ABSTRACT
BACKGROUND: Interpretation of changes in serial laboratory results is necessary for both clinicians and laboratories; however, setting decision limits is not easy. Although the reference change value (RCV) has been widely used for auto-verification, it has limitations in clinical settings. We introduce the concept of overlapping confidence intervals (CIs) to determine whether the changes are statistically significant in clinical chemistry laboratory test results.METHODS: In total, 1,202,096 paired results for 33 analytes routinely tested in our clinical chemistry laboratory were analyzed. The distributions of delta% absolute values and cut-off values for certain percentiles were calculated. The CIs for each analyte were set based on biological variation, and data were analyzed at various confidence levels. Additionally, we analyzed the data using RCVs and compared their clinical utility.RESULTS: Most analytes had low indexes of individuality with large inter-individual variability. The 97.5th percentile cut-offs for each analyte were much larger than conventional RCVs. The percentages of results exceeding RCV(95%) and RCV(99%) corresponded to those with no overlap at the 83.4% and 93.2% confidence levels, respectively.CONCLUSIONS: The use of overlapping CIs in serial clinical chemistry test results can overcome the limitations of existing RCVs and replace them, especially for analytes with large intra-individual variation.
Subject(s)
Chemistry, Clinical , Clinical Chemistry Tests , Confidence Intervals , IndividualityABSTRACT
El valor de referencia del cambio (VRC) es el valor máximo que es permisible cambie el resultado de un analito entre dos mediciones sucesivas en un mismo paciente, sin que esta diferencia sea de relevancia clínica. Incluye critérios basados en la variabilidad biológica intraindividual (CVI) y la imprecisión analítica (CVA). La principal utilidad de los marcadores tumorales (MT) es el monitoreo de pacientes, resultando más apropiado informar el VRC que evaluar un resultado con su valor de referencia, como lo indica su bajo índice de individualidad. El objetivo fue evaluar la utilidad del VRC para detectar un cambio significativo entre resultados sucesivos en los principales MT. Se analizaron datos de sueros de controles de calidad de MT desde mayo de 2010 a febrero de 2014, se calculó el CVA%, y los datos de CVI % fueron obtenidos de bibliografía. Se calcularon los VRC para cada MT. Para los MT evaluados: AFP, CEA, CA125, CA15-3, CA19-9, PSA y tiroglobulina, los VRC fueron: 29.7, 32.3, 58.0, 16.3, 38.3, 42.7 y 34.2% respectivamente (p<0.05). Estos valores se compararon con datos bibliográficos. El VRC es un dato útil para el médico ya que colabora en la correcta interpretación de resultados seriados durante el seguimiento de pacientes, en la evaluación del tratamiento o en la estimación de recurrencias. Le permite saber si la diferencia encontrada entre dos valores consecutivos representa un cambio em el estado de salud del paciente. Nuestros VRC resultaron comparables con los de literatura
The reference change value (RCV) is the maximum allowable change between two consecutive results with no meaningful clinical relevance. It is analyzed within individual biological variability (CVI ) and analytical imprecision (CVA) criteria. For tumor markers (TM) monitoring is more appropriate to report RCV than reference interval due to their low individuality index. The aim of the study was to evaluate the usefulness of RCV to indicate a significant change between two consecutives TM results. Data from MT quality control serums (QC) were analyzed from May 2010 to February 2014, the imprecision was calculated as CVA% and CVI % data was obtained from literature. The RCV for each MT was calculated. The RCV for AFP, CEA, CA125, CA15-3, CA19-9, PSA and thyroglobulin were 29.7, 32.3, 58.0, 16.3, 38.3, 42.7 and 34.2% respectively (p < 0.05). These values were compared with literature data. The RCV is an appropriate tool for the clinicians and aids for the correct interpretation of results in the monitoring of patients, in treatment evaluation or estimation of recurrence. Physicians can determine whether the differences found between two successive values represent a change in the health status of the patient. The RCV calculated were comparable with those obtained in literature
Subject(s)
Humans , Reference Values , Mass Screening , LaboratoriesABSTRACT
Objective To evaluate the reference change values (RCV),individual indexes of TSH,T4,T3,FT3,and FT4 and the limitations of population-based reference ranges.Furthermore,to determine the quality standards based on the biological varia-tion.Methods Acorrding to intra-and inter-individual biological variations,and analytical variations ,RCV and individual indexes of TSH,T4,T3,free T3,and free T4 were calculated,and analytical variations of quality standards based on biological variation were induced.Results RCV of TSH,T4,T3,FT3,and FT4 is 54.0%,16.8%,26.8%,42.8%,23.8%,respectively.Individ-uality index is 0.78,0.45,0.49,0.47,0.45,respectively,and satisfied analytical variation based on biological variation is less than 9.6%,2.5%,4.4%,2.9%,4.0%,respectively.Conclusion When monitoring thyroid functions,the RCV values should be considered.It is important to recognize population-based reference ranges limitations for use in individuals.Quality standards based on biological variation should be meeted when laboratory analysis of variance is determined.
