SARS-CoV-2 Antigen detecting rapid diagnostic test implementation projects

The World Health Organization Health Emergencies Department is  pleased to announce an expression of interest 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. 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, applicants will be free to 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 identify candidates 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 will be 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. 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: 

• The capacity to perform data entry into a database coordinated by local staff 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;
  • Expertise in implementation research and informing evidence-based policy development at national and/or global level;
  • previous experience with enhanced program monitoring and evaluation, particularly with the implementation and scale-up of new technologies.
• At least one WHO EUL approval SARS-CoV-2 Ag-RDT registered according to national requirements in effect at the time of the application;
• 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;
• Capacity to train and supervise health workers and/or lay persons in safe and accurate performance and reporting of SARS-CoV-2 Ag-RDT;
• 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)
  
• 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 (either locally or internationally) to a laboratory with the following:
    • 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))
    • Documented quality management system
      
    • Participation in proficiency testing scheme for SARS-CoV2 is desirable.

• Permission to export samples to international reference laboratories is an advantage
• Agree to the terms and conditions laid out by WHO in Annex 1.

Expected duration of projects

6-9 months

Financial support

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

How to complete the EOI:

Complete the survey at the following link: https://extranet.who.int/dataformv3/index.php/541177

All those completing the EOI by the 17 November, 2020 will be notified of the Request for Proposals and provided with the WHO Master Protocol template.