Mindray Pediatric Hematology Reference Intervals Study

Establish Hematology Reference Intervals Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04758208
• Other study ID #: REB1000069402
• Status: Completed
• Start date: July 12, 2021
• Est. completion date: February 11, 2022

Study information

• Verified date: March 2022
• Source: The Hospital for Sick Children
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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'

Recruitment information / eligibility

• Status: Completed
• Enrollment: 691
• Est. completion date: February 11, 2022
• Est. primary completion date: January 28, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Establish Hematology Reference Intervals

Intervention

Diagnostic Test:
• Hematology Parameters
Measurement of hematology parameters on BC-6800Plus

Locations

Country	Name	City	State
Canada	The Hospital for Sick Children	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
The Hospital for Sick Children	MINDRAY

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	White Blood Cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Basophil number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Basophil percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Neutrophil number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Neutrophil percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Eosinophil number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Eosinophil percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Lymphocyte number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Lymphocyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Monocyte number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Monocyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Immature Granulocyte number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Immature Granulocyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Reticulocyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Reticulocyte number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Reticulocyte Hemoglobin Expression	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Immature reticulocyte fraction	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Low fluorescent ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Middle fluorescent ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	High fluorescent ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Red blood cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Hemoglobin Concentration	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Mean Corpuscular Volume	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Mean Corpuscular Hemoglobin	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Mean Corpuscular Hemoglobin Concentration	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	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
Primary	Red Blood Cell Distribution Width - Standard Deviation	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Hematocrit	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Nucleated red blood cell (NRBC) number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Nucleated red blood cell percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Platelet count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Mean Platelet Volume	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Platelet Distribution Width	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Plateletcrit	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Immature Platelet Fraction	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Platelet-large cell ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Primary	Platelet-large cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	High fluorescent Cell number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	High fluorescent Cell percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Optical Red Blood Cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Optical Platelet count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Platelet count - Impedance	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Optical White Blood Cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	White blood cell counts - Differential (DIFF)	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Total nucleated cell counts - DIFF	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Immature Eosinophil percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Immature Eosinophil number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	High forward scatter NRBC ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Low forward scatter NRBC ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Neutrophil-to-lymphocyte ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Platelet-to-lymphocyte ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	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
Secondary	Total nucleated cell counts	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Infected Red Blood Cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Infected Red Blood Cell permillage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Microcyte count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Microcyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Macrocyte count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Macrocyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Mean Reticulocyte Volume	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Red Blood Cell Fragment Count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Red Blood Cell Fragment Percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Platelet Distribution Width Standard Deviation	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Reticulocyte Production Index	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	High fluorescent Immature Platelet Fraction	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Immature Platelet Count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Dimorphic population, smaller distribution RBC count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Dimorphic population, larger distribution RBC count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Dimorphic population, smaller distribution mean corpuscular volume	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Dimorphic population, larger distribution mean corpuscular volume	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Mean Corpuscular Hemoglobin of Reticulocyte	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	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
Secondary	Mean Platelet Concentration	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Mean Platelet Matter Content	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Hyperchromic Red Blood Cell percentage (Hyper%)	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Secondary	Hypochromic Red Blood Cell percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection