Upsala J Med Sci 98: 445-486, 1993 10. Vocabulary for Describing the Metrological Quality of a Measurement Procedure With an alphabetic index Rene Dybkzr Department of Clinical Chemistry Frederiksberg Hospital, Frederiksberg, Danmark Laboratory medicine is characteristic in having practitioners with various educational backgrounds. Current terms have therefore not been chosen according to a systematic plan and seldomly with adequate knowledge of modern metrological and statistical terminology work. The following vocabulary comprises sections of salient concepts related to quality, metrology, statistics, metrological performance characteristics, and reference measure- ment systems. When a definition is given with a reference in brackets, the sign "=" indicates that the definition is taken verbatim, the sign "M" shows that editorial differences have been introduced for consistency, and no sign means that the reference is a source in general. If no reference is given, the definition is materially different from the set of references given att the end of the vocabulary. The notes are not necessarily taken directly from any source of the definition - unless followed by a reference in [ 1, which then also applies to the definition unless it has a reference already. It should be emphasized that definitions of concepts and their terms are continuously being developed and changed so that it is always useful to consult the latest editions of relevant documents from standards bodies. The terminological evolution also means that disagreement may exist between the standards or recommendations from different organizations and even from different committees within a given body. 445 i The present selection has taken the International vocabulary of basic and general terms in metrology (see BIPM et aZ.) as the highest authority, followed by ISO, CEN, and I professional international unions. 1 QUALITY WHO - HEALTH for All by the Year 2000 Ensuring the quality of services Target 31 By 1990, all member states should have built effective mechanisms for ensuring quality of patient care within their health care systems. 1.1 quality totality of features and characteristics of a product or service that bear on its ability to satisfy stated or implied needs [ = I S 0 8402:1986] 1.2 quality policy overall quality intentions and directions of an organization as regards quality, as formally expressed by top management [ = I S 0 8402:1986] 1.3 quality management that aspect of the overall management function that determines and implements the quality policy Notes 1. The attainment of desired quality requires the commitment and participation of all members of the organization whereas the responsibility for quality management belongs to top management. 2. Quality management includes strategic planning, allocation of resources and other systematic activities for quality such as quality planning, operations and evaluations. [ = I S 0 8402:1986] 1.4 quality system organizational structure, responsibilities, processes, and resources for implementing quality management [ = I S 0 8402:1986] 446 1.5 quality assurance all those planned and systematic actions necessary to provide adequate confidence that a product or service will satisfy given requirements for quality [ = I S 0 8402:1986] 1.6 quality control operational techniques and activities that are used to fulfil requirements for quality [ = I S 0 8402:1986] Notes 1. In order to avoid confusion, care should be taken to include a modifying term when referring to a subset of quality control. 2. Quality control involves operational techniques and activities aimed both at monitoring a process and at eliminating causes of unsatisfactory performance. 1.7 quality audit systematic and independent examination to determine whether quality activities and related results comply with planned arrangements and whether these arrangements are implemented effectively and are suitable to achieve objectives [ = I S 0 840219861 Notes 1. Quality audits are carried out by independent staff. 2. One purpose of a quality audit is to evaluate the need for improvement or corrective action. The concept should not be confused with "surveillance" or "inspection" performed for the sole purpose of process control or product acceptance. 2 MEASURABLE QUANTITY 2.1 system demarcated part of the perceivable or conceivable universe, material or immaterial, that may be regarded as a set of elements and a set of relationships between these elements, and that may be observed at a given calendar time Note This concept is allied to "object", i.e. any part of the perceivable or conceivable world [ I S 0 1087:1990]. 447 2.2 set well-defined finite or infinite collection of elements Note The elements may be physical objects, numbers, concepts, or sets. 2.3 measurable quantity quantity attribute of a phenomenon, body or substance that may be distinguished qualitatively and determined quantitatively [ = VIM, 19931 2.4 component definable part of a system Notes 1. Components can be mechanical, physical, chemical, mathematical, or functional. 2. Components are sometimes divided in analyte, concornitant(s), and solvent. 2.5 elementary entity relevant structure of a chemical component such as an atom, molecule, ion, electron, other particle, or specified group of such particles Note The elementary entity may be chosen as convenient, not necessarily as physically real, individual particles, for example 0,5 Ca2+. 2.6 kindsf-quantity quantity in a general sense definition of how to obtain a value of a quantity by measuring a quantity of its system or of its components or both Examptec. length; volume; amount-of-substance; mass concentration; volume fraction Nore This concept is called "quantity in a general sense" by VIM. 2.7 generic quantity description of an attribute of a generic system 448 Note A generic system is a system lacking specification of space or calendar time or both. 2.8 value of a measurable quantity value 4 Y magnitude of a measurable quantity generally expressed as a unit of measurement multiplied by a number Note A measurable quantity that cannot be expressed as a unit of measurement multiplied by a number may be expressed by reference to a conventional reference scale or to a measurement procedure or to both. [= VIM, 19931 2.9 unit of measurement unit measurable quantity, defined and adopted by convention, with which other measurable quantities of the same kind are compared in order to express their magnitudes relative to that quantity [= VIM, 19931 2.10 numerical value of a measurable quantity numerical value number by which the unit of measurement is multiplied in the expression of the value of a measurable quantity [= VIM, 19931 2.11 truth quality of being in accordance with the definition of a measurable quantity that may be represented by a distribution of true values 2.12 true value of a measurable quantity true value CL value consistent with the definition of a given measurable quantity [= VIM, 19931 449 2.13 conventional true value of a measurable quantity conventional true value P value attributed to a measurable quantity and accepted, sometimes by convention, as having an uncertainty of measurement appropriate for a given purpose [= VIM, 19931 Note Quasi-synonyms are "assigned value", "best estimate of the value", "accepted reference value". 3 METROLOGY 3.1 metrology science of measurement Note Metrology includes all aspects both theoretical and practical with reference to measurements, whatever their uncertainty, and in whatever fields of science or technology they occur. [ = VIM, 19931 3.2 measurement set of operations having the object of determining a value of a quantity Note The operations may be performed automatically. [ = VIM, 19931 3.3 principle of measurement scientific basis of a measurement [ = VIM, 19931 3.4 method of measurement logical sequence of operations, described generically, used in the performance of measurements [ = VIM, 19931 3.5 measurement procedure set of operations, described specifically, used in the performance of particular measurements according to a given method [ = VIM, 19931 450 3.6 measurand measurable quantity subject to measurement Note A specification of a measurand may require statements about quantities such as time, temperature and pressure. [:: VIM, 19931 3.7 measuring instrument device intended to be used to make measurements, alone or in conjunction with supplementary device(s) [ = VIM, 19931 3.8 measuring system complete set of measuring instruments and other equipment assembled to carry out specified measurements [ = VIM, 19931 Note A measuring system may include materials, such as chemical or biological substances and material measures. 3.9 indication of a measuring system indication value of a measurable quantity provided by a measuring system Notes 1. The value read from the displaying device may be called the "direct indication"; it is multiplied by the instrument constant to give the indication. 2. The measurable quantity may be the measurand, a measurement signal, or another quantity to be used in calculating the value of the measurand. [= VIM, 19931 3.10 input measurable quantity input quantity xs measurable quantity whose value is used in calculating a value for the output measurable quantity according to a function Examples indication of the measuring system; quantity represented by a calibrator; any influence quantity 45 1 Notes 1. All input quantities may be regarded as random variables. 2. The measurand can be considered an output quantity. 3.11 observed value of a measurable quantity observed value value of a measurable quantity obtained as the outcome of a single observation Note One or more observed values of each input measurable quantity may be needed and may have to be corrected before applying a specified function to obtain a result of a measurement. 3.12 result of a measurement result Y value attributed to a measurand, obtained by measurement [ = VIM, 19931 Notes 1. When a result is given, it should be made clear whether it refers to - the indication - the uncorrected result - the corrected result and whether several values are averaged. 2. A complete statement of the result of a measurement includes information about the uncertainty of measurement. [ = VIM, 19931 3.13 sampling process of taking samples, usually qualified by a description of the sampling procedure [- rso/Drs 3534-2:19861 3.14 sample one or more parts taken from a system and intended to provide information on the system or to serve as a basis for a decision on the system 452 Notes 1. Unless otherwise specified, the sample is assumed to be representative of a "static system". 2. The system from which a sample is taken may not be of the same type as that of the measurand. 3. For a "dynamic system", the calendar time of sampling has to be specified. 3.15 primary sample collection of one or more parts initially taken from a system [= IUPAC, 19901 3.16 laboratory sample primary sample or a subsample of it as prepared for sending to or as received by the laboratory and intended for measurement Note The laboratory sample is the final sample of sample collection and the initial sample in the laboratory. 3.17 analytical sample sample prepared from the laboratory sample and from which analytical portions may be taken 3.18 analytical portion portion of material taken from the analytical sample and on which the measurement of an appropriate measurable quantity is actually carried out 3.19 analytical run analytical series set of measurements performed under repeatability conditions 4 STATISTICS 4.1 probability real number in the scale of 0 to I attached to a random event f = ISOfDIS 3534-1:1990] 453 Note Probability can be related to a long-run number fraction of occurrence or to a degree of belief that an event will occur. For a high degree of belief, the probability is near 1. 4.2 random variable variate x , y variable that may take any of the values of a specified set of values and with which is associated a probability distribution [ = ISO/DIS 3534-1:1990] 4.3 probability distribution of a random variable probability distribution function that gives the probability that a random variable takes any given value or belongs to a given set of values Note The probability on the whole set of values of the random variable equals 1. [ = ISO/DIS 3534-1:1990] 4.4 location typical magnitude of a distribution of values Examples arithmetic mean; median; mode 4.5 dispersion degree of scatter shown by a set of values Examples standard deviation; central 0,95-interfractile interval 4.6 population totality of items under consideration [ = ISO/DIS 3534-1:1990] Note In the case of a random variable, the probability distribution is considered as defining the population of that variable. 