The World Health Organization Health Emergencies Department is  pleased to announce  request for proposals concerning monitored implementation of SARS-CoV-2 antigen detecting rapid diagnostic  tests (RDTs) in low- and middle-income countries  to better understand field performance, acceptability, feasibility, cost-effectiveness and impact of these tests when used as part of an algorithm in resource limited settings during the COVID-19 crisis. Proposals should be based on the provided Master Protocol. This information will be utilized to inform the development of evidence-based policy and implementation guidance.

Background

The COVID-19 pandemic has created a  need to rapidly scale-up testing services and provide diagnoses to implement test-trace-isolate strategies which are essential to effectively treatment, care and controlling the spread of the virus. Hundreds of new tests have become available on the market, with limited or no independent data on their performance. Countries have faced challenges in selection and effective deployment of molecular and serological diagnostics and are most recently in need of support for rolling out antigen-detecting rapid diagnostic tests (Ag-RDTs) appropriately. The reference standard recommended for diagnosis of COVID-19 is currently nucleic acid amplification testing (NAAT). However, NAAT is resource intensive and is not widely accessible in many low- and -middle- income countries (LMICs) requiring specialized laboratory technicians limited the ability to conduct the volume of tests needed and rapidly deliver results to those tested. Shipping clinical samples to centralized laboratory facilities has been organized in many countries, but it is associated with significant delays in result reporting, often negating any impact on clinical decision-making and transmission interruption. Ag-RDTs for SARS-CoV-2, usually in a lateral flow immunoassay (LFI) cassette format, have recently been developed and commercialized. These simple-to-use tests offer the possibility of rapid case detection, especially of the most infectious patients in the first week of illness, at or near the point of care. Performance is highly variable based on the test characteristics and the population tested. The RDTs are sensitive only for detection of patients with a high viral load e.g. cycle  threshold (Ct) values ≈25-30 or 10E6 genomic copies/mL. WHO along with key stakeholders has defined minimum performance specifications for point of care Ag-RDTs in a Target Product Profile[1] and some products have received WHO emergency use listing[2] emergency authorization for use in countries[3],[4]. Although WHO has released interim guidance on use of Ag-RDTs for SARS-CoV-2 featuring important considerations for implementation, there is limited experience with these tests in routine settings and specific implementation guidance for use of these new tests is entirely lacking. Therefore, WHO is sponsoring a multi-country, multi-site program to monitor the implementation of Ag-RDTs for COVID-19 to assess field performance, acceptability, feasibility and/or impact and inform and optimize settings for most effective utilization. Following current WHO recommendations and based on a Master Protocol, applicants will select the settings of use and objectives of highest priority and most compatible with existing infrastructure and capacity. Applicants should also consider settings and approaches which will enable high quality data collection which can be used to inform evidence-based policy development.

The Aim of this call

The aim of this call is to invite proposals based on a WHO Master Protocol, from applicants who are interested in carrying out SARS-CoV-2 Antigen RDT  implementation  projects to assess:

1. the field performance, feasibility, acceptability and impact of antigen detecting SARS-CoV-2 rapid diagnostic tests in variable use settings[5] in low- and middle-income countries.  

2. cost and cost-effectiveness of testing strategies using SARS-CoV-2 antigen RDTs in low- and middle-income countries.

Applicants are required to adapt a WHO master protocol according to settings and endpoints of  greatest relevance and interest relating to epidemiology; field performance; feasibility; acceptability; impact on diagnosis and quarantine and cost-effectiveness.  Endpoints will be compared to baseline measures where relevant. 

Eligible Countries

Public health institutions under the umbrella of ministries of health (such as: national public health institutes, centers for disease control), universities or research institutions or NGOs based in low or middle-income countries and their implementing partners. Implementing partners may be based in the same country or internationally.  Collaborations are encouraged particularly between academic institutions, NGOs or development agencies and Ministries of Health. Collaborations may be within or between countries. There must be community transmission of SARS-CoV-2 in the target country(s) at the time of the application for funding.

