIA with Zosyn®. Nevertheless, as Platelia™ Aspergillus EIA can detect galactomannan antigen well before clinical or radiological signs appear, the occurrence of Invasive Aspergillosis cannot be ruled out. Therefore, patients treated with Zosyn® with positive test results should be followed carefully.

Bio-Rad has notified their customers and modified the Platelia™ Aspergillus EIA package insert to include a new Limitation of Use alerting laboratory users that positive test results in patients treated with Zosyn® should be interpreted cautiously and confirmed by other diagnostic methods.

It is therefore recommended that when reporting a positive Platelia™ Aspergillus EIA galactomannan test result, laboratories should inform physicians of the limitations of the test with regard to the potential interaction with Zosyn® and that the patient’s previous drug therapy should be taken into account.

FDA reminds users that life threatening or potentially threatening adverse device failures should be reported to the agency through MEDWATCH medical device reporting system. This may be done by visiting the MEDWATCH site at http://www.fda.gov/medwatch/ or calling 1-800-FDA-1088. Less serious adverse device failures may be reported to the FDA by sending an e-mail to fdalabtests@cdrh.fda.gov.

References:

1. Sulahian, A., S. Touratier, T. LeBlanc, P. Rousselot, F. Derouin, P. Ribaud. False Positive Aspergillus antigenemia related to concomitant administration of Tazocillin. Abstract M-2062a, 43^rd ICAAC Program.
2. Viscoli, C., M. Machetti, C. Cappellano, B. Bucci, P. Bruzzi, A. Bacigalupo. False-Positive Platelia Aspergillus test in patients receiving Piperacillin/Tazobactam. Abstract M-2062b, 43rd ICAAC Program.

Cautionary Note: Use of Backup Testing for Negative Rapid Group A Strep Tests

(posted 11/5/03)

Pharyngitis (sore throat) is caused by a number of different viruses or bacteria which set up shop in the throat and tonsil area. One of the most clinically significant bacterial organisms is group A beta-hemolytic streptococcus (GAS). Infection with GAS causes local pain and redness, bad breath, tonsillar or pharyngeal exudates and systemic symptoms like fever. Alternatively, patients may present with only mild throat pain and no fever. Anecdotal experience shows that some patients may only complain of bad breath and a history of GAS in a schoolmate or family member.^1,2,3

Serious complications of GAS include rheumatic fever, rheumatic heart disease and death. Historically, treatment with intramuscular penicillin within the first several days of symptoms prevented the rheumatic complications. Because intramuscular injection of penicillin is painful this has evolved into treatment with oral penicillins.^1,2

While the local throat infection may clear on its own in many patients, these untreated patients are still thought to be at increased risk of rheumatic complications. Unfortunately, the literature is clear that physical examination is insufficient to accurately distinguish GAS from other causes of pharyngitis which do not present any risk of rheumatic complications. Therefore, if a patient presents with appropriate signs and symptoms a throat test for strep is performed.

The historic test of choice was throat culture. A variety of very useful non-culture based methods are available which offer quick results. These rapid tests are invaluable when they are positive for strep, but caution is required when they are negative for a variety of reasons. Pediatric practice guidelines recommend all negative rapid tests in the face of overt clinical symptoms need to be supported with follow up testing.^1,4,5 This is conventionally viewed as throat culture on media which is designed to augment growth of GAS, though newer methodologies may change this recommendation.⁶ Notwithstanding, there is at least one study supporting clinical superiority of a rapid method compared to culture method.⁷

The situation in adults is more complex. While 15%-30% of children who present with pharyngitis have GAS, the percentage in adults may be as low as 5%-10%.^2,3 Also, it has been reported that adults who get GAS are at a lower risk for rheumatic complications. This has been offered as a rational supporting the lack of need for confirmatory testing in adults with a negative rapid test.⁸ However, there are studies suggesting that the rate of rheumatic complications in adults who present with local suppurative disease is equal to the rate in children.³ Further, some sources quote that up to 20% of first attacks occur in middle to later life.²

Since no rapid test has been cleared, approved, or waived through the regulatory process as a stand alone test in the face of locally suppurative disease, lack of a backup method for a negative rapid GAS test result constitutes off label use.