454 4.7 population parameter parameter quantity used in describing the distribution of a random variable in a population [ = ISO/DIS 3534-1:1990] 4.8 expectation of a random variable expectation E K ) , E(Y) expected value mean sum of products of values xi of a discrete random variable X and their respective probabilities pi’ the sum being extended over all values xi that can be taken by X E ( X ) = ~ p r y i 4.9 variance of a random variable variance of a probability distribution variance a2,, WC), V(Y) expectation of the square of the centred random variable u2x = E{(X - E ( X ) I 2 ) [ = ISO/DIS 3534-1:1990] 4.10 standard deviation of a random variable standard deviation of a probability distribution standard deviation positive square root of the variance of a random variable 0 [z ISO/DIS 3534-1:1990] 4.11 coefficient of variation of a random variable coefficient of variation of a probability distribution coefficient of variation O/E(X), U / P ratio of the standard deviation to the expectation of a non-negative random variable [ = ISO/DIS 3534-1:1990] DO NOT USE: relative standard deviation (deprecated) 455 4.12 statistic function of the sample random variables [ = ISO/DIS 3534-1:1990] Notes 1. The value of the statistic obtained by using the observed values or results of measurements in this function may be used in a statistical test or as an estimate of a population parameter such as an expectation of a random variable or a standard deviation of a random variable. 2. A statistic is itself a random variable. 4.13 estimator statistic used to estimate a population parameter [ = ISO/DIS 3534-1: 19901 4.14 estimate, noun value of an estimator obtained as a result of an estimation [ = ISO/DIS 3534-1:1990] 4.15 number fraction distribution relative frequency distribution empirical relationship between the values of a random variable and their number fractions Note The term "frequency distribution" is often used for the different concepts "number distribution" and "number fraction distribution". 4.16 arithmetic mean average 2, Y sum of values divided by the number of values [ = ISO/DIS 3534-1:2990] Note The term "mean" or "expectation" should be used only for the population parameter. 456 4.17 median with n values arranged in non-decreasing order of magnitude 1 to n, the ( ( n + 1)/2)th value of n odd values or a value between (n/2)th and (n/2 + 1)th even values with the arithmetic mean of these values chosen if not otherwise specified [ X ISO/DIS 3534-1:1990] Note An alternative definition is: 0,s-fractile. 4.18 sample variance sum of the squared deviations of results of measurements from their arithmetic mean divided by one less than the number of results Note The sample variance is an unbiased estimator of the population variance [e ISO/DIS 3534-1:1990] 4.19 fractile of a random variable fractile X P variate value equal to or below which lies a stated number fraction of the cumulative number fraction distribution 4.20 confidence interval closed interval within which the value of a population parameter may be expected to lie with a stated probability Note This approximate definition is valid for a two-sided confidence interval. 4.21 statistical coverage interval interval for which it can be stated with a given level of confidence that it contains at least a specified proportion of the population [ = ISO/DIS 3534-1:1990] 451 4.22 tolerance interval variate values between and including the tolerance limits giving upper and lower limits to permissible values 4.23 statistical outlier outlier observed value in a sample, so far separated in value from the remainder as to suggest that it may be from a different population [M ISO/DIS 3534-1:1990] 5 ERROR 5.1 error of a result of a measurement error of measurement error result of a measurement minus a true value of the measurand [ = VIM, 19931 Notes 1. Since a true value cannot be determined, in practice, a conventional true value is used [ = VIM, 19931. Error is the sum of random error and systematic error [ISO/DIS 3534-1:1990]. If several components of error are listed, “error” may be named “total error”. 2. 3. 5.2 deviation value minus its reference value [ = VIM, draft 2. ed.] 5.3 random error of a result of a measurement random error e result of a measurement minus the mean that would result from an infinite number of measurements of the same measurand carried out under repeatability conditious e = Y -‘(Yi, r,) [ = VIM, 19931 Notes 1. Since the mean is not known, in practice, the arithmetic mean is usually substituted. 458 2. It is not possible to correct for random error as it varies unpredictably in successive results. 5.4 systematic error of a result of a measurement systematic error mean that would result from an infinite number of measurements of the same measurand carried out under repeatability conditions minus a true value of the measurand [ = VIM, 19931 Notes 1. Since the mean (or expectation) is not known, in practice, the arithmetic mean is usually substituted. 2. Since a true value cannot be determined, in practice, a conventional true value is used. 3. The systematic error of successive results remains constant or varies in a predictable way. 5.5 correction value added algebraically to the uncorrected result of a measurement to compensate for systematic error [ = VIM, 19931 Notes 1. The correction is equal to the negative of the estimated systematic error. 2. Some systematic errors may be estimated, and compensated by applying appropriate corrections. However, since the systematic error cannot be known perfectly, the compensation cannot be complete. 5.6 correction factor numerical factor by which the uncorrected result of a measurement is multiplied to compensate for systematic error [ = VIM, 19931 Note Since the systematic error cannot be known perfectly, the compensation cannot be complete. [ = VIM, 19931 18-935253 459 5.7 mistake blunder unauthorized departure from the prescribed measurement procedure Note The mistake can take the form of an omission or an incorrect action. This is to be distinguished from "error of measurement". 6 ACCURACY 6.1 accuracy of measurement accuracy closeness of the agreement between the result of a measurement and a true value of the measurand [ = VIM, 19931 DO NOT USE: precision (deprecated) Notes 1. Accuracy of measurement can be measured on an ordinal scale such as (poor, fair, good). 2. Accuracy is usually expressed numerically by statistical measures of the inverse concept "inaccuracy of measurement". 3. The term "accuracy", when applied to a set of results, describes a combination of "random error of measurement" and "systematic error of measurement". 6.2 trueness of measurement trueness closeness of the agreement between the average value obtained from a large run of results of measurements and a true value Notes 1. Trueness of measurement can be measured on an ordinal scale such as (low, medium, high). 2. Trueness is usually expressed numerically by the statistical measure "bias" that is inversely related to trueness. 460 6.3 bias of measurements bias difference between the expectation of the results of measurements and a true value DO NOT USE: inaccuracy Notes 1. Bias is a "systematic error of results of measurements" and it may have several components. Since a true value cannot be determined, in practice, a "conventional true value" is used. 2. 