Eligible settings for monitored implementation

SARS-CoV-2 Ag-RDTs are likely to be used in situations where there is limited or no access to molecular testing and where laboratory professionals are in very short supply. This includes primary health care facilities reliant on shipment/transport of samples to a central laboratory, humanitarian settings or for rapid response outbreak investigation. Ag-RDTs may also be particularly useful in settings where molecular testing is available but there are significant delays in obtaining test results, due to a high demand for testing or irregular transport of samples to the laboratory.  The following scenarios require that WHO recommendations for use of Ag-RDTs that meet minimum performance criteria (≥80% sensitivity and ≥97% specificity )[6] are met  and that tests are approved for use in the implementing country. 

  1. Point of care Ag-RDT use for case management in settings with access to confirmatory molecular testing but slow turnaround times.

    Description: Health facility that sends samples to an external lab for NAAT, often with delayed result reporting. These delays in turnaround time may occur due to centralization of NAAT facilities or when capacity of NAAT facilities is overwhelmed due to high demand for testing and/or insufficient trained personnel to perform the testing. Ag-RDTs would be first-line test to allow for rapid implementation of isolation procedures amongst positives and prioritization of negatives for either repeat Ag-RDT testing or confirmatory testing by NAAT at centralized facility. 

  2. Point of care Ag-RDT use for case management with no access to confirmatory molecular testing

    Description: The target location for this scenario would be at a health facility with no access to NAAT and no secure means for safe and timely transport of samples to centralized facilities. Ag-RDTs are the only feasible tool to aid in diagnosis of SARS-CoV-2 infection. Health facilities may include primary care centers, health centers in remote or hard to access areas, or those located within humanitarian settings such as an internally displaced persons (IDP) camp.

  3. Point of care Ag-RDT for surveillance and/or outbreak investigations in settings with access to confirmatory molecular testing but slow turnaround times.

Description: This scenario could address sentinel surveillance in different risk groups (e.g. health-care workers) to efficiently monitor incidence and for investigation of suspected outbreaks or new clusters.

Eligibility criteria for applicants

Applicants for funding to support SARS-CoV-2 Ag RDT monitored implementation project must be able  to ensure acceptable data quality and completeness. Each site must have a designated Project Coordinator (PC), who will be responsible for all communication with WHO.  Sites will be selected based on their ability to meet the following criteria: 

  1. SARS-CoV-2 Ag-RDTs are included in the national testing strategy/policy and use cases are aligned with those outlined in this protocol and in the WHO interim guidance;
  2. At least one WHO EUL approval SARS-CoV-2 Ag-RDT registered according to national requirements in effect at the time of the application;
  3. Capacity to train and supervise health workers and/or lay persons in safe and accurate performance and reporting of SARS-CoV-2 Ag-RDT;
  4. The capacity to perform data entry into a database developed by WHO and to keep personal data confidential, noting that:
    • One or more members of staff will be needed to dedicate time to project implementation and data quality management;
    • Experience using DHIS-2 is highly desirable;
  5. Expertise in implementation research and informing evidence-based policy development at national and/or global level;
  6. Previous experience with enhanced program monitoring and evaluation is an asset, particularly with the implementation and scale-up of new technologies.
  7. If any proposed activities constitute research, applicants must be able to seek and feasibly obtain ethics approvals within the proposed timeline for the project (6-9 months)
  8. For sites with access to NAAT, the following will also be required:  
    • Staff competent in specimen packaging, transport (for example, cold chain logistics) and storage;  
    • Access to a laboratory with the following:
      1. Adequate infrastructure and trained personnel for performing NAAT for SARS-CoV-2 infection (for example, using real-time reverse transcription polymerase chain reaction (rRT-PCR));
      2.  Demonstrated quality system[1];
      3. Participation in proficiency testing scheme for SARS-CoV2 is desirable.
  9. Permission to export samples to international reference laboratories is an advantage;
  10. Agree to the terms and conditions laid out in the Grant Letter of Agreement WHO in Annex 1 of the Master Protocol.