While the practice of medicine is not the province of FDA regulation, regulatory medicine, like clinical medicine, is always in the process of change and FDA welcomes information from academia or industry which may contribute to the evolution of this opinion.

Bibliography:

1. Committee on Infectious Diseases, Red Book: 2003 Report of the Committee on Infectious Diseases, 26’th Edition, Elk Grove Village IL, American Academy of Pediatrics, 2003, p 573-584.

2. Cotran RS, Kumar V, Collins T. Robbins Pathologic Basis of Disease, 6’th Edition, Philadelphia PA, WB Saunders Company, 1999, p 572.

3. Mandell GL, Bennett JE, Dolin R. Mandell. Douglass and Bennet’s Principles and Practice of Infectious Disease, 5’th Edition, Philadelphia PA, Churchill Livingstone, 2000, p 2119.

4. Bisno AL, et al. Diagnosis and management of Group A Streptococcal pharyngitis: A practice guideline. Clinical Infectious Diseases. 1997; 25:574-583.

5. Gieseker KE, et al. Comparison of two rapid Streptococcus pyogenes diagnostic tests with a rigorous culture standard. Pediatr Infect Dis J, 2002; 21:p 922-926.

6. Gieseker KE, et al. Evaluating the American Academy of Pediatrics diagnostic standard for Streptococcus pyogenes pharyngitis: backup culture versus repeat rapid antigen testing. PEDIATRICS June 2003. 111(6): e666-e670.

7. Uhl JR, et al. Comparison of LightCycler PCR, Rapid Antigen Immunoassay, and culture for detection of Group A Streptococci from throat swabs. J Clin Microbiol Jan 2003, 41(1): p 242-249.

8. Bisno AL, et al. Practice guidelines for the diagnosis and management of Group A Streptococcal pharyngitis. CID 2002; 35: p 113-125.

Lab Safety Tip # 1

Follow Good Laboratory Practices with Waived Laboratory Tests

Background:

The Department of Health and Human Services has evaluated laboratory tests for complexity since 1992 as part of the implementation of the Clinical Laboratory Amendments of 1988 (CLIA '88). The more complicated the test, the more stringent the CLIA '88 requirements. Tests designated as high or moderate complexity can be used only by clinical laboratories that comply with CLIA '88 standards for a quality system (including quality assurance assessment and quality control) , and patient test management, and personnel. Simple, low-risk tests designated as waived can be used by laboratories that enroll in CLIA and pay a biennial certification fee but are exempt from CLIA '88 standards (i.e. community clinics, physicians' offices, or other small laboratories).

By law, waived tests must be simple to use and must provide a low risk of an incorrect result acceptable results in the hands of untrained users. The only CLIA requirement for performing waived tests is that laboratories must follow the manufacturer’s instructions for testing. It is also recommended that However, users must follow the manufacturer's instructions as well as good laboratory practices to ensure that test results are reliable.

Recommendations for Running Waived Tests:

In order to maximize the performance and reliability of waived tests, laboratories are encouraged to consider the following:

1. Read and follow the information found in the package inserts.
   Small deviations from the written instructions about product storage or procedural steps can have a significant impact on results. Test kits and reagents must be stored under the proper conditions and used prior to their expiration dates. You should take precautions to make sure that the correct reagents are used for each test, and reagents from different test kits are not inadvertently mixed up.
    
2. Follow the manufacturer's recommendations for running quality control (QC).
   Many waived tests have built-in quality controls that only monitor certain aspects of the test. In these cases, external quality controls may be the only way to monitor the entire test system. Read the information concerning built-in controls carefully. Manufacturers list minimum frequency requirements for their products in the package insert, but they may not be adequate for all laboratories. Take into account the environment where testing is performed when deciding how often you should run external QC. There are many factors that may be unique to your laboratory that can effect this decision, such as:
    
• what information is provided by the built-in control;
• the extent of safe-guards that are provided with the test system (such as a temperature monitor that alerts you when the test has been stored outside of acceptable limits),
• the ambient environmental conditions of your laboratory;
• storage conditions (such as whether the freezer has recycling phases);
• personnel issues (understaffing or high turnover); or
• the danger of a false negative test result. 

