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Step 7.1 – Implement a comprehensive QA system
A comprehensive QMS is needed to ensure the accuracy, reliability and reproducibility of test results. Essential elements of a QA system include:
- SOPs, training and competency assessment (Area 9);
- instrument verification and maintenance (Area 3);
- method validation or verification (Area 2);
- lot-to-lot testing (Area 4);
- internal QC;
- EQA; and
- quality indicator monitoring and continuous quality improvement.
A comprehensive discussion of the essential elements of a QA system can be found in the Practical manual on TB laboratory strengthening, 2022 update (65). This section describes QC, EQA and quality indicator monitoring. Additionally, a variety of QA manuals are available for multiple WHO-recommended tests through the GLI (12).
Step 7.2 – Establish and monitor QC
Internal QC monitors the activities related to the analytical phase of testing, with the goal of detecting non-conforming events (e.g. errors due to test failure, environmental conditions or operator performance) before results are reported. Internal QC typically involves examining control materials or known substances that are included in the assay at the same time as patient specimens, to monitor the quality of all steps of testing, from specimen preparation to result reporting. If QC results are not acceptable (e.g. positive results are obtained on negative controls), patient results must not be reported, and a root cause investigation and corrective action plan should be put in place and monitored to resolve the challenge.
QC is important for all tests, irrespective of their placement or complexity. Programmes should ensure availability of QC programmes across all levels of the testing network. Because of the complexity of the targeted NGS workflow and the need for multiple reagent kits and processes, it is important to conduct quality checks after each of the main steps in the process. Further information is given in The use of next-generation sequencing for the surveillance of drug-resistant tuberculosis: an implementation manual (33).
Step 7.3 – Develop an EQA programme
An EQA programme includes quality and performance indicator monitoring, external QC or proficiency testing, re-checking or making comparisons between laboratories, regular onsite supportive supervision and timely feedback, corrective actions and follow-up. Onsite supervision should be prioritized at poorly performing sites identified through proficiency testing, monthly monitoring of performance indicators or site assessments. Failure to enrol in a comprehensive EQA programme is a missed opportunity to identify and correct problems that affect the quality of testing. Where EQA programmes are available, their use should be considered during test selection, planning and budgeting processes before tests are introduced.
The GLI has developed an EQA dashboard that lists available EQA panel and programme providers (56). The products are not endorsed by GLI; however, the dashboard is a resource where countries can find suitable panels or programmes (56).
Proficiency testing
For many laboratory tests, the EQA programme includes proficiency testing to determine the quality of the results generated at the testing site. Proficiency testing compares testing site results with a reference result to determine comparability. The purpose of such testing is to identify sites with serious testing deficiencies, target support to the most poorly performing sites and evaluate the proficiency of users following training.
Re-checking of samples
Comparisons between laboratories can also be used as an external assessment of quality. This usually involves the retesting of samples at a higher level laboratory. Many TB laboratories are familiar with this approach because blinded re-checking is a routine method of EQA for acid-fast bacilli (AFB) smear microscopy.
Onsite supervisory visits
Onsite supervisory visits are especially critical during the early stages of implementing a new test because they provide motivation and support to staff. Supervisory visits are opportunities to provide refresher training, mentoring, troubleshooting advice and technical updates. Onsite assessments should be documented using standardized checklists, to ensure consistency and completeness of information, enable monitoring of trends, and allow follow-up on recommendations and corrective actions. An onsite supervisory programme requires substantial planning and resources (both financial and human).
Although not performed in laboratories, skin tests for TB infection need continuous internal QC and EQA. In many countries, certification of such tests is required after complex training and control, but a follow-up quality assessment is not in place. Mobile health (mHealth) technologies have been developed to allow quality assessment and QC of the performance of health care personnel even in remote areas (69).
For TST and TBST, resources include a guide for reviewers performing quantitative assessment of the skin test for TB infection (70), and instructions for health care personnel on how to take mTST photos (71) (Annex 4).
Step 7.4 – Monitor and analyse quality indicators
Routine monitoring of quality indicators, also known as performance indicators, is a critical element of assuring the quality of any diagnostic test. In addition to the general laboratory quality indicators recommended in the 2022 update to the practical manual on TB laboratory strengthening (65), quality indicators specific to the new diagnostic test should be adapted from international guidelines or developed from scratch. Quality indicators for NGS-based DST have been developed and are described in the WHO implementation manual (33). The indicators should be collected using a standardized format and analysed on a monthly or quarterly basis, disaggregated according to test.
Programmes should establish a baseline for all indicators. Targets should be set for all indicators monitored, and any unexplained change in quality indicators (e.g. an increase in error rates or a change in MTBC positivity) should be documented and investigated. A standard set of quality indicators should be used for all sites conducting a particular test, to allow for comparison between sites.
The continuous quality improvement process is a cyclical, continuous, data-driven approach to improving the quality of diagnostic testing. The process relies on a cycle of monitoring quality indicators, planning interventions to correct or improve performance, and implementing the interventions. Quality indicators should be reviewed by the laboratory manager and must always be linked to corrective actions if any unexpected results or trends are observed. Critical to the process is documentation of corrective actions, and subsequent improvement and normalization of laboratory indicators following the corrective actions.