6.4 precision of measurements precision closeness of the agreement between independent results of measurements obtained under prescribed conditions [z ISO/DIS 3534-1:1990] Notes 1. Precision of measurements can be measured on an ordinal scale such as (low, medium, high). 2. Precision is usually expressed numerically by statistical measures of the inverse concept "imprecision of measurements". 3. Precision depends only on the distribution of "random errors of measurement". 6.5 precision conditions statement of conditions of measurement under which independent results of measure- ments of the same measurand are obtained, specifying which sources of variation operate Note The term "independent results" means that a given result must not be influenced by any previous result. 7 COMPONENTS OF A RESULT 7.1 overall expectation of results of measurements overall expectation EV), m expectation of results of measurements of a given measurand as obtained from all 46 I laboratories using the same measurement procedure in a collaborative assessment experiment Note The overall expectation is the sum of a true value of the measurand and the bias of the measurement procedure, E(Y) = p + 6, that is the overall expectation depends solely on a true value and the measurement procedure. In some cases, however, an in- dependent true value does not exist and the overall expectation is exclusively defined by the measurement procedure. 7.2 bias of results of a measurement procedure bias of a measurement procedure difference between the expectation of all results of measurements made by a stated measurement procedure and a true value of a given measurand to be expected to apply to all measurements made by that procedure 6 = E f l ) - p = m - p Notes 1. The bias of a measurement procedure may depend on the value of the measurand. 2. A n estimator of this bias is the difference between the general average and a conventional true value, d = y - f i . 7.3 laboratory deviation B difference between the expectation of the results of measurements of a laboratory for a given measurand obtained under stated precision conditions and the overall expectation of results of measurements Notes 1. The laboratory deviation may depend on the value of the measurand. 2. An estimator of this deviation is the difference between the average in the laboratory and the general average of results of measurements, B =Ji - y’ 3. The laboratory deviation is given specific names for typical precision conditions. A 7.4 laboratory bias of results of a measurement procedure laboratory bias A difference between the expectation of all results of measurements made in a given 462 laboratory using a specified measurement procedure and a true value of the measurand A = E(YJ - /.L Notes 1. The laboratory bias may depend on the value of the measurand. 2. An estimator of this bias is the difference between the average of all results obtained by a given laboratory and a conventional true value, A A = j i . - f i . 7.5 aberrant-sample bias of the result of measurement aberrant-sample bias S difference between the expectation of the results of measurements on a given sample of unusual composition and the expectation for a measurand of the same magnitude pertaining to a sample having a usual composition 7.6 bias caused by an undetected mistake A4 difference between the result of a measurement on a given sample in a given run and the expectation of repeated results of the same measurand, in excess of any random error 8 REPEATABILITY (see also 7) 8.1 repeatability conditions conditions of measurement where independent results of measurements of the same measurand are obtained with the same measurement procedure in the same laboratory by the same observer using the same equipment, used under the same conditions within a short period of time Note The term "independent results" means that a given result must not be influenced by any previous result. 46.3 8.2 laboratory component of bias of results of a measurement procedure laboratory component of bias Bi, r difference between the laboratory bias of results of a measurement procedure and the bias of results of a measurement procedure Bi, Notes 1. The laboratory component of bias is related to the expectation of results of measurements, E(Y) = rn, not to a true value. The laboratory component of bias is considered constant under repeatability conditions, r, in one laboratory for one measurand, but its value may depend on the value of the measurand. An estimator of this bias is the difference between the average of all results of measurements obtained by a given laboratory and the general average, B i , = A i , - 6 = E(YiIr) - E ( Y ) = E(YiIr) - m 2. 3. = A i , - d = yi, - A t = yi, -3;. 8.3 repeatability of results of measurements repeatability closeness of the agreement between the results of successive measurements of the same measurand carried out under the same conditions of measurement Notes 1. Repeatability conditions (see 8.1) include: - the same measurement procedure, - the same observer, - - the same location, - Repeatability depends solely on the dispersion of random error and does not relate to a true value. Repeatability can be measured on an ordinal scale of measurement such as (poor, good, excellent). the same measuring instrument, used under the same conditions, repetition over a short period of time 2. 3. [ = VIM, 19931 464 8.4 within-laboratory repeatability variance of results of measurements within-laboratory repeatability variance 2 2 i,rj w variance of the distribution of random errors within a single laboratory under repeatability conditions Notes 1. An alternative definition, which includes the dispersion of true values is: variance of the distribution of results of measurements within a single laboratory under repeatability conditions. 2. The value may depend on the value of the measurand. 3. An estimator of u2, is the sample within-laboratory repeatability variance, s2,. 8.5 repeatability variance of results of measurements repeatability variance average of the within-laboratory repeatability variances of results of measurements taken over all t h e laboratories using a given measurement procedure in a precision experiment - aZr = UZw Notes 1. It is assumed that for a given measurement procedure any variation in the variances between the laboratories is small. 2. The value of the repeatability variance may depend on the value of the measurand. 3. An estimator of 02r is the sample repeatability variance, s2,. 9 INTERMEDIATE PRECISION (see also 7) 9.1 intermediate precision conditions conditions of measurement where independent results of measurement of the same measurand are obtained with the same measurement procedure in the same laboratory subject to stated changes in one or more sources of variation such as time, observer, and measuring system Note The term "independent results" means that a given result must not be influenced by any previous result. 