Select concentrations of control materials to challenge the medical decision points of the test. Selecting a control that has a concentration three times the cutoff concentration of a qualitative test will not allow you to detect reagent deterioration until patient results have already been compromised.  

3. Train staff members to perform tests correctly. Make sure your staff is familiar with product operating instructions, quality control procedures, and record keeping. Professional organizations sponsor educational and proficiency testing programs geared toward staff that performs waived tests in outpatient or clinic laboratories. Some training courses are available over the internet.

See Also:

Good Laboratory Practices for Waived Testing Sites

Centers for Medicaid and Medicare Services: CLIA '88 Program

Tests Waived by FDA from January 2000 to Present

Lab Safety Tip # 2

Performance and Cautions in Using Rapid Influenza Virus Diagnostic Tests

FDA has cleared for marketing 7 rapid influenza diagnostic tests that can produce results within 30 minutes. These tests directly detect influenza A or B virus associated antigens or enzyme in throat swabs, nasal swabs, or nasal washes.

For the various products that have been FDA cleared for marketing Becton Dickinson’s Directogen Flu A test can detect only antigens associated with influenza A virus. Binax’s NOW Flu A, Binax’s NOW Flu B, and Becton Dickinson’s Directogen Flu A+B can detect and distinguish between influenza A and B virus antigens. Quidel’s QuickVue Influenza and Thermo BioStar FLU OIA can detect but do not distinguish between influenza A and B antigens. ZymeTx's ZstatFlu test can detect neuraminidase the presence of which denotes a high probability that infectious virions are present; it also does not distinguish between influenza A and B.

The Quidel Quick Vue and ZymeTx’s ZstatFlu and Quidel’s QuickVue influenza tests are considered low complexity and may be used in physicians’ offices. The other five tests mentioned above are considered moderately complex and are for use in a hospital or clinical reference laboratories.

If performed on individuals with signs and symptoms consistent with influenza, rapid influenza diagnostic tests appear to be moderately to reasonably accurate for detecting influenza virus dependent on when testing is performed during the influenza season. Potentially the rapid time for results can be very useful for managing patients with suspected influenza and for detection of institutional influenza outbreaks. However, positive testing must not be used alone to determine the cause of an individual’s symptoms. Often an individual may be co-infected with another pathogen that is the underlying cause of the symptom. Use of rapid influenza virus testing and missing an underlying cause was the subject of a public health advisory from the Centers for Drugs Evaluation and Research. ^1,2 The basis for this advisory were several deaths where individuals were treated with antiviral medication but died from an underlying bacterial infection.

Laboratories should make sure that physicians using these rapid test results understand the limitations of the tests, use clinical experience, further laboratory testing, and consider local surveillance data about circulating influenza viruses when interpreting test results.

²FDA Talk Paper, FDA Reminds Prescribers of Important Considerations Before Prescribing Flu Drugs, January 12, 2000, http://www.fda.gov/bbs/topics/ANSWERS/ANS00995.html

The accuracy of an influenza test is determined by the sensitivity and specificity of the test to detect influenza virus antigens/enzyme compared with a reference method (cell culture) and the prevalence of influenza in the population being tested. Sensitivity is the percentage of culture confirmed influenza virus isolates detected by a test. Specificity is the percentage of virus negative cell cultures with negative rapid test results. Positive predictive value (PPV) of a test is the percentage of rapid test positive patients that have influenza virus isolated from cell culture. Negative predictive value (NPV) is the percentage of rapid test negative patients that do not have influenza virus isolated from cell culture.

