Volume 45, Issue 6

The Institute of Medicine (IOM) report, To err is human , galvanized a dramatically increased level of concern about adverse events and patient safety in healthcare, including errors in laboratory medicine. While a significant decrease in the error rates of clinical laboratories has been achieved and documented in recent decades, available evidence demonstrates that the pre- and post-analytical phases of the total testing process are more vulnerable to errors than the analytical phase. However, analytical quality is still a major issue, particularly in some areas of laboratory medicine such as immunoassaying. In the present paper, current trends and factors that could effect future changes in the frequency and types of errors in laboratory services are analyzed and discussed. A more effective integration of automation and information technology could allow clinical laboratories to identify, control and decrease error rates in the total testing process, but interdepartmental cooperation and communication with clinicians and other stakeholders are essential to improving patient safety. Moreover, a fundamental shift in improving patient safety in laboratory medicine is to move from error reporting to risk management. Clin Chem Lab Med 2007;45:700–7.

Background : Diagnostic errors occur in laboratory medicine resulting from an error or delay in diagnosis, a failure to employ indicated tests, and the use of outmoded tests. Since laboratory tests provide essential information used by physicians to make medical decisions, it is important to determine how often laboratory testing mistakes occur, whether they cause patient harm, where they are most likely to occur in the testing process, and how to prevent them from occurring. Methods : The US Quality Institute Conference in 2003 and the Institute for Quality in Laboratory Medicine in 2005 brought together providers of, users of, and payers for laboratory services to explore how working together they could help to reduce laboratory testing errors and enhance patient safety. Results and conclusions: Users of and payers for laboratory services must become partners in the laboratory's efforts to reduce laboratory testing errors and enhance patient safety. They must be linked to a laboratory information system that provides assistance in decisions on test ordering, patient preparation, and test interpretation. Laboratory quality assessment efforts need to be expanded to encompass the detection of non-analytical mistakes. Healthcare institutions need to adopt a culture of safety that is implemented at all levels of the organization. Clin Chem Lab Med 2007;45:708–11.

Data from recent studies suggest that the highest incidence of laboratory-related errors occurs in the pre-analytical phase of laboratory testing. However, few studies have examined the frequency of errors in laboratory test selection and interpretation. A survey of physicians who use our clinical laboratory demonstrated that the largest number of test ordering errors appear to involve physicians simply ordering the wrong test. Diagnostic algorithms providing guidance for test selection in specific disorders are also used as the basis for the establishment of reflex protocols in the clinical laboratory. The provision of an expert-driven interpretation by laboratory professionals resulted in improvements both in the time to and the accuracy of diagnosis. A survey of our physician staff has shown that in the absence of such an interpretation, for patients being assessed for a coagulation disorder, approximately 75% of the cases would have involved some level of test result misinterpretation. Clin Chem Lab Med 2007;45:712–9.

The clinical laboratory is no longer its own limited ecosystem, as it is increasingly integrated with patient care, assisting diagnosis, monitoring therapies and predicting clinical outcomes. Although efforts and resources are continuously focused to achieve a satisfactory degree of analytical quality, there is clear evidence that the preanalytical phase is much more vulnerable to uncertainties and accidents, which can substantially influence patient care. Most errors within the preanalytical phase result from system flaws and insufficient audit of the operators involved in specimen collection and handling responsibilities, leading to an unacceptable number of unsuitable specimens due to in vitro hemolysis, clotting, insufficient volume, wrong container, contamination and misidentification. A reliable approach to overcome this problem entails prediction of accidental events (exhaustive process analysis, reassessment and rearrangement of quality requirements, dissemination of operating guidelines and best-practice recommendations, reduction of complexity and error-prone activities, introduction of error-tracking systems and continuous monitoring of performances), an increase in and diversification of defenses (application of multiple and heterogeneous systems to identify non-conformities), and a decrease in vulnerability (implementation of reliable and objective detection systems and causal relation charts, education and training). This policy, which requires integration between requirements and design, full commitment and interdepartmental cooperation, should make laboratory activity more compliant to the inalienable paradigm of total quality in the testing process. Clin Chem Lab Med 2007;45:720–7.