46 5 9.2 intermediate precision of results of measurements intermediate precision closeness of agreement between the results of measurements of the same measurand, where the measurements are carried out in the same laboratory by the same measure- ment procedure, but with stated changes in one or more sources of variation such as time, observer, and measuring system Notes 1. Results are here usually understood to be corrected results. 2. The Notes 1, 2, and 3 to precision of measurements apply analogously. 10 REPRODUCIBILITY (see also 7) 10.1 reproducibility conditions conditions of measurement where independent results of measurement of the same measurand are obtained with the same measurement procedure in different laboratories with different observers using different equipment Notes 1. The term "independent results" means that a given result must not be influenced by any previous result. 2. The definition in VIM, 1993, allows principle of measurement, methods of measurement, and conditions of use as added possible sources of variation. 3. The conditions changed must always be specified. 10.2 reproducibility of results of measurements reproducibility closeness of the agreement between the results of measurements of the same measurand, where the measurements are carried out by the same measurement procedure, but in different laboratories with different observers using different equipment Notes 1. A valid statement of reproducibility requires specification of the conditions changed. 2. Results are here usually understood to be corrected results. 3. The Notes 1, 2, and 3 to precision of results of measurements apply analogously. 4. The definition in VIM, 1993, allows principle of measurement, method of measurement, and conditions of use as added possible sources of variation. 466 10.3 between-laboratory variation B R distribution of the individual laboratory-component-of-bias of results of measurements obtained under defined precision conditions. 10.4 between-laboratory variance of results of measurements between-laboratory variance (JZBR = CJZL variance of the distribution of the laboratory components of bias of results of a measurement procedure obtained under reproducibility conditions Notes 1. The distribution is assumed to be at least approximately Gaussian. 2 . The between-laboratory variance may depend on the value of the measurand. 3. An estimator of a2L is the sample between-laboratory variance, s2L. 10.5 reproducibility variance of results of measurements reproducibility variance ( J R sum of the repeatability variance of results of measurements and the between-laboratory variance of results of measurements C J ~ ~ = a2r + aZL Notes 1. The reproducibility variance may depend on the value of the measurand. 2. An estimator of uZR is the sample reproducibility variance, s2R = s2r + sZL. 2 10.6 between-procedure variation 6P distribution of individual bias of results of measurement procedures under defined precision conditions 467 11 ANALYTICAL RELIABILITY METROLOGICAL RELIABILITY 11.1 analytical reliability metrological reliability ability of a measurement procedure to perform a required function under stated conditions for a stated period of time [=: I S 0 8402:1986] 11.2 analytical performance characteristic metrological performance characteristic performance characteristic property in the set of properties that is necessary for assessing the suitability of a measurement procedure for any given purpose and where each property can be given an experimentally determined value Examples analytical sensitivity; repeatability standard deviation; limit of detection 11.3 analytical calibration function metrological calibration function calibration function signal of the measuring system as a function of the stated value of the rneasurand Note The stated value may be the assigned value of a reference material. 11.4 analytical sensitivity si slope of the analytical calibration function Notes 1. The analytical sensitivity may vary with the magnitude of the measurand involving the component i or with influence quantities. 2. The term "analytical sensitivity" must not be used as a synonym for "limit of detection". 468 11.5 analytical measuring function measuring function value of the measurand as a function of the signal of the measuring system related to that measurand and derived from the analytical calibration function Note The analytical measuring function, in principle, is the inverse of the analytical calibration function, but this relationship may not hold if the measurement procedure is not specific for one analyte or where analytical interference occurs. 11.6 influence quantity measurable quantity that is not the measurand but that affects the result of measurement [= VIM, 19931 Example bilirubin concentration in the measurement of hemoglobin concentration in human blood plasma 11.7 analytical specificity ability of a measurement procedure to determine solely the measurable quantity it purports to measure Note The analytical specificity is usually expressed in terms of the effect of any component of the sample other than the analyte causing an indication of the measuring instrument and thereby introducing an error of measurement. 11.8 analytical interference systematic error of measurement caused by an analytical interferent 11.9 analytical interferent influence quantity which does not by itself produce a signal in the measuring system, but which causes an enhancement or depression of its indication Note Sone analytical chemists prefer that an analytical interferent can itself produce a signal. 11.10 reagent blank measurement measurement on a material lacking natural sample 469 Note The result of the measurement is used as a correction for that part of the indication caused by the reagent(s). 11.11 matrix blank measurement measurement on a material containing matrix material, but lacking analyte Notes 1. If matrix material is unavailable, the measurement may be made on sample material, by a modified procedure omitting a reagent or inactivating the analyte. The result of the measurement is used as a correction for that part of the indication caused by the sample matrix. 2. 11.12 recovery measurement subtracting of the indication of a measuring instrument obtained by measurement on an analytical sample from the indication of another analytical sample of the same laboratory sample containing an added amount of the analyte and comparing with the added amount. 