Although the sensitivity and specificity of a test are unaffected by the prevalence of disease, the PPV and the NPV of a test are affected by disease prevalence. An influenza test will have the highest PPV (and lowest NPV) during peak influenza activity and the lowest PPV (and highest NPV) during periods of low influenza prevalence, i.e., at the beginning and ending of the influenza season.

Diagnostic antigen/enzyme tests for influenza are more likely to produce false positive results when the prevalence of influenza virus infections is low, such as during the late spring, summer, and early fall in North America. Confirming positive test results with viral culture is particularly important during this time period. Even when a positive test result reflects true influenza virus infection, this does not rule out the possibility of other co-existing infections. Persons with influenza are at risk for bacterial superinfections, and coincidental dual infections with other pathogens. Since some bacterial infections may have a fulminant course requiring urgent intervention, a positive test for influenza should not be used as a reason for withholding antibacterial therapy if clinical evaluation suggests a need.

False negative test results will be more common during periods of high influenza activity, such as during the winter in North America. Clinical judgment and local influenza surveillance data should be utilized to guide patient management. When compared to culture, FDA has found that the majority of rapid influenza virus assays have sensitivity >= 80 and <= 90%, and specificity in the same range. Most of these studies were performed during influenza season in the U.S. or the Southern Hemisphere.

Proper sample collection is the major determinant for obtaining accurate results. It has been reported in the literature and shown during studies conducted by companies that throat swabs are the poorest specimen source with properly collected nasal swabs or washes being the best. The adequacy of samples being tested should be carefully monitored before performing rapid tests and should be factored into interpretation of results.

FDA reminds users that life threatening or potentially threatening adverse device failures should be reported to the agency through the MEDWATCH medical device reporting system. This may be done by visiting the MEDWATCH WWW site at http://www.fda.gov/medwatch/ or calling 1-800-FDA-1088. Less serious adverse device failures may be reported to the FDA by simply sending an e-mail to fdalabtests@cdrh.fda.gov.

References

1. Covalciuc KA, Webb KH, Carlson CA. Comparison of four clinical specimen types for detection of Influenza A and B viruses by optical immunoassay (FLU OIA Test) and cell culture methods. J Clin Micro 1999; 37:3971-3974.

2. Boivin G, Hardy I, Kress A. Evaluation of a rapid optical immunoassay for influenza viruses (FLU OIA Test) in comparison with cell culture and reverse transcription-PCR. J Clin Micro 2002; 39:730-732.

3. Schultze D, Thomas Y, Wunderli W. Evaluation of an optical immunoassay for the rapid detection of influenza A and B viral antigens. Eur J Clin Microbiol Infect Dis 2001; 20:280-382.

4. Tucker SP, Cox C, Steaffens J. A flu optical immunoassay (ThermoBioStar’s FLU OIA): a diagnostic tool for improved influenza management. Philos Trans R Soc Lond B Biol Sci 2001; 356:1915-1024.

5. Yamazaki M, Mitamura K, Kimura K, Komiyama O. et al. Clinical evaluation of an immunochromatography test for rapid diagnosis of influenza. Kansenshogaku Zasshi. 2001; 75:1047-1053.

6. Rodriguez WJ, Schwartz RH, Thorne MM. Evaluation of diagnostic tests for influenza in a pediatric practice. Pediatr Infect Dis J 2002; 21:193-196.

7. Reina J, Padilla E, Alonso F, Ruiz DGE et al. Evaluation of a new dot blot enzyme immunoassay (Directigen flu A+B) for simultaneous and differential detection of influenza A and B virus antigens from respiratory samples. J Clin Micro 2002;40:3513-3517.

8. Uyeki TM. Influenza diagnosis and treatment in children: a review of studies on clinically useful tests and antiviral treatment for influenza. Pediatric Infect. Dis. J 2003; 22:164-177.

Updated 4/3/03

Lab Safety Tip #3

Functions and Limitations of Built-in Controls for Single Use Disposable Tests

Single-use disposable tests, such as visually read tests used for pregnancy or drug testing, often contain a built-in control. These controls are sometimes referred to as process or procedural controls. The following tips will help you understand how these controls function and their limitations.

