Fitness for purpose

Fitness for purpose and intra-individual biological variation

The International Organization for Standardization (ISO) defines quality as the “totality of characteristics of an entity that bear on its ability to satisfy stated and implied needs." In the medical context, this definition can be translated to mean that the quality of either laboratory or point-of-care testing must allow clinicians to practice good medicine. This definition also contains an implied requirement to understand the quality required to ensure satisfactory clinical decision making and to understand if a given test is fit for the purpose for which it is intended (that is, fit for purpose).

Australian Standard AS 4633 (ISO standard 15189; Medical laboratories – particular requirements for quality and competence) to which all accredited pathology laboratories in Australia must comply, makes an explicit statement to this effect:

AS 4633, 5.5.1: “The laboratory shall use examination procedures, … which meet the needs of the users of laboratory services and are appropriate for the examinations”.

The fundamental role of medical testing laboratories and POCT providers is to produce test results that are fit for their purpose. A test result must have appropriate analytical accuracy and precision in order for it to be considered fit for purpose; that is, suitable for the clinical purpose for which the test is being used. In order to determine whether a method is routinely producing results which are fit for purpose, there needs to be a relevant analytical goal against which the estimated uncertainty of measurement can be compared. Some methods have internationally agreed analytical goals (for example; glucose, cholesterol and haemoglobin A1c), but in their absence various approaches have been used to set goals for both inaccuracy (bias) and imprecision. A widely used and internationally recommended concept is to define the upper acceptable limit for imprecision as a proportion of the intra- individual biological variation of the measurand in question. With correct choice of the proportionality factor, analytical imprecision should not contribute significant additional variation to the test result when compared with the natural variation of the analyte being measured. A similar approach to goal-setting can be used for total analytical error (inaccuracy plus imprecision).⁸⁷ These concepts are clearly described in the NPAAC document Requirements for the estimation of measurement uncertainty and the AACB publication Uncertainty of measurement in quantitative medical testing – A laboratory implementation guide.⁸⁸,²⁴

Quality goals

Procedures for the determination of quality goals (quality specifications) based on clinical requirements have been reviewed by Fraser²⁵,²⁶,⁸⁷, Fraser and Scott²⁷, and Klee⁸⁹. A detailed discussion of POC glucose measurement and the relationship between analytical performance and clinical decision-making is given by Boyd and Burns⁹⁰ and by Fraser and Scott²⁷. Shephard has also considered this issue in some detail for the Australian rural environment in relation to the QAAMS program, with publications discussing quality goal setting for haemoglobin A1c, lipids and urine albumin-creatinine ratio⁹¹ and related POCT quality issues (Shephard and Gill,⁹²,⁹³ Shephard etal⁹⁴, Gill and Shephard⁹⁵). The other two major Australian networks of POCT devices, iCCnet and Pathology Queensland, have also described their approaches to clinical governance, quality issues and quality control in POCT.⁹⁶,⁹⁷,⁸³

The practical problems associated with selecting appropriate quality goals (quality specifications) are exemplified by the most widely used POCT device, the glucose meter. The American Diabetes Association (ADA) and the National Academy of Clinical Biochemistry (NACB) have documented this dilemma in considerable detail.⁷⁵,⁷⁶,⁹⁸ They reinforce the WHO recommendation that a laboratory measurement of plasma glucose be used for the diagnosis of diabetes mellitus, and not whole blood glucose measured on a glucose meter with the statement “Portable meters are used by healthcare workers in acute and chronic care facilities, in physicians’ offices, and by patients. Because of the imprecision and variability among meters, they should not be used to diagnose diabetes and have limited value in screening.”.⁹⁸ One of the issues which should also be considered as part of this argument, particularly for hospital in-patients whose insulin infusion (and consequent insulin dosage) is adjusted in association with POC glucose testing, is that relatively small changes in measured glucose are associated with relatively large changes in insulin infusion rate.⁹⁹ Blood glucose monitoring is used to guide therapy in two distinct situations, one to adjust insulin dosage in diabetic patients, and one for adjusting insulin requirement in acutely ill patients on “tight glucose control”. The quality specifications for these two situations have been reviewed by Price.¹⁰⁰ In a recent evaluation study by Freckmann etal, eleven of twenty seven home-use blood glucose monitoring systems (40%) did not fulfill the rather generous minimum accuracy requirements of ISO 15197 (that is; +/- 0.83 mmol/L at blood glucose less than 4.2 mmol/L, or +/- 20% at blood glucose levels 4.2 or greater).¹⁰¹ From their study, Freckmann etal concluded that inaccurate results which lead to false treatment decisions by diabetic patients may cause severe health injury.

In addition to portable POC glucose meters, the fitness for purpose of portable devices which measure haemoglobin A1c (HbA1c) has also been questioned recently.¹⁰²,¹⁰³ The main reason for this concern is the questionable ability of some HbA1c devices to provide a clear analytical distinction between the recommended HbA1c treatment levels of 7.0% and 8.0%. To clearly distinguish between HbA1c values of 7.0% and 8.0%, an analytical (method) uncertainty (expressed as coefficient of variation, CV%) of less than 3.0% is required. Methods which produce analytical CV’s of 4.0% or greater are not considered appropriate, as this degree of analytical imprecision cannot distinguish changes in the HbA1c level of over 1% (that is, can not distinguish an HbA1c level of 7.0% from 8.0%). A more detailed discussion of these concepts and of the relationship between HbA1c measurement and analytical performance is given by White and Farrance.²⁴ The direct influence of analytical imprecision and inaccuracy (bias) on the measurement of glucose and HbA1c for the diagnosis and prognosis of diabetes mellitus has been considered in more detail by Petersen etal.¹⁰⁴