1. Tests in the Essential Diagnostics List (EDL)
William Sewell
WHO Consultant
A/Prof University of NSW & St Vincent’s Hospital Sydney Australia
13 Dec 2018
Adriana Velazquez Berumen | Senior advisor on medical devices, EMP, Geneva

2. Drug-related reasons for Diagnostics Tests
Screening
Detection of disease in asymptomatic individuals
Diagnosis
Identification of disease in patients with symptoms
Treatment Selection
Antimicrobial resistance testing
Companion diagnostics in cancer management
Check for G6PD deficiency before prescribing certain anti-malarials
Monitoring
HIV viral load monitoring
INR for Warfarin
Therapeutic drug monitoring
Measuring adverse effects e.g. CBC for toxic effects of chemotherapy
The EDL is not intended to be prescriptive and member states will need to take various local factors into consideration as they develop their national EDL’s.
More about that in the next workshop.
While the EDL provides a list of important tests required at various levels of the health care system, it is important to note that the EDL itself cannot have an impact without an integrated, connected, tiered laboratory system, with adequate, well qualified human resources, laboratory infrastructure, and regulatory/quality assurance systems. Impact also requires Member States to adopt and adapt the EDL and develop national and regional EDLs, as well as to implement the selection and supply mechanisms necessary to ensure access to the IVDs. This will be discussed further in the next workshop.
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3. Content of the first edition of the EDL
Published in May 2018
Section I & II.a
Section I & II.b
General IVDs
Disease Specific IVDs
12 Test Categories
11 Test Categories
23 Test Categories
16 Test Categories
62 Test Categories
Section I
Primary Care
(No lab available)
The EDL is arranged to divide test categories between those for use in the Primary Care setting where laboratory trained personnel are not available, and those that require laboratory facilities.
In each of those settings, the test categories are arranged in General Laboratory Tests and Disease Specific tests
You can see that there are a total of 62 test categories listed in the first edition of the EDL
We talk about “TEST CATEGORIES” because each category may include several individual tests on the market for that application, and we do not refer to test brand names in the EDL.
ADVANCE SLIDE:
The General Laboratory Tests are organized by discipline as shown and further disciplines such as Anatomical Pathology will be added in future editions
The Disease specific tests are arranged by disease
You can see that the first edition covers WHO high priority disease areas, and this will be expanded in future editions to cover non-communicable diseases as well as neglected tropical diseases.
Section II
Facilities with Laboratories
14/04/2019

4. Content of the first edition of the EDL
Published in May 2018
Section I & II.a
Section I & II.b
General IVDs
Disease Specific IVDs
12 Test Categories
11 Test Categories
23 Test Categories
16 Test Categories
62 Test Categories
Organised by Disease:
HBV
HCV
HIV
Malaria
Tuberculosis
HPV
Syphilis
Organised by Discipline:
Clinical Chemistry and Immunology
Blood Transfusion
Serology
Microbiology, Mycology and Parasitology
Haematology
Section I
Primary Care
(No lab available)
The EDL is arranged to divide test categories between those for use in the Primary Care setting where laboratory trained personnel are not available, and those that require laboratory facilities.
In each of those settings, the test categories are arranged in General Laboratory Tests and Disease Specific tests
You can see that there are a total of 62 test categories listed in the first edition of the EDL
We talk about “TEST CATEGORIES” because each category may include several individual tests on the market for that application, and we do not refer to test brand names in the EDL.
ADVANCE SLIDE:
The General Laboratory Tests are organized by discipline as shown and further disciplines such as Anatomical Pathology will be added in future editions
The Disease specific tests are arranged by disease
You can see that the first edition covers WHO high priority disease areas, and this will be expanded in future editions to cover non-communicable diseases as well as neglected tropical diseases.
Section II
Facilities with Laboratories
14/04/2019