• Built-in controls may not monitor the entire test system. There is significant variability among different devices in terms of how procedural controls work and the functions they serve. It is recommended that you read the package insert carefully, and pay particular attention to the description of the chemical or immunological reaction that takes place at the control line in the device being used. Use this information to determine what aspects of the test are monitored by the control and what variables are not monitored.

• Built-in controls are sometimes not a good indicator of the viability of test reagents. This is because the reactions occurring at control lines may be more robust than reactions occurring at the test line. For some immunochromatographic tests, the presence of a control line merely indicates that an adequate volume of sample was added and that the membrane strip is intact.

• You should select external control materials that have concentrations of the targeted analyte that are near to the cutoff concentration or medical decision level of the test. This will optimize your ability to detect early stages of reagent degradation.

• External controls are often the only way to monitor the entire test procedure, including pre-analytical steps, operator technique, procedural steps, and reagent viability.

• If the control line does not appear within the read time identified in the package insert, or if the appearance of the line or the background varies from the description provided by the manufacturer, e.g., the line is speckled instead of solid, you should not report patient results.

• When determining when and how often external controls should be run all laboratories should follow local, state, and federal regulatory requirements. Decisions about control frequency and type should be made in the context of the particular operating environment for the laboratory taking into account operator proficiency, the stability of the environment, the volume of testing, and other relevant factors.

Updated 5/1/03

Lab Safety Tip #4

Common Problems with the Use of Glucose Meters

Glucose Testing Tips:

Diabetes care has come a long way since the introduction of insulin and the first oral anti-hyperglycemic medicines. Life span and quality of life have improved for majority of affected individuals. Even better, a large part of diabetic care formerly performed in hospital clinics can now be managed at home with use of well designed home based glucose meters, a telephone and a good patient-doctor relationship.

The Office of In Vitro Diagnostics (OIVD) is charged with the job of evaluating many devices, including glucose meters. OIVD helps these meters come to the public market. Another of its tasks is the continuous evaluation of the same devices for long term safety and effectiveness not just of the devices, but of how the devices are used.

OIVD is taking this opportunity to provide some friendly tips in Point of Care glucose testing inspired by some comments we have received from manufactures and users of these devices.

Causes of false results may be patient/sample based or user/device based. Some common problems and their effects on meter glucose readings are listed below.

The advantage of Point of Care testing is eliminated if proper technique is not followed. In addition to the above recommendations, laboratory professionals must remember to wash hands and change gloves between patients. Also, clean the surface of the meter if blood gets on it. This each time, every time approach helps protect both the patient and the health care worker from blood borne agents like HIV and HCV.

All operators, from patients to non-lab health care workers to medical technologists and physicians, should be thoroughly familiar with any device prior to using it. The best way to do this is to read the package insert and user manual carefully before using a device for the first time. It sounds simple, and it is. If you have any questions, ask someone who is familiar with the device. Another option is calling the customer service telephone number located on most package inserts. The people on the other end are there to help. Another good tip is to reread the package insert every few months. It is a good practice and their may be changes.

Next, watch an experienced laboratory professional, doctor, nurse or diabetic educator perform the test. Then perform the test in front of someone who has experience in using the glucose meter and instructing others on its performance. Ask for tips.

Specific problems come up from time to time including glucose readings that don’t make sense. For example you might feel fine when the glucose meter reading is obviously too high or too low. Remember, the best way to resolve any questionable result, and the best sample from any sick patient, is still a venous blood sample tested at a central lab. Even then any result that does not fit the clinical picture needs to be investigated and, at a minimum, repeated.