Expected duration of projects

6-9 months

Financial support

Up to $200,000 USD per project and up to 200,000 WHO EUL SARS-CoV-2 Ag-RDTs, provided free of charge.

How to complete the Request for Proposals:

The proposal submission process is via completion of two web-based forms:

Step 1: Details of the proposal (contact information, objectives, methods, justification of eligibility criteria): https://forms.office.com/Pages/ResponsePage.aspx?id=KVxybjp2UE-B8i4lTwEzyBzdd6RRnDxInkoFGyPUmpZUNTJGQVBUN1BDSldJVlBDTDNQSE40VUI5VC4u

  1. Unfortunately, it is not possible to save and resume work in this form; therefore, we strongly advise that you use the attached pdf form to review and prepare answers in advance and/or do not close the webpage once you begin filling in the form.
  2. The proposal pdf form contains all possible question/answer combinations and therefore some questions may not apply
  3. If there is insufficient space for completing your responses, please upload a separate file as per instructions below
  4. We will confirm receipt of your proposal via email within 24-36 hrs of submission.

Step 2: Uploading of files: https://extranet.who.int/dataformv3/index.php/997936?lang=en 

  1. Please ensure the project coordinator details are identical to those submitted in part I (proposal form)
  2. Name each file with ‘ Project Coordinator’s Last Name_Country_type of form’ – for form indicate ‘RDT policy’, ‘ budget’, ‘timeline’, ‘consent’, ‘narrative_question#’.
  3. It is possible to save and return to this form so documents can be uploaded as they become available

Important Conditions:

  1. All proposals should be based on the WHO Master Protocol for Monitored Implementation of Antigen Rapid Diagnostic Test for COVID-19 (attached).  The master protocol outlines Ag-RDT use scenarios  aligned with current WHO guidance and a ‘menu’ of objectives and possible endpoints. Protocol forms are designed to capture these endpoints.
  2. Applicants should only choose the objective(s) and endpoints that are greatest interest, relevance and within their capacity to  measure.  Applicants are not expected to include all objectives and endpoints listed in the Master protocol.
  3. Applicants can propose objectives related to Ag-RDT implementation that are not included in the Master Protocol but it must be possible to conduct this work within the scope of the project budget and timeframe (6-9 months).
  4. Applicants must agree to the terms in the Grant Letter of Agreement template included in Annex 1 of the Master protocol
    • Successful applicants will be asked to sign this agreement to allow the release of funds by 31 December 2020

 

Deadlines:

The deadline for submission of proposals is  8 December 2020, 23:00 CET.

Notification of Successful Applicants:

Applicants will be contacted by 14 December, 2020

Signature of agreement and disbursement of funds

Agreements will be signed by both parties and funds disbursed between 15 Dec-31 December, 2020

Contact information:

If you have any questions or encounter any difficulties submitting your proposal, please contact:

cunninghamj@who.int - attention: SARS-CoV-2 Ag RDT Monitored Implementation Projects

 

References:

[1]https://www.who.int/publications/m/item/covid-19-target-product-profiles-for-priority-diagnostics-to-support-response-to-the-covid-19-pandemic-v.0.1

[2] https://www.who.int/diagnostics_laboratory/EUL/en/

[3]https://www.fda.gov/medical-devices/emergency-situations-medical-devices/emergency-use-authorizations-medical-devices#covid19ivd

[4] https://www.who.int/diagnostics_laboratory/200929_eul_covid19_ivd_update.pdf?ua=1

[5] Use settings include symptomatic suspected COVID-19 cases attending health facilities and asymptomatic contacts of COVID-19 cases with i) no access to NAAT for diagnosis or ii) limited access with prolonged turnaround times precluding clinical utility of results and for surveillance at sentinel sites in areas without NAAT capacity and where shipment of samples is infeasible.

[6] https://www.who.int/publications/m/item/covid-19-target-product-profiles-for-priority-diagnostics-to-support-response-to-the-covid-19-pandemic-v.0.1