11.13 repeatability standard deviation ur standard deviation of results of measurements obtained under repeatability conditions [z ISO/DIS 3534-1:1990] Notes 1. Synonyms of "repeatability standard deviation" are "within-run standard deviation", "within-series standard deviation", "intra-run standard deviation", and "intra-serial standard deviation". 2. The estimator of "repeatability standard deviation" is the "sample repeatability standard deviation", s,. 11.14 repeatability limit r; '0,95 value less than or equal to which the absolute difference between two single results of measurements, obtained under repeatability conditions, is expected to be with a probability of 0,95 [z ISO/DIS 3534-1:1990] 470 Note In practice, the estimate of the repeatability is taken as 2 4 sr = 2,8 s,, see repeatability standard deviation. 11.15 intermediate precision standard deviation standard deviation of results of measurements obtained under defined intermediate precision conditions Note The estimator of "intermediate precision standard deviation" is the "sample intermediate precision standard deviation". 11.16 reproducibility standard deviation OR standard deviation of results of measurements obtained under reproducibility conditions [- ISO/DIS 3534-1:1990] Note The estimator of "reproducibility standard deviation" is the "sample reproducibility standard deviation", sR. 11.17 reproducibility limit R; R0,95 value less than or equal to which the absolute difference between two single results of measurements, obtained under reproducibility conditions, is expected to be with a probability of 0,95 [= ISO/DIS 3534-1:1990] Note In practice, the estimate of the reproducibility limit is taken as 2 a s R = 2,8 sR, see reproducibility standard deviation. 11.18 reproducibility standard deviation divided by analytical sensitivity a R / S j 11.19 limit of detection detection limit lowest result of a measurement by a given measurement procedure that can be accepted 47 I with a stated confidence level as being different from the value obtained on matrix blank material Note An experimental procedure for determining the limit of detection consists in using the average value of, say, 20 results of measurements on matrix blank material and adding three times their sample standard deviation. At these low values with probably non- Gaussian distribution, the corresponding confidence level should be taken to be about 0,90. 11.20 lower limit of determination lowest result of a measurement, that can be obtained by a stated measurement procedure, and that can be given with a statement of uncertainty of measurement. 11.21 higher limit of determination highest result of a measurement, that can be obtained by a stated measurement procedure, and that can be given with a statement of uncertainty of measurement 11.22 uncertainty of measurement parameter, associated with the result of a measurement, that characterizes the dispersion of the values that could reasonably be attributed to the measurand [ = VIM, 19931 Notes 1. The parameter may be, for example, a standard deviation (or a given multiple of it), or the half-width of an interval having a stated level of confidence. Uncertainty of measurement comprises, in general, many components. Some of these components may be evaluated from the statistical distribution of the results of series of measurements and can be characterized by experimental standard deviations. The other components, which can also be characterized by standard deviations, are evaluated from assumed probability distributions based on experience or other information. 3. It is understood that the result of the measurement is the best estimate of the value of the measurand, and that all components of uncertainty, including those arising from systematic effects, such as components associated with corrections and reference standards, contribute to the dispersion. 2. 472 11.23 robustness of a measurement procedure robustness ability to yield acceptable results of measurements in spite of deviation from details of the measurement procedure 11.24 transferability of a measurement procedure transferability ability of a measurement procedure to allow observers in different laboratories to perform measurements giving results in accordance with the stated analytical performan- ce characteristics 11.25 interchangeability of a measurement procedure interchangeability ability of one measurement procedure to be used in place of another to fulfil the same requirements [ISO/IEC Guide 2:1986] 11.26 commutability of a measurement procedure commutability ability of a measurement procedure to produce results of measurement that, within the uncertainty of measurement, are in a constant relationship with the results of another stated measurement procedure when both are applied to natural samples and reference materials 11.27 compatibility suitability of products, processes or services for use together under specific conditions to fulfil relevant requirements without causing unacceptable interactions [ = ISO/IEC Guide 2:1986] 12 PRACTICABILITY 12.1 practicability of a measurement procedure practicability properties of a measurement procedure concerning number rate of results of measure- ments, production time of one result, cost, requirements of technical skill, requirements of services and environment, reliability of measuring system, and safety 473 13 REFERENCE MEASUREMENT SYSTEM 13.1 reference measurement procedure thoroughly investigated and described measurement procedure having analytical performance characteristics, especially bias and expressions of precision of measure- ments, permitting its use for assessing the accuracy of other procedures and charac- terizing reference materials [IS0 Guide 30:1981] 13.2 measurement standard standard etalon material measure, measuring instrument, reference material or measuring system intended to define, realize, conserve or reproduce a unit of measurement or one or more values of a quantity to serve as a reference [:: VIM, 19931 13.3 primary measurement standard primary standard measurement standard that is designated or widely acknowledged as having the highest metrological qualities and whose value is accepted without reference to other standards of the same [generic] quantity, within a specified context [:: VIM, 19931 13.4 secondary measurement standard secondary standard measurement standard whose value is assigned by comparison with a primary standard of the same [generic] quantity [:: VIM, 19931 13.5 reference measurement standard reference standard measurement standard generally having the highest metrological quality available at a given location or in a given organization, from which measurements made there are derived [:: VIM, 19931 13.6 working measurement standard working standard measurement standard that is used routinely to calibrate or check material measures, 474 measuring instruments or reference materials Notes 1. A working standard is usually calibrated against a reference standard. 