For more information also see FDA’s diabetes website at: http://www.fda.gov/diabetes/

Updated 5/1/03

Lab Safety Tip #5

Make sure glucose meters used in testing neonates are FDA cleared for testing in neonates

Glucose Monitoring in Neonates:

Glucose determination in the blood or plasma is used in the diagnosis, monitoring and treatment of persons with diabetes mellitus. Neonates (full term birth to 30 days old) and premature infants (gestational age in weeks at birth up to original due date) represent a mixed group of individuals in whom glucose monitoring is crucial and who have a physiology that differs significantly from older children and adults. Prevention or treatment of hypoglycemia (low blood sugar) in this group is just as important as the recognition and treatment of hyperglycemia (high blood sugar.)

Most full term neonates are born with glucose reserves that last for about 6-24 hours and if feeding or intravenous nutrition is not started in that time period, glucose levels can fall dangerously low. Since if left untreated the child can die or survive with serious impairment, it is common practice to measure the blood glucose of neonates.

When “bedside” glucose monitors were first used for neonates, it was discovered that increased hematocrit levels could interfere with the function of some glucose monitors and produce false low glucose results. The precise mechanism of this interference is debated and may be method dependant. Some people think that the blood may interfere with color based reactions by interfering with light transmittance. An analogy is trying to count the raised fingers on someone’s hand when seen through glass versus tissue paper. In the first case it is easy. In the second situation the hand with some fingers may be recognized but the precise number is undefined. For other methods the blood may be too thick for the chemical reactions to go to completion so less glucose is detected.

FDA has published guidelines to aid the makers of these devices and several have been cleared for use in the neonatal period.

Clinicians should carefully review the claims made to help determine if the device in question is appropriate for neonatal use. It is also a good idea to perform a literature search to see if there are studies published in refereed journals investigating the candidate glucose meter in the population in question (e.g.: healthy full term newborns or critically ill preterm neonates.) Even so, no matter what device is used it is crucial that the end user clinicians validate the meters they are considering for use. The clinicians should work closely with the central lab and compare candidate devices against their central laboratory’s current reference method. Given the acuity of care, it may also be a good idea to periodically reevaluate these meters against the reference standard and to develop quality assurance and quality control programs.

In closing, increased hematocrit may interfere with some blood glucose meters. If a result does not make sense the clinician needs to do two things. First, reassess the patient. Second, if it is clinically appropriate, get a new sample and verify the result using an accepted reference method.

Bibliography:

Anonymous. Points to consider for portable blood glucose monitoring devices intended for bedside use in the neonate nursery. FDA Guidance Document (http://www.fda.gov/cdrh/ode/122.pdf). February 20, 1996.

Anonymous. Review Criteria Assessment of Portable Blood Glucose Monitoring In Vitro Diagnostic Devices Using Glucose Oxidase, Dehydrogenase or Hexokinase Methodology (Draft Document). FDA Guidance Document (http://www.fda.gov/cdrh/ode/gluc.html). February 14, 1996.

Girouard J, et al. Multicenter Evaluation of the Glucometer Elite XL Meter; an Instrument Specifically Designated for Use With Neonates. Diabetes Care. 23(8); 1149-1153. August 2000.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods, 19’th Ed. Philadelphia, WB Saunders, 1996. pp 197-199.

Perkins SL, et al. Laboratory and Clinical Evaluation of Two Glucose Meters for the Neonatal Intensive Care Unit. Clinical Biochemistry. 31(2); 67-71. 1998.

Soldin SJ, Devairakkam PD, Adarwalla PK. Evaluation of the Abbot PCx® Point of Care Glucose Analyzer in a Pediatric Hospital. Clinical Biochemistry. 33(4); 319-321. 2000.

St-Louis P, Ethier J. An Evaluation of three glucose meter systems and their performance in relation to criteria of acceptability for neonatal specimens. Clinical Chimica Acta. 322; 139-148. 2002.

Updated June 19, 2003

Glucose Meter Test Results: Useful Tips to Increase Accuracy and Reduce Errors

Have you ever wondered why you got a bad glucose meter test result when there is nothing obvious wrong with your meter, your test strips are new, and you’ve been running glucose tests for years? The simple answer is that glucose meters are not perfect, and neither are the people who use them! This chart lists some tips to help you get the most accurate results from your glucose meter.

Updated July 14, 2003

Lab Safety Tip Archive

There are no lab safety tips archived at this time.

Reporting Problems with Laboratory Tests and Equipment

Once an IVD device goes into widespread use, unforeseen problems can arise. FDA's premarket review cannot always detect adverse events that are rare or if the problems are related to the clinical use of the device, manufacturing problems, product labeling (including instructions for use), or user technique and skill. To identify these problems, FDA and manufacturers depend on reports from the individuals and facilities that use IVD devices.

What types of problems should be reported?

• Device problems including
  • reagent or instrument failure
  • defects in product design or development
  • product instability
  • any other device problems that compromise patient health or safety
  • failure to perform according to performance characterized in package insert
  • incorrect test results that cause or contributed to an incorrect patient diagnosis and/or treatment
     
• Use-related problems including
  • inadequate and/or misleading labeling or confusing user instructions
  • inadequate packaging or poor package design
  • any other user problems that compromise patient health or safety

Who should report IVD device problems?

• User facilities, including hospitals, ambulatory surgical facilities, nursing homes, outpatient treatment facilities, or outpatient diagnostic facilities are required to report
   
  • device-related events that have caused, or may have caused or contributed to a death to both the FDA and the manufacturer.
  • device-related events that have caused, or may have caused or contributed to a serious illness or injury to the manufacturer. If the medical device manufacturer is unknown, the serious injury is reported by the facility to FDA.
     
• All other IVD device users, including doctors and patients, are encouraged to voluntarily report device problems directly to the manufacturer and/or FDA whenever it is suspected that the product caused or contributed to an adverse outcome. FDA is interested in reports of:
   
  • product problems such as erroneous results (false positive or false negative),
  • unexplained quality control (QC) failures,
  • inaccurate or unreadable instructions for use,
  • packaging or product mix-up,
  • contamination or stability problems,
  • defective devices,
  • product confusion caused by name, labeling, design, or packaging,
  • "near misses" where under slightly different circumstances, a serious injury or death might have occurred, or
  • use error

How should IVD device problems be reported?

• Mandatory Reporting by User Facilities (MDR)
• Voluntary Reporting by Consumers (MedWatch)
• Voluntary Reporting by Healthcare Professionals (MedWatch)

If you want to notify OIVD directly of a problem with a laboratory test or other equipment, contact us at fdalabtest@cdrh.fda.gov.

What happens to your report?

When FDA receives a report from a user facility, device user or an individual healthcare professional, it is entered in the medical device postmarket surveillance database. FDA continually reviews the database to detect problems, trends, and potential hazards. When FDA detects risks or potential risks associated with the use of a particular product, the agency can take corrective actions and notify the public.

Who has access to your report?

FDA is aware that IVD device users are concerned about the issue of confidentiality and public availability of reports. For all reports, FDA holds the patient's identity in strict confidence and protects it to the fullest extent of the law. FDA will not release any patient identifiers to the public. Reporters can assist in this process by not using the patient's name, initials, or other identifying information. The reporter's identity, including the identity of a self-reporter, may be shared with the manufacturer unless requested otherwise (there is a check-off box on the report form). However, FDA will not disclose the reporter's identity in response to a request from the public, pursuant to the Freedom of Information Act.

See also:

Medical Device Reporting for User Facilities

MedWatch: The FDA Safety Information and Adverse Event Reporting Program

Patient Safety News

Patient Safety News is a televised series for health care personnel, carried on satellite broadcast networks across the country. Each edition features information on new medical devices, on FDA safety notifications and product recalls, and on ways to protect patients when using medical devices. The Patient Safety News website contains the text for each broadcast, plus links for more information on each story. It also has instructions for purchasing videotapes of previous broadcasts and sending comments to FDA about the broadcast.

See also:

FDA Patient Safety News

Lab Tests Online

This link from the American Association for Clinical Chemistry gives detailed information about clinical laboratory tests. You can use this website to learn general information about lab tests as well as specific information about a particular test.

Lab Tests Online