5. Example of an EDL Entry General In Vitro Diagnostic Tests
I.a General IVDs for primary health care
Diagnostic test
Test purpose
Assay format
Specimen type
Haematology
Haemoglobin (Hb)
Diagnosis and monitoring of anaemia
Key clinical marker for severe infections (i.e. malaria, dengue, VHFs)
Safety monitoring when using certain drugs (e.g. zidovudine for HIV)
Haemoglo-
binometer
Capillary whole blood
Venous whole blood
Diagnostic Test:
The analyte being measured
Test Purpose:
Brief outline of the common reasons for performing the test
Assay format:
Recommended method(s) for performing the test (no brand names)
Specimen type:
Typical specimens used for this test
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6. Example of an EDL entry Disease Specific In Vitro Diagnostic Tests
I.a Disease-specific IVDs for primary health care
Diagnostic test
Test purpose
Assay format
Specimen type
WHO prequalified or endorsed products
WHO supporting documents
Hepatitis B
Hepatitis B surface antigen (HBsAg)
Screening for acute and chronic hepatitis B (HBV) infection: infants over 12 months of age, children, adolescents, adults
RDT
Oral fluid
Capillary whole blood
Guidelines on hepatitis B and C testing (February 2017):
WHO prequalified or endorsed products:
Where products have been prequalified, the link to relevant documents is provided
WHO Supporting Documents:
Links to WHO supporting evidence, guidelines or manuals
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7. Primary care tests in EDL 1.0
Nearly all blood tests can be performed on capillary whole blood
Other specimens are urine (urinalysis & microscopy), stool (microscopy), oral fluid (microbiological RDT) and sputum (TB).
The blood-based general laboratory tests are listed on a variety of simple devices.
Most disease-specific assays are RDTs or microscopy
Section I & II.a
Section I & II.b
General IVDs
Disease Specific IVDs
The EDL is arranged to divide test categories between those for use in the Primary Care setting where laboratory trained personnel are not available, and those that require laboratory facilities.
In each of those settings, the test categories are arranged in General Laboratory Tests and Disease Specific tests
You can see that there are a total of 62 test categories listed in the first edition of the EDL
We talk about “TEST CATEGORIES” because each category may include several individual tests on the market for that application, and we do not refer to test brand names in the EDL.
ADVANCE SLIDE:
The General Laboratory Tests are organized by discipline as shown and further disciplines such as Anatomical Pathology will be added in future editions
The Disease specific tests are arranged by disease
You can see that the first edition covers WHO high priority disease areas, and this will be expanded in future editions to cover non-communicable diseases as well as neglected tropical diseases.
12 Test Categories
11 Test Categories
23 Test Categories
16 Test Categories
62 Test Categories
Section I
Primary Care
(No lab available)
Section II
Facilities with Laboratories
14/04/2019

8. Laboratory-supported tests in EDL 1.0
Assay formats are more complex
Assay formats include chemistry and haematology analyzers, bacterial culture, immunoassay, nucleic acid tests (NAT), flow cytometry (for CD4 T cell count in HIV) and interferon-gamma release assays (for TB).
Section I & II.a
Section I & II.b
General IVDs
Disease Specific IVDs
The EDL is arranged to divide test categories between those for use in the Primary Care setting where laboratory trained personnel are not available, and those that require laboratory facilities.
In each of those settings, the test categories are arranged in General Laboratory Tests and Disease Specific tests
You can see that there are a total of 62 test categories listed in the first edition of the EDL
We talk about “TEST CATEGORIES” because each category may include several individual tests on the market for that application, and we do not refer to test brand names in the EDL.
ADVANCE SLIDE:
The General Laboratory Tests are organized by discipline as shown and further disciplines such as Anatomical Pathology will be added in future editions
The Disease specific tests are arranged by disease
You can see that the first edition covers WHO high priority disease areas, and this will be expanded in future editions to cover non-communicable diseases as well as neglected tropical diseases.
12 Test Categories
11 Test Categories
23 Test Categories
16 Test Categories
62 Test Categories
Section I
Primary Care
(No lab available)
Section II
Facilities with Laboratories
14/04/2019

9. General IVDs in EDL 1.0
As mentioned earlier, the General Laboratory Tests are arranged according to their disciplines
The total of 35 test categories listed, provide basic diagnostic support for a wide range of diseases
WHO documentation supporting General Laboratory Tests are presented at the end of the EDL
Section I & II.a
Section I & II.b
General IVDs
Disease Specific IVDs
The EDL is arranged to divide test categories between those for use in the Primary Care setting where laboratory trained personnel are not available, and those that require laboratory facilities.
In each of those settings, the test categories are arranged in General Laboratory Tests and Disease Specific tests
You can see that there are a total of 62 test categories listed in the first edition of the EDL
We talk about “TEST CATEGORIES” because each category may include several individual tests on the market for that application, and we do not refer to test brand names in the EDL.
ADVANCE SLIDE:
The General Laboratory Tests are organized by discipline as shown and further disciplines such as Anatomical Pathology will be added in future editions
The Disease specific tests are arranged by disease
You can see that the first edition covers WHO high priority disease areas, and this will be expanded in future editions to cover non-communicable diseases as well as neglected tropical diseases.
12 Test Categories
11 Test Categories
23 Test Categories
16 Test Categories
62 Test Categories
Section I
Primary Care
(No lab available)
Section II
Facilities with Laboratories
14/04/2019

10. Disease Specific IVDs in EDL 1.0
Disease-specific tests in EDL1 focus on high priority infectious diseases:
Hep B, Hep C, HIV, malaria, TB, syphilis and HPV.
Tests include multiple formats e.g. antigen, antibody, nucleic acid, flow cytometry, microscopy, culture, and others
Many disease specific tests are WHO pre-qualified, and all have WHO supporting documents.
Section I & II.a
Section I & II.b
General IVDs
Disease Specific IVDs
The EDL is arranged to divide test categories between those for use in the Primary Care setting where laboratory trained personnel are not available, and those that require laboratory facilities.
In each of those settings, the test categories are arranged in General Laboratory Tests and Disease Specific tests
You can see that there are a total of 62 test categories listed in the first edition of the EDL
We talk about “TEST CATEGORIES” because each category may include several individual tests on the market for that application, and we do not refer to test brand names in the EDL.
ADVANCE SLIDE:
The General Laboratory Tests are organized by discipline as shown and further disciplines such as Anatomical Pathology will be added in future editions
The Disease specific tests are arranged by disease
You can see that the first edition covers WHO high priority disease areas, and this will be expanded in future editions to cover non-communicable diseases as well as neglected tropical diseases.
12 Test Categories
11 Test Categories
23 Test Categories
16 Test Categories
62 Test Categories
Section I
Primary Care
(No lab available)
Section II
Facilities with Laboratories
14/04/2019

11. Approach for EDL 2.0 Principles of EDL1 continue:
General IVDs plus disease specific IVDs
Tests for primary health care and laboratory facilities
Requirement for devices to have regulatory approval
Improve General IVD section:
Flag tests that are time sensitive for Emergency Medicine
Expand Disease-specific IVDs to non-communicable diseases
Cancer (includes new Anatomical Pathology section under General IVDs)
Sources of potential additions in EDL2:
Submissions were advertised.
EDL Secretariat reviewed EDL1 for gaps.
14/04/2019

12. Process for review of applications for inclusion in the EDL
Application assessed by EDL Secretariat for completeness & circulated to WHO departments
Successful candidates invited to make full submissions
Submission posted on WHO website for review
Submission assessed by experts selected by WHO
Expert reviews published on WHO website
Assessment reports presented at SAGE IVD meeting
SAGE IVD recommend inclusions & exclusions to WHO
SAGE IVD recommendations presented to WHO DG
Screening application received

13. EDL 2.0 submissions to date
Infectious diseases:
Gonorrhoea/chlamydia
Histoplasmosis
Dengue
Zika
Procalcitonin for Sepsis
Cancer tests:
Screening, e.g. faecal occult blood, Pap test
Diagnosis, e.g. bcr-abl PCR
Choice of therapy, e.g. immunohistochemistry for ER, PR ^ Her-2 in breast cancer
Immunodeficiency tests:
Serum immunoglobulins and blood lymphocyte subsets
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14. Further Test Proposals for EDL 2.0
WHO commissioned a study to match:
medicines in the EML (446)
medical conditions (279)
diagnostic tests (325)
Many of the General IVDs in EDL1 were linked to very large numbers of medicines and conditions.
E.g. CBC is relevant to:
270 medicines on the EML
187 medical conditions
Schroeder, Guarner & Amukele (2018) Clin Chem 64:
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15. “Higher Priority Tests”
Tests were put on the higher priority list if all 3 authors in Schroeder et al agreed they should be higher priority on the basis of clinical priority, disease burden and test utility - Expert opinion
The majority of these tests are already in EDL1.
30 higher priority tests are not in EDL1:
7 had been independently submitted to EDL2
11 Therapeutic Drug Monitoring are now undergoing independent assessment through the EML team
4 in discussion with WHO teams
8 other tests
Schroeder, Guarner & Amukele (2018) Clin Chem 64:
14/04/2019
| Title of the presentation

16. The 8 other tests… Anatomical Pathology section
General IVDs
Anatomical Pathology section
Ketones etc in urinalysis
TSH
Further coagulation assays
GGT
Urine protein/creatinine ratio
Further transfusion testing
B-type natriuretic peptide (BNP)
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17. Draft Anatomical Pathology Section
Supporting the new Disease Specific Tests Section for Cancer
Diagnostic Tests:
Macroscopic assessment
Histopathology
Cytology (cytopathology)
Histopathology with special stains, e,g, Ziehl-Nielsen, silver
Immunohistochemistry e.g. ER, PR, HER-2 in breast cancer
The draft does not include:
Fluorescence microscopy
Cytogenetics
In situ hybridization
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18. Conclusion: The need to implement the EDL
The EDL is only part of provision of a quality diagnostics service
Reliable diagnostics results also need to be supported by:
Laboratory infrastructure
Qualified personnel
Supply chain/communication
Quality assurance
WHO welcomes your collaboration
Emphasise the importance of adoption and implementation.
Implementation is the focus of the workshop discussions at this Forum and WHO will be seeking input and opinions from member states on ways to support you in that task.
Source: Image from iStock.com
14/04/2019

19. Gracias Thank you Merci Shokran Xie xie Spasiva
WHO
20, Avenue Appia Geneva
EDL Secretariat
EDL website: s/diagnostics/Selection_in- vitro_diagnostics/en/
Switzerland