Adding value to proficiency testing programs.

The Clinical Laboratory Improvement Amendments of 1988 (CLIA 88) (1 ) have caused great changes not only in US laboratories but in clinical laboratories throughout the world. CLIA’s requirements for preand postanalytical control were harbingers of more complete approaches to the implementation of quality systems in clinical laboratories, such as the quality model just introduced by the National Committee for Clinical Laboratory Standards (2 ). CLIA’s maximum allowable error specifications for proficiency testing (the so-called CLIA limits) are being used by manufacturers to help set analytical performance goals for new laboratory analyzers. These specifications have ignited a transatlantic debate (3 ) regarding the formulation of analytical goals based strictly on patient variation vs the CLIA goals, which were based on a host of variables, including physician surveys, patient variation, analytical performance, and even prior proficiency testing (PT) performance. The enactment of CLIA 88 unraveled the comfortable existence of a few large PT providers who primarily served hospital laboratories. In the early 1990s, thousands of previously unregulated physician office laboratories were added to the PT pool. Many of these laboratories eventually subscribed to newly established PT providers whose missions were more closely aligned to the participants’ medical organizations, e.g., the American Academy of Family Physicians and the American Society of Internal Medicine. As of 1998, there were 20 different CLIA-certified PT programs (4 ). The presumably decreased profitability of the PT business has led to a commoditization of PT products and less effort expended in the design and manufacture of PT specimens for analytes that are not directly regulated by CLIA. Another result, coincident with the enactment of CLIA 88, was the development of PT programs that serve a narrow spectrum of users, such as those using instruments of a specific manufacturer. Finally, the requirement to subscribe to CLIA-approved PT programs has eroded the use of voluntary external quality assessment programs that provided specimens far more frequently, such as the Murex program, which provides unknowns every 2 weeks, and Toxi-Lab, which provides an unknown every 2 months. Not only did CLIA prescribe maximum limits on deviations of PT results from peer means, CLIA 88 also increased the numbers of unknowns analyzed by the participating laboratory, from the usual two specimens to five. The increased numbers of unknowns allows the PT provider to more accurately characterize analytical performance and thus more accurately identify the poorly performing laboratory. The rules used by the PT provider to characterize unsatisfactory performance evolved from extremely empiric rules that required results to be within 6 2 SD of the group mean to currently requiring at least four of five results to be within the CLIA error limits. Under CLIA 88, if two or more results are outside the error limits, performance is deemed unsatisfactory and the participating laboratory is at risk of various sanctions. In this issue of Clinical Chemistry, Richard Jenny and Kathryn Jackson-Tarentino (5 ) of the New York State Department of Health report an analysis of causes of PT failures in their therapeutic drug program. Most of the participant failures, roughly 60%, are attributable to analytical error. Although modern analytical instruments are inherently capable of producing results that are accurate and precise enough to meet clinical requirements, the authors conclude that many of today’s quality-control (QC) practices are not optimized to detect the presence of significant error. They recommend that laboratories use QC procedures that limit their instruments’ analytical error to that specified by the instrument’s stable performance. The New York State PT program applies more stringent criteria for allowable error than those in the CLIA requirements for therapeutic drugs (e.g., 15% vs CLIA’s 25% for theophylline). For a participating laboratory to be confident of keeping PT results within these limits, instruments must perform according to manufacturers’ specifications and analytical variation must be tightly controlled. In the study by Jenny and Jackson-Tarentino (5 ), approximately one-half of the PT participants used QC procedures whose allowable deviations exceeded the allowable deviations of the PT program. This is disappointing because the tools to develop efficient QC procedures that can control errors to 15% have been available for many years. These procedures have been made so simple that they can be implemented easily, often without sophisticated statistical calculations. The first step in developing a testing process that will perform well on PT is to select an instrument whose analytical method can be controlled within the limits of allowable error with commonly used QC procedures such as the multirule procedure. The inherent error of the method must be less than the allowable error, and there must be some “working room” that allows the QC procedure to detect errors before they exceed allowable error. Westgard and Burnett (6) have provided the following criterion to accomplish this. In the absence of bias, the standard deviation must be less than 25% of allowable error: