Actions to support point-of-care early infant diagnosis: a strategic framework and a resource pack for community-based organisations 

Ehiopia, Kenya, Malawi, Mozambique, Tanzania, Uganda, Zimbabwe, Senegal, Democratic Republic of the Congo, and Cameroon, one important lesson learned is the role of communities in the success of project utilization through creating demands among communities and addressing stigma around accessing POC services.

Moving forward, the expansion of POC-EID projects will continue to strengthen informed engagement of communities and introduce them as an integral part. To build informed communities within the context of innovations to scale a strategic framework and resource pack were developed recently, by UNICEF and GNP+, with the support of UNITAID – these materials are called: NO TIME TO WAIT! Action to support Point-of-Care Early Infant Diagnosis: A strategic framework for Community-Based Organisations.

Site Selection
When selecting sites, it is important for countries to consider their primary objectives for integrating POC technologies into national diagnostic networks.  They could include decreasing turn-around-time for test results; increasing the proportion of test results returned to patients; and/or increasing access to testing.  

When selecting sites, countries may also wish to explore a range of models of service delivery, for example:

• Hub and spoke: The “hub” is the anchor site that provides the POC testing that is extended to additional neighboring sites/facilities (“spokes”).
• Platform sharing: A POC platform is shared across different health facilities/sites.
• Co-location of services: Patients are referred across clinics and services within the same facility (e.g., nutrition clinics, in-patient wards and outpatient services) to maximize the use of the POC device.

Product Selection
The selection of POC products should be objective and transparent, deploying the most appropriate products to sites, complementing the existing laboratory network to maximize impact on patient access to testing. POC products should be selected in response to the specific needs, capacity, and limitations of selected sites and the laboratory-clinic network as a whole, as well as to ensure instruments are fit-for-purpose.

For countries receiving Global Fund grants, the Global Fund’s Viral Load and Early Infant Diagnosis Selection and Procurement Information Tool is designed to guide countries receiving Global Fund grants with the selection and procurement of viral load (VL) and early infant diagnosis (EID) technologies, including POC diagnostic technologies approved by the Global Fund. It is advised that countries using Global Fund funding to purchase POC diagnostic products discuss their needs with Global Fund procurement as part of the product selection process.

Tools and Guidance

• EID and VL Product and Site Selection Tool and Guidance
• CHAI selection guidance tool
• Guidance Note on Product Selection, Facility Upgrades, and Sample Transportation 
• Side-by-Side Analysis of POC EID Products
• LabEQIP: Laboratory Efficiency and Quality Improvement Planning Tool

Regulatory oversight ensures that in vitro diagnostic medical devices (IVDs) conform to established quality and safety standards. IVDS are devices that whether used alone or in combination, are intended by the manufacturer for the in-vitro examination of specimens derived from the human body to provide information for diagnostic, monitoring or compatibility purposes.

Regulatory requirements are in place to prevent sub-standard or poor quality technologies from entering the market and being used for patient care.

The International Diagnostics Center at the London School of Hygiene and Tropical Medicine has numerous resources on a variety of regulatory topics, including:

• Regulation of in-vitro diagnostic medical devices
• National and regional regulatory legislation and requirements
• Global and regional harmonization initiatives

Where local regulatory capacity is limited, global, regional, or other national frameworks can help guide decisions on setting minimum standards, identifying candidate technologies, and registering high quality POC IVDs in country. These frameworks include (amongst others), the International Standards Organization (ISO), the United States Food and Drug Administration (US FDA), Conformité Européene (CE) marking, and WHO’s Prequalification of In Vitro Diagnostics (IVD).

These frameworks help

• Ensure the quality, safety and performance of IVDs
• Harmonize regulatory requirements for pre-market assessment and post-market surveillance Improve transparency of regulatory review processes
• Facilitate exchange of regulatory information between concerned regulatory authorities and
• Accelerate the approval of new IVDs across multiple countries with minimal duplication of effort.

The WHO Prequalification (PQ) of In Vitro Diagnostics focuses particularly on IVDs for priority diseases and their suitability for use in resource-limited settings. Attaining PQ status means that a device satisfies WHO requirements for quality, safety and performance based upon WHO’s review of a product dossier, laboratory evaluation of the product, and inspection of a manufacturing facility.  The WHO has developed numerous guidance materials, including technical guidance for manufacturers, guidance on post-market surveillance and guidance on procurement and product selection of IVDs.

It is essential that POC IVDs are evaluated independently of the manufacturer for an unbiased assessment of their performance. To simplify processes, MOH partners and regulatory agencies are advised to use the results of product evaluations from other countries to grant regulatory approval in their own countries, accelerating the process for countries to approve and introduce new products.

