Clinical trial NCT04758208: Mindray Pediatric Hematology Reference Intervals Study
Official title: Establishment of Pediatric Reference Intervals for Mindray Hematology Parameters for Worldwide Application in Clinical Laboratories
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Establish Hematology Reference Intervals
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
Collaborators: name: MINDRAY
First posted: 2021-02-17
Enrollment: 691
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy community children and adolescents as well as healthy children and adolescents recruited from outpatient clinics at the Hospital for Sick Children.

Brief summary: 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: 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'

Eligibility criteria: 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

Primary outcomes:
measure: White Blood Cell count
timeFrame: Within 8 hours of sample collection
measure: Basophil number
timeFrame: Within 8 hours of sample collection
measure: Basophil percentage
timeFrame: Within 8 hours of sample collection
measure: Neutrophil number
timeFrame: Within 8 hours of sample collection
measure: Neutrophil percentage
timeFrame: Within 8 hours of sample collection
measure: Eosinophil number
timeFrame: Within 8 hours of sample collection
measure: Eosinophil percentage
timeFrame: Within 8 hours of sample collection
measure: Lymphocyte number
timeFrame: Within 8 hours of sample collection
measure: Lymphocyte percentage
timeFrame: Within 8 hours of sample collection
measure: Monocyte number
timeFrame: Within 8 hours of sample collection
measure: Monocyte percentage
timeFrame: Within 8 hours of sample collection
measure: Immature Granulocyte number
timeFrame: Within 8 hours of sample collection
measure: Immature Granulocyte percentage
timeFrame: Within 8 hours of sample collection
measure: Reticulocyte percentage
timeFrame: Within 8 hours of sample collection
measure: Reticulocyte number
timeFrame: Within 8 hours of sample collection
measure: Reticulocyte Hemoglobin Expression
timeFrame: Within 8 hours of sample collection
measure: Immature reticulocyte fraction
timeFrame: Within 8 hours of sample collection
measure: Low fluorescent ratio
timeFrame: Within 8 hours of sample collection
measure: Middle fluorescent ratio
timeFrame: Within 8 hours of sample collection
measure: High fluorescent ratio
timeFrame: Within 8 hours of sample collection
measure: Red blood cell count
timeFrame: Within 8 hours of sample collection
measure: Hemoglobin Concentration
timeFrame: Within 8 hours of sample collection
measure: Mean Corpuscular Volume
timeFrame: Within 8 hours of sample collection
measure: Mean Corpuscular Hemoglobin
timeFrame: Within 8 hours of sample collection
measure: Mean Corpuscular Hemoglobin Concentration
timeFrame: Within 8 hours of sample collection
measure: Red Blood Cell Distribution Width - Coefficient of Variation
timeFrame: Within 8 hours of sample collection
measure: Red Blood Cell Distribution Width - Standard Deviation
timeFrame: Within 8 hours of sample collection
measure: Hematocrit
timeFrame: Within 8 hours of sample collection
measure: Nucleated red blood cell (NRBC) number
timeFrame: Within 8 hours of sample collection
measure: Nucleated red blood cell percentage
timeFrame: Within 8 hours of sample collection
measure: Platelet count
timeFrame: Within 8 hours of sample collection
measure: Mean Platelet Volume
timeFrame: Within 8 hours of sample collection
measure: Platelet Distribution Width
timeFrame: Within 8 hours of sample collection
measure: Plateletcrit
timeFrame: Within 8 hours of sample collection
measure: Immature Platelet Fraction
timeFrame: Within 8 hours of sample collection
measure: Platelet-large cell ratio
timeFrame: Within 8 hours of sample collection
measure: Platelet-large cell count
timeFrame: Within 8 hours of sample collection
Secondary outcomes:
measure: High fluorescent Cell number
timeFrame: Within 8 hours of sample collection
measure: High fluorescent Cell percentage
timeFrame: Within 8 hours of sample collection
measure: Optical Red Blood Cell count
timeFrame: Within 8 hours of sample collection
measure: Optical Platelet count
timeFrame: Within 8 hours of sample collection
measure: Platelet count - Impedance
timeFrame: Within 8 hours of sample collection
measure: Optical White Blood Cell count
timeFrame: Within 8 hours of sample collection
measure: White blood cell counts - Differential (DIFF)
timeFrame: Within 8 hours of sample collection
measure: Total nucleated cell counts - DIFF
timeFrame: Within 8 hours of sample collection
measure: Immature Eosinophil percentage
timeFrame: Within 8 hours of sample collection
measure: Immature Eosinophil number
timeFrame: Within 8 hours of sample collection
measure: High forward scatter NRBC ratio
timeFrame: Within 8 hours of sample collection
measure: Low forward scatter NRBC ratio
timeFrame: Within 8 hours of sample collection
measure: Neutrophil-to-lymphocyte ratio
timeFrame: Within 8 hours of sample collection
measure: Platelet-to-lymphocyte ratio
timeFrame: Within 8 hours of sample collection
measure: White blood cell count - white cell nucleated basophil channel (WNB)
timeFrame: Within 8 hours of sample collection
measure: Total nucleated cell counts
timeFrame: Within 8 hours of sample collection
measure: Infected Red Blood Cell count
timeFrame: Within 8 hours of sample collection
measure: Infected Red Blood Cell permillage
timeFrame: Within 8 hours of sample collection
measure: Microcyte count
timeFrame: Within 8 hours of sample collection
measure: Microcyte percentage
timeFrame: Within 8 hours of sample collection
measure: Macrocyte count
timeFrame: Within 8 hours of sample collection
measure: Macrocyte percentage
timeFrame: Within 8 hours of sample collection
measure: Mean Reticulocyte Volume
timeFrame: Within 8 hours of sample collection
measure: Red Blood Cell Fragment Count
timeFrame: Within 8 hours of sample collection
measure: Red Blood Cell Fragment Percentage
timeFrame: Within 8 hours of sample collection
measure: Platelet Distribution Width Standard Deviation
timeFrame: Within 8 hours of sample collection
measure: Reticulocyte Production Index
timeFrame: Within 8 hours of sample collection
measure: High fluorescent Immature Platelet Fraction
timeFrame: Within 8 hours of sample collection
measure: Immature Platelet Count
timeFrame: Within 8 hours of sample collection
measure: DIFF scattergram, mean neutrophil distribution-side scatter intensity
timeFrame: Within 8 hours of sample collection
measure: DIFF scattergram, mean neutrophil distribution-side fluorescent light intensity
timeFrame: Within 8 hours of sample collection
measure: DIFF scattergram, mean neutrophil distribution-forward scatter intensity
timeFrame: Within 8 hours of sample collection
measure: DIFF scattergram, mean lymphocyte distribution-side scatter intensity
timeFrame: Within 8 hours of sample collection
measure: DIFF scattergram, mean lymphocyte distribution-side fluorescent intensity
timeFrame: Within 8 hours of sample collection
measure: DIFF scattergram, mean lymphocyte distribution-forward scatter intensity
timeFrame: Within 8 hours of sample collection
measure: DIFF scattergram, mean monocyte distribution-side scatter intensity
timeFrame: Within 8 hours of sample collection
measure: DIFF scattergram, mean monocyte distribution-side fluorescent light intensity
timeFrame: Within 8 hours of sample collection
measure: DIFF scattergram, mean monocyte distribution-forward scatter intensity
timeFrame: Within 8 hours of sample collection
measure: Dimorphic population, smaller distribution RBC count
timeFrame: Within 8 hours of sample collection
measure: Dimorphic population, larger distribution RBC count
timeFrame: Within 8 hours of sample collection
measure: Dimorphic population, smaller distribution mean corpuscular volume
timeFrame: Within 8 hours of sample collection
measure: Dimorphic population, larger distribution mean corpuscular volume
timeFrame: Within 8 hours of sample collection
measure: Mean Corpuscular Hemoglobin of Reticulocyte
timeFrame: Within 8 hours of sample collection
measure: Mean Hemoglobin Distribution Width of Red Blood Cell
timeFrame: Within 8 hours of sample collection
measure: Mean Platelet Concentration
timeFrame: Within 8 hours of sample collection
measure: Mean Platelet Matter Content
timeFrame: Within 8 hours of sample collection
measure: Hyperchromic Red Blood Cell percentage (Hyper%)
timeFrame: Within 8 hours of sample collection
measure: Hypochromic Red Blood Cell percentage
timeFrame: Within 8 hours of sample collection
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Khosrow Khosrow, PhD
role: PRINCIPAL_INVESTIGATOR
References: