What is the aim of this review?
We aimed to understand the experiences and opinions of people using rapid automated tests that identify tuberculosis and resistance to tuberculosis drugs (molecular diagnostic tests). Users include people who might have tuberculosis and their families or caregivers, doctors, nurses, laboratory staff, and managers of services or programmes.
What was studied in this review?
Rapid molecular diagnostic tests were designed to make diagnosis easier and faster for people with signs and symptoms of tuberculosis, because they do not require a well-equipped laboratory, but can be done in clinics closer to where people live. Since these tests can also suggest whether an individual suffers from drug-resistant tuberculosis (including multidrug-resistant tuberculosis (MDR-TB)), the right treatment can be started earlier. We collected and analysed all relevant studies and found 32 studies conducted in areas where tuberculosis is common in low- and middle-income countries.
MDR-TB is tuberculosis caused by resistance to at least rifampicin and isoniazid, the two most effective first-line drugs used to treat tuberculosis.
This qualitative evidence synthesis links to another Cochrane Review that examines the diagnostic accuracy of a rapid molecular test for tuberculosis drug resistance. Yet, diagnostic tests only have an impact on health if they are put to use in a correct and timely manner. Accuracy studies do not reveal what users think of or how they experience the test in question. We need to understand the perspectives and experiences of all users. Otherwise, we risk these tests not fitting settings where they are to be used or not being accessible for those in need.
What are the main findings?
People with tuberculosis value knowing what is wrong with them. People valued having an accurate diagnosis, avoiding delays in being diagnosed, having accessible testing facilities, and keeping cost low. Similarly, healthcare providers value having accurate tests that give them confidence in the diagnosis, rapid results, and keeping cost low, being able to use different specimens (such as sputum and stool) and receiving information about drug resistance as part of the test results. Laboratory personnel appreciated that laboratory work was made easier and that staff was more satisfied thanks to rapid molecular diagnostic tests.
Our review also identified several challenges to realizing these values. Some people with tuberculosis and some healthcare providers were reluctant to use rapid molecular diagnostic tests because of fears of testing positive, concerns of stigma or discredit in the community, or expenses related to the testing. Additional support is required to overcome these barriers that are common to other approaches to testing for tuberculosis. Other challenges that led to delays and underuse of rapid molecular diagnostic tests were health system inefficiencies; poor quality of specimens; difficulty in transporting specimens; lack of sufficient resources such as staff or equipment; increased workload for providers; inefficiencies in integrating the test into routines at clinics; the complicated or lengthy steps involved in obtaining a tuberculosis diagnosis; clinicians relying too much on the test result while neglecting their own experience with diagnosing tuberculosis; and processes of implementing the test in national programmes that lacked data about real-life situations and did not include all relevant stakeholders such as local decision-makers, providers or people seeking a diagnosis.
Lastly, people expressed concerns about unsustainable funding, maintenance requirements of the tests, lengthy delays in diagnosis, underuse of rapid molecular diagnostic tests, lack of tuberculosis diagnostic facilities in local communities, conflicts of interest between donors and people who utilize the tests, and too many restrictions on who was allowed to access the test. These concerns hampered access to prompt and accurate testing and treatment. This was particularly the case for vulnerable people, such as children, people with MDR-TB, or those with limited ability to pay.
Overall, these challenges risk undoing the added value of rapid molecular diagnostic tests. They risk leading to less frequent use of these tests. Implementation of new diagnostic tests, like those considered in this review, will need to tackle the challenges identified in this review including weak infrastructure and systems, as well as insufficient data about real-life situations before and during implementation in order to ensure the tests are accessible for those in need.
How up to date is this review?
We included studies published between 1 January 2007 and 20 October 2021. We limited all searches to 2007 onward because the development of Xpert MTB/RIF, the first rapid molecular diagnostic test in this review, was completed in 2009.
Low-complexity diagnostics have been presented as a solution to overcome deficiencies in laboratory infrastructure and lack of skilled professionals. This review indicates this is misleading. The lack of infrastructure and human resources undermine the added value new diagnostics of low complexity have for recipients and providers. We had high confidence in the evidence contributing to these review findings.
Implementation of new diagnostic technologies, like those considered in this review, will need to tackle the challenges identified in this review including weak infrastructure and systems, and insufficient data on ground level realities prior and during implementation, as well as problems of conflicts of interest in order to ensure equitable use of resources.
