Medical devices; exception from general requirements for informed consent. Final rule.

The Food and Drug Administration (FDA) is issuing a final regulation to confirm, with one change, the interim final rule (IFR) entitled "Medical Devices; Exception From General Requirements for Informed Consent." This final rule confirms the IFR's establishment of a new exception from the general requirements for informed consent to permit the use of investigational in vitro diagnostic devices to identify chemical, biological, radiological, or nuclear agents without informed consent in certain circumstances. FDA has created this exception to help ensure that individuals who may have been exposed to a chemical, biological, radiological, or nuclear agent are able to benefit from the timely use of the most appropriate diagnostic devices, including those that are investigational. This final rule adds a requirement that the investigator submit the required documentation to FDA, in addition to submitting it to the reviewing Institutional Review Board (IRB).

The truth about quality: medical usefulness and analytical reliability of laboratory tests.

BACKGROUND: In this age of evidence-based medicine, nothing is more important than the quality of laboratory tests. It is commonly thought that laboratory tests provide two-thirds to three-fourths of the information used for making medical decisions. If so, test results had better tell the truth about what is happening with our patients. METHODS: The age-old "truth standard" for the quality of evidence describes three dimensions that are important-a test should tell the truth, the whole truth, and nothing but the truth. This three-dimensional model can be used to characterize the clinical and analytical reliability of laboratory tests and guide the translation of outcome criteria, or quality goals, into practical specifications for method performance. RESULTS: Clinical reliability, or medical usefulness, should assess the correctness of patient classifications based on stated test interpretation guidelines, taking into account the precision and accuracy of the laboratory method, and allowing for the known within-subject biologic variation and the QC needed to detect method instability. Analytical reliability should assess the correctness of a test result based on a stated error limit, taking into account the precision and accuracy of the method and allowing for the QC necessary to detect method instability. These assessments challenge the reliability of current tests for cholesterol, glucose, and glycated hemoglobin in the implementation of U.S. national clinical guidelines. CONCLUSIONS: Evidence-based medicine must employ scientific methodology for translating test interpretation guidelines into practical, bench-level, operating specifications for the imprecision and inaccuracy allowable for a method and the QC necessary to detect method instability.

Test result variation and the quality of evidence-based clinical guidelines.

BACKGROUND: There is a plethora of supposedly evidence-based published clinical guidelines, most often prepared under the auspices of professional bodies. Many guidelines contain numerical laboratory test results as criteria for clinical action, very often simply quoted as single numbers. Every test result is subject to a number of sources of variation. Analytical imprecision and within-subject biological variation are particularly important. The influence of both of these on the dispersion of a single test result and on the number of samples required to make clinical decisions can be easily calculated using simple formulae. The effect of performing replicate analyses of one sample and of taking multiple samples can also be easily investigated. Authors of scientific statements, clinical guidelines, and practice recommendations should undertake such calculations before promulgating their efforts in the public domain. Guidelines on cholesterol and high sensitivity C-reactive protein have been examined using these approaches and these investigations allow the following conclusions. CONCLUSIONS: Analytical imprecision should be made low. If analytical imprecision is generally greater than biological variation, then reduction in analytical imprecision is valuable. If biological variation is greater than imprecision, then collection of more than one sample from an individual prior to decision-making is useful.

Alcohol and the laboratory in the United Kingdom.

Reliable and rapid assays for the measurement of ethanol in breath and body fluids are now widely available. In view of the importance of alcohol abuse as a cause of a wide variety of both acute and chronic clinical conditions, hospital laboratories should be prepared to perform these assays for clinical purposes, although many will choose not to become involved in the assay of medico-legal samples.

Medical devices; clinical chemistry and clinical toxicology devices; classification of newborn screening test systems for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. Final rule.

The Food and Drug Administration (FDA) is classifying newborn screening test systems for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry into class II (special controls). The special control that will apply to the device is the guidance document entitled "Class II Special Controls Guidance Document: Newborn Screening Test Systems for Amino Acids, Free Carnitine, and Acylcarnitines Using Tandem Mass Spectrometry." The agency is taking this action in response to a petition submitted under the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of 1990, the Food and Drug Administration Modernization Act of 1997, and the Medical Device User Fee and Modernization Act of 2002. The agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device. Elsewhere in this issue of the Federal Register, FDA is publishing a notice of availability of a guidance document that is the special control for this device.

Education of medical biochemists in Bosnia and Herzegovina.

In this paper we would like to briefly introduce readers to the situation in the field of laboratory medicine in Bosnia and Herzegovina, with a focus on training in the field of medical biochemistry. As in some of neighboring countries, term Medical biochemist is the usual name for the Clinical biochemist or Clinical chemist in Bosnia and Herzegovina. Despite the difficult period through which the profession had passed in the last two decades, laboratory work, particularly clinical biochemistry, has managed to retain the necessary quality and keep pace with the developed world. In post war period, Society of Medical Biochemists of Bosnia and Herzegovina held regular meetings each year as a part of "life long learning" process, where both scientific and vocational lecturers presented their work. A single law on the state level would provide us with more defined and precise answers, such as: who can get a specialization, how long should last the training for medical biochemistry specialists (duration in years). This law should be in consent with the program described in EC4 or other documents given by the EFCC (European Federation of Clinical Chemistry and Laboratory Medicine) and IFCC (International Federation of Clinical Chemistry and Laboratory Medicine).

The regulation of clinical chemistry in Slovenia.

The practice of medical biochemistry in Slovenia includes clinical biochemistry (including toxicology, therapeutic drug monitoring, endocrinology, molecular diagnostics, immunology), hematology and coagulation. To start the vocational medical biochemistry training programme it's necessary to have a completed university degree (second cycle) in pharmacy, chemistry, biochemistry, medicine or other relevant university study and 1 year supervised practical training in medical laboratories, completed with mandatory state exam at Ministry of Health. The duration of vocational training programme is 4 years and is completed with final exam. The title after passed final examination is Medical biochemistry specialist. In October 2005 EC4 (Communities Confederation of Clinical Chemistry and Laboratory Medicine) approved Equivalence of standards of Slovenian national standards for medical biochemistry specialists. Since 2006 it is mandatory to be registered and to have valid license for medical biochemistry specialists and other professionals in laboratory medicine with at least university degree (second cycle) of education. Laboratory medicine in Slovenia is regulated globally through the Law of health-care activity and particularly through the Bylaw of laboratory medicine. The latter is based on standard ISO 15189, ratified in 2004. The Bylaw envisages granting working license to laboratories, valid for 5 years period. Granting of working licenses is ongoing process and first licenses have been granted in 2009. Important improvement toward the quality requirements for medical laboratories can be observed in the last 5 years. Parallel with the Bylaw of medical laboratories, Slovenian Accreditation (SA), the legal national accreditation body, started the initiative for accreditation of medical laboratories according to ISO 15189. It is in the implementation phase.

Clinical chemistry and laboratory medicine in Croatia: regulation of the profession.

Heterogeneity exists across Europe in the definition of the profession of clinical chemistry and laboratory medicine and also in academic background of specialists in this discipline. This article provides an overview of the standards of education and training of laboratory professionals and quality regulations in Croatia. Clinical chemistry in Croatia is almost exclusively practiced by medical biochemists. Although term Medical biochemist often relates to medical doctors in other European countries, in Croatia medical biochemists are not medical doctors, but university degree professionals who are qualified scientifically. Practicing the medical biochemistry is regulated by The Health Care Law, The Law of the Medical Biochemistry Profession and The Law of the State and Private Health Insurance. According to the law, only medical biochemists are entitled to run and work in the medical biochemistry laboratory. University degree is earned after the 5 years of the studies. Register for medical biochemists is kept by the Croatian Chamber of Medical Biochemists. Licensing is mandatory, valid for 6 years and regulated by the government (Law on the Health Care, 1993). Vocational training for medical biochemists lasts 44 months and is regulated by the national regulatory document issued by the Ministry of Health. Accreditation is not mandatory and is provided by an independent, non-commercial national accreditation body. The profession has interdisciplinary character and a level of required competence and skills comparable to other European countries.

Quality regulations and accreditation standards for clinical chemistry in Turkey.