For early infant diagnosis, one of the challenges is that while evaluations of new IVDs for EID are essential to inform national regulatory approval and implementation, the low incidence of HIV infection in infants limits the ability to have adequately-sized evaluation studies. To address this challenge and to generate evidence to support EID POC implementation, the EID Consortium was established as a multi-stakeholder effort to help accelerate the evaluation of EID POC IVDs through pooling data from field evaluations.

The EID Consortium has conducted pooled analyses of the field performance of POC HIV testing for early infant diagnosis across 6 countries in sub-Saharan Africa (Kenya, Malawi, Mozambique, Tanzania, South Africa and Zimbabwe). Analysis of the data shows that both the Alere q HIV-1/2 Detect (now m-Pima HIV - 1/2 Detect) and Cepheid Xpert HIV-1 qualitative assays perform well in the field with high sensitivity and specificity, and relatively low error rates (4-7%). In addition to informing national regulatory approval and registration, this pooled EID data, combined to the results of the WHO prequalification assessment and listing of these platforms can also help guide implementers, partners and healthcare workers as they plan for the introduction and roll out of POC IVDs.

Wherever an evaluation is required, scientifically sound evaluation protocols should be used for evaluations of new IVDs. The International Diagnostics Centre at the London School of Hygiene and Tropical Medicine contains various resources on diagnostic tools, including generic protocols for a POC EID Test Evaluation and POC HIV Viral Load Assay Evaluation.

National registration of manufacturers and their products is viewed as a basic regulatory requirement for any IVD. Manufacturers seeking national approval for a given IVD are generally required to supply a dossier to the appropriate national regulatory authority, describing the IVD and documenting evidence relating to the quality of the manufacturer, as well as the safety and stability of the components, including analytical studies and clinical evidence. Current regulatory oversight of IVDs in low and middle-income countries however is highly variable, and the pathways for regulatory approval are not always clearly defined.

Harmonizing regulatory processes across countries, where mutual reliance and/or recognition allows products registered in one country to be registered in another, can help facilitate national approval and registration processes. For additional information, see Improving Access to New Diagnostics through Harmonised Regulation: Priorities for Action.

This guidance provides practical step-by-step guidance on enrolling a POC EID site including pre-installation orientation and planning; installation, training, and start up; and post-installation monitoring and follow-up.

Author: EGPAF

Year: 2016

Site Enrollment Guidance EGPAF.pdf

This training package provides materials to guide onsite training for the introduction of POC EID testing. 

The topics focus on what health workers at each facility need to learn in order to confidently begin POC EID high quality testing; the package provides materials for both classroom and hands-on learning opportunities.

Training overview and preparatory materials
Overview Slides for Trainings
Training Package Overview and Guide for Trainers
POC EID Training Agenda Example 
Checklist for POC Device Site Deployment and Onsite Training

Training Modules
MO1: Introduction to EID and Point of Care EID Testing
MO2: Lab Systems and POC Testing
MO3: Clinical Systems

Supplementary Content
SC1: Sample Collection and Handling
SC2: Data management for POC EID
SC3: QA Approach and Mentorship for POC EID

Tools
Error and Specimen Rejection Log
Facility Consumption and Requisition Form
POC EID Mentorship Supervision Checklist
Site Level Consumption Reporting Template
Safety Preventive Maintenance Checklist.

Regular assessments of the competency of POC EID device operators are crucial for ensuring the quality of the testing procedure at an individual level, and can also serve as a key component of a POC EID quality assurance scheme.

Author: EGPAF

Year: 2019

Form_Cepheid-Xpert-HIV-1-qual_POC-EID_0.docx

Form_Abbott-mPIMA_POC_0.docx

Guidance on Competency Assessments for POC EID Testing_0.docx

Regular monitoring of sites is crucial for ensuring the quality and efficacy of point-of-care EID implementation.

This guidance and associated checklists are useful instruments for routinely monitoring the quality of POC EID implementation in both hub-and-spoke and stand-alone testing sites.

“Standalone” sites contain a POC EID platform, but do not have spoke sites providing samples.

With hub-and-spoke models, hub sites contain a POC EID platform, and are linked with spoke sites. Spoke sites do not contain a POC EID platform, but rather send their samples to their associated hub site for testing.

Author: EGPAF

Year: 2017

Site Monitoring Guidance_0.pdf

Hub Testing Site - POC-EID_0.pdf

Spoke Site - POC-EID_0.pdf

Stand Alone Testing Site - POC-EID_0.pdf

Post-market surveillance aims to ensure that IVDs continue to meet the same quality, safety and performance requirements as when they were initially placed on the market. WHO has developed normative guidance on post-market surveillance of in vitro diagnostics, emphasizing the importance of both reactive post-market surveillance and proactive post-market surveillance activities.

