Step 1.1 – Establish a technical working group (TWG) and define roles and responsibilities
Step 1.2 – Review WHO policies and available technical and implementation guides
Step 1.3 – Define immediate and future purposes of the test
Step 1.4 – Update national diagnostic algorithm and guidelines
Step 1.5 – Perform a situational analysis, including biosafety
Step 1.6 – Develop a costed operational plan for phased implementation
Step 1.1 – Establish a TWG and define roles and responsibilities
A TWG comprising representatives from all key stakeholders should be established, to guide the implementation process of the new diagnostic tests and technologies. It is important to include representatives from other disease programmes if multidisease testing is planned. The establishment of the TWG should be led by the MoH, NTP and national TB reference laboratory (NTRL). The TWG should be mandated to advise the MoH, NTP and NTRL on test implementation; develop action plans; oversee the test’s implementation; and assess the impact and success of the test’s introduction. Representatives from the following key stakeholders may be invited to participate:
- MoH, NTP, NTRL(s) and regional laboratories;
- research institutes or other organizations with experience using the new diagnostic test;
- implementing partners, including those outside of TB;
- peripheral laboratories and clinical facilities that will participate in the testing;
- regulatory bodies;
- data management or IT experts;
- specimen transport systems logisticians for centralized or regional testing (TB and non-TB);
- community representatives; and
- clinical staff.
A suitably qualified individual should lead the team; for example, a national TB laboratory officer or laboratory focal person from the NTP or NTRL. An integral component of the planning process should be defining the roles and responsibilities of members of the implementation team, and those of external partners and donors.
Step 1.2 – Review WHO policies and available technical and implementation guides
The TWG members should familiarize themselves with the contents of the relevant WHO policies, guidance and reports, as well as any available implementation guides from WHO, GLI, FIND and implementing partners. Particular attention should be paid to WHO policies and recommendations on using the test to aid in the diagnosis of TB or detection of drug resistance, the test’s limitations and interpretation of test results.
Step 1.3 – Define immediate and future purposes of the test
Programmes must clearly define the purpose, scope and intended use of the new diagnostic test because that will affect many aspects of the implementation plan. For example, the laboratory system or network needed to provide timely results for patient-care decisions is quite different from that needed to conduct a once-a-year drug-resistance survey.
Step 1.4 – Update national diagnostic algorithm and guidelines
The TWG should lead a review of existing national diagnostic algorithms, taking into consideration the needs of people with TB, clinical needs, country epidemiology, existing testing algorithms, sample referral systems and other operational considerations, and make recommendations to the MoH and NTP. Section 4 provides details on model algorithms for the use of WHO-recommended tests in detail.
The TWG should also lead a review of guidelines for the use of the new diagnostic test results in patient-care decisions. Clinical guidelines should provide clear guidance to clinicians, nurses and health care professionals on the intended use of the new diagnostic test; outline target populations; explain how to order the test; and explain how to interpret, use and communicate test results.
Step 1.5 – Perform a situational analysis, including biosafety
To inform plans for implementing the new diagnostic test, a situational analysis of the existing laboratory network and capacities should be conducted. For most tests, key elements to be assessed include regulatory requirements; laboratory and network infrastructure; existing sample transportation system; staff skills, expertise and experience; IT capabilities and infrastructure; diagnostics connectivity; availability and adequacy of SOPs; supply chain; financial resources; and QA systems. The assessment should also determine needs for revision of training, recording and reporting forms, and tools for monitoring and evaluation. Of particular relevance is the specimen referral system; a checklist for evaluating such a system can be found in the relevant GLI publication (31), and a checklist for implementing targeted NGS tests can be found in the NGS technical guide (30).
For the prospective testing site, detailed assessments of the laboratory’s readiness with respect to physical facilities, staffing and infrastructure will be needed. Because laboratory-acquired TB infection is a well-recognized risk for laboratory workers, undertaking a risk assessment for conducting the new test in the prospective site is critical, to ensure that the required biosafety requirements are in place before the new test is implemented (35).
For implementing targeted NGS-based DST, particular attention must be paid to the availability of highly skilled staff that can meticulously perform the library preparation steps, and to the laboratory’s capacity to analyse and store large amounts of data. IT requirements include:
- adequate computing resources, including the instrument computer and computers for data analysis;
- sufficient data storage capacity (local or cloud-based services), including external storage for data backups;
- appropriate data security measures;
- access to data analysis tools;
- staff trained in the use of the analytic tools for NGS data;
- IT resources and expertise for the installation and ongoing maintenance of hardware, software and networks; and
- a network and high-speed internet connection; and data connectivity solutions to link NGS data to other relevant patient data.
Step 1.6 – Develop a costed operational plan for phased implementation
The final step in this area is to develop a detailed, costed, prioritized action plan for phased implementation, with targets and timeline. Often, implementation of a new test must overcome potential obstacles such as cost of instruments, ancillary equipment and consumables; requirements for improving or establishing the necessary laboratory and network infrastructure (e.g. a specimen transport system); the need for specialized, skilled and well-trained staff; the need for expert technical assistance; maintenance of confidentiality of patient information; and the need to establish a QA system.
Successful implementation of the plan will require financial and human resource commitments from the MoH or NTP, with possible support from implementing partners. A budget should be developed to address activities in collaboration with key partners. Budget considerations are summarized in Annex 1.
Because of the high cost of targeted NGS-based DST (i.e. initial equipment and running costs), a carefully worked out plan covering all costs of implementation and operation will be needed. Testing volumes and batch sizes will impact cost and the turnaround times of NGS-based DST; they are described in detail elsewhere (30).