OBJECTIVE: The purpose of this paper is to review the current status of laboratory quality regulations and accreditation standards in Turkey. DESIGN AND METHOD: This paper is written based on the current regulations, information collected by available websites and congress proceedings, and personal communications. RESULTS: A total of 14 private and one public laboratory have been accredited according to ISO 15189 voluntarily. The total number of the JCI accredited hospitals is 24. One hospital has been accredited by HQS. A few medical laboratories have been accredited according to ISO 17025, whereas a lot of them have ISO 9001 certification from Turkish Accreditation Agency, TURKAK. There are no comprehensive laboratory standards and/or regulations to maintain a mandatory minimum quality of laboratories. External QC is not mandatory and there is no national proficiency testing program. It is a requirement to get a license to open a laboratory. There are residency programs for clinical chemistry and clinical microbiology. The Association of Clinical Biochemists, KBUD, is the youngest society in the field of clinical chemistry and is a leader in quality and accreditation activities. KBUDEK is an external QC program of KBUD. KBUD has organized four national and an international symposiums on quality and accreditation in addition to annual congresses and courses. CONCLUSION: The new standard and regulation should be designed and applied to all laboratories to increase the quality of laboratory service in Turkey. It will be useful if the ISO 15189 standard can be incorporated into the national standards and regulations.

Governmental perspectives on evaluating laboratory performance.

The quality of laboratory analytical performance required to support medical decision-making has been defined in four major ways: (a) by the analytical variance of the state of the practice; (b) by the total variance, including analytical and biological variability; (c) by the loss of diagnostic efficiency attributable to analytical error; and (d) by medical-usefulness criteria. From the federal government's perspective, the answer to the question "How good must a laboratory test result be to be medically relevant?" must take into account the clinical context of the test, with accompanying concerns about access, timeliness, and cost, as well as limits for precision and accuracy in the analytical process and the frequency and potential patient-care impact of error in the pre- and postanalytical steps of the total testing process. Therefore, medically relevant goals should encompass not only analytical precision and accuracy but also goals to provide access to clinically effective tests and to reduce errors in the total testing process that can lead to medically misleading information. Development of more appropriate regulatory requirements for laboratories, as well as any needed improvements in instrumentation and methodology, should focus on ensuring that goals for medically relevant results are met by appropriate design and management of the entire process of laboratory testing.

Cholesterol--a model system to relate medical needs with analytical performance.

The evolution of cholesterol testing provides an example of a systematic approach that developed to relate the medical use of a laboratory test with the analytical performance requirements for that test. Laboratories today have the capability to perform cholesterol testing with the accuracy and precision necessary to meet medical needs. This statement can be made because (a) a standard diagnostic process has been established by the National Cholesterol Education Program; (b) an accuracy base is provided through a reference method that is readily available to manufacturers and laboratories; (c) the precision of analytical systems has been improved by manufacturers; (d) operating specifications for all such systems can be established, with statistical quality-control rules to ensure adequate within-run method performance; and (e) analytical performance is monitored by proficiency testing by using national quality requirements defined by CLIA '88 for acceptability. This cholesterol model provides a logical and scientific approach that should be applicable with other analytes to assure that the analytical performance of the laboratory test satisfies medical needs.

Quality: the next six months.

The eclectic mix of participants in the forum had a surprisingly singular focus when it came to the topic of quality in clinical laboratories. All sensed that the time is right for a transition from laws, rules, and inspections to a true quality-based system. Such a system can achieve the goals, implicit and explicit, that are the rationale for the multiplicity of regulations affecting today's laboratories. A true quality-based system has great potential benefits to laboratories, regulators, and manufacturers, and ultimately to our true customers, the patients. The benefits include lower costs, superior products, and better test results; in short, better patient care. This transition will be possible only through formation of a "Quality Alliance," composed of those skilled in the "theory" of quality-laboratory personnel, manufacturers, and regulators, acting as one to implement the quality system. The Quality Alliance requires a team of individuals with different skills, aligned as one, for the purpose of achieving a common goal. On the basis of views expressed in this Forum, our collective future will be defined by the evolving Quality Alliance, an alliance focused on true quality systems in clinical laboratories.

Probable impact of the 1994 elections on laboratory medicine.

During the past quarter century, federal health policy makers concerned themselves with: (a) improving the quality of healthcare delivered to the American public; (b) increasing access to needed healthcare services; and (c) curtailing the escalating cost of such services. These goals led Congress to expand the role of the federal government in regulating the delivery of healthcare. The enactment of the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) was a significant and widely discussed example of how Congress, when controlled by the Democrats, sought to correct healthcare problems and achieve federal objectives. In November 1994, the Republicans won majorities in both the Senate and the House, promising to reduce the federal government's power. Many now believe that CLIA '88, or significant parts of it, could be substantially modified as part of this effort. This paper addresses the developments that led the Democrats to seek enactment of CLIA '88 and the likely arguments that may be offered by the Republicans to lessen the rigor and scope of the law.