Evaluation of a Diagnostic to Identify Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency in Brazil

Not Applicable

Completed

Conditions: G6PD Deficiency

Interventions: Diagnostic Test: SD Biosensor STANDARD G6PD Test
Diagnostic Test: Pointe Scientific Test Kit
Diagnostic Test: HemoCue System
Diagnostic Test: Complete blood count (CBC)

Registration Number: NCT04033640

Lead Sponsor: PATH

Brief Summary: Th objectives of this study are:

* To determine the performance of G6PD tests in detecting G6PD activity and hemoglobin (Hb) compared to a reference assay

* To assess the comprehension of the G6PD test packaging and labelling among intended users

* To assess the usability of G6PD test result outputs among intended users

Detailed Description: This is a cross-sectional diagnostic accuracy study that includes both participants and health worker participants.

The participant population will be recruited at clinics and through a household survey using an enriched sample of a population with known G6PD status, established through previous epidemiological studies. Clinic staff will take capillary blood samples and conduct two point of care (POC) tests: 1) HemoCue® hemoglobin test, and 2) the investigational Standard Diagnostics (SD) Biosensor STANDARD POC test for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Venous blood will be collected and transferred to a laboratory where reference assays will be performed on venous samples using the Pointe Scientific G6PD Analyzer and hemoglobin tests.

The health worker participants will include trained intended users of the G6PD tests. Trained health workers will be surveyed to assess product usability through a questionnaire to assess label and packing comprehension as well as results interpretation.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1754

Inclusion Criteria

Provides malaria case management at study facility or study site
Considered an intended user of quantitative POC G6PD tests
Trained and proficient in the use of the POC G6PD test
Willing to provide informed consent

Exclusion Criteria

Does not provide malaria case management at study facility or study site
Not considered an intended user of quantitative POC G6PD tests
Not trained or not proficient in the use of the POC G6PD test
Unwilling to provide informed consent

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
G6PD Diagnostic Testing	SD Biosensor STANDARD G6PD Test	Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed the SD Biosensor STANDARD G6PD test and the POC HemoCue hemoglobin test on finger stick blood samples. At the reference laboratories, G6PD activity was measured from whole blood samples using the SD Biosensor STANDARD G6PD test and the Pointe Scientific G6PD reference assay and hemoglobin was measured using the HemoCue hemoglobin test and by a complete blood count (CBC) using an automated hematology analyzer (Manaus site only).
G6PD Diagnostic Testing	Complete blood count (CBC)	Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed the SD Biosensor STANDARD G6PD test and the POC HemoCue hemoglobin test on finger stick blood samples. At the reference laboratories, G6PD activity was measured from whole blood samples using the SD Biosensor STANDARD G6PD test and the Pointe Scientific G6PD reference assay and hemoglobin was measured using the HemoCue hemoglobin test and by a complete blood count (CBC) using an automated hematology analyzer (Manaus site only).
G6PD Diagnostic Testing	Pointe Scientific Test Kit	Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed the SD Biosensor STANDARD G6PD test and the POC HemoCue hemoglobin test on finger stick blood samples. At the reference laboratories, G6PD activity was measured from whole blood samples using the SD Biosensor STANDARD G6PD test and the Pointe Scientific G6PD reference assay and hemoglobin was measured using the HemoCue hemoglobin test and by a complete blood count (CBC) using an automated hematology analyzer (Manaus site only).
G6PD Diagnostic Testing	HemoCue System	Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed the SD Biosensor STANDARD G6PD test and the POC HemoCue hemoglobin test on finger stick blood samples. At the reference laboratories, G6PD activity was measured from whole blood samples using the SD Biosensor STANDARD G6PD test and the Pointe Scientific G6PD reference assay and hemoglobin was measured using the HemoCue hemoglobin test and by a complete blood count (CBC) using an automated hematology analyzer (Manaus site only).

Primary Outcome Measures

Name	Time	Method
Specificity of SD Biosensor STANDARD G6PD Test for Identifying Women With Intermediate G6PD Activity	All samples were collected on study day 1	To investigate the performance of the SD Biosensor STANDARD 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 STANDARD G6PD test was calculated from both venous and capillary blood samples.
Specificity of SD Biosensor STANDARD G6PD Test for Identifying G6PD Deficient Individuals	All samples were collected on study day 1	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 STANDARD G6PD test was calculated from both venous and capillary blood samples.
Sensitivity of SD Biosensor STANDARD G6PD Test for Identifying Women With Intermediate G6PD Activity	All samples were collected on study day 1	To investigate the performance of the SD Biosensor STANDARD 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 STANDARD 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 STANDARD G6PD test for identifying females with intermediate G6PD activity was calculated from both venous and capillary blood samples.
Sensitivity of SD Biosensor STANDARD G6PD Test for Identifying G6PD Deficient Individuals	All samples were collected on study day 1	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 STANDARD 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 STANDARD G6PD test was calculated from both venous and capillary blood samples.

Secondary Outcome Measures

Name	Time	Method
Accuracy Between the SD Biosensor STANDARD G6PD Test Measure of Hemoglobin and the Hemoglobin Measured in a Complete Blood Count	All samples were collected on study day 1	Accuracy between the SD Biosensor STANDARD G6PD test measure of hemoglobin and the hemoglobin result from the complete blood count (CBC) reference assay (using an automated hematology analyzer) 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). Complete blood counts were only conducted for participants enrolled at the site in Manaus.
Accuracy Between the SD Biosensor STANDARD G6PD Test Assay and the Pointe Scientific Test Kit	All samples were collected on study day 1	Accuracy between the SD Biosensor STANDARD 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 STANDARD G6PD test was calculated from both venous and capillary blood samples.
Median G6PD Values Measured by the SD Biosensor STANDARD G6PD Test for Venous and Capillary Blood Samples	All samples were collected on study day 1
Accuracy Between the SD Biosensor STANDARD G6PD Test Measure of Hemoglobin and the Reference HemoCue Hemoglobin Test	All samples were collected on study day 1	Accuracy between the SD Biosensor STANDARD G6PD test measure of hemoglobin and the HemoCue 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).
Number of Participants Who Met Acceptance Criteria for Label Comprehension	Day 1	After completing training, health worker participants were asked to complete a questionnaire to assess their comprehension of the test label. The questionnaire consisted of 13 multiple-choice questions with mutually exclusive options and a single correct answer focused on aspects of the product label including key warnings, limitations, and restrictions as well as the proper test procedure. Acceptance (success) criterion for label comprehension was defined as at least 85% correct responses (11 out of 13 possible points).
Number of Participants Who Met Acceptance Criteria for Accurate Results Interpretation	Day 1	After completing training, health worker participants were asked to complete a questionnaire to assess their ability to interpret the test result outputs. The questionnaire consisted of seven short-answer questions (5 valid results, 2 invalid results) focused on the participant's ability to read the results screen, record the simulated G6PD and hemoglobin quantitative results, and classify the results as normal, intermediate, deficient, or invalid. For each valid result, three points were possible: (one for G6PD result transcription, one for hemoglobin result transcription, and one for result interpretation) and for each invalid result, one point was possible, resulting in a total of 17 possible points. Acceptance (success) criterion for results interpretation was defined as at least 85% correct responses (15 out of 17 possible points).

Trial Locations

Locations (2): Tropical Medicine Foundation Doctor Heitor Vieira Dourado
🇧🇷
Manaus, Amazonas, Brazil
Centro de Pesquisa em Medicina Tropical de Rondônia
🇧🇷
Porto Velho, Rondônia, Brazil