A large body of evidence attests that quality programs developed around the analytical phase of the total testing process would only produce limited improvements, since the large majority of errors encountered in clinical laboratories still prevails within extra-analytical areas of testing, especially in manually intensive preanalytical processes. Most preanalytical errors result from system flaws and insufficient audit of the operators involved in specimen collection and handling responsibilities, leading to an unacceptable number of unsuitable specimens due to misidentification, in vitro hemolysis, clotting, inappropriate volume, wrong container or contamination from infusive routes. Detection and management of unsuitable samples are necessary to overcome this variability. The present document, issued by the Italian Inter-society SIBioC-SIMeL-CISMEL (Society of Clinical Biochemistry and Clinical Molecular Biology-Italian Society of Laboratory Medicine-Italian Committee for Standardization of Hematological and Laboratory Methods) Study Group on Extra-analytical Variability, reviews the major causes of unsuitable specimens in clinical laboratories, providing consensus recommendations for detection and management. Clin Chem Lab Med 2007;45:728–36.

Background : This study uses the Isotope Dilution Mass Spectrometer-Traceable Modification of Diet in Renal Disease (MDRD) equation to evaluate the effects of analytic variation of serum creatinine on estimated glomerular filtration rate (eGFR). The equation was inverted to provide critical creatinine levels corresponding to eGFRs equal to 15, 30, and 60 mL/min/1.73 m 2 . Methods : eGFRs were calculated for two populations of patients representing clinic outpatients and hospitalized inpatients. Simulation studies evaluated the effects of analytic bias for these populations. Differences between creatinine tests ordered on consecutive blood draws were analyzed for within-subject eGFR variation. Finally, propagation of error techniques established the relationship between creatinine imprecision and eGFR imprecision. Results : eGFR of 60 mL/min/1.73 m 2 corresponds to creatinine levels of 80–156 μmol/L. A 20-μmol/L negative shift of creatinine approximately doubles the percentage of patients classified in various stages of decreased renal function, whereas a positive shift approximately halves the percentage. The central 95% limits for within-subject variation of eGFR are 33% for outpatients, 38% for inpatients and 40% across the groups. eGFR imprecision is approximately 15%–20% higher than creatinine imprecision. Conclusions : Small analytic changes in serum creatinine create major shifts in the distributions of eGFR, which can cause large differences in the classification of patients. The within-subject variations in eGFR over time, especially between hospital and clinic measurements, can be large. Therefore, tight control of laboratory analysis is important. Clin Chem Lab Med 2007;45:737–41.

Background : An important point in improving laboratory quality is the definition of some indicators to be monitored as measures of a laboratory trend. The continuous observation of these indicators can help to reduce errors and risk of errors, thus enhancing the laboratory outcome. In addition, the standardization of risk evaluation techniques and the definition of a set of indicators can eventually contribute to a benchmarking process in clinical laboratories. Methods : Five Italian hospital laboratories cooperated in a project in which methodologies for process and risk analysis, usually applied in fields other than healthcare (typically aeronautical and transport industries), were adapted and applied to laboratory medicine. The collaboration of a board of experts played a key role in underlining the limits of the proposed techniques and adapting them to the laboratory situation. A detailed process analysis performed in each center was the starting point, followed by risk analysis to evaluate risks and facilitate benchmarking among the participants. Results and conclusions : The techniques applied allowed the formulation of a list of non-conformities that represented risks of errors. The level of risk related to each was quantified and graphically represented for each laboratory to identify the risk area characteristic for each of the centers involved. Clin Chem Lab Med 2007;45:742–8.

Background : The clinical laboratory generates large amounts of patient-specific data. Detection of errors that arise during pre-analytical, analytical, and post-analytical processes is difficult. We performed a pilot study, utilizing a multidimensional data reduction technique, to assess the utility of this method for identifying errors in laboratory data. Methods : We evaluated 13,670 individual patient records collected over a 2-month period from hospital inpatients and outpatients. We utilized those patient records that contained a complete set of 14 different biochemical analytes. We used two-dimensional generative topographic mapping to project the 14-dimensional record to a two-dimensional space. Results and conclusions : The use of a two-dimensional generative topographic mapping technique to plot multi-analyte patient data as a two-dimensional graph allows for the rapid identification of potentially anomalous data. Although we performed a retrospective analysis, this technique has the benefit of being able to assess laboratory-generated data in real time, allowing for the rapid identification and correction of anomalous data before they are released to the physician. In addition, serial laboratory multi-analyte data for an individual patient can also be plotted as a two-dimensional plot. This tool might also be useful for assessing patient wellbeing and prognosis. Clin Chem Lab Med 2007;45:749–52.

Laboratory accreditation and External Quality Assessment (also called proficiency testing) are mainstays of laboratory quality assessment and performance. Both practices are associated with examples of improved laboratory performance. The relationship between laboratory performance and improved patient safety is more difficult to assess because of the many variables that are involved with patient outcome. Despite this difficulty, the argument to continue external evaluation of laboratories is too compelling to consider the alternative. Clin Chem Lab Med 2007;45:753–5.