Reactive post-market surveillance refers to activities undertaken after an issue has occurred related to the IVD test (e.g., complaint reporting/monitoring; end user quality control programs, etc.), whereas proactive post-market surveillance refers to scans for potential issues related to the IVD (e.g., pre- and/or post-distribution lot testing). Lot testing involves testing samples from a manufacturing lot to ensure performance meets an acceptable standard.

For additional information on post-market surveillance, including sample reporting forms, see http://www.who.int/diagnostics_laboratory/postmarket/en/

This guidance note explains how to use a mix of forecasting approaches that are responsive to program scale up and rapidly changing deployment plans, when a new device or technology is scaled-up.

Authors: CHAI, EGPAF, UNICEF, USAID, and Unitaid
Year: 2018

Forecasting for Scale-up of POC-EID Technologies.pdf

This excel-based tool is designed to help countries model the cost of a comprehensive quality assurance (QA) program. It is composed of eight approaches to providing QA for diagnostic equipment. These include internal controls; mentorship; external quality control proficiency testing (international and national); duplicate testing; data management through connectivity; paper-based external quality assurance; and e-modules. 

Author: CHAI
Year: 2017

Quality Assurance Costing Tool_0.xlsx

Quality Assurance Costing Tool Guidance.pdf

Preface by Alex Costa, Project Lead, UNICEF

This document was developed to compile knowledge, insights and recommendations from UNICEF focal points in country offices implementing a project aimed at introducing, scaling up, and integrating point-of-care (POC) diagnostics into national health systems. The project was implemented by UNICEF, CHAI and ASLM with funding from Unitaid in 10 sub-Saharan African countries between 2016-2020. As the project was winding down, we thought it was important to document the lessons learned from those with direct, hands-on experience in project implementation to offer guidance to other countries interested in adopting POC technologies to increase access to diagnostics.

Innovative POC diagnostics can be a game changer in health systems as it enables testing outside the laboratory and closer to patients, can be used for the diagnosis of multiple diseases, addresses key limitations of conventional laboratory networks, and significantly increases access to diagnostic testing in a decentralized fashion. Decentralization of testing also carries an additional benefit as it strengthens elements of the health system around diagnostics (e.g., supply chain management, quality management, connectivity and data management, waste management) that have a broader impact on the health system. The multi-disease testing capacity of POC devices also contributes to pandemic preparedness and response, as has been shown by its use in the Ebola outbreak in West Africa (2014-2016) as well as its widespread use during the COVID-19 pandemic.

Accelerating Access to Innovative Point-of-Care HIV Diagnostics - Lessons Learned from UNICEF

The impact of POC diagnostic technologies cannot be overstated. This is particularly important in communities in low-resource settings with limited access to diagnostics as well as patients whose clinical management depends upon quick diagnostic test results – such as children infected with HIV. Without treatment, up to 50 per cent of children living with HIV die by their second birthday, with a peak mortality between two and three months of age. Thus, HIV-exposed infants need to be diagnosed before two months of age using molecular diagnostic methods until recently only available in conventional laboratories. However, such conventional laboratory systems carry inherent limitations that restrict their ability to provide timely results in various settings, particularly low-resource settings. It was this urgent need to diagnose HIV-positive infants and initiate them on treatment as soon as possible that motivated this project. POC diagnostics introduction and scale up allowed faster diagnosis, which in turn increased the number of HIV-infected children diagnosed and initiated on treatment within two months of age.

Although the project was focused on increasing access to early infant diagnosis of HIV through POC testing, it also demonstrated the cost-effectiveness of POC diagnostics and the benefits of multi-disease testing by integrating HIV viral load and TB testing on the same POC diagnostic platforms. In spite of the focus on HIV, the lessons reported here are broadly relevant for other disease programmes. These lessons are organized in seven main topics: (1) Leadership commitment and support; (2) Laboratories and the supply chain; (3) Engagement with civil society organizations(CSOs); (4) Diagnostics network optimization (DNO); (5) Innovative approaches; (6) Transition to national governments and other long-term funding partners; and (7) Grant design and management.

These lessons build upon the 'Key Considerations for Introducing New HIV Point-of-Care Diagnostic Technologies in National Health Systems' published in 2017, and 'Lessons Learned from Integrating Point-of-Care testing Technologies for Early Infant Diagnosis of HIV into National Diagnostic Networks' published by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) in 2019. Together, these resources offer a comprehensive perspective on the strategies, challenges, and lessons learned in the course of integrating POC diagnostics into national health systems that countries should consider when introducing and/or scaling up POC diagnostics.

I would like to thank all UNICEF POC focal points in country offices, regional offices, and Supply Division who have generously shared their experiences, reflections, insights and recommendations contained in this document. In particular, I would like to thank Maria Souza who developed the concept, carried out the interviews, consolidated the findings, coordinated the translation and design, and facilitated the dissemination of this document. Lastly, I would like to thank our project partners (CHAI, ASLM and EGPAF) as well as funding and support by Unitaid, which has made this project possible.