Validation of Diagnostics to Identify Glucose-6-phosphate Dehydrogenase Activity in the US

The primary objective of this study is to assess the accuracy of the SD Biosensor STANDARD G6PD Analyzer in measuring G6PD activity when used by trained health care workers.

Study Overview

• Status: Completed
• Conditions: G6PD Deficiency
• Intervention / Treatment: Diagnostic test: Pointe Scientific Test Kit; Diagnostic test: HemoCue System; Diagnostic test: SD Biosensor G6PD Analyzer

Detailed Description

This is a cross-sectional diagnostic accuracy study with up to 250 participants with a goal of obtaining 20 deficient and 20 intermediate samples. The clinic will recruit and consent study participants. Clinic staff will draw 3 whole blood samples and obtain finger stick capillary blood.

G6PD activity is reported in terms of grams of hemoglobin (Hb), hence the hemoglobin concentration must be measured.

Clinic staff will perform the investigational Standard Diagnostics (SD) Biosensor point-of-care (POC) test for glucose-6-phosphate dehydrogenase (G6PD) deficiency and a HemoCue® hemoglobin test on finger stick capillary blood and on the venous blood samples.

Another venous blood sample will be sent to a clinical laboratory improvement amendments (CLIA)-certified laboratory for reference testing by the gold standard assays:

• G6PD measurement by spectrophotometry using the Pointe Scientific G6PD reference assay
• hemoglobin measurement by a hematology analyzer

Individuals identified as G6PD deficient with the reference test will be notified of their results by the clinic and referred to their physician for follow-up.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchison Prevention Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

-Willingness to provide consent

Exclusion Criteria:

-Blood transfusion in the past 90 days by self-report

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: G6PD Diagnostic Testing; Participants provided whole blood samples as well as fingerstick capillary blood samples. At the clinic site lab, study staff conducted the SD Biosensor point-of-care G6PD test and the point-of-care HemoCue Hb test on both finger stick blood and whole blood samples. At the reference laboratory, G6PD activity was measured from whole blood samples using the Pointe Scientific G6PD reference assay and hemoglobin was measured using a hematology analyzer.

Diagnostic test: Pointe Scientific Test Kit; The Pointe Scientific test kit will serve as the reference assay to assess G6PD activity. Its intended use is for the quantitative, kinetic determination of G6PD in blood at 340 nm.; Diagnostic test: HemoCue System; The HemoCue hemoglobin (Hb) 201+ system is designed for quantitative point-of-care whole blood hemoglobin determination in primary care using a specially designed analyzer, the HemoCue Hb 201+ Analyzer, and specially designed microcuvettes, the HemoCue Hb 201+Microcuvettes.; Diagnostic test: SD Biosensor G6PD Analyzer; The SD Biosensor G6PD Analyzer is designed to measure the quantitative determination of total hemoglobin concentration and G6PD enzymatic activity in fresh human whole blood specimens based on reflectometry assays in a point-of-care setting. The test is intended to aid in the identification of people with G6PD deficiency. The test is currently not licensed for use in the US and is considered an investigational product.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity of SD Biosensor POC G6PD Test for Identifying G6PD Deficient Individuals	For the purposes of this study, an individual was considered G6PD deficient if they tested positive in the Pointe Scientific assay. A true positive was defined as a participant with ≤ 30% of normal G6PD activity in circulating venous blood determined by the Pointe Scientific test. Diagnostic sensitivity of the SD Biosensor G6PD test is defined as the percentage of participants who tested positive for G6PD deficiency on the reference test who were identified by the test assay as positive, calculated as: Number of participants who were both test and true positive / (Number of participants who were test and true positive + Number of participants who were test negative but true positive [ie false negative]) * 100%. Sensitivity of the SD Biosensor POC G6PD test was calculated from both venous and capillary blood samples.	All samples were collected on study day 1
Sensitivity of SD Biosensor POC G6PD Test for Identifying Women With Intermediate G6PD Activity	To investigate the performance of the SD Biosensor G6PD test to distinguish females with intermediate G6PD activity from females with normal activity, assay sensitivity was determined at a G6PD activity threshold of 70%. A true positive for intermediate G6PD activity in females was defined as G6PD activity between 30 and 70% of normal in circulating venous blood as determined by the Pointe Scientific test. Sensitivity of the SD Biosensor POC G6PD test is the percentage of women who tested positive for intermediate G6PD activity on the reference test who were identified by the test assay as positive, calculated as: Number of women who were both test and true positive / (Number of women who were test and true positive + Number of women who were test negative but true positive [ie false negative]) * 100%. Sensitivity of the SD Biosensor G6PD test for identifying females with intermediate G6PD activity was calculated from both venous and capillary blood samples.	All samples were collected on study day 1
Specificity of SD Biosensor POC G6PD Test for Identifying G6PD Deficient Individuals	For the purposes of this study, an individual was considered G6PD deficient if they tested positive by the Pointe Scientific assay. A true negative was defined as > 30% of normal G6PD activity in circulating venous blood as determined by the Pointe Scientific test. Specificity is the percentage of participants who tested negative for G6PD deficiency on the reference test who were identified as negative using the test assay, calculated as: Number of participants who were both test and true negative / (Number of participants who were test and true negative + Number of participants who were test positive but true negative [ie false positive]) * 100%. Specificity of the SD Biosensor G6PD test was calculated from both venous and capillary blood samples.	All samples were collected on study day 1
Specificity of SD Biosensor G6PD Test for Identifying Women With Intermediate G6PD Activity	To investigate the performance of the SD Biosensor G6PD test to distinguish females with intermediate G6PD activity from females with normal activity, the specificity was determined at a G6PD activity threshold of 70%. A true negative for intermediate G6PD activity in females was defined as G6PD activity > 70% of normal in circulating venous blood as determined by the Pointe Scientific test. Specificity is the percentage of participants who tested negative for G6PD deficiency on the reference test who were identified as negative using the test assay, calculated as: Number of participants who were both test and true negative / (Number of participants who were test and true negative + Number of participants who were test positive but true negative [ie false positive]) * 100%. Specificity of the SD Biosensor G6PD test was calculated from both venous and capillary blood samples.	All samples were collected on study day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accuracy Between the SD Biosensor POC G6PD Test Assay and the Pointe Scientific Test Kit	Accuracy between the SD Biosensor POC G6PD test assay and the Pointe Scientific G6PD reference assay was calculated as the percent agreement between both G6PD tests, ie, the percentage of participants with the same diagnosis according to both tests (either deficient, intermediate, or normal G6PD levels). Accuracy of the SD Biosensor G6PD test was calculated from both venous and capillary blood samples.	All samples were collected on study day 1
Accuracy Between the SD Biosensor POC G6PD Test Measure of Hemoglobin and the Reference Hemoglobin Test	Accuracy between the SD Biosensor POC G6PD test measure of hemoglobin and the hemoglobin reference assay was calculated as the percentage agreement between both tests, ie, the percentage of participants with the same diagnosis according to both tests (either non/mild anemia, moderate anemia or severe anemia).	All samples were collected on study day 1
Median G6PD Values Measured by the SD Biosensor G6PD Test for Venous and Capillary Blood Samples		All samples were collected on study day 1

Collaborators and Investigators

• Sponsor: PATH
• Collaborators: Fred Hutchinson Cancer Center
• Investigators: Principal Investigator: James Kublin, MD, MPH, Fred Hutchinson Cancer Center

Publications and helpful links

General Publications

• Pal S, Myburgh J, Bansil P, Hann A, Robertson L, Gerth-Guyette E, Ambler G, Bizilj G, Kahn M, Zobrist S, Manis MR, Styke NA, Allan V, Ansbro R, Akingbade T, Bryan A, Murphy SC, Kublin JG, Layton M, Domingo GJ. Reference and point-of-care testing for G6PD deficiency: Blood disorder interference, contrived specimens, and fingerstick equivalence and precision. PLoS One. 2021 Sep 20;16(9):e0257560. doi: 10.1371/journal.pone.0257560. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2019
• Primary Completion (Actual): September 19, 2019
• Study Completion (Actual): September 19, 2019

Study Registration Dates

• First Submitted: May 21, 2019
• First Submitted That Met QC Criteria: July 4, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: G6PD deficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Glucosephosphate Dehydrogenase Deficiency
• Other Study ID Numbers: G6PD Validation Seattle

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Not planning to share IPD to other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No