The role of Food and Drug Administration regulation of in vitro diagnostic devices--applications to genetics testing.
(9/1942)
The Food and Drug Administration (FDA) has been involved in the regulation of in vitro diagnostic devices (IVDs or laboratory tests) since the introduction of the Medical Device Amendments of 1976. IVDs developed as kits or systems intended for use in multiple laboratories require review by the FDA before being marketed to ensure appropriate performance and labeling. IVDs developed as in-house, or so-called "home-brew", tests or laboratory test services are considered medical devices, but historically have not been subject to premarket review as a matter of enforcement discretion. FDA recently established a new regulatory paradigm for in-house tests based on classification of the active ingredients or building blocks of these tests as analyte-specific reagents (ASRs). ASRs are exempt from premarket review but subject to both manufacturing and labeling controls. Currently, genetic tests are received and reviewed by the FDA in the same manner as other in vitro diagnostic tests. The FDA currently is in the process of chartering a new genetics advisory panel to provide the agency with outside expertise to deal with genetic testing issues. We are also continuing to work with other agencies within the Department of Health and Human Services to determine how we can cooperatively help foster this important new area of testing. (+info)
Enhanced Amplified Mycobacterium Tuberculosis Direct Test for detection of Mycobacterium tuberculosis complex in positive BACTEC 12B broth cultures of respiratory specimens.
(10/1942)
The reliability of the Gen-Probe enhanced Amplified Mycobacterium Tuberculosis Direct Test (MTD) for identification of Mycobacterium tuberculosis complex (MTBC) in BACTEC 12B broth cultures of respiratory specimens was evaluated by testing aliquots from 268 bottles with a growth index of >/=50. MTD results were compared to those obtained by usual laboratory protocol, whereby MTBC was identified by DNA probe (Gen-Probe, Inc.) testing sediment from broth samples or colonies on a solid medium. For the first 134 cultures, from which 68 mycobacterial isolates (including 27 MTBC isolates) were recovered, both fresh and frozen aliquots were tested. MTD results for the frozen aliquots agreed with the identification by usual protocol in all cases, whereas there was one false-negative MTD result with fresh aliquots. For the remaining 134 cultures, only frozen aliquots were tested. Of the total 268 broth cultures (from 210 patients) evaluated, 137 (51.1%) grew mycobacteria, including 60 MTBC isolates. All 60 isolates were MTD positive, as was one additional culture that grew Mycobacterium gordonae. The latter culture was from a patient who was diagnosed with tuberculosis a few months earlier and was on therapy; therefore, the MTD result was considered a true positive. Sensitivity, specificity, and positive and negative predictive values of MTD were 100%. The mean times from specimen receipt to identification of MTBC were 15 (+/-1) days (range, 4 to 27 days) for BACTEC plus MTD and 19 (+/-1) days (range, 6 to 36 days) for the usual protocol (P < 0.001). These data indicate that the MTD is a rapid, reliable method for identification of MTBC in fresh or frozen aliquots of broth from positive BACTEC 12B cultures of respiratory specimens. (+info)
Evaluation of vocabularies for electronic laboratory reporting to public health agencies.
(11/1942)
Clinical laboratories and clinicians transmit certain laboratory test results to public health agencies as required by state or local law. Most of these surveillance data are currently received by conventional mail or facsimile transmission. The Centers for Disease Control and Prevention (CDC), Council of State and Territorial Epidemiologists, and Association of Public Health Laboratories are preparing to implement surveillance systems that will use existing laboratory information systems to transmit electronic laboratory results to appropriate public health agencies. The authors anticipate that this will improve the reporting efficiency for these laboratories, reduce manual data entry, and greatly increase the timeliness and utility of the data. The vocabulary and messaging standards used should encourage participation in these new electronic reporting systems by minimizing the cost and inconvenience to laboratories while providing for accurate and complete communication of needed data. This article describes public health data requirements and the influence of vocabulary and messaging standards on implementation. (+info)
Elder mistreatment.
(12/1942)
Elder mistreatment is a widespread problem in our society that is often under-recognized by physicians. As a result of growing public outcry over the past 20 years, all states now have abuse laws that are specific to older adults; most states have mandated reporting by all health care professionals. The term "mistreatment" includes physical abuse and neglect, psychologic abuse, financial exploitation and violation of rights. Poor health, physical or cognitive impairment, alcohol abuse and a history of domestic violence are some of the risk factors for elder mistreatment. Diagnosis of elder mistreatment depends on acquiring a detailed history from the patient and the caregiver. It also involves performing a comprehensive physical examination. Only through awareness, a healthy suspicion and the performing of certain procedures are physicians able to detect elder mistreatment. Once it is suspected, elder mistreatment should be reported to adult protective services. (+info)
Necessary sample size for method comparison studies based on regression analysis.
(13/1942)
BACKGROUND: In method comparison studies, it is of importance to assure that the presence of a difference of medical importance is detected. For a given difference, the necessary number of samples depends on the range of values and the analytical standard deviations of the methods involved. For typical examples, the present study evaluates the statistical power of least-squares and Deming regression analyses applied to the method comparison data. METHODS: Theoretical calculations and simulations were used to consider the statistical power for detection of slope deviations from unity and intercept deviations from zero. For situations with proportional analytical standard deviations, weighted forms of regression analysis were evaluated. RESULTS: In general, sample sizes of 40-100 samples conventionally used in method comparison studies often must be reconsidered. A main factor is the range of values, which should be as wide as possible for the given analyte. For a range ratio (maximum value divided by minimum value) of 2, 544 samples are required to detect one standardized slope deviation; the number of required samples decreases to 64 at a range ratio of 10 (proportional analytical error). For electrolytes having very narrow ranges of values, very large sample sizes usually are necessary. In case of proportional analytical error, application of a weighted approach is important to assure an efficient analysis; e.g., for a range ratio of 10, the weighted approach reduces the requirement of samples by >50%. CONCLUSIONS: Estimation of the necessary sample size for a method comparison study assures a valid result; either no difference is found or the existence of a relevant difference is confirmed. (+info)
Proficiency of clinical laboratories in Spain in detecting vancomycin-resistant Enterococcus spp. The Spanish VRE Study Group.
(14/1942)
Studies in a variety of U.S. clinical laboratories have demonstrated difficulty in detecting intermediate and low-level vancomycin-resistant enterococci (VRE). The misclassification of "at least intermediate resistant isolates" as vancomycin susceptible may have both clinical implications and a negative impact on measures to control the spread of VRE. No published study has assessed the ability of clinical laboratories in Europe to detect VRE. So, the apparent low prevalence of VRE in European hospitals may be, in part, secondary to the inability of these laboratories to detect all VRE. In an effort to assess European laboratories' proficiency in detecting VRE, we identified 22 laboratories in Spain and asked them to test four VRE strains and one susceptible enterococcal strain from the Centers for Disease Control and Prevention collection. Each organism was tested by the routine antimicrobial susceptibility testing method used by each laboratory. Overall, VRE were correctly identified in 61 of 88 (69.1%) instances. The accuracy of VRE detection varied with the level of resistance and the antimicrobial susceptibility method. The high-level-resistant strain (Enterococcus faecium; MIC, 512 microg/ml) was accurately detected in 20 of 22 (91. 3%) instances, whereas the intermediate-resistant isolate (Enterococcus gallinarum; MIC, 8 microg/ml) was accurately detected in only 11 of 22 (50%) instances. Classification errors occurred in 27 of 88 (30.9%) instances. Misclassification as vancomycin susceptible was the most common error (16 of 27 [59.3%] instances). Our study shows that the participating Spanish laboratories had an overall acceptable proficiency in detecting VRE but that a substantial proportion of VRE isolates with low or intermediate levels of resistance were not detected. We recommend that studies be conducted to validate laboratory proficiency testing as an important step in the prevention and control of the spread of antimicrobial resistance. (+info)
Fluconazole susceptibilities of bloodstream Candida sp. isolates as determined by National Committee for Clinical Laboratory Standards method M27-A and two other methods.
(15/1942)
The in vitro activity of fluconazole against 143 Candida spp. obtained from the bloodstreams of 143 hospitalized patients from 1995 to 1997 was studied. Susceptibility tests were carried out by two macrodilution methods, the M27-A and a modified M27-A method (0. 165 M, pH 7/morpholinepropanesulfonic acid-buffered RPMI 1640 medium supplemented with 20 g of D-dextrose per liter), and by the agar diffusion method (with 15-microg fluconazole [Neo-Sensitab] tablets). With 2 microg of fluconazole per ml, 96.92% of 65 C. albicans isolates, 86.2% of 58 C. parapsilosis isolates 7 of 8 C. tropicalis isolates, and 1 of 6 C. glabrata isolates were inhibited. Only one strain of C. albicans and one strain of C. tropicalis were resistant. The agreement between the two macrodilution methods was greater than 90% within +/-2 log2 dilutions for all strains except C. glabrata (83.3%) and C. tropicalis (87.5%). Generally, MICs were 1 log2 dilution lower in glucose-supplemented RPMI 1640 medium. No correlation between zone sizes and MICs was found. All strains susceptible by the diffusion test were susceptible by the dilution method, but the converse was not necessarily true. Interestingly, inhibition zones were smaller for C. albicans, for which the geometric mean MIC was 0.29 microg/ml and the mean inhibition zone diameter was 25.7 mm, while for C. parapsilosis the geometric mean MIC was 0.96 microg/ml and the mean inhibition zone diameter was 31. 52 mm. In conclusion, the two macrodilution methods give similar results. The modified M27-A method with 2% dextrose has the advantage of shortening the incubation time and simplifying the endpoint determination. (+info)
Laboratory practices for prenatal Group B streptococcal screening and reporting--Connecticut, Georgia, and Minnesota, 1997-1998.
(16/1942)
Group B Streptococcus (GBS) is a leading cause of neonatal sepsis in the United States. CDC, in collaboration with the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics, recommends that laboratories adopt optimal screening practices to identify GBS and to promptly report test results so that GBS-colonized pregnant women can receive antibiotics during labor. To assess GBS screening practices in clinical laboratories, state health departments surveyed laboratories in Connecticut, Georgia, and Minnesota, participants in the Emerging Infections Program. The survey found that the practices of some participating laboratories were suboptimal, particularly in their lack of use of selective broth media for culture of GBS. (+info)