2. A working standard used routinely to ensure that measurements are being carried out correctly is called a check standard. [- VIM, 19931 13.7 reference material R M material or substance one or more of whose property values are sufficiently homogene- ous and well established to be used for the calibration of an apparatus, the assessment of a measurement procedure, or for assigning values to materials [ = I S 0 Guide 30:1992] 13.8 certified reference material CRM reference material, accompanied by a certificate, one or more of whose property values are certified by a measurement procedure which establishes traceability to an accurate realization of the measurement unit in which the property values are expressed, and for which each certified value is accompanied by an uncertainty at a stated level of confidence Note Some reference materials and certified reference materials have properties which, because they cannot be correlated with an established chemical structure or for other reasons, cannot be determined by exactly defined physical and chemical measurement procedures. Such materials include certain biological materials such as vaccines to which an International unit has been assigned by the World Health Organization. [a I S 0 Guide 30:1992] 13.9 calibration material calibrator reference material used for calibration 13.10 control material material used for the purposes of internal quality control or external quality assessment and subjected to measurement according to the same or part of the same measurement procedure as that used for unknown samples in order to monitor analytical performance 19 - 935253 475 Notes 1. Analyte and matrix should closely resemble those of unknown samples. 2. Control material may or may not meet the requirements of reference materials. 13.11 blank material material lacking the analyte or another component necessary to produce an indication of a measuring system that is specific to the analyte Note Reagent blank material contains no natural sample. Sample blank material contains natural sample, but a modified measurement procedure yields no signal for the analyte. 13.12 calibration set of operations that establish, under specified conditions, the relationship between values of measurable quantities indicated by a measuring instrument or measuring system, or values represented by a material measure or a reference material, and the corresponding values realized by measurement standards [= VIM, 19931 13.13 traceability property of the result of a measurement or the value of a measurement standard whereby it can be related to stated references, usually national or international measurement standards, through an unbroken chain of comparisons having stated uncertainties [= VIM, 19931 14 ANALYTICAL QUALITY ASSURANCE METROLOGICAL QUALITY ASSURANCE 14.1 See 1.5 14.2 internal quality control set of procedures undertaken by the laboratory staff for continuous monitoring of operations and results of measurements in order to decide whether the results are reliable enough to be released and to eliminate causes of unsatisfactory performance Notes 1. Internal quality control primarily monitors the batchwise trueness of results of 476 measurements on control materials and precision on replicate measurements of natural samples. Internal quality control in the wider sense applies to all stages of activity in the production of results of measurements from assessing clinical needs, via preparation of the patient, collection of sample, and measurement to reporting of results. 2. 14.3 interlaboratory measurement comparisons interlaboratory test comparisons organization, performance and evaluation of measurements on the same or similar items or materials by two or more laboratories in accordance with predetermined conditions [= ISO/IEC Guide 2:1986] 14.4 laboratory proficiency testing proficiency testing external quality assessment system for objectively checking laboratory results of measurements by an external agency, and including comparison of a laboratory’s results at intervals with those of other laboratories, the main object being the establishment of trueness [= ISO/REMCO N231:1991] Note The main purposes of laboratory proficiency testing are to establish between-laboratory comparability of results and long term stability of analytical performance. 14.5 technical specification document that prescribes technical requirements to be fulfilled by a product, process or service Notes 1. A technical specification should indicate, whenever appropriate, the procedure(s) by means of which it may be determined whether the requirements given are fulfilled. 2. A technical specification may be a standard, a part of a standard or independent of a standard. [ = ISO/IEC Guide 2:1986] 14.6 requirement provision that conveys criteria to be fulfilled [ = ISO/IEC Guide 2:1986] 477 Note In a standard, requirements will be indicated by the auxiliary "shall". 14.7 regulation document providing binding legislative rules, that is adopted by an authority [ = ISO/IEC Guide 2:1986] 15 SCHEMES OF RECOGNITION 15.1 Good Laboratory Practice GLP organizational process and the conditions under which laboratory studies are planned, performed, monitored, recorded, and reported [ = OECD:1981] 15.2 certification of conformity action by a third party, demonstrating that adequate confidence is provided that a duly identified product, process or service is in conformity with a specific standard or other normative document [ = ISO/IEC Guide 2: 19861 15.3 laboratory accreditation formal recognition that a testing laboratory is competent to carry out specific tests or specific types of tests Note The term "laboratory accreditation" may cover the recognition of both the technical competence and the impartiality of a testing laboratory or only its technical competence. Accreditation is normally awarded following successful laboratory assessment and is followed by appropriate surveillance. [ = ISO/IEC Guide 2:1986] WHO - Health for All by the Year 2000 Health technology assessment Target 38 Before 1990, all member states should have established a formal mechanism for the systematic assessment of the appropriate use of health technologies and their effectiveness, efficiency, safety and acceptability, while reflecting national health policies and economic restraints. 