Driver dependent factors and the risk of causing a collision for two wheeled motor vehicles.
(73/341)
OBJECTIVE: To assess the effect of driver dependent factors on the risk of causing a collision for two wheeled motor vehicles (TWMVs). DESIGN: Case control study. SETTING: Spain, from 1993 to 2002. SUBJECTS: All drivers of TWMVs involved in the 181 551 collisions between two vehicles recorded in the Spanish registry which did not involve pedestrians, and in which at least one of the vehicles was a TWMV and only one driver had committed a driving infraction. The infractor and non-infractor drivers constituted the case and control groups, respectively. MAIN OUTCOME MEASURES: Logistic regression analyses were used to obtain crude and adjusted odds ratio estimates for each of the driver related factors recorded in the registry (age, sex, nationality, psychophysical factors, and speeding infractions, among others). RESULTS: Inappropriate speed was the variable with the greatest influence on the risk of causing a collision, followed by excessive speed and driving under the influence of alcohol. Younger and older drivers, foreign drivers, and driving without a valid license were also associated with a higher risk of causing a collision. In contrast, helmet use, female sex, and longer time in possession of a driving license were associated with a lower risk. CONCLUSIONS: Although the main driver dependent factors related to the risk of causing a collision for a TWMV were similar to those documented for four wheeled vehicles, several differences in the pattern of associations support the need to study moped and motorcycle crashes separately from crashes involving other types of vehicles. (+info)
Evaluation of particulate filtering respirators using inward leakage (IL) or total inward leakage (TIL) testing--Korean experience.
(74/341)
Korean certification regulation for particulate filtering respirators requires inward leakage (IL) or total inward leakage (TIL) testing according to European Standard EN 13274-1, and the standard levels of compliance are similar to those of the European Standard. This study was conducted to evaluate particulate filtering respirators being commercially used in the Korean market using an IL or TIL test and the validity of standard level in Korea. Three half masks and 10 filtering facepieces (two top class, four 1st class and four 2nd class)-a total of 13 brand name respirators-were selected for the test with panels of 10 subjects. Each subject was classified with nine facial dimension grid squares in accordance with face length and lip length. IL or TIL testing was conducted at the laboratory of the 3M Innovation Center in which the experimental instruments and systems were established in compliance with European standards. The testing procedure followed EN 13274-1 (2001). As expected, leakages of half masks were less than those of filtering facepieces and the latter were significantly different among brands. TILs of the 1st class filtering facepieces were found to be much more than those of the 2nd class and the result may cause a wearer to get confused when selecting a mask. The main route leakage for filtering facepieces may not be the filter medium but the face seal. Therefore, it is necessary to develop well-fitting filtering facepieces for Koreans. Because leakages were significantly different for different facial dimensions, a defined test panel for IL or TIL testing according to country or race should be developed. A more precise method to demonstrate fit, for example, fit testing such as in the US regulations, will be needed before IL or TIL testing or when selecting a respirator. Another finding implies that geometric mean of five exercises for IL or TIL may be better than arithmetic mean to establish a standard individual subject mean. (+info)
Ten years of marketing approvals of anticancer drugs in Europe: regulatory policy and guidance documents need to find a balance between different pressures.
(75/341)
Despite important progress in understanding the molecular factors underlying the development of cancer and the improvement in response rates with new drugs, long-term survival is still disappointing for most common solid tumours. This might be because very little of the modest gain for patients is the result of the new compounds discovered and marketed recently. An assessment of the regulatory agencies' performance may suggest improvements. The present analysis summarizes and evaluates the type of studies and end points used by the EMEA to approve new anticancer drugs, and discusses the application of current regulations. This report is based on the information available on the EMEA web site. We identified current regulatory requirements for anticancer drugs promulgated by the agency and retrieved them in the relevant directory; information about empirical evidence supporting the approval of drugs for solid cancers through the centralised procedure were retrieved from the European Public Assessment Report (EPAR). We surveyed documents for drug applications and later extensions from January 1995, when EMEA was set up, to December 2004. We identified 14 anticancer drugs for 27 different indications (14 new applications and 13 extensions). Overall, 48 clinical studies were used as the basis for approval; randomised comparative (clinical) trial (RCT) and Response Rate were the study design and end points most frequently adopted (respectively, 25 out of 48 and 30 out of 48). In 13 cases, the EPAR explicitly reported differences between arms in terms of survival: the range was 0-3.7 months, and the mean and median differences were 1.5 and 1.2 months. The majority of studies (13 out of 27, 48%) involved the evaluation of complete and/or partial tumour responses, with regard to the end points supporting the 27 indications. Despite the recommendations of the current EMEA guidance documents, new anticancer agents are still often approved on the basis of small single arm trials that do not allow any assessment of an 'acceptable and extensively documented toxicity profile' and of end points such as response rate, time to progression or progression-free survival which at best can be considered indicators of anticancer activity and are not 'justified surrogate markers for clinical benefit'. Anticipating an earlier than ideal point along the drug approval path and the use of not fully validated surrogate end points in nonrandomised trials looks like a dangerous shortcut that might jeopardise consumers' health, leading to unsafe and ineffective drugs being marketed and prescribed. The present Note for Guidance for new anticancer agents needs revising. Drugs must be rapidly released for patients who need them but not be at the expense of adequate knowledge about the real benefit of the drugs. (+info)
How good are clinical laboratories? An assessment of current performance.
(76/341)
The Clinical Laboratory Improvement Act of 1967 and Amendments of 1988 (CLIA '67 and CLIA '88) were enacted to ensure that clinical laboratories within the U.S. provide a quality of service that meets clinical needs for good patient care. Approved proficiency-testing programs are to judge the quality of laboratory testing by promulgated performance criteria. We examine the quality of analytical results reported in 1991 to the New York State Department of Health Proficiency Testing program in light of these criteria and analytical goals, based on medical usefulness. Analytical performance is examined for cholesterol, potassium, sodium, calcium, glucose, aspartate aminotransferase, digoxin, and theophylline. In general, proposed CLIA '88 performance standards are compatible with the current state of practice for the population of laboratories examined. Exceptions appear to be digoxin and sodium (failure rate exceeding average) and most therapeutic substances (low failure rate). Sources of analytical bias relative to an accuracy-based target value must be characterized as method-, laboratory-, or matrix-dependent if regulatory programs are to achieve the objective of improving analytical accuracy across all testing sites. (+info)
Charts of operational process specifications ("OPSpecs charts") for assessing the precision, accuracy, and quality control needed to satisfy proficiency testing performance criteria.
(77/341)
"Operational process specifications" have been derived from an analytical quality-planning model to assess the precision, accuracy, and quality control (QC) needed to satisfy Proficiency Testing (PT) criteria. These routine operating specifications are presented in the form of an "OPSpecs chart," which describes the operational limits for imprecision and inaccuracy when a desired level of quality assurance is provided by a specific QC procedure. OPSpecs charts can be used to compare the operational limits for different QC procedures and to select a QC procedure that is appropriate for the precision and accuracy of a specific measurement procedure. To select a QC procedure, one plots the inaccuracy and imprecision observed for a measurement procedure on the OPSpecs chart to define the current operating point, which is then compared with the operational limits of candidate QC procedures. Any QC procedure whose operational limits are greater than the measurement procedure's operating point will provide a known assurance, with the percent chance specified by the OPSpecs chart, that critical analytical errors will be detected. OPSpecs charts for a 10% PT criterion are presented to illustrate the selection of QC procedures for measurement procedures with different amounts of imprecision and inaccuracy. Normalized OPSpecs charts are presented to permit a more general assessment of the analytical performance required with commonly used QC procedures. (+info)
Limitations of proficiency testing under CLIA '67.
(78/341)
Proficiency testing (PT), recognized as a quality-assurance (QA) and quality-improvement tool, also has become the cornerstone of the Health Care Financing Administration's (HCFA) regulatory strategy under the revised Clinical Laboratory Improvement Act of 1967 (CLIA '67) and the proposed Clinical Laboratory Improvement Amendments of 1988 (CLIA '88). Use of PT as a regulatory tool corrupts it for things it can do better. PT as a primary regulatory strategy has severe limitations. We explore the nature of these limitations and their implications for clinical laboratories as they impact on the long-term success of HCFA's approved regulatory PT programs in 1991 and beyond, and CLIA '88 PT, which is to be implemented in 1994. (+info)
Review of actual proficiency-testing performance under CLIA '67 (March 14, 1990) rules: perspective from the first year's data.
(79/341)
Under the Clinical Laboratory Improvement Act of 1967 the Health Care Financing Administration's proficiency-testing requirement applies to approximately 12,000 hospital, reference, and large-clinic laboratories in the United States. The Wisconsin State Laboratory of Hygiene is approved by the Health Care Financing Administration to provide proficiency testing in all specialties and subspecialties. The focus of the program is to provide highly specialized service and support to a limited number of participants in order to assess intralaboratory performance correctly. We report the findings over the four proficiency-testing events in 1991 for the subspecialty of routine chemistry, which serves approximately 470 participants. Failure rates for individual analytes on single proficiency testing events ranged from 0% to 13%. After four events or one year, if the mandated evaluation criteria and failure rules were strictly applied, as many as 11% of the laboratories could have found themselves involuntarily suspended from offering all routine chemistry testing. (+info)
Proficiency testing linked to the national reference system for the clinical laboratory: a proposal for achieving accuracy.
(80/341)
I propose using proficiency testing (PT) to achieve one of the important goals of CLIA: accurate and reliable clinical testing. Routine methods for the clinical laboratory are traceable to Definitive (DM) or Reference Methods (RM) or to Methodological Principles (MP) through a modification of the National Reference System for the Clinical Laboratory. PT is the link used to monitor consistent field performance. Although PT has been effective as a relative measure of laboratory performance, the technical limitations of PT fluids and of routine methods currently in use make it unlikely that PT alone can be used as a reliable measure of laboratory accuracy. Instead, I recommend calibration of routine systems through correlation to DM, RM, or MP with use of patients' specimens. The manufacturer is in the best position to assume this responsibility because of also being responsible for consistent, reliable product. Analysis of different manufactured batches of reagent would be compared with predetermined goals for precision and accuracy, as illustrated with data from product testing of Kodak Ektachem clinical chemistry slides. Adoption of this proposal would give manufacturers of PT materials, manufacturers of analytical systems, PT providers, and government agencies time to understand and resolve sources of error that limit the utility of PT for the job required by law. (+info)