ABSTRACT
El objetivo de este trabajo fue determinar la variabilidad biológica (VB) de Aldolasa (ALD) en individuos sanos, el índice de individualidad (II) del analito y evaluar la utilidad del intervalo de referencia poblacional (IRP) considerando al IRP de los analitos útil cuando el II es > 1,4 y de poca utilidad si es <0,6. También se evaluó el valor de referencia para el cambio (VRC) en la interpretación de dos determinaciones seriadas del mismo individuo, especialmente en el seguimiento de enfermedades músculo-esqueléticas en las que los niveles de creatinquinasa (CK) permanecen dentro del intervalo de referencia, mientras que los de ALD están elevados. Se obtuvieron 8 muestras de sangre de 10 individuos aparentemente sanos en días diferentes según protocolo preestablecido. Se determinó la actividad de ALD por método enzimático UV y se calcularon los parámetros de VB, II y VRC. Se obtuvo una VB intraindividual: 31%; VB interindividual: 21%, II 1.47 y VRC 90%. De acuerdo a los coeficientes de VB y el II obtenidos, los IRP son útiles para la interpretación de los resultados de ALD. Un resultado seriado será estadísticamente diferente del dato previo cuando el mismo tenga una diferencia mayor al 90% en relación al valor previo. El VRC entre dos determinaciones seriadas debe ser calculado en cada laboratorio con su propia variabilidad analítica para una correcta interpretación de los resultados.
The aim of this study was to determine the Biological Variation (BV) of Aldolase (ALD) in healthy patients, the individuality index (II) of the analyte and to assess how useful the population reference interval (PRI) is for the interpretation of the results, considering PRI useful when the II is >1.40 and useless when it is <0.6. Reference change values (RCV) were also assessed in the interpretation of two serial measurements of the same individual, specially in the monitoring of patients in which the serum level of Creatine Kinase (CK) remain within the reference range while ALD values are increased. Eight bloodsam-ples were obtained from ten apparently healthy subjects in different days according to a predetermined protocol. ALD activity was measured by an enzymatic UV method and BV, II and RCV were calculated. Intraindividual BV was 31 %, interindividual BV 21 %, II 1.47 and RCV 90%. Based on the results obtained for BV and II, PRIs are useful for the interpretation of ADL results. A serial result will be statistically different from the previous one when the variability between both results is higher than 90%. RCV must be determined in each laboratory using their own analytical variability in order to obtain a correct interpretation of the results.
O objetivo deste trabalho foi determinar a variabilidade biológica (VB) de Aldolase (ALD) em individuos saudáveis, o índice de individualidade (II) do analito e avaliar a utilidade do intervalo de referencia populacional (IRP) considerando o IRP dos analitos útil quando o II é > 1,4 e de pouca utilidade se é <0,6. Também foi avaliado o valor de referencia da variagáo (VRV) na interpretagáo de duas determinagóes seriadas do mesmo individuo, especialmente no seguimento de doengas músculo-esqueléticas nas quais os níveis de creatinoquinase (CK) permanecem dentro do intervalo de referencia, enquanto que os de ALD estáo elevados. Foram obtidas 8 amostras de sangue de 10 individuos aparentemente saudáveis em dias diferentes conforme protocolo preestabelecido. Determinou-se a atividade de ALD por método enzimático UV e se calcularam os parámetros de VB, II e VRC. Foi obtida uma VB intra-individual: 31 %; VB interindividual: 21 %, II 1.47 e VRV 90%. De acordo com os coeficientes de VB e o II obtidos, os IRP sáo úteis para a interpretagáo dos resultados de ALD. Um resultado seriado será estatisticamente diferente do dado prévio quando o mesmo tenha uma diferenga maior a 90% em relagáo ao valor prévio. O VRV entre duas determinagóes seriadas deve ser calculado em cada laboratório com sua própria variabilidade analítica para uma correta interpretagáo dos resultados.