Mindray Pediatric Hematology Reference Intervals Study

Study Overview
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Brief Summary
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This study is a collaborative initiative between the CALIPER (Canadian Laboratory Initiative on Pediatric Reference Intervals) program at the Hospital for Sick Children (HSC) and Mindray Medical International Limited to establish a database of pediatric reference intervals for hematology parameters on BC-6800Plus.

Detailed Description
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The purpose of this study is to establish accurate and robust ethnic-, age- and sex-specific reference intervals for hematology parameters during childhood and adolescence on the Mindray analyzer (BC-6800Plus). Subjects will be recruited for this study through the CALIPER initiative and will include healthy children and adolescents in the community and in outpatient clinics at the Hospital for Sick Children (HSC). Since all participants will be recruited through the CALIPER initiative, the CALIPER consent forms will be used to obtain consent from each child and their parent/guardian. These forms obtain consent to use the samples to develop reference intervals for a range of tests. This study aims to measure hematology parameters in these samples and is therefore encompassed within the CALIPER consent. Recruitment will focus on subjects from three ethnic groups: Caucasians, Hispanics, and South Asians. A total of 960 subjects will be recruited for this study through the CALIPER initiative. The total sample size was determined by considering the requirement of 60-120 samples per partition for five age groups (0-<1 years, 1-<5 years, 5-<10 years, 10-<15 years, 15-<19 years). Each age group will consist of an equal number of females and males. Additional samples may be required if data analysis suggests further age and/or sex partitioning for specific parameters. Each subject will provide a blood sample, which will be collected through the CALIPER initiative. These samples will be analyzed as part of this study in a secondary-use/retrospective fashion. Specifically, fresh whole blood specimens will be collected in K2EDTA tubes, placed in biohazard bags, stored on ice, and analyzed on the Mindray hematology platform within 8 hours of collection. All available hematology parameters for the BC-6800Plus will be measured (37 report and 48 research hematology parameters, as per the user manual). All procedures will be performed according to the user manual. Mindray quality control materials will be used to monitor the performance of the assays during the study. HSC will retain all quality controls data, maintenance record and reagents/calibrators lot numbers. Quality controls will be run daily and analysis of the CALIPER samples will proceed only after all the quality control (QC) data are acceptable. Data analysis will be performed by the CALIPER team in accordance with Clinical & Laboratory Standards Institute (CLSI) EP28-A3c guidelines on defining, establishing, and verifying reference intervals in the clinical laboratory. The statistical approach for reference interval establishment has been described in-depth previously. In brief, analyte concentrations will be plotted against age and colour-coded by sex. Following visual inspection, extreme outliers will be removed and suspected age- and sex-specific partitions will be confirmed using the Harris and Boyd statistical method. Normality of data will be qualitatively assessed using quantile-quantile plots and quantitatively assessed using the Shapiro-Wilk's test. If skewed, the Box-Cox transformation will be applied in an effort to transform the data to a normal distribution. Outliers will be subsequently identified and removed using the Tukey or adjusted Tukey method for Gaussian and non-Gaussian data distributions, respectively. Reference intervals for partitions with ≥120 participants will be calculated using the nonparametric method. Reference intervals for partitions with ≥40 and <120 participants (60 for group 0-<1 years and 1-<5 years, 120 for group 5-<10 years, 10-<15 years and 15-<19 years) will be calculated using the robust method. 90% percent confidence intervals will also be calculated for the lower and upper limit of each reference interval. Ethnic-specific reference intervals will be calculated if sample size for each ethnic group is adequate. Otherwise, reference value distributions for South Asian and Hispanic children will be compared to those of Caucasian children. Oversight Authority (additional information) This study is regulated by 'Canada: Health Canada' This study has been reviewed and approved by 'Canada: Ethics Review Committee'

Official Title
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Establishment of Pediatric Reference Intervals for Mindray Hematology Parameters for Worldwide Application in Clinical Laboratories

Conditions
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Establish Hematology Reference Intervals

Intervention / Treatment
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* Diagnostic Test: Hematology Parameters


