Wednesday, 1 November 2017

Computation of the “Gray Zone” Based on Experimental Data and Its Effect on the Trueness in HIV Results in the Blood, Cells and Tissues Banks

A screening test is recognized as a technique “used to evaluate large populations of individuals for the presence of a disease or analyte”. The physician interprets the HIV result tested in a screening immunoassay as the in vivo condition/true result. Based on this result a clinical decision is taken. However, there is a chance for some binary results (positive/negative) in medical laboratory tests to be false. This situation represents a serious risk of incorrect clinical decision with impact on the patient safety. This could also be viewed not only at healthcare but also at other stages, such as on the validation of components in human blood components, cells, and tissues banks. 

The risk to the customer significantly increases in these banks when compared to a hospital laboratory where typically negative results from individuals in groups of risk are retested on a second collection due to the chance of a seroconversion window period occurs. On the banks’ scenario, the collection of a second sample occurs only on the vigilance and surveillance when a post-transfusion or post-transplant infection is reported, so, it is not related directly to post-transfusion or post-transplant infection safety but indirectly with the corrective actions/preventive actions (CAPA) development. Let consider a result equal to the cutoff and the condition: positive if equal or higher than the cutoff. In this case, a true positive result of a Gaussian distribution is 50% false negative in an infinite number of determinations. It could be interpreted that true positive results close to the decision value have a significant statistical chance to be classified as false. 

The “gray zone” is understood as the area around the cutoff where numerical results are classified as indeterminate. Further testing is required to a final classification. In this condition, the numerical results have a trinary classification: positive/indeterminate/negative. Adopting the ratio of the screening immunoassays s/co as the expression of the division of the sample raw data (s) by the cutoff (co): negative results are those with an s/co lower than the cutoff (1 s/co) minus the “gray zone”, indeterminate are those in the “gray zone”, and positive those equal or higher than the cutoff. Therefore, it is well recognized that the use of a “gray zone” in the classification of screening immunoassays results reduces the chance of positive samples with low concentrations of measurand to be classified as negative. The numerical results in the “gray zone” are presumed to be sporadic principally in tests with high diagnostic sensitivity. Currently, the use of the “gray zone” in screening immunoassays is not systematically required to classify the numerical results in an ordinal scale in commercial tests. Its use is also not claimed by ISO 15189, intended to the accreditation of medical laboratory tests. Probably, the manufacturer interprets the “gray zone” importance as minor to tests highly reactive to weak concentrations of measurand (antibodies and or antigens tested under stable laboratory conditions), and poorly reactive when the measurand is absent. Nevertheless, the impact of wrong medical decisions has a strong social impact, principally when related to the post-transfusion/posttransplant infection. 

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