To guarantee excellent performance and service, the process of identifying and treating error risks must be integrated into the total testing process. Quality Assurance Programs (QAPs) represent an important tool that allows us to identify errors and pinpoint any need for further systematic investigations, and to rectify procedures to improve the inputs and processes by which the service is delivered. The models used by the laboratory to assure quality and manage the risk of errors have been modified in line with an approach in which the identification of quality goals and the redefinition of professionals duties and responsibilities are indispensable. Error risk is currently high in some areas of laboratory activity, and QAP is needed now more than ever. The present paper provides some descriptive examples of an approach that can be followed to manage an External Quality Assessment Scheme (EQAS) and quality indicators (QIs), the main tools used by laboratories to assure the quality of their service, for the prevention of error risk. In particular, we describe the correct approach to choose EQAS, to use information from the EQAS report, to design a QI model, and to analyze any QI data. The examples highlight that any well-designed quality system can be ineffective if it is not managed by highly competent professionals with a deep sense of responsibility. Clin Chem Lab Med 2007;45:756–65.

Point-of-care testing (POCT) is the fastest growing segment of a US$30 billion worldwide market. “Errors” in the testing process, as well as medical data interpretation and treatment associated with POCT, are recognized as leading to major compromises of patient safety. In today's environment, most testing errors (pre-analytical, analytical and post-analytical) can be virtually eliminated by proper design of testing systems. We cite examples of two systems that have made exceptional progress in this respect. It has been recently suggested that the basic errors associated with the testing process are amplified in the POC setting. Two of the amplifiers – incoherent regulations and failure of clinician/caregivers to respond appropriately to POCT results – lead us to recognize additional changes in today's POCT environment. The first is a willingness of manufacturers, not laboratories, to take responsibility for the quality of test results – an outgrowth of an industrial philosophy called autonomation. The second is a need to substantially modify the clinician/caregiver test utilization paradigm to take full advantage of POCT results, available on site in real time. Both have already begun to take place. Clin Chem Lab Med 2007;45:766–73.

It is the responsibility of health organizations to guarantee a high level of healthcare by using adequate methodologies and instruments, creating secure conditions for treatment, and preventing adverse events due to human or system errors. It is necessary to introduce Risk Management programs, and in particular to promote Clinical Risk Management, one of the constituent elements of Clinical Governance, to assure the delivery of high-quality performance and services. In the point-of-care testing (POCT) context, using an analysis of our experiences, we discuss the entire analytical process, including acquisition and usage, while focusing on blood gas analyzers. Our experience confirms that within a Clinical Governance framework, it is necessary to apply, even when choosing instruments, a systematic vision that is not limited to analytical validation, but also includes an in-depth analysis of the impact in a specific context. Assessment of the correlated risks, independent of the analytical methodology used, is indispensable in a clinical environment to identify the most suitable approach for such risks. A study of the latent factors can be proactively performed to identify (and stimulate) what the pre-organizational environment (producer companies) can offer in terms of product orientation to effectively reduce correlated risk during use. Among the different options for possible treatment of risk, one involves the transfer of the assumption of risk to third parties (e.g., maintenance and quality controls). Transferring the responsibility for control operations to the operator of the instrument, which follows the quality controls with total autonomy, is equivalent to transferring the correlated risk for the clinician (in the POCT case) to the producer, who becomes the guarantor. In practice this is equivalent to a specific assurance stipulation with zero cost. Clin Chem Lab Med 2007;45:774–80.

Laboratory errors have a significant impact on patient safety. The manufacturers of in vitro diagnostic (IVD) products play an important role in the reduction of laboratory errors by ensuring the highest possible safety and efficacy of their products. In order to achieve this, the IVD industry has implemented rigorous product development and manufacturing processes. Many IVD companies apply Six Sigma principles in order to minimize variability within the whole product life cycle, starting with customer requirements, through product design and manufacture, as well as management of the potential issues that occur after the products have been released for use. A closer look into this process is presented here, using an evacuated blood collection tube as a model device. Clin Chem Lab Med 2007;45:781–8.

Six Sigma is a global management strategy introduced to the industrial world in the 1980s. This methodology has been widely implemented in companies such as Motorola, General Electric, Allied Signal and many others, with tremendous success in terms of customer satisfaction and global profitability. To achieve similar benefits in the healthcare field, Six Sigma is currently being deployed in several laboratories around the world. Despite this situation, few articles have been published in the peer-reviewed literature on this subject. The aim of this article is to clarify the different aspects of Six Sigma and their potential applications in clinical laboratories, as well as to systematically review articles and books discussing Six Sigma strategy implementation in the laboratory field. Clin Chem Lab Med 2007;45:789–96.