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 0-<19 years Exclusion Criteria: History of chronic illness Use of prescription medications within 2 weeks of collection Acute illness within 7 days of collection Pregnancy

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy CALIPER Participants<br>Healthy community children and adolescents recruited through the CALIPER initiative as well as healthy children and adolescents recruited from outpatient clinics at the Hospital for Sick Children through the CALIPER initiative. Blood samples from these participants will be tested on the Mindray BC-6800Plus device to measure hematology parameters and establish reference intervals. | Diagnostic Test: Hematology Parameters<br>* Measurement of hematology parameters on BC-6800Plus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| White Blood Cell count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Basophil number | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Basophil percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Neutrophil number | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Neutrophil percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Eosinophil number | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Eosinophil percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Lymphocyte number | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Lymphocyte percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Monocyte number | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Monocyte percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Immature Granulocyte number | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Immature Granulocyte percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Reticulocyte percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Reticulocyte number | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Reticulocyte Hemoglobin Expression | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Immature reticulocyte fraction | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Low fluorescent ratio | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Middle fluorescent ratio | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| High fluorescent ratio | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Red blood cell count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Hemoglobin Concentration | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Mean Corpuscular Volume | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Mean Corpuscular Hemoglobin | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Mean Corpuscular Hemoglobin Concentration | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Red Blood Cell Distribution Width - Coefficient of Variation | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Red Blood Cell Distribution Width - Standard Deviation | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Hematocrit | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Nucleated red blood cell (NRBC) number | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Nucleated red blood cell percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Platelet count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Mean Platelet Volume | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Platelet Distribution Width | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Plateletcrit | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Immature Platelet Fraction | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Platelet-large cell ratio | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Platelet-large cell count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High fluorescent Cell number | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| High fluorescent Cell percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Optical Red Blood Cell count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Optical Platelet count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Platelet count - Impedance | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Optical White Blood Cell count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| White blood cell counts - Differential (DIFF) | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Total nucleated cell counts - DIFF | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Immature Eosinophil percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Immature Eosinophil number | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| High forward scatter NRBC ratio | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Low forward scatter NRBC ratio | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Neutrophil-to-lymphocyte ratio | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Platelet-to-lymphocyte ratio | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| White blood cell count - white cell nucleated basophil channel (WNB) | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Total nucleated cell counts | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Infected Red Blood Cell count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Infected Red Blood Cell permillage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Microcyte count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Microcyte percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Macrocyte count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Macrocyte percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Mean Reticulocyte Volume | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Red Blood Cell Fragment Count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Red Blood Cell Fragment Percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Platelet Distribution Width Standard Deviation | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Reticulocyte Production Index | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| High fluorescent Immature Platelet Fraction | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Immature Platelet Count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| DIFF scattergram, mean neutrophil distribution-side scatter intensity | Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| DIFF scattergram, mean neutrophil distribution-side fluorescent light intensity | Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| DIFF scattergram, mean neutrophil distribution-forward scatter intensity | Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| DIFF scattergram, mean lymphocyte distribution-side scatter intensity | Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| DIFF scattergram, mean lymphocyte distribution-side fluorescent intensity | Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| DIFF scattergram, mean lymphocyte distribution-forward scatter intensity | Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| DIFF scattergram, mean monocyte distribution-side scatter intensity | Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| DIFF scattergram, mean monocyte distribution-side fluorescent light intensity | Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| DIFF scattergram, mean monocyte distribution-forward scatter intensity | Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Dimorphic population, smaller distribution RBC count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Dimorphic population, larger distribution RBC count | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Dimorphic population, smaller distribution mean corpuscular volume | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Dimorphic population, larger distribution mean corpuscular volume | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Mean Corpuscular Hemoglobin of Reticulocyte | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Mean Hemoglobin Distribution Width of Red Blood Cell | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Mean Platelet Concentration | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Mean Platelet Matter Content | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Hyperchromic Red Blood Cell percentage (Hyper%) | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection | 
| Hypochromic Red Blood Cell percentage | Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer | Within 8 hours of sample collection |