Emerging Point of Care Tests for Influenza
Emerging Point of Care Tests for Influenza
We identified 12 emerging POCTs for influenza; one (3M Rapid Detection Flu test) has since been discontinued. Eleven were reported to provide type and/or subtype differentiation, including identification of H1N1(2009) and H3 in most cases. Tests claiming to offer this capability included several which incorporate RT-PCR, in addition to those which enhance currently available assays. Many of these tests are also expected to be fully automated and in some cases use closed systems (e.g. Liat influenza A/2009 H1N1 assay and XPERT Flu A&B panel), which can reduce the potential for human error and contamination, and those using an RT-PCR methodology are reported to take from 45 minutes to 1 hour to produce a result. In a busy clinic, this may itself represent a barrier to 'point of care' use, requiring a patient to remain isolated in the clinic, whilst results are awaited. In addition, whilst some of the identified emerging POCTs appear to have comparable sensitivity and specificity for influenza with the 'gold standard' RT-PCR methodology, most currently lack published clinical data on which to base an assessment. Improvement in the negative predictive value and also the positive predictive value of emerging POCTs compared with currently available POCTs is critical to their usefulness; though, it is likely that laboratory confirmation will still be required at times of low influenza activity (to reduce false-positive results) and to confirm negative results. In addition, the performance of individual tests and their effective use are likely to depend on training and familiarity, use of suitable sample type and appropriate quality assurance processes. The likely future cost of these tests once launched (including the replacement costs and shelf-life of the consumable components) is also unknown at present.
The methods used in this study rely on obtaining information on technologies from developers. Good existing relationships between the National Horizon Scanning Centre and the in vitro diagnostic industry, the comprehensive search strategy and involvement of commercial trade associations meant that we were able to produce a complete list of likely large and medium sized commercial developers. However, such developers may be unwilling or unable to provide useful intelligence at an early stage of development and may regard information as commercially confidential, particularly on the performance of the test and marketing plans. The majority of the tests identified were either being developed by, or with the support of, a major in vitro diagnostic manufacturer. Tests may initially be developed by individuals, academic institutions or small start-up companies, and those likely to be commercially successful are frequently acquired by larger companies prior to market; as such, it may be difficult to determine whether a company or product development is still active, which may account for the limited response to our information requests.
The adoption of POCTs for influenza into routine UK clinical practice is currently limited by the poor performance and high relative costs of currently available tests, as well as the inability to distinguish influenza types and subtype; a truly innovative POCT would need to be rapid, able to distinguish influenza A and B, differentiate key influenza A subtypes and have a sensitivity equivalent to that of the gold standard. We have identified a number of tests in a late stage of development that have the potential to offer benefits over the currently available options. In particular, POCTs employing RT-PCR methodology may be available and marketed over the next 1–2 years, and these have the potential to overcome many of these barriers to more widespread acceptance; though, their cost (as yet unknown) and the time taken to produce a result may still limit their diffusion into routine practice. The outcome of studies on the clinical application and usefulness of these POCTs once available will be of much interest.
Discussion
We identified 12 emerging POCTs for influenza; one (3M Rapid Detection Flu test) has since been discontinued. Eleven were reported to provide type and/or subtype differentiation, including identification of H1N1(2009) and H3 in most cases. Tests claiming to offer this capability included several which incorporate RT-PCR, in addition to those which enhance currently available assays. Many of these tests are also expected to be fully automated and in some cases use closed systems (e.g. Liat influenza A/2009 H1N1 assay and XPERT Flu A&B panel), which can reduce the potential for human error and contamination, and those using an RT-PCR methodology are reported to take from 45 minutes to 1 hour to produce a result. In a busy clinic, this may itself represent a barrier to 'point of care' use, requiring a patient to remain isolated in the clinic, whilst results are awaited. In addition, whilst some of the identified emerging POCTs appear to have comparable sensitivity and specificity for influenza with the 'gold standard' RT-PCR methodology, most currently lack published clinical data on which to base an assessment. Improvement in the negative predictive value and also the positive predictive value of emerging POCTs compared with currently available POCTs is critical to their usefulness; though, it is likely that laboratory confirmation will still be required at times of low influenza activity (to reduce false-positive results) and to confirm negative results. In addition, the performance of individual tests and their effective use are likely to depend on training and familiarity, use of suitable sample type and appropriate quality assurance processes. The likely future cost of these tests once launched (including the replacement costs and shelf-life of the consumable components) is also unknown at present.
The methods used in this study rely on obtaining information on technologies from developers. Good existing relationships between the National Horizon Scanning Centre and the in vitro diagnostic industry, the comprehensive search strategy and involvement of commercial trade associations meant that we were able to produce a complete list of likely large and medium sized commercial developers. However, such developers may be unwilling or unable to provide useful intelligence at an early stage of development and may regard information as commercially confidential, particularly on the performance of the test and marketing plans. The majority of the tests identified were either being developed by, or with the support of, a major in vitro diagnostic manufacturer. Tests may initially be developed by individuals, academic institutions or small start-up companies, and those likely to be commercially successful are frequently acquired by larger companies prior to market; as such, it may be difficult to determine whether a company or product development is still active, which may account for the limited response to our information requests.
The adoption of POCTs for influenza into routine UK clinical practice is currently limited by the poor performance and high relative costs of currently available tests, as well as the inability to distinguish influenza types and subtype; a truly innovative POCT would need to be rapid, able to distinguish influenza A and B, differentiate key influenza A subtypes and have a sensitivity equivalent to that of the gold standard. We have identified a number of tests in a late stage of development that have the potential to offer benefits over the currently available options. In particular, POCTs employing RT-PCR methodology may be available and marketed over the next 1–2 years, and these have the potential to overcome many of these barriers to more widespread acceptance; though, their cost (as yet unknown) and the time taken to produce a result may still limit their diffusion into routine practice. The outcome of studies on the clinical application and usefulness of these POCTs once available will be of much interest.