Abstract
Abstract Reference intervals (RIs) can be determined by direct and indirect procedures. Both approaches identify a reference population from which the RIs are defined. The crucial difference between direct and indirect methods is that direct methods select particular individuals after individual anamnesis and medical examination have confirmed the absence of pathological conditions. These individuals form a reference subpopulation. Indirect methods select a reference subpopulation in which the individuals are not identified. They isolate a reference population from a mixed population of patients with pathological and non-pathological conditions by statistical reasoning. At present, the direct procedure internationally recommended is the “gold standard”. It has, however, the disadvantage of high expenses which cannot easily be afforded by most medical laboratories. Therefore, laboratories adopt RIs established by direct methods from external sources requiring a high responsibility for transference problems which are usually neglected by most laboratories. These difficulties can be overcome by indirect procedures which can easily be performed by most laboratories without causing economic problems. The present review focuses on indirect approaches. Various procedures are presented with their benefits and limitations. Preliminary simulation studies indicate that more recently developed concepts are superior to older approaches.
Highlights
Laboratory results released to requesters require interpretative support usually established by reference limits (RLs), which must not be confused with other interpretative guide limits [1,2,3]
Several tests have been proposed for this purpose: – Harris and Boyd [42] recommended to separate Reference intervals (RIs) when the ratio of the standard deviation between the subgroups exceeds 1.5, or when the z-statistics between the two subgroup distributions exceeds 3. – Lahti et al [43] proposed partitioning when more than 4.1% of a subgroup falls outside the RLs. – Equivalence test: see below
If RLs estimated by intra-laboratory indirect models are compared with those from direct methods usually taken from extra-laboratory sources, it is essential to consider comprehensive transference aspects and the effect of posture for all corpuscular and protein-dependent blood components
Summary
Laboratory results released to requesters require interpretative support usually established by reference limits (RLs), which must not be confused with other interpretative guide limits [1,2,3]. Both need a transformation parameter that has to be specified by the user or estimated from the data If such specification seems not feasible, and in the absence of better information, a simple general approach is to assume a logarithmic normal distribution (LND) for non-pathological laboratory data [47]. This avoids the need of dealing with positive probabilities for negative values and has the convenient feature that after taking logarithms the data has a ND, for which many statistical procedures are readily available. Pryce [61], Becktel [62], Kairisto et al [63]: resolution in two different distributions with one common mode
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