478 REFERENCES Abbreviations of international organizations BIPM IEC IFCC I S 0 IUPAC IUPAP OECD OIML International Bureau of Weights and Measures International Electrotechnical Commission International Federation of Clinical Chemistry International Organization for Standardization International Union of Pure and Applied Chemistry International Union of Pure and Applied Physics Organization for Economic Co-operation and Development International Organization of Legal Metrology BIPM, IEC, IFCC, ISO, IUPAC, IUPAP, OIML. International vocabulary of basic and general terms in metrology (VIM). 2nd ed. Geneva: ISO, 1993 (in press). ISO. Terms and definitions used in connection with reference materials. I S 0 Guide 30, 1st ed. Geneva: ISO, 19815 pp. ISO. Quality - Vocabulary. I S 0 8402, 1st ed. Geneva: ISO, 1986:12 pp. ISO. Statistics - Vocabulary and symbols. Part 2. Statistical quality control. ISO/DIS 3534-2. Geneva: ISO, 1986:iii i- 30 pp. ISO. Statistics - Vocabulary and symbols. Part 1. Probability and general statistical terms. ISO/DIS 3534-1. Geneva: ISO, 1990230 pp. ISO. Harmonized proficiency testing protocol. ISO/REMCO N 231, 1991:46 pp. ISO, IEC. General terms and their definitions concerning standardization and related activities. ISO/IEC Guide 2. Geneva: ISO, 1986:iii + 45 pp. IUPAC. Nomenclature for sampling in analytical chemistry. Recommendations 1990. Pure Appl Chem 1990;62: 1193-1208. 479 OECD. OECD principles of good laboratory practice. ENV/CHEM/MC/81.14.1981: 15- 44. VIM. See. BIPM et al. 480 ALPHABETICAL INDEX aberrant-sample bias of the result of measurement 7.5 accuracy of measurement 6.1 analytical calibration function 11.3 analytical interference 11.8 analytical interferent 11.9 analytical measuring function 11.5 analytical performance characteristic 11.2 analytical portion 3.18 analytical reliability 11.1 analytical run 3.19 analytical sample 3.17 analytical sensitivity 11.4 analytical series 3.19 analytical specificity 11.7 arithmetic mean 4.16 average 4.16 between-laboratory variance of results of measurements 10.4 between-laboratory variation 10.3 between-procedure variation 10.6 bias caused by an undetected mistake 7.6 bias of a measurement procedure 7.2 bias of measurements 6.3 bias of results of a measurement procedure 7.2 blank material 13.11 blunder 5.7 calibration 13.12 calibration function 11.3 calibration material 13.9 calibrator 13.9 certification of conformity 15.2 certified reference material 13.8 48 1 coefficient of variation of a probability distribution 4.11 coefficient of variation of a random variable 4.11 commutability of a measurement procedure 11.26 compatibility 11.27 component 2.4 confidence interval 4.20 control material 13.10 conventional true value of a measurable quantity 2.13 correction 5.5 correction factor 5.6 detection Iimit 11.19 deviation 5.2 dispersion 4.5 elementary entity 2.5 error of a result of a measurement 5.1 error of measurement 5.1 estimate, noun 4.14 estimator 4.13 etalon 13.2 expectation of a random variable 4.8 fractile of a random variable 4.19 generic quantity 2.7 Good Laboratory Practice 15.1 higher limit of determination 11.21 indication of a measuring system 3.9 influence quantity 11.6 input measurable quantity 3.10 input quantity 3.10 482 interchangeability of a measurement procedure 11.25 interlaboratory measurement comparisons 14.3 interlaboratory test comparisons 14.3 intermediate precision conditions 9.1 intermediate precision of results of measurements 9.2 intermediate precision standard deviation 11.15 internal quality control 14.2 kind-of-quantity 2.6 laboratory accreditation 15.3 laboratory bias of results of a measurement procedure 7.4 laboratory component of bias of results of a measurement procedure 8.2 laboratory deviation 7.3 laboratory proficiency testing 14.4 laboratory sample 3.16 limit of detection 11.19 location 4.4 lower limit of determination 11.20 matrix blank measurement 11.11 measurable quantity 2.3 measurand 3.6 measurement 3.2 measurement procedure 3.5 measurement standard 13.2 measuring function 11.5 measuring instrument 3.7 measuring system 3.8 median 4.17 method of measurement 3.4 metrological calibration function 11.3 metrological performance characteristic metrological reliability 11.1 metrology 3.1 11.2 20- 935253 483 mistake 5.7 number fraction distribution 4.15 numerical value of a measurable quantity 2.10 observed value of a measurable quantity 3.1 1 outlier 4.23 overall expectation of results of measurements 7.1 parameter 4.7 performance characteristic 11.2 population 4.6 population parameter 4.7 practicability of a measurement procedure 12.1 precision conditions 6.5 precision of measurements 6.4 primary measurement standard 13.3 primary sample 3.15 primary standard 13.3 principle of measurement 3.3 probability 4.1 probability distribution of a random variable 4.3 proficiency testing 14.4 quality 1.1 quality assurance 1.5 quality audit 1.7 quality control 1.6 quality management 1.3 quality policy 1.2 quality system 1.4 quantity 2.3 quantity in a general sense 2.6 random error of a result of a measurement 5.3 484 random variable 4.2 reagent blank measurement 11.10 recovery measurement 11.12 reference material 13.7 reference measurement procedure 13.1 reference measurement standard 13.5 reference standard 13.5 regulation 14.7 relative frequency distribution 4.15 repeatability conditions 8.1 repeatability limit 11.14 repeatability of results of measurements 8.3 repeatability standard deviation 11.13 repeatability variance of results of measurements 8.5 reproducibility conditions 10. I reproducibility limit 11.17 reproducibility of results of measurements 10.2 reproducibility standard deviation 11.16 reproducibility standard deviation divided by analytical sensitivity 11.18 reproducibility variance of results of measurements 10.5 requirement 14.6 result of a measurement 3.12 robustness of a measurement procedure 11.23 sample 3.14 sample variance 4.18 sampling 3.13 secondary measurement standard 13.4 secondary standard 13.4 set 2.2 standard 13.2 standard deviation of a probability distribution 4.10 standard deviation of a random variable 4.10 statistic 4.12 statistical coverage interval 4.21 48 5 statistical outlier 4.23 system 2.1 systematic error of a result of a measurement 5.4 technical specification 14.5 tolerance interval 4.22 traceability 13.13 transferability of a measurement procedure 11.24 true value of a measurable quantity 2.12 trueness of measurement 6.2 truth 2.11 uncertainty of measurement 11.22 unit of measurement 2.9 value of a measurable quantity 2.8 variance of a probability distribution 4.9 variance of a random variable 4.9 variate 4.2 within-laboratory repeatability variance of results of measurements 8.4 working measurement standard 13.6 working standard 13.6 Correspondence: RenC Dybkzr Department of Clinical Chemistry Frederiksberg Hospital DK-2000 Frederiksberg, Danmark 486