Programmes that introduce rapid molecular tests for tuberculosis and tuberculosis drug resistance aim to bring tests closer to the community, and thereby cut delay in diagnosis, ensure early treatment, and improve health outcomes, as well as overcome problems with poor laboratory infrastructure and inadequately trained personnel. Yet, diagnostic technologies only have an impact if they are put to use in a correct and timely manner. Views of the intended beneficiaries are important in uptake of diagnostics, and their effective use also depends on those implementing testing programmes, including providers, laboratory professionals, and staff in health ministries. Otherwise, there is a risk these technologies will not fit their intended use and setting, cannot be made to work and scale up, and are not used by, or not accessible to, those in need.
To synthesize end-user and professional user perspectives and experiences with low-complexity nucleic acid amplification tests (NAATs) for detection of tuberculosis and tuberculosis drug resistance; and to identify implications for effective implementation and health equity.
We searched MEDLINE, Embase, CINAHL, PsycInfo and Science Citation Index Expanded databases for eligible studies from 1 January 2007 up to 20 October 2021. We limited all searches to 2007 onward because the development of Xpert MTB/RIF, the first rapid molecular test in this review, was completed in 2009.
We included studies that used qualitative methods for data collection and analysis, and were focused on perspectives and experiences of users and potential users of low-complexity NAATs to diagnose tuberculosis and drug-resistant tuberculosis. NAATs included Xpert MTB/RIF, Xpert MTB/RIF Ultra, Xpert MTB/XDR, and the Truenat assays. Users were people with presumptive or confirmed tuberculosis and drug-resistant tuberculosis (including multidrug-resistant (MDR-TB)) and their caregivers, healthcare providers, laboratory technicians and managers, and programme officers and staff; and were from any type of health facility and setting globally. MDR-TB is tuberculosis caused by resistance to at least rifampicin and isoniazid, the two most effective first-line drugs used to treat tuberculosis.
We used a thematic analysis approach for data extraction and synthesis, and assessed confidence in the findings using GRADE CERQual approach. We developed a conceptual framework to illustrate how the findings relate.
We found 32 studies. All studies were conducted in low- and middle-income countries. Twenty-seven studies were conducted in high-tuberculosis burden countries and 21 studies in high-MDR-TB burden countries. Only one study was from an Eastern European country. While the studies covered a diverse use of low-complexity NAATs, in only a minority of studies was it used as the initial diagnostic test for all people with presumptive tuberculosis.
We identified 18 review findings and grouped them into three overarching categories.
Critical aspects users value
People with tuberculosis valued reaching diagnostic closure with an accurate diagnosis, avoiding diagnostic delays, and keeping diagnostic-associated cost low. Similarly, healthcare providers valued aspects of accuracy and the resulting confidence in low-complexity NAAT results, rapid turnaround times, and keeping cost to people seeking a diagnosis low. In addition, providers valued diversity of sample types (for example, gastric aspirate specimens and stool in children) and drug resistance information. Laboratory professionals appreciated the improved ease of use, ergonomics, and biosafety of low-complexity NAATs compared to sputum microscopy, and increased staff satisfaction.
Challenges reported to realizing those values
People with tuberculosis and healthcare workers were reluctant to test for tuberculosis (including MDR-TB) due to fears, stigma, or cost concerns. Thus, low-complexity NAAT testing is not implemented with sufficient support or discretion to overcome barriers that are common to other approaches to testing for tuberculosis. Delays were reported at many steps of the diagnostic pathway owing to poor sample quality; difficulties with transporting specimens; lack of sufficient resources; maintenance of low-complexity NAATs; increased workload; inefficient work and patient flows; over-reliance on low-complexity NAAT results in lieu of clinical judgement; and lack of data-driven and inclusive implementation processes. These challenges were reported to lead to underutilization.
Concerns for access and equity
The reported concerns included sustainable funding and maintenance and equitable use of resources to access low-complexity NAATs, as well as conflicts of interest between donors and people implementing the tests. Also, lengthy diagnostic delays, underutilization of low-complexity NAATs, lack of tuberculosis diagnostic facilities in the community, and too many eligibility restrictions hampered access to prompt and accurate testing and treatment. This was particularly the case for vulnerable groups, such as children, people with MDR-TB, or people with limited ability to pay